Neoplasia — MCQs
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A 61-year-old Caucasian male presents to your office complaining of morning headaches of 6 weeks duration. A head MRI reveals a likely metastasis of unknown origin in the supratentorial region of the brain. On biopsy, the neoplastic mass is shown to have a mutation in BRAF, a protein kinase, in which a glutamic acid is substituted for valine at position 600 of the protein. Where did this metastasis most likely originate?
A 31-year-old woman comes to the emergency department because of a 4-week history of worsening headache, nausea, and vomiting. The headache is worse at night. Fundoscopic examination shows swelling of the optic discs. A CT scan of the brain shows a heterogeneous, hyperintense, intraventricular mass. The patient undergoes surgical excision of the mass. Pathologic examination of the surgical specimen confirms that the tumor is of neuronal origin. The cells in this specimen are most likely to stain positive for which of the following immunohistochemical markers?
A 67-year-old man comes to the physician because of a 4-month history of fatigue and weight loss. Physical examination shows jaundice. The liver is palpated 3 cm below the right costal margin. Serum studies show an elevated alpha-fetoprotein and a prolonged prothrombin time. Genetic analysis of a liver biopsy specimen shows a G:C to T:A transversion in codon 249 of the gene coding for the TP53 protein in affected cells. Which of the following risk factors is most specific to the patient's condition?
A 41-year-old construction worker presents to the office complaining of a progressively worsening breathlessness for the last 2 months. He has no other complaints. His medical history is significant for hypertension being treated with lisinopril-hydrochlorothiazide and gastroesophageal reflux disease being treated with pantoprazole. He has a 30-pack-year smoking history and drinks alcohol on the weekends. He works mainly with insulation and drywall placing. His temperature is 37.0°C (98.6°F), the blood pressure is 144/78 mm Hg, the pulse is 72/min, and the respirations are 10/min. Upon further questioning about his employment, the patient admits that he does not regularly use a mask or other protective devices at work. Which of the following malignancies is this patient most likely at risk for?
A 58-year-old woman with a history of breast cancer, coronary artery disease, gastroesophageal reflux, and diabetes mellitus is diagnosed with angiosarcoma. Which of the following most likely predisposed her to this condition?
A 56-year-old man presents to his primary care physician complaining of a dark spot on his left thigh. He says that he first noticed the spot about 3 years ago when he went to the beach with his family; however, at the time it was very small and he didn't think that it was worth mentioning. Since then, it has been growing slowly and he is now concerned about its size. He says that he does not have any other symptoms associated with the lesion. Physical exam reveals an asymmetric 2.5 centimeter plaque with irregular borders and a varying pattern of brown coloration. The lesion is studied and found to have a mutation in a tumor suppressor gene that normally prevents uncontrolled cell cycle progression by inhibiting cyclin-CDK complexes. Which of the following is most likely true of this gene?
A 50-year-old man presents to his primary care provider complaining of smelling abnormal odors on several occasions. He says that he smells burnt rubber even though there is nothing burning and no one around him can smell what he does. This symptom has been intermittently bothering him for the past 6 months. Also during this period, he had occasional nosebleeds. He works as a high school teacher. Although his work gets a little stressful around the exam season, he says he is able to cope well. Family history is unremarkable. He does not smoke or drink alcohol and denies the use of any medication. Physical examination reveals unilateral nasal obstruction with some dried blood in the nasal passage. What is the most likely diagnosis?
A 57-year-old woman presents to the hospital complaining of 4 months of persistent abdominal pain and early satiety that has recently gotten worse. The patient says that she was prompted to come to the emergency department because she had several episodes of hematemesis. Her last menstrual period was approximately 8 years ago. The patient is sexually active with her husband and notes that she has recently had pain with intercourse as well as 'spotting' after intercourse. The patient states that she has also been experiencing nausea and weight loss associated with abdominal pain. Her blood pressure is 125/84 mm Hg, respiratory rate is 15/min, and heart rate is 76/min. Which of the following would be pathognomonic of this patient’s most likely diagnosis?
A 6-month-old boy is brought to the pediatrician for multiple swellings on his scalp. His mother reports that she first noticed 3 softened and swollen areas over the child's scalp 2 months ago that have grown in size. The child is also urinating more frequently than usual. He was born by cesarean section at 39 weeks gestation. The mother had appropriate prenatal care. She has a history of gastroesophageal reflux disease for which she takes omeprazole. Her family history is unknown as she was adopted at a young age. The boy's temperature is 99°F (37.2°C), blood pressure is 100/60 mmHg, pulse is 110/min, and respirations are 20/min. On exam, he has 3 areas of soft tissue swelling on his skull that are tender to palpation. Moderate asymmetric exophthalmos is noted. A water deprivation test is performed which demonstrates a urine specific gravity of 1.005. The urine specific gravity rises with desmopression administration. A head computerized tomography (CT) scan is performed which demonstrates multifocal lytic calvarial lesions. A biopsy of one of the lesions is performed. Analysis of the biopsy would most likely reveal which of the following findings?
A 46-year-old overweight male presents to his primary care physician for an annual checkup. He has a history of gastroesophageal reflux disease (GERD) with biopsy confirming Barrett's esophagus on therapy with omeprazole. Review of systems is unremarkable, and the patient is otherwise doing well. Vitals are within normal limits and stable. The patient asks about the need for continuing his omeprazole therapy. You recommend he continue his medication because of which of the following most probable long-term sequelae associated with Barrett's esophagus?
Neoplasia US Medical PG Practice Questions and MCQs
Question 1: A 61-year-old Caucasian male presents to your office complaining of morning headaches of 6 weeks duration. A head MRI reveals a likely metastasis of unknown origin in the supratentorial region of the brain. On biopsy, the neoplastic mass is shown to have a mutation in BRAF, a protein kinase, in which a glutamic acid is substituted for valine at position 600 of the protein. Where did this metastasis most likely originate?
- A. Stomach
- B. Skin (Correct Answer)
- C. Breast
- D. Brain
- E. Bone
Explanation: ***Skin*** - A brain metastasis with a **V600E BRAF mutation** is highly suggestive of **melanoma**, a type of skin cancer. - Melanoma frequently metastasizes to the **brain**, and the BRAF V600E mutation is a common and actionable target in advanced melanoma. *Stomach* - Stomach cancers (gastric adenocarcinomas) less commonly metastasize to the brain compared to melanoma. - While BRAF mutations can occur in gastric cancer, the **V600E mutation** is not typically a defining feature of gastric cancer metastases to the brain. *Breast* - Breast cancer can metastasize to the brain, but the presence of a **BRAF V600E mutation** is not a characteristic genetic alteration for breast cancer. - Common mutations in breast cancer include those in **ER, PR, and HER2** receptors or **PIK3CA**, not BRAF V600E. *Brain* - The question states the mass is a **metastasis of unknown origin**, implying it did not originate in the brain itself. - Primary brain tumors like **gliomas** would not be described as metastases and have a different mutational spectrum. *Bone* - Bone cancers (sarcomas) or metastases to the bone usually do not present with a **BRAF V600E mutation** as their primary driver for brain metastasis. - While various cancers can metastasize to bone, the specific mutation points away from a bone origin.
Question 2: A 31-year-old woman comes to the emergency department because of a 4-week history of worsening headache, nausea, and vomiting. The headache is worse at night. Fundoscopic examination shows swelling of the optic discs. A CT scan of the brain shows a heterogeneous, hyperintense, intraventricular mass. The patient undergoes surgical excision of the mass. Pathologic examination of the surgical specimen confirms that the tumor is of neuronal origin. The cells in this specimen are most likely to stain positive for which of the following immunohistochemical markers?
- A. Synaptophysin (Correct Answer)
- B. S-100
- C. Glial fibrillary acidic protein
- D. Cytokeratin
- E. Desmin
Explanation: ***Synaptophysin*** - This marker is characteristic of **neuronal and neuroendocrine differentiation**, strongly supporting the diagnosis of a tumor of neuronal origin. - Tumors like **gangliogliomas** and **central neurocytomas**, which are neuronal tumors, typically stain positive for synaptophysin. *S-100* - S-100 protein is a marker typically associated with cells of **glial**, **Schwann cell**, or **melanocytic** origin. - While some neuronal tumors can show focal S-100 positivity, it is not the primary or most specific marker for neuronal differentiation. *Glial fibrillary acidic protein* - **GFAP** is the canonical marker for **astrocytes and other glial cells**, indicating a glial rather than neuronal origin for the tumor. - An intraventricular mass of neuronal origin would not primarily stain for GFAP. *Cytokeratin* - **Cytokeratins** are intermediate filament proteins exclusively found in **epithelial cells** and are markers for carcinomas. - They are not expressed in cells of neuronal origin, making this option incorrect. *Desmin* - **Desmin** is an intermediate filament protein found in **muscle cells** (smooth, skeletal, and cardiac). - Its presence indicates a myogenic origin, which is inconsistent with a tumor described as being of neuronal origin.
Question 3: A 67-year-old man comes to the physician because of a 4-month history of fatigue and weight loss. Physical examination shows jaundice. The liver is palpated 3 cm below the right costal margin. Serum studies show an elevated alpha-fetoprotein and a prolonged prothrombin time. Genetic analysis of a liver biopsy specimen shows a G:C to T:A transversion in codon 249 of the gene coding for the TP53 protein in affected cells. Which of the following risk factors is most specific to the patient's condition?
- A. Dietary aflatoxin exposure (Correct Answer)
- B. Alcoholism
- C. Schistosomiasis
- D. Hemochromatosis
- E. Hepatitis C infection
Explanation: ***Dietary aflatoxin exposure*** - The **TP53 mutation** (G:C to T:A transversion at codon 249) is a **signature mutation** strongly associated with **aflatoxin B1 exposure**, particularly in hepatocellular carcinoma. - Aflatoxins are potent **carcinogens produced by Aspergillus fungi**, often found in contaminated food storage in tropical regions. *Schistosomiasis* - This parasitic infection is a risk factor for **squamous cell carcinoma of the bladder** and, to a lesser extent, **cholangiocarcinoma**, but not typically hepatocellular carcinoma with this specific TP53 mutation signature. - It primarily affects the **urinary bladder** and intestines, leading to chronic inflammation and fibrosis. *Alcoholism* - Chronic alcoholism is a major risk factor for **cirrhosis** and **hepatocellular carcinoma** due to continuous liver damage and regeneration. - However, it does not typically cause the **specific TP53 codon 249 mutation** seen in this patient. *Hemochromatosis* - This genetic disorder causes **iron overload**, leading to liver damage, **cirrhosis**, and an increased risk of **hepatocellular carcinoma**. - While it predisposes to liver cancer, it is not associated with the **specific G:C to T:A TP53 mutation** described. *Hepatitis C infection* - Chronic hepatitis C is a leading cause of **cirrhosis** and **hepatocellular carcinoma** worldwide due to chronic inflammation and hepatocyte turnover. - Similar to alcoholism, it is a significant risk factor for liver cancer but does not specifically cause the **TP53 codon 249 mutation** linked to aflatoxin.
Question 4: A 41-year-old construction worker presents to the office complaining of a progressively worsening breathlessness for the last 2 months. He has no other complaints. His medical history is significant for hypertension being treated with lisinopril-hydrochlorothiazide and gastroesophageal reflux disease being treated with pantoprazole. He has a 30-pack-year smoking history and drinks alcohol on the weekends. He works mainly with insulation and drywall placing. His temperature is 37.0°C (98.6°F), the blood pressure is 144/78 mm Hg, the pulse is 72/min, and the respirations are 10/min. Upon further questioning about his employment, the patient admits that he does not regularly use a mask or other protective devices at work. Which of the following malignancies is this patient most likely at risk for?
- A. Hepatocellular carcinoma
- B. Bronchogenic carcinoma
- C. Adenocarcinoma
- D. Mesothelioma (Correct Answer)
- E. Squamous cell carcinoma
Explanation: ***Mesothelioma*** - This patient's occupation as a construction worker involved with **insulation and drywall** places him at high risk for **asbestos exposure**, a primary cause of mesothelioma. - The presenting symptom of **progressive breathlessness** is consistent with mesothelioma, which often affects the pleura. *Hepatocellular carcinoma* - This cancer is primarily associated with **chronic viral hepatitis (HBV, HCV)**, **cirrhosis**, or **alcoholism**, none of which are strongly indicated as the primary risk factor here. - The patient's alcohol use is "on weekends" and without evidence of cirrhosis; his symptoms are respiratory, not hepatic. *Bronchogenic carcinoma* - While the patient's **30-pack-year smoking history** is a significant risk factor for bronchogenic carcinoma, the specific occupational exposure to asbestos points more strongly towards mesothelioma as the most likely malignancy in this context. - Bronchogenic carcinoma typically presents with a range of symptoms including cough, hemoptysis, and weight loss, though dyspnea is also common. *Adenocarcinoma* - Adenocarcinoma is a type of lung cancer, and while smoking is a risk factor, occupational asbestos exposure is a more specific and direct link to mesothelioma. - It does not specifically account for the unique occupational hazard in this patient's history. *Squamous cell carcinoma* - Squamous cell carcinoma is another type of lung cancer strongly associated with **smoking**. - However, similar to adenocarcinoma and bronchogenic carcinoma, the specific occupational exposure to **asbestos** makes mesothelioma a more direct and likely diagnosis given the information provided.
Question 5: A 58-year-old woman with a history of breast cancer, coronary artery disease, gastroesophageal reflux, and diabetes mellitus is diagnosed with angiosarcoma. Which of the following most likely predisposed her to this condition?
- A. Inherited dysfunction of a DNA repair protein
- B. History of mastectomy with lymph node dissection (Correct Answer)
- C. History of exposure to asbestos
- D. History of chemotherapy
- E. Hereditary disorder
Explanation: ***History of mastectomy with lymph node dissection*** - **Lymphedema**, a common complication following **mastectomy with lymph node dissection**, is a significant risk factor for developing **angiosarcoma** in the affected limb or chest wall. - This condition is known as **Stewart-Treves syndrome**, where chronic lymphedema leads to endothelial cell proliferation and malignant transformation. *Inherited dysfunction of a DNA repair protein* - While inherited DNA repair protein dysfunctions can increase cancer risk (e.g., Lynch syndrome, BRCA mutations), they are not directly linked to angiosarcoma in the context described. - This type of genetic predisposition typically leads to specific solid tumors or hematological malignancies, not typically angiosarcoma due to lymphedema. *History of exposure to asbestos* - **Asbestos exposure** is primarily associated with **mesothelioma** and lung cancer. - There is no direct significant link between asbestos exposure and the development of angiosarcoma. *History of chemotherapy* - Certain **chemotherapy agents** can be cytotoxic and increase the risk of secondary malignancies, particularly leukemias and myelodysplastic syndromes. - However, chemotherapy is not a primary or direct predisposing factor for angiosarcoma, especially compared to the strong association with chronic lymphedema. *Hereditary disorder* - While some hereditary disorders increase cancer risk, angiosarcoma is not typically linked to a specific, common hereditary disorder in this context. - The presented scenario points more strongly to an acquired risk factor related to cancer treatment rather than an underlying genetic predisposition.
Question 6: A 56-year-old man presents to his primary care physician complaining of a dark spot on his left thigh. He says that he first noticed the spot about 3 years ago when he went to the beach with his family; however, at the time it was very small and he didn't think that it was worth mentioning. Since then, it has been growing slowly and he is now concerned about its size. He says that he does not have any other symptoms associated with the lesion. Physical exam reveals an asymmetric 2.5 centimeter plaque with irregular borders and a varying pattern of brown coloration. The lesion is studied and found to have a mutation in a tumor suppressor gene that normally prevents uncontrolled cell cycle progression by inhibiting cyclin-CDK complexes. Which of the following is most likely true of this gene?
- A. Both copies of the gene encoding the target are non-functional in tumors (Correct Answer)
- B. The protein experienced gain of function mutation
- C. The gene is involved in DNA repair
- D. Overproduction of the gene product leads to disease
- E. The gene is located on the X chromosome
Explanation: ***Both copies of the gene encoding the target are non-functional in tumors*** - Tumor suppressor genes follow the **two-hit hypothesis**, meaning both alleles must be inactivated for their protective function against cancer to be lost. - The mutation in a tumor suppressor gene, as described, aligns with this hypothesis, where the remaining functional copy could initially keep tumor growth in check before its eventual inactivation allows uncontrolled cell proliferation. *The protein experienced gain of function mutation* - This statement typically describes **oncogenes**, where a single activating mutation leads to uncontrolled cell growth. - Tumor suppressor genes normally function to inhibit cell growth; their inactivation (loss of function), rather than gain of function, contributes to cancer. *The gene is involved in DNA repair* - While some tumor suppressor genes, like **BRCA1** and **BRCA2**, are involved in DNA repair, the problem specifically states this gene prevents uncontrolled cell cycle progression by inhibiting cyclin-CDK complexes. - This function points more directly to cell cycle regulation rather than DNA repair. *Overproduction of the gene product leads to disease* - Overproduction of a gene product leading to disease is more characteristic of situations where excess protein causes toxicity or disrupts normal pathways, not typically how the inactivation of a tumor suppressor gene presents. - Tumor suppressor genes prevent disease when they are active; their loss of function, not overproduction, is linked to cancer. *The gene is located on the X chromosome* - While it is possible for a tumor suppressor gene to be on the X chromosome, the problem provides no information to suggest this specific chromosomal location. - The critical information revolves around its function as a tumor suppressor and its mechanism of action, not its chromosomal address.
Question 7: A 50-year-old man presents to his primary care provider complaining of smelling abnormal odors on several occasions. He says that he smells burnt rubber even though there is nothing burning and no one around him can smell what he does. This symptom has been intermittently bothering him for the past 6 months. Also during this period, he had occasional nosebleeds. He works as a high school teacher. Although his work gets a little stressful around the exam season, he says he is able to cope well. Family history is unremarkable. He does not smoke or drink alcohol and denies the use of any medication. Physical examination reveals unilateral nasal obstruction with some dried blood in the nasal passage. What is the most likely diagnosis?
- A. Sinonasal malignancy (Correct Answer)
- B. Substance abuse
- C. Hypnagogic hallucination
- D. Schizophrenia
- E. Psychomotor epilepsy
Explanation: ***Sinonasal malignancy*** - The patient's **phantom smell (phantosmia)** of burnt rubber, along with **unilateral nasal obstruction** and **nosebleeds**, are classic symptoms suggestive of a sinonasal tumor. - While phantosmia can have other causes, its association with local obstructive and hemorrhagic symptoms points towards a space-occupying lesion in the sinonasal region. *Substance abuse* - Although certain substances can cause olfactory hallucinations, there's no history of substance use, and the presence of **unilateral nasal obstruction** and **dried blood** is not typical. - The patient denies smoking or drinking and is otherwise healthy. *Hypnagogic hallucination* - These are vivid perceptual experiences that occur as one is *falling asleep* and are usually visual or auditory, not typically olfactory phantosmia. - They are not associated with **nasal obstruction** or **nosebleeds**. *Schizophrenia* - Schizophrenia is characterized by **delusions**, **disorganized speech**, and **negative symptoms**; olfactory hallucinations are uncommon as initial or isolated symptoms. - It does not explain the **physical findings** of unilateral nasal obstruction and nosebleeds. *Psychomotor epilepsy* - Also known as **temporal lobe epilepsy**, this can cause olfactory hallucinations (auras), but these are usually brief and episodic, often accompanied by other **complex partial seizure** symptoms such as automatisms or altered consciousness. - The patient's symptoms are more persistent over 6 months and are accompanied by local nasal findings, which are not typical for psychomotor epilepsy alone.
Question 8: A 57-year-old woman presents to the hospital complaining of 4 months of persistent abdominal pain and early satiety that has recently gotten worse. The patient says that she was prompted to come to the emergency department because she had several episodes of hematemesis. Her last menstrual period was approximately 8 years ago. The patient is sexually active with her husband and notes that she has recently had pain with intercourse as well as 'spotting' after intercourse. The patient states that she has also been experiencing nausea and weight loss associated with abdominal pain. Her blood pressure is 125/84 mm Hg, respiratory rate is 15/min, and heart rate is 76/min. Which of the following would be pathognomonic of this patient’s most likely diagnosis?
- A. Hyperplasia of gastric mucosa
- B. PAS-positive macrophages
- C. Intestinal metaplasia in the stomach
- D. Signet ring cells (Correct Answer)
- E. Ectopic thyroid tissue
Explanation: ***Signet ring cells*** - The patient's symptoms (persistent abdominal pain, early satiety, hematemesis, weight loss, and dyspareunia with post-coital spotting) are highly suggestive of a **metastatic gastric adenocarcinoma**, possibly to the ovaries (Krukenberg tumor). - **Signet ring cells** are characteristic histological features of diffuse-type gastric adenocarcinoma, a highly aggressive form that often presents with metastasis. *Hyperplasia of gastric mucosa* - While gastric mucosal hyperplasia can occur in various conditions (e.g., Ménétrier disease, Zollinger-Ellison syndrome), it is not a direct indicator or pathognomonic feature of advanced gastric adenocarcinoma with metastasis. - The patient's severe symptoms, especially hematemesis and weight loss, point to a more aggressive pathology than simple hyperplasia. *PAS-positive macrophages* - **PAS-positive macrophages** are characteristic of **Whipple's disease**, a rare systemic bacterial infection primarily affecting the small intestine. - The constellation of symptoms in this patient, particularly the localized abdominal pain, hematemesis, and gynecological symptoms, does not align with Whipple's disease. *Intestinal metaplasia in the stomach* - **Intestinal metaplasia** is a common precursor lesion for intestinal-type gastric adenocarcinoma, but it is not a pathognomonic feature of an advanced, metastatic tumor itself. - While it indicates an increased risk, the presence of specific malignant cells (like signet ring cells) is more definitive for the diagnosis of adenocarcinoma. *Ectopic thyroid tissue* - **Ectopic thyroid tissue** refers to thyroid tissue found outside its normal anatomical location, most commonly in the neck or mediastinum. - It is an anatomical variant and has no direct relevance to the gastrointestinal and gynecological symptoms described by the patient.
Question 9: A 6-month-old boy is brought to the pediatrician for multiple swellings on his scalp. His mother reports that she first noticed 3 softened and swollen areas over the child's scalp 2 months ago that have grown in size. The child is also urinating more frequently than usual. He was born by cesarean section at 39 weeks gestation. The mother had appropriate prenatal care. She has a history of gastroesophageal reflux disease for which she takes omeprazole. Her family history is unknown as she was adopted at a young age. The boy's temperature is 99°F (37.2°C), blood pressure is 100/60 mmHg, pulse is 110/min, and respirations are 20/min. On exam, he has 3 areas of soft tissue swelling on his skull that are tender to palpation. Moderate asymmetric exophthalmos is noted. A water deprivation test is performed which demonstrates a urine specific gravity of 1.005. The urine specific gravity rises with desmopression administration. A head computerized tomography (CT) scan is performed which demonstrates multifocal lytic calvarial lesions. A biopsy of one of the lesions is performed. Analysis of the biopsy would most likely reveal which of the following findings?
- A. B cells with hair-like cytoplasmic projections
- B. Cytoplasmic azurophilic granules forming needle-like structures
- C. Atypical lymphocytes with cerebriform nuclei
- D. Rod-shaped granules with a latticed matrix (Correct Answer)
- E. Proliferative monoclonal plasma cells
Explanation: ***Rod-shaped granules with a latticed matrix*** - The clinical presentation of **lytic calvarial lesions**, **exophthalmos**, and **diabetes insipidus** (polyuria, low urine specific gravity correcting with desmopressin) in an infant is highly suggestive of **Langerhans cell histiocytosis (LCH)**. - A biopsy would reveal characteristic **Langerhans cells** which contain **Birbeck granules** (also known as rod-shaped granules with a latticed matrix or tennis-racket shaped granules) and express S-100 and CD1a. *B cells with hair-like cytoplasmic projections* - This describes **hairy cell leukemia**, a **B-cell lymphoproliferative disorder** primarily affecting older adults, not infants, and presenting with pancytopenia and splenomegaly rather than lytic bone lesions. - The clinical picture of lytic skull lesions, exophthalmos, and diabetes insipidus does not align with hairy cell leukemia. *Cytoplasmic azurophilic granules forming needle-like structures* - This finding refers to **Auer rods**, which are characteristic of **acute myeloid leukemia (AML)**, particularly in **myeloblasts**. - While AML can cause **bone lesions** (chloromas), it would not typically present with the triad of lytic skull lesions, exophthalmos, and diabetes insipidus as the primary features in this age group, nor would it be expected to form soft tissue swellings of several months' duration. *Atypical lymphocytes with cerebriform nuclei* - This describes the characteristic cells of **Sézary syndrome** or **mycosis fungoides**, which are **cutaneous T-cell lymphomas** primarily seen in adults. - The clinical presentation with scalp swellings, exophthalmos, and diabetes insipidus in an infant is incompatible with these diagnoses. *Proliferative monoclonal plasma cells* - This is characteristic of **multiple myeloma** or **plasmacytoma**, which are plasma cell dyscrasias affecting older adults and typically causing lytic bone lesions, hypercalcemia, renal failure, and anemia. - It is exceedingly rare in infants and would not explain the exophthalmos or diabetes insipidus in this context.
Question 10: A 46-year-old overweight male presents to his primary care physician for an annual checkup. He has a history of gastroesophageal reflux disease (GERD) with biopsy confirming Barrett's esophagus on therapy with omeprazole. Review of systems is unremarkable, and the patient is otherwise doing well. Vitals are within normal limits and stable. The patient asks about the need for continuing his omeprazole therapy. You recommend he continue his medication because of which of the following most probable long-term sequelae associated with Barrett's esophagus?
- A. Adenocarcinoma (Correct Answer)
- B. Gastro-intestinal stromal tumor (GIST)
- C. Squamous cell carcinoma (SCC)
- D. Transitional cell carcinoma
- E. MALT lymphoma
Explanation: ***Adenocarcinoma*** - **Barrett's esophagus** is a premalignant condition characterized by the change of the normal stratified squamous epithelium of the esophagus to columnar epithelium with goblet cells. - This metaplasia is a significant risk factor for the development of **esophageal adenocarcinoma**, making long-term acid suppression crucial. *Gastro-intestinal stromal tumor (GIST)* - **GISTs** are rare tumors arising from the interstitial cells of Cajal, most commonly found in the stomach or small intestine, not typically associated with Barrett's esophagus. - They are generally not influenced by acid-suppressive therapy and do not originate from the esophageal mucosa affected by metaplasia. *Squamous cell carcinoma (SCC)* - **Squamous cell carcinoma** of the esophagus is typically linked to risk factors like smoking and alcohol consumption, and arises from the normal squamous lining. - While it is a type of esophageal cancer, it is not the type associated with Barrett's esophagus; adenocarcinoma is the primary malignancy linked to this condition. *Transitional cell carcinoma* - **Transitional cell carcinoma** primarily affects the urinary tract (bladder, ureters, renal pelvis), not the esophagus. - This type of cancer has no known association with Barrett's esophagus or chronic acid reflux. *MALT lymphoma* - **MALT lymphoma** (Mucosa-Associated Lymphoid Tissue lymphoma) is a type of non-Hodgkin lymphoma often associated with chronic inflammation, such as *H. pylori* infection in the stomach. - It is not a sequela of Barrett's esophagus and does not arise from the metaplastic epithelium of the esophagus.
Question 11: A 43-year-old woman presents to a physician with repeated bruising, which she noticed over the last week. Some bruises developed spontaneously, while others were observed following minor trauma. The patient also mentions that she has been experiencing significant fatigue and weakness for the past 4 months and that her appetite has been considerably reduced for a few months. Past medical history is noncontributory. Both of her parents are still alive and healthy. She drinks socially and does not smoke. On physical examination, her temperature is 37.6°C (99.7°F), pulse rate is 88/min, blood pressure is 126/84 mm Hg, and respiratory rate is 18/min. Her general examination reveals mild bilateral cervical and axillary lymphadenopathy with multiple petechiae and ecchymoses over the body. Palpation of the abdomen reveals the presence of hepatomegaly and splenomegaly. Her detailed diagnostic workup, including complete blood counts, coagulation studies, and bone marrow biopsy, confirms the diagnosis of a subtype of acute myeloid leukemia, which is characterized by neoplastic proliferation of promyelocytes and good response to all-trans retinoic acid. The neoplastic cells are myeloperoxidase positive and contain azurophilic crystal rods. Which of the following genetic abnormalities is most likely to be present in this patient?
- A. t(15;17)(q24;q21) (Correct Answer)
- B. inv(16)(p13q22)
- C. t(1;22)(p13;q13)
- D. t(9;11)(p22;q23)
- E. t(8;21)(q22;q22)
Explanation: ***t(15;17)(q24;q21)*** - This translocation is the hallmark of **acute promyelocytic leukemia (APL)**, a subtype of **AML** characterized by the proliferation of **promyelocytes**. - **APL** is uniquely responsive to **all-trans retinoic acid (ATRA)** and is associated with the presence of **Auer rods (azurophilic crystal rods)**, which are myeloperoxidase positive. *inv(16)(p13q22)* - This inversion is characteristic of acute myelomonocytic leukemia with **eosinophilia**, a subtype of **AML**. - While it is a recurrent cytogenetic abnormality in **AML**, it does not typically present with the classic features of **APL**, such as sensitivity to **ATRA** or the presence of numerous **Auer rods** in promyelocytes. *t(1;22)(p13;q13)* - This translocation is associated with **acute megakaryoblastic leukemia (AMKL)** in infants. - **AMKL** is a rare subtype of **AML** that primarily affects infants and toddlers and is not consistent with the patient's age or the specific morphology described. *t(9;11)(p22;q23)* - This translocation involves the **MLL gene** and is commonly seen in **acute monoblastic or myelomonocytic leukemia**, particularly in young children. - While it is associated with **AML**, it does not lead to the promyelocytic morphology, **Auer rods**, or **ATRA** sensitivity seen in the patient's case. *t(8;21)(q22;q22)* - This translocation is frequently found in **AML with maturation** (M2 subtype according to the FAB classification). - Patients with this translocation generally have a favorable prognosis but do not present with the specific features of **APL**, such as **promyelocytic differentiation** and **ATRA responsiveness**.
Question 12: A 38-year-old woman comes to the physician for a 3-month history of bloody discharge from the right nipple. Her mother died of breast cancer at the age of 69 years. Mammography 6 months ago did not show any abnormalities. Examination of the breast shows expression of a small amount of serosanguinous fluid from the right nipple; there are no palpable breast masses or axillary lymphadenopathy. Ultrasonography of the right breast shows a single dilated duct. Which of the following is the most likely diagnosis?
- A. Invasive ductal carcinoma
- B. Paget disease of the breast
- C. Phyllodes tumor
- D. Breast lipoma
- E. Intraductal papilloma (Correct Answer)
Explanation: ***Intraductal papilloma*** - This lesion typically presents with **bloody or serosanguinous nipple discharge** from a single duct, as described in the patient. - It is a **benign proliferative lesion** that grows within a major lactiferous duct, often leading to ductal dilatation on ultrasound, without a palpable mass or suspicious mammographic findings. *Invasive ductal carcinoma* - While it can cause bloody nipple discharge, it is more commonly associated with a **palpable mass**, skin changes, or abnormal findings on mammography. - The absence of a palpable mass, normal mammogram 6 months prior, and isolated ductal dilatation on ultrasound make it less likely in this scenario. *Paget disease of the breast* - This condition presents as an **eczematous lesion of the nipple and areola**, often with itching, scaling, and ulceration. - While it can be associated with an underlying invasive or in situ carcinoma, the primary presenting symptom is skin changes, not solely nipple discharge in a seemingly normal breast. *Phyllodes tumor* - These are **biphasic fibroepithelial tumors** that typically present as a rapidly growing, palpable breast mass. - They do not characteristically present with isolated nipple discharge, especially without any palpable mass. *Breast lipoma* - A breast lipoma is a **benign fatty tumor** that presents as a soft, mobile, non-tender lump. - It does not cause nipple discharge and is usually easily identifiable on imaging as a fatty lesion.
Question 13: A 68-year-old man comes to the physician for evaluation of a lump in his left axilla that he first noticed 1 year ago. He reports that the size of the mass has varied over time and that there have been similar masses in his neck and groin. He has not had fever, weight loss, or night sweats. Physical examination shows a nontender, rubbery mass in the left axilla and a similar, smaller mass in the right groin. His spleen is palpable 3 cm below the left costal margin. Laboratory studies, including complete blood count, are within reference ranges. Genetic analysis obtained on resection of the axillary mass shows a t(14;18) translocation. Which of the following is the most likely diagnosis?
- A. Diffuse large B-cell lymphoma
- B. Follicular lymphoma (Correct Answer)
- C. Burkitt lymphoma
- D. Hodgkin lymphoma
- E. Marginal zone lymphoma
Explanation: ***Follicular lymphoma*** - The presence of a **t(14;18) translocation**, which leads to overexpression of the **BCL2 gene**, is a hallmark of follicular lymphoma. - The clinical presentation of **waxing and waning lymphadenopathy** in multiple sites (axilla, neck, groin) and **splenomegaly** in an elderly patient is classic for follicular lymphoma. *Diffuse large B-cell lymphoma* - This lymphoma is typically characterized by **rapid growth** and often presents with B symptoms (fever, weight loss, night sweats), which are absent here. - The **t(14;18) translocation** is typically associated with follicular lymphoma, though it can occasionally be seen in transformed DLBCL, but the waxing and waning course points away from de novo DLBCL. *Burkitt lymphoma* - Characterized by the **t(8;14) translocation** resulting in c-MYC overexpression, not t(14;18). - It presents with **very aggressive growth** and typically affects children or young adults, often involving extranodal sites like the jaw or abdomen. *Hodgkin lymphoma* - Diagnosed by the presence of **Reed-Sternberg cells** and typically presents with contiguous lymphadenopathy and often B symptoms, which are not described. - It does not involve the **t(14;18) translocation**. *Marginal zone lymphoma* - Does not typically involve the **t(14;18) translocation** and commonly arises in extranodal sites, often related to chronic inflammation or autoimmune disease. - The clinical picture of multifocal, waxing and waning lymphadenopathy with splenomegaly is less characteristic for marginal zone lymphoma.
Question 14: A 45-year-old woman gravida 1, para 1, comes to the physician because of a 2-month history of a right breast lump and a 4.5-kg (10-lb) weight loss. She has not had any breast pain or nipple discharge. She had right breast mastitis 10 years ago while breastfeeding but has no other history of serious illness. Palpation of the right breast shows a 3-cm firm mass with well-defined margins lateral to the right nipple. There is dimpling of the overlying skin but no rash. The left breast is normal. A mammogram shows a density with calcifications in a star-shaped formation in the same location of the mass. Histological examination of a biopsy specimen from the breast mass is most likely to show which of the following?
- A. Large, pink-staining cells in the epidermis
- B. Orderly rows of monomorphic cells that do not stain with E-cadherin
- C. Dilated ducts lined with neoplastic cells and necrotic centers
- D. Disorganized nests of glandular cells with surrounding fibrosis (Correct Answer)
- E. Infiltration of ductal cells blocking the dermal lymphatics
Explanation: ***Disorganized nests of glandular cells with surrounding fibrosis*** - The presentation of a **firm breast mass with dimpling**, **weight loss**, and **mammographic calcifications in a star-shaped formation** (spiculated mass) is highly indicative of **invasive ductal carcinoma (IDC)**, the most common type of breast cancer. - Histologically, IDC is characterized by **disorganized nests, cords, or single cells of malignant glandular epithelium** infiltrating the surrounding stroma, often provoking a significant **desmoplastic reaction** (fibrosis). *Large, pink-staining cells in the epidermis* - This description is characteristic of **Paget disease of the nipple**, which involves the spread of adenocarcinoma cells into the epidermis of the nipple and areola. - While Paget disease can be associated with an underlying invasive carcinoma, the primary histological finding of the mass itself would not be epidermal cells, and the described mass and mammographic findings are more direct for IDC. *Orderly rows of monomorphic cells that do not stain with E-cadherin* - This histological pattern is characteristic of **invasive lobular carcinoma (ILC)**, where cells invade in **single-file lines** due to the loss of **E-cadherin** adhesion protein. - However, ILC typically presents with a **poorly defined mass** on mammogram due to its diffuse infiltrative growth pattern, rather than a firm mass with spiculated calcifications. *Dilated ducts lined with neoplastic cells and necrotic centers* - This describes **ductal carcinoma in situ (DCIS)**, particularly the **comedo type**, which is characterized by malignant cells filling the ducts, often with central necrosis. - While DCIS can present with calcifications, the presence of a **palpable firm mass**, **skin dimpling**, and **weight loss** strongly suggests an **invasive process**, not just in situ disease. *Infiltration of ductal cells blocking the dermal lymphatics* - This finding is characteristic of **inflammatory breast cancer**, where tumor cells invade and obstruct the **dermal lymphatic vessels**, leading to skin changes resembling mastitis ("peau d'orange" or erythema and warmth). - While skin dimpling is present, the absence of diffuse redness, warmth, and "peau d'orange" makes inflammatory breast cancer less likely than IDC, and the histological description refers to the secondary effect on lymphatics rather than the primary tumor architecture.
Question 15: A 1-year-old, pale-looking boy presents with high-grade fever and ecchymosis, which he has been experiencing for the past 2 weeks. The boy has achieved all developmental milestones on time and has no history of medical illness in the past. Lab investigations reveal the following: Hemoglobin 5.5 g/dL WBC 112,000/mm3 Platelets 15,000/mm3 ESR 105/1st hour The boy is referred to a hematologist, who suspects that he may be suffering from the neoplastic proliferation of immature B cells. The physician decides to do a flow cytometry analysis. Detection of which of the following markers would help confirm the suspected diagnosis?
- A. CD16
- B. CD3, TCR
- C. CD56
- D. CD19, terminal deoxynucleotidyl transferase (Tdt) (Correct Answer)
- E. MHC II
Explanation: ***CD19, terminal deoxynucleotidyl transferase (Tdt)*** - The combination of **CD19** (a pan B-cell marker) and **terminal deoxynucleotidyl transferase (Tdt)** (an enzyme found in immature lymphocytes) is highly specific for **B-cell acute lymphoblastic leukemia (B-ALL)**. - The clinical presentation with **fever**, **pallor**, **ecchymosis**, and laboratory findings of **anemia**, **thrombocytopenia**, and **markedly elevated WBC count** (primarily blasts) is consistent with ALL, and therefore these markers would confirm the suspected diagnosis of neoplastic proliferation of immature B cells. *CD16* - **CD16** is typically found on **natural killer (NK) cells**, macrophages, and neutrophils. - Its presence would suggest a different lineage and would not confirm a B-cell precursor malignancy. *CD3, TCR* - **CD3** and **T-cell receptor (TCR)** are specific markers for **T lymphocytes**. - While T-ALL is another form of acute lymphoblastic leukemia, the question specifically suspects neoplastic proliferation of **immature B cells**, making these markers irrelevant for the suspected diagnosis. *CD56* - **CD56** is a marker primarily associated with **natural killer (NK) cells** and some T-cell lymphomas. - It would not be expected on immature B cells and therefore would not support the suspected diagnosis. *MHC II* - **MHC Class II** molecules are found on professional antigen-presenting cells (APCs) such as **B cells**, macrophages, and dendritic cells. - While B cells do express MHC class II, its presence alone is not specific enough to confirm a **neoplastic proliferation of immature B cells**, as mature B cells and some other cell types also express it, and it does not indicate immaturity or malignancy on its own in this context.
Question 16: A 55-year-old man comes to the physician because of worsening fatigue and recurrent bleeding from his gums for 2 weeks. Physical examination shows marked pallor. There are scattered red, nonblanching pinpoint spots on his trunk and extremities. Laboratory studies show a hemoglobin of 8.0 g/dL, a leukocyte count of 80,000/mm3, and a platelet count of 104,000/mm3. Genetic analysis of a bone marrow aspirate shows leukemic cells with a balanced translocation between the long arms of chromosome 15 and 17. These cells are most likely to stain positive for which of the following?
- A. Periodic acid-Schiff
- B. Cluster of differentiation 1a
- C. Tartrate resistant acid phosphatase
- D. Terminal deoxynucleotidyl transferase
- E. Myeloperoxidase (Correct Answer)
Explanation: ***Myeloperoxidase*** - The presence of **fatigue**, **bleeding gums**, **pallor**, and **petechiae**, along with a **high WBC count (80,000/mm3)** and **anemia (Hb 8.0 g/dL)**, are characteristic of **acute myeloid leukemia (AML)**. - The key diagnostic feature of this specific type of AML is the **t(15;17) translocation**, which is indicative of **acute promyelocytic leukemia (APL)**. Leukemic cells in APL are **promyelocytes** and are strongly positive for **myeloperoxidase (MPO)**. *Periodic acid-Schiff* - **PAS positivity** is characteristic of **acute lymphoblastic leukemia (ALL)**, particularly the L1 and L2 subtypes, due to the presence of **glycogen**. - This patient's symptoms and the **t(15;17) translocation** are consistent with AML, not ALL. *Cluster of differentiation 1a* - **CD1a** is a marker expressed on **Langerhans cells** and is characteristic of **Langerhans cell histiocytosis**, a rare disorder involving proliferation of immature dendritic cells. - This condition does not present with the specific hematologic and genetic features described in the patient. *Tartrate resistant acid phosphatase* - **TRAP positivity** is a hallmark of **hairy cell leukemia**, a rare, chronic B-cell lymphoproliferative disorder. - Hairy cell leukemia typically presents with **splenomegaly**, **pancytopenia**, and characteristic "hairy" cells, none of which are detailed in this case. *Terminal deoxynucleotidyl transferase* - **TdT** is a nuclear enzyme found in **pre-B and pre-T lymphocytes** and is a reliable marker for **acute lymphoblastic leukemia (ALL)**. - Given the **t(15;17) translocation**, consistent with acute promyelocytic leukemia (a subtype of AML), TdT would not be expected to be positive.
Question 17: An 85-year-old man who recently immigrated to the US from Spain presents to your office complaining of hoarseness and dysphagia for the past 2 months. He says his symptoms have been getting progressively worse, and he expresses concerns about the difficulty swallowing as he cannot eat well and has even lost 9 kg (20 lb) since his last visit 3 months ago. He denies any shortness of breath, coughing of blood, and chest pain. His bowel and bladder habit are normal. Past medical history is unremarkable. He has a 60-pack-year history of smoking tobacco and drinks alcohol occasionally. Which of the following is the most likely cause of his symptoms?
- A. Malignant proliferation of squamous cells (Correct Answer)
- B. Transformation leading to metaplasia in the lower esophagus
- C. Chronic autoimmune gastritis
- D. Malignant proliferation of glandular tissue in the esophagus
- E. Reduced lower esophageal pressure
Explanation: ***Malignant proliferation of squamous cells*** - The patient's presentation with **progressive hoarseness, dysphagia, and significant weight loss** in an 85-year-old male with a significant **60-pack-year smoking history** strongly suggests **squamous cell carcinoma of the esophagus or larynx/pharynx**. - **Tobacco and alcohol use** are major risk factors for squamous cell carcinoma of the upper aerodigestive tract, and his symptoms align with advanced disease. *Transformation leading to metaplasia in the lower esophagus* - This describes **Barrett's esophagus**, a metaplastic change from squamous to columnar epithelium in the lower esophagus, usually due to **chronic gastroesophageal reflux disease (GERD)**. - While Barrett's esophagus can progress to **adenocarcinoma** (with smoking as an additional risk factor), the primary presentation here with **hoarseness** strongly suggests squamous cell carcinoma of the upper aerodigestive tract rather than adenocarcinoma of the distal esophagus. *Chronic autoimmune gastritis* - This condition primarily affects the **stomach**, leading to **vitamin B12 deficiency** and megaloblastic anemia, and generally does not cause hoarseness or dysphagia as primary symptoms. - The patient's symptoms are localized to the throat and esophagus, with systemic signs of disease progression (weight loss), rather than gastric issues. *Malignant proliferation of glandular tissue in the esophagus* - This refers to **esophageal adenocarcinoma**, which typically arises from **Barrett's esophagus** in the **distal esophagus**. - While dysphagia and weight loss can occur, the prominent **hoarseness** points more towards a lesion affecting the pharynx or larynx, which are more commonly sites of **squamous cell carcinoma** due to smoking, rather than glandular tissue (adenocarcinoma). *Reduced lower esophageal pressure* - This is a characteristic feature of **achalasia**, a motility disorder where the lower esophageal sphincter fails to relax, leading to **dysphagia** and regurgitation. - However, achalasia does not typically cause **hoarseness**, nor does it inherently explain the rapid and significant **weight loss** in the context of extensive smoking history, which strongly points to malignancy.
Question 18: A previously healthy 27-year-old man comes to the physician because of a 3-week history of anxiety, diarrhea, and a 4.1-kg (9-lb) weight loss. On questioning, he also reports that he noticed a painless mass on his left testicle 2 weeks ago. His pulse is 110/min and irregular and blood pressure is 150/70 mm Hg. Examination shows diaphoresis and a fine tremor of the outstretched fingers. Testicular examination shows a 3-cm, firm, nontender mass on the left scrotum that does not transilluminate. This patient's underlying condition is most likely to be associated with which of the following findings?
- A. Elevated serum AFP
- B. Elevated serum hCG (Correct Answer)
- C. Elevated serum TSH
- D. Proptosis on exophthalmometry
- E. Positive urine metanephrines
Explanation: ***Elevated serum hCG*** - The patient presents with symptoms of **hyperthyroidism** (anxiety, weight loss, tachycardia, tremor, diaphoresis) and a **testicular mass**. - Some **testicular germ cell tumors**, particularly **choriocarcinoma** and some **mixed germ cell tumors**, can produce **hCG**, which has structural similarity to TSH and can stimulate the thyroid gland, leading to **paraneoplastic hyperthyroidism**. - **Serum hCG** is an important tumor marker for germ cell tumors and would be elevated in this clinical scenario. *Elevated serum AFP* - **Alpha-fetoprotein (AFP)** is a tumor marker often elevated in **non-seminomatous germ cell tumors** like **yolk sac tumors** and **embryonal carcinomas**. - While AFP may be elevated in some testicular tumors, it does not explain the hyperthyroid symptoms, as hCG (not AFP) has TSH-like activity. *Elevated serum TSH* - In **hyperthyroidism**, the **thyroid stimulating hormone (TSH)** level is typically **suppressed** due to negative feedback from high thyroid hormone levels. - An elevated TSH would indicate **primary hypothyroidism**, which contradicts the patient's clinical presentation. *Proptosis on exophthalmometry* - **Proptosis** (exophthalmos) is a common finding in **Graves' disease**, an autoimmune cause of hyperthyroidism. - However, the presence of a **testicular mass** strongly suggests a paraneoplastic etiology for the hyperthyroidism, making Graves' disease less likely as the primary underlying condition. *Positive urine metanephrines* - **Urine metanephrines** are markers elevated in **pheochromocytoma**, a tumor of the adrenal medulla that secretes catecholamines. - While pheochromocytoma can cause hypertension, tachycardia, and anxiety, it does not typically present with a testicular mass or directly cause weight loss through a thyroid-like mechanism.
Question 19: A 6-year-old boy is brought to the physician because of worsening headaches and a rash for 2 weeks. His mother reports that the rash started on his abdomen and diffusely spread to other areas. Over the past 2 months, he has had recurrent episodes of otitis media. Examination shows a diffuse, erythematous, papular rash involving the groin, abdomen, chest, and back. His cervical lymph nodes are palpable bilaterally. An x-ray of the skull shows well-defined lytic lesions of the left occipital bone and the mastoid bone. Electron microscopy of a biopsy of the patient's posterior cervical lymph nodes shows polygonal cells with organelles shaped like tennis rackets. The cells stain positive for S-100. Clonal proliferation of which of the following types of cells is most likely seen on microscopy?
- A. Eosinophils
- B. Plasma cells
- C. Natural killer cells
- D. Langerhans cells (Correct Answer)
- E. B cells
Explanation: ***Langerhans cells*** - The presence of **Birbeck granules** (tennis racket-shaped organelles) on electron microscopy and **S-100 positivity** are pathognomonic for **Langerhans cells histiocytosis (LCH)**. - The clinical presentation with **lytic bone lesions**, **recurrent otitis media**, **headaches**, and a **diffuse rash** in a child is highly characteristic of LCH. *Eosinophils* - While **eosinophils** can be present in some forms of LCH, the primary clonal proliferation in LCH is of Langerhans cells, not eosinophils themselves. - **Eosinophilia** is a common finding in various allergic and parasitic conditions, but it does not explain the widespread lytic bone lesions or the specific electron microscopy and immunohistochemical findings. *Plasma cells* - **Plasma cell proliferations** are typically associated with **multiple myeloma** or **plasmacytomas**, presenting with monoclonal gammopathy and different types of bone lesions (punch-out lesions often without an osteoblastic rim). - Plasma cells do not contain Birbeck granules and are negative for S-100. *Natural killer cells* - **Natural killer (NK) cell proliferations** are rare and typically manifest as lymphomas, often aggressive, with different clinical features and no association with Birbeck granules or S-100 positivity. - NK cell lymphomas would not present with multifocal lytic bone lesions as described. *B cells* - **B-cell proliferations** lead to **lymphomas** or **leukemias**, which present with different clinical features like prominent lymphadenopathy, splenomegaly, or bone marrow infiltration. - B cells do not contain Birbeck granules, are typically CD20 positive, and are negative for S-100.
Question 20: A 67-year-old woman comes to the physician because of a 3-week history of fatigue and worsening back and abdominal pain. During this period, she has also had excessive night sweats and a 4.6-kg (10-lb) weight loss. She has had swelling of the neck for 3 days. She does not smoke or drink alcohol. Vital signs are within normal limits. Physical examination shows a 4-cm, supraclavicular, nontender, enlarged and fixed lymph node. The spleen is palpated 2 cm below the left costal margin. Laboratory studies show: Hemoglobin 10.4 g/dL Mean corpuscular volume 87 μm3 Leukocyte count 5,200/mm3 Platelet count 190,000/mm3 Serum Lactate dehydrogenase 310 U/L A CT scan of the thorax and abdomen shows massively enlarged paraaortic, axillary, mediastinal, and cervical lymph nodes. Histopathologic examination of an excised cervical lymph node shows lymphocytes with a high proliferative index that stain positive for CD20. Which of the following is the most likely diagnosis?
- A. Hairy cell leukemia
- B. Adult T-cell lymphoma
- C. Diffuse large B-cell lymphoma (Correct Answer)
- D. Marginal zone lymphoma
- E. Follicular lymphoma
Explanation: ***Diffuse large B-cell lymphoma*** - The patient presents with **B symptoms** (fever, night sweats, weight loss), rapid progression, generalized **lymphadenopathy** (cervical, supraclavicular, paraaortic, axillary, mediastinal), **splenomegaly**, and elevated **LDH**. - **Histopathologic examination** showing lymphocytes with a **high proliferative index** and positive **CD20 staining** confirms a B-cell lymphoma with aggressive features, highly characteristic of DLBCL. *Hairy cell leukemia* - This condition typically presents with **splenomegaly** and **pancytopenia**, but **lymphadenopathy** is rare and often absent. - The characteristic "hairy cells" are identified by specific markers (CD103, CD123, CD25), and a **high proliferative index** is not a feature. *Adult T-cell lymphoma* - This lymphoma is associated with **HTLV-1 infection** and often presents with hypercalcemia, skin lesions, and generalized lymphadenopathy, but it is a **T-cell lymphoma**. - The **CD20 positivity** in the histology rules out a T-cell lineage lymphoma. *Marginal zone lymphoma* - This is an **indolent B-cell lymphoma** that typically progresses slowly and is often associated with chronic inflammation or autoimmune diseases. - The patient's aggressive symptoms, rapid progression, significant **B symptoms**, and **high proliferative index** are not consistent with indolent lymphoma. *Follicular lymphoma* - This is also an **indolent B-cell lymphoma** characterized by a follicular growth pattern and usually presents with painless lymphadenopathy. - The rapid onset of symptoms, significant **B symptoms**, and elevated **LDH** indicate an aggressive lymphoma, which is not typical of follicular lymphoma.
Question 21: A 71-year-old woman comes to the physician with a 2-month history of fatigue, anorexia, abdominal swelling, shortness of breath, and a 5-kg (11-lb) weight loss. She appears chronically ill. Examination shows jaundice, bilateral temporalis muscle wasting, hepatosplenomegaly, and tense ascites. Ultrasonography of the abdomen shows multiple hepatic masses and enlargement of the portal vein. Which of the following is the most likely cause of these masses?
- A. Hyperplasia of atypical bile duct tissue
- B. Metastatic spread of malignant cells from the colon (Correct Answer)
- C. Lymphoproliferative disorder of hepatic sinusoids
- D. Proliferation of hepatic capillaries
- E. Malignant transformation of hepatocytes
Explanation: ***Metastatic spread of malignant cells from the colon*** - The constellation of symptoms (fatigue, anorexia, weight loss, jaundice, hepatosplenomegaly, ascites) and multiple hepatic masses in an elderly patient is highly suggestive of **widespread metastatic disease** to the liver. - The **colon** is a very common primary site for cancers that metastasize to the liver due to its venous drainage via the portal system. *Hyperplasia of atypical bile duct tissue* - This description typically refers to **cholangiocarcinoma**, which usually presents as a single mass or a few localized masses, not multiple widespread hepatic lesions and marked hepatosplenomegaly. - While cholangiocarcinoma can cause jaundice and weight loss, the extensive nature of the findings in this patient makes widespread metastases more likely. *Lymphoproliferative disorder of hepatic sinusoids* - This could refer to conditions like **hepatic lymphoma**, which can cause hepatosplenomegaly and liver masses. - However, primary hepatic lymphoma is rare, and the symptoms are often more specific to lymphadenopathy or systemic B symptoms, rather than presenting primarily with multiple liver masses and extensive symptomatology without other clear signs of lymphoma. *Proliferation of hepatic capillaries* - This typically describes **hemangiomas**, which are benign vascular tumors of the liver. - Hemangiomas are usually asymptomatic, found incidentally, and do not cause significant systemic symptoms like jaundice, cachexia, or hepatosplenomegaly, nor do they typically present as widespread "multiple hepatic masses" in this clinical context. *Malignant transformation of hepatocytes* - This refers to **hepatocellular carcinoma (HCC)**, which can present with similar symptoms and liver masses. - However, HCC more commonly arises in the context of chronic liver disease (e.g., cirrhosis), and while it can be multifocal, "multiple hepatic masses" in a patient without a clear history of liver disease, but with signs of systemic malignancy, make metastatic carcinoma more probable.
Question 22: A 55-year-old woman comes to the physician with concerns about swelling and pain in her right breast. Physical examination shows erythema and prominent pitting of the hair follicles overlying the upper and lower outer quadrants of the right breast. There are no nipple changes or discharge. A core needle biopsy shows invasive carcinoma of the breast. Which of the following is the most likely explanation for this patient's skin findings?
- A. Infiltration of the lactiferous ducts
- B. Obstruction of the lymphatic channels (Correct Answer)
- C. Involution of the breast parenchyma and ductal system
- D. Tightening of the suspensory ligaments
- E. Bacterial invasion of the subcutaneous tissue
Explanation: ***Obstruction of the lymphatic channels*** - The characteristic skin findings of **erythema** and **prominent pitting of the hair follicles** (peau d'orange) in the context of breast cancer are pathognomonic for **inflammatory breast cancer**. - This appearance results from **tumor cells obstructing dermal lymphatic channels**, leading to localized fluid accumulation or lymphedema in the skin. *Infiltration of the lactiferous ducts* - While **ductal carcinoma** is a common type of breast cancer, infiltration of the lactiferous ducts alone doesn't directly cause a diffuse inflammatory skin change like *peau d'orange*. - This type of infiltration often leads to nipple discharge or retraction, which are specifically noted as absent in this patient. *Involution of the breast parenchyma and ductal system* - **Involution** is a normal physiological process of breast tissue regression, typically with aging, and does not cause **inflammatory skin changes** or focal swelling. - It is not associated with breast cancer or its characteristic skin manifestations. *Tightening of the suspensory ligaments* - Tightening of the **Cooper's ligaments** can occur with tumor infiltration, leading to skin dimpling or retraction, but not the diffuse **edema** and **erythema** characteristic of *peau d'orange*. - This typically creates a puckering effect rather than the widespread pitting seen in this case. *Bacterial invasion of the subcutaneous tissue* - **Bacterial infections** (e.g., cellulitis) would typically present with more acute signs of infection such as fever, warmth, and rapidly spreading erythema, often with tenderness. - The presented symptoms are chronic and associated with an underlying malignancy, rather than an infectious process.
Question 23: A 25-year-old man presents with a mass on his neck. He says that he first noticed the mass a few weeks ago while taking a shower. Since then, the mass has not increased in size. He denies any pain or difficulty in swallowing. Past medical history is unremarkable. Family history is significant for his father who had his thyroid removed when he was around his age but doesn’t know why. Review of systems is significant for occasional episodes of anxiety that include a pounding headache, racing heart, and sweating. His vital signs include: pulse 88/min, blood pressure 133/87 mm Hg, temperature 37.2°C (99.0°F), and respiratory rate 14/min. He is 183 cm (6 ft 2 in) tall with long extremities. On physical examination, the patient appears cachectic. There is a palpable 4 cm x 4 cm nodule present on the left lobe of the thyroid. Which of the following is the most likely thyroid pathology in this patient?
- A. Follicular adenoma
- B. Medullary carcinoma (Correct Answer)
- C. Giant cell thyroiditis
- D. Papillary carcinoma
- E. Anaplastic carcinoma
Explanation: ***Medullary carcinoma*** - This patient's presentation with a **neck mass**, family history of thyroid removal at a young age, and episodic symptoms of **pounding headache, racing heart, and sweating** (suggestive of **pheochromocytoma**) strongly points to medullary thyroid carcinoma (MTC) as part of **Multiple Endocrine Neoplasia type 2B (MEN 2B)**. - The **tall stature, long extremities, and cachectic appearance** (Marfanoid habitus) are characteristic features of **MEN 2B syndrome**, which consists of MTC, pheochromocytoma, Marfanoid habitus, and mucosal neuromas. - MTC arises from **parafollicular C cells** and secretes **calcitonin**; it is associated with **RET proto-oncogene mutations** in hereditary cases. *Follicular adenoma* - While follicular adenomas can present as a **solitary thyroid nodule**, they are **benign** and do not present with the systemic symptoms (anxiety-like episodes, palpitations, headaches) or family history suggestive of a hereditary cancer syndrome. - There is no association with **pheochromocytoma** or **Marfanoid habitus**. *Giant cell thyroiditis* - **Giant cell thyroiditis (subacute thyroiditis/De Quervain thyroiditis)** is characterized by a **painful, tender thyroid** nodule, often preceded by a viral upper respiratory infection. - The patient's nodule is described as **non-painful**, and his symptoms do not align with the typical course of thyroiditis (fever, elevated ESR, transient hyperthyroidism). *Papillary carcinoma* - **Papillary thyroid carcinoma** is the most common type of thyroid cancer and typically presents as a **painless thyroid nodule**. - However, it is **not associated** with a strong family history of early-onset thyroid disease, episodic symptoms suggesting **pheochromocytoma**, or **Marfanoid habitus**, unlike medullary carcinoma in MEN 2B. *Anaplastic carcinoma* - **Anaplastic thyroid carcinoma** is a highly aggressive cancer, usually presenting in **older individuals (>60 years old)** with a **rapidly enlarging, painful neck mass** and symptoms of local **compression** (dyspnea, dysphagia, hoarseness). - The patient's **young age** (25 years) and the **non-aggressive nature** of the mass (stable size over weeks) make anaplastic carcinoma highly unlikely.
Question 24: A 65-year-old African-American man presents to your office with dysphagia. He reports that he has found it progressively more difficult to swallow food over the past year. At the time of presentation, he is able to eat only soup. Social history is significant for asbestos exposure, multiple daily drinks of hard alcohol, and a 70 pack-year smoking history. What would you most expect to see on an esophageal biopsy of this patient?
- A. Esophageal varices
- B. Ferruginous bodies
- C. Keratin nests and pearls (Correct Answer)
- D. Glandular metaplasia
- E. Mucosal abrasions
Explanation: ***Keratin nests and pearls*** - This patient's significant **smoking history** and **alcohol consumption** are major risk factors for **esophageal squamous cell carcinoma**, which is characterized microscopically by **keratin nests and pearls** on biopsy. - The progressive **dysphagia** (difficulty swallowing) over a year, especially progressing to difficulty with solids, is a classic symptom of **esophageal cancer**. *Esophageal varices* - Esophageal varices are typically caused by **portal hypertension**, most commonly due to cirrhosis from chronic alcohol abuse. - While alcohol abuse is present, varices would present with **hematemesis** or melena due to rupture, not progressive dysphagia as the primary symptom. *Ferruginous bodies* - These are indicative of **asbestos exposure** in the lungs, typically seen in conditions like asbestosis or mesothelioma. - They are found in the **lungs**, not in the esophagus, although asbestos exposure is noted in the history. *Glandular metaplasia* - **Glandular metaplasia** of the esophagus, also known as **Barrett's esophagus**, is a precursor to **esophageal adenocarcinoma**. - This typically results from chronic **gastroesophageal reflux disease (GERD)** symptoms, which are not mentioned in this patient. *Mucosal abrasions* - Mucosal abrasions would suggest trauma or inflammation but would not explain the **progressive, obstructive dysphagia** over a year. - Abrasions are generally acute findings and not consistent with the underlying pathology suggested by this patient's long history and risk factors.
Question 25: An 8-year-old girl is brought to the clinic by her parents for fever and easy bruising. Her parents report that the child has been bruising easily ever since an upper respiratory infection 3 months ago. For example, a bump into the table resulted in a large bruise on the side of her hip for a week. Three days ago, her mother noticed that the child felt warm and subsequently measured a temperature of 101.8°F (38.8°C) that did not respond to acetaminophen. The patient denies any chills, cough, rhinorrhea, pharyngitis, sick contacts, headache, or urinary symptoms. A physical examination demonstrates a nontender, firm, and rubbery node along her left neck and splenomegaly. Laboratory findings are shown below: Leukocyte count and differential: Leukocyte count: 19,000/mm³ Neutrophils: 39% Bands: 12% Eosinophils: 2% Basophils: 0.5% Lymphocytes: 40% Monocytes: 6.5% Hemoglobin: 9.7 g/dL Platelet count: 100,000/mm³ Mean corpuscular hemoglobin concentration: 30% Mean corpuscular volume: 76 μm³ Reticulocyte count: 0.7% What cytogenetic abnormality would be most likely in this patient?
- A. t(9;22) - Philadelphia chromosome (BCR-ABL)
- B. t(8;14) - MYC translocation
- C. t(12;21) - TEL-AML1 translocation (Correct Answer)
- D. t(15;17) - PML-RARA translocation
- E. t(4;11) - MLL rearrangement
Explanation: ***t(12;21) - TEL-AML1 translocation*** - This is the **most common cytogenetic abnormality** in pediatric B-cell acute lymphoblastic leukemia (B-ALL), occurring in approximately **25% of cases**. - The clinical presentation of an **8-year-old child** with fever, easy bruising, pancytopenia (anemia, thrombocytopenia), lymphadenopathy, and splenomegaly is **classic for B-ALL**. - TEL-AML1 translocation is associated with a **favorable prognosis** and is most common in children aged **2-10 years**. - The laboratory findings show leukocytosis with lymphocytosis, anemia, and thrombocytopenia—typical of acute leukemia with bone marrow infiltration. *t(9;22) - Philadelphia chromosome (BCR-ABL)* - The Philadelphia chromosome occurs in only **3-5% of pediatric ALL cases** but is more common in adults (~25%). - While it can present with similar clinical features, it is associated with a **poor prognosis** and is much less common in this age group. - This translocation is a high-risk feature that often requires more aggressive therapy including tyrosine kinase inhibitors. *t(8;14) - MYC translocation* - This translocation is characteristic of **Burkitt lymphoma**, not B-ALL. - Burkitt lymphoma typically presents with **rapidly growing masses** (often jaw or abdominal masses) rather than the pancytopenia and systemic symptoms seen in this patient. - The clinical presentation does not fit Burkitt lymphoma. *t(15;17) - PML-RARA translocation* - This translocation is **pathognomonic for acute promyelocytic leukemia (APL)**, a subtype of acute myeloid leukemia (AML). - APL typically presents with severe coagulopathy and DIC, not the lymphoid features seen in this case. - The patient's age and presentation are not consistent with APL, which is more common in adults. *t(4;11) - MLL rearrangement* - MLL rearrangements are associated with **infant ALL** (particularly in children <1 year old) and confer a **poor prognosis**. - While possible in older children, this is much less common than t(12;21) in the **8-year-old age group**. - MLL-rearranged ALL often presents with hyperleukocytosis and CNS involvement.
Question 26: A 19-year-old man comes to the physician because of a 2-day history of blood-speckled stools and a protruding rectal mass. He has no abdominal pain, altered bowel habits, or fever. His mother has inflammatory bowel disease. His vital signs are within normal limits. Examination shows multiple, small, hyperpigmented maculae on the lips, buccal mucosa, palms, and soles. The abdomen is soft with no organomegaly. Rectal examination shows a 4-cm pedunculated polyp with superficial excoriations on the mucosa. A colonoscopy shows 14 polyps. A biopsy shows hamartomatous mucosal polyps. This patient's diagnosis is most likely?
- A. Crohn's disease
- B. Juvenile polyposis syndrome
- C. Ulcerative colitis
- D. Familial adenomatous polyposis
- E. Peutz-Jeghers syndrome (Correct Answer)
Explanation: ***Peutz-Jeghers syndrome*** - The presence of **multiple hamartomatous polyps** in the gastrointestinal tract, coupled with **hyperpigmented macules** on the lips, buccal mucosa, palms, and soles, is pathognomonic for Peutz-Jeghers syndrome. - This condition carries an increased risk of various cancers, including colorectal, breast, gastric, and pancreatic cancers. *Crohn's disease* - While Crohn's disease can cause bloody stools and rectal involvement, it is characterized by **chronic inflammation**, often with **skip lesions** and **granulomas**, and does not present with mucocutaneous hyperpigmented macules or hamartomatous polyps. - Symptoms typically include abdominal pain, diarrhea, and weight loss, which are absent here. *Juvenile polyposis syndrome* - This syndrome is characterized by **multiple juvenile polyps**, primarily in the colon, but it does **not involve the characteristic mucocutaneous hyperpigmentation** seen in Peutz-Jeghers syndrome. - The polyps are typically inflammatory rather than purely hamartomatous in the same way as Peutz-Jeghers. *Familial adenomatous polyposis* - This condition is characterized by hundreds to thousands of **adenomatous polyps** in the colon and rectum, with a very high risk of colorectal cancer. - It does **not typically involve hamartomatous polyps** or the mucocutaneous pigmented lesions seen in this patient. *Ulcerative colitis* - Ulcerative colitis is characterized by **continuous inflammation** of the colon and rectum, typically causing bloody diarrhea, abdominal pain, and tenesmus. - It is an inflammatory bowel disease and does **not involve the presence of hamartomatous polyps** or mucocutaneous hyperpigmentation.
Question 27: A 42-year-old woman is seen by her primary care physician for her annual checkup. She has no current concerns and says that she has been healthy over the last year except for a bout of the flu in December. She has no significant past medical history and is not currently taking any medications. She has smoked 1 pack per day since she was 21 and drinks socially with her friends. Her family history is significant for prostate cancer in her dad when he was 51 years of age and ovarian cancer in her paternal aunt when she was 41 years of age. Physical exam reveals a firm, immobile, painless lump in the upper outer quadrant of her left breast as well as 2 smaller nodules in the lower quadrants of her right breast. Biopsy of these lesions shows small, atypical, glandular, duct-like cells with stellate morphology. Which of the following pathways is most likely abnormal in this patient?
- A. Nucleotide excision repair
- B. Base excision repair
- C. Non-homologous end joining
- D. Mismatch repair
- E. Homologous recombination (Correct Answer)
Explanation: ***Homologous recombination*** - The patient's presentation with **multiple, bilateral breast lumps** and a strong family history of **early-onset breast, ovarian, and prostate cancers** suggests a hereditary cancer syndrome, most notably related to **BRCA1/2 mutations**. - **BRCA1 and BRCA2 genes** are crucial for **homologous recombination**, a major pathway for repairing **double-strand DNA breaks**. Defects in this pathway lead to genomic instability and increased cancer risk. *Nucleotide excision repair* - This pathway primarily repairs bulky DNA adducts, such as **pyrimidine dimers** caused by UV radiation, and maintains DNA integrity by excising the damaged segment. - Deficiencies in nucleotide excision repair are associated with diseases like **xeroderma pigmentosum**, which is characterized by extreme sensitivity to sunlight and skin cancers, not the pattern seen in this patient. *Base excision repair* - **Base excision repair** is responsible for repairing small, non-bulky DNA lesions, such as **oxidized or deaminated bases**, by removing the damaged base and replacing it. - While essential for DNA integrity, its malfunction is not typically linked to the **hereditary breast and ovarian cancer syndrome** suggested by the patient's family history and clinical presentation. *Non-homologous end joining* - **Non-homologous end joining (NHEJ)** is an error-prone pathway for repairing **double-strand DNA breaks** by directly ligating the broken ends without a homologous template. - While critical for DNA repair, defects in NHEJ are not the primary cause of hereditary breast and ovarian cancer, which is more specifically linked to the **BRCA1/2 genes** and the homologous recombination pathway. *Mismatch repair* - **Mismatch repair (MMR)** corrects errors that occur during DNA replication, such as mismatched bases or small insertions/deletions. - Deficiencies in MMR lead to **microsatellite instability** and are characteristic of **Lynch syndrome (hereditary nonpolyposis colorectal cancer)**, which primarily increases the risk of colorectal, endometrial, and other specific cancers, but not the pattern of breast, ovarian, and prostate cancers seen here.
Question 28: A sexually active 37-year-old man comes to the physician because of a 7-day history of itching in the area of his genitals. He also reports burning on micturition. He has type 2 diabetes mellitus, which is well controlled with oral metformin. Pelvic examination shows tender, atrophic white papules on the glans and prepuce, with erythema of the surrounding skin. The urinary meatus is narrowed and sclerotic. Which of the following is the most appropriate next step in diagnosis?
- A. Local application of fluconazole
- B. Test lesion with acetic acid application
- C. Biopsy of the lesion (Correct Answer)
- D. Local application of tacrolimus
- E. Local application of clobetasol
Explanation: ***Biopsy of the lesion*** - The patient's symptoms, including **atrophic white papules**, **sclerosis**, and **meatal narrowing**, are highly suggestive of **lichen sclerosus** (LS), a chronic inflammatory skin condition. - A **biopsy** is crucial for confirming the diagnosis of LS and ruling out other conditions, including **squamous cell carcinoma**, which can coexist or develop from LS. *Local application of fluconazole* - **Fluconazole** is an antifungal medication indicated for **candidal infections** which typically present as pruritus, erythema, and white discharge or plaques, but not atrophic papules or sclerosis associated with meatal narrowing. - While patients with diabetes are prone to fungal infections, the description of **atrophic papules** and **sclerosis** makes a fungal infection less likely as the primary diagnosis. *Test lesion with acetic acid application* - **Acetic acid application** is used to identify **acetowhite lesions**, which are characteristic of human papillomavirus (HPV) infection causing **genital warts**. - The described lesions (atrophic white papules, sclerosis) are not typical for genital warts, making this test less appropriate as a primary diagnostic step. *Local application of tacrolimus* - **Tacrolimus** is a topical calcineurin inhibitor often used for inflammatory skin conditions like eczema or sometimes lichen planus, but it's not the initial diagnostic step for suspected LS with atypical features. - While tacrolimus might be considered for treatment in some cases of lichen sclerosus, it should only be initiated after a definitive diagnosis, preferably with a biopsy to exclude malignancy. *Local application of clobetasol* - **Clobetasol** is a potent topical corticosteroid used to treat inflammatory skin conditions, including lichen sclerosus, to reduce inflammation and itching. - While it's a potential treatment for LS, applying it before a definitive diagnosis via biopsy could mask features or delay the detection of a possible malignancy.
Question 29: A 29-year-old man comes to the physician because of a 3-month history of fatigue, weight loss, and multiple painless swellings on his neck and axilla. He reports that his swellings become painful after he drinks alcohol. Physical examination shows nontender cervical and axillary lymphadenopathy. A lymph node biopsy specimen shows giant binucleate cells. Which of the following is the most likely diagnosis?
- A. Diffuse large B-cell lymphoma
- B. Acute retroviral syndrome
- C. Hodgkin lymphoma (Correct Answer)
- D. Acute lymphocytic leukemia
- E. Adult T-cell lymphoma
Explanation: ***Hodgkin lymphoma*** - The presence of **fatigue, weight loss, and painless lymphadenopathy** (B symptoms) in a young man is highly suggestive of Hodgkin lymphoma. - The **lymph node biopsy showing giant binucleate cells** (Reed-Sternberg cells) is pathognomonic for Hodgkin lymphoma, and **alcohol-induced lymph node pain** is a classic, though uncommon, symptom. *Diffuse large B-cell lymphoma* - This is an **aggressive non-Hodgkin lymphoma** that can present with rapidly enlarging lymph nodes and B symptoms. - However, the characteristic **Reed-Sternberg cells** found on biopsy are not seen in diffuse large B-cell lymphoma. *Acute retroviral syndrome* - This syndrome typically presents with **flu-like symptoms, fever, sore throat, and generalized lymphadenopathy** within weeks of HIV infection. - It is usually **self-limiting** and does not feature the specific histopathology of giant binucleate cells on lymph node biopsy. *Acute lymphocytic leukemia* - This is a **hematologic malignancy** characterized by the proliferation of immature lymphoid cells. - It often presents with symptoms of **bone marrow failure** (anemia, bleeding, infections) and can have lymphadenopathy, but the diagnostic lymph node biopsy features are not consistent with Reed-Sternberg cells. *Adult T-cell lymphoma* - This rare lymphoma is associated with **human T-lymphotropic virus type 1 (HTLV-1) infection** and is more common in endemic regions. - It can present with lymphadenopathy, skin lesions, and hypercalcemia, but the histopathology would show **pleomorphic T-cells**, not Reed-Sternberg cells.
Question 30: A 32-year-old Caucasian man presents to the physician because of the swelling and discomfort of the right testis for 3 weeks. There is no history of trauma, fever, or night sweats. He had surgery for an undescended right testis when he was 6 months old. There is no history of liver disease or hypogonadism. He has fathered 2 children. He takes no medications and denies any illicit drug use. The vital signs are within normal limits. Palpation of the scrotum reveals a firm nontender mass that cannot be separated from the right testis. Examination of the left testis shows no abnormalities. There is no supraclavicular or inguinal lymphadenopathy. Gynecomastia is present. The rest of the physical examination is unremarkable. Ultrasound shows an enlarged right testicle with a hypoechoic mass replacing a large portion of the normal architecture. The left testis is normal. The laboratory test results are as follows: HCG Elevated AFP Elevated LDH Normal Which of the following is the most likely diagnosis?
- A. Leydig cell tumor
- B. Embryonal carcinoma (Correct Answer)
- C. Lymphoma
- D. Seminomatous germ cell tumor
- E. Metastasis to testis
Explanation: ***Embryonal carcinoma*** - This is the best answer among the options because embryonal carcinomas can produce **both HCG and AFP**, unlike the other tumor types listed. While **both markers being elevated** is more classically seen in **mixed germ cell tumors**, embryonal carcinoma is the only pure tumor type among the options that can explain this marker profile. - The presence of **gynecomastia** is consistent with elevated HCG production. - The history of **undescended testis (cryptorchidism)** is a significant risk factor for testicular germ cell tumors, increasing risk 3-5 fold. - The **firm, nontender mass** with a **hypoechoic mass** on ultrasound is characteristic of a germ cell tumor. *Leydig cell tumor* - Leydig cell tumors are **sex cord-stromal tumors** (non-germ cell) and do **not produce HCG or AFP**. - They can cause **gynecomastia** due to estrogen production, but the elevated tumor markers rule this out. *Lymphoma* - Testicular lymphoma is more common in **older men** (typically over 60) and presents as a rapidly enlarging, firm testicular mass. - Lymphoma does **not produce HCG or AFP**, making it incompatible with the laboratory findings. *Seminomatous germ cell tumor* - While seminomas can elevate **HCG** in 10-20% of cases (due to syncytiotrophoblastic giant cells), they **never produce AFP**. - The presence of **elevated AFP** in this patient definitively rules out a pure seminoma. *Metastasis to testis* - Metastatic disease to the testis is rare and usually occurs from **prostate, lung, melanoma, or kidney** primaries. - Metastases would **not produce HCG or AFP**. The tumor marker profile and risk factors strongly favor a primary testicular germ cell tumor.
Question 31: A 72-year-old man presents to the clinic for the evaluation of a lesion on his nose that has been slowly getting larger for the past 2 months. The patient notes no history of trauma, pruritus, or pain, but states that the size of the lesion is making his nose feel uncomfortable. On exam, the nodule is pink with rolled borders. Telangiectasias are also present within the lesion, with central ulceration. What is the characteristic histologic appearance of this lesion?
- A. Palisading nuclei (Correct Answer)
- B. Keratin pearls
- C. Sawtooth lymphocytic infiltrate
- D. Epidermal hyperplasia with cutaneous darkening
- E. Atypical melanocytes
Explanation: ***Palisading nuclei*** - The clinical presentation of a **slowly enlarging, pink nodule with rolled borders**, **telangiectasias**, and **central ulceration** on the nose is highly suggestive of **basal cell carcinoma (BCC)**. - Histologically, BCC is characterized by nests of **basaloid cells** with **palisading nuclei** at the periphery of the tumor nests. *Keratin pearls* - **Keratin pearls**, or **dyskeratosis**, are characteristic histologic features of **squamous cell carcinoma (SCC)**, which typically presents with a more scaly or ulcerating lesion, often firmer and redder. - While SCC can ulcerate, the **rolled borders** and **telangiectasias** are less common than in BCC. *Sawtooth lymphocytic infiltrate* - A **sawtooth lymphocytic infiltrate** at the dermo-epidermal junction is a classic histological finding in **lichen planus**, a pruritic, papular rash. - This condition does not match the description of a solitary, enlarging nodule on the nose. *Epidermal hyperplasia with cutaneous darkening* - **Epidermal hyperplasia with cutaneous darkening** (acanthosis nigricans) is a velvety, hyperpigmented thickening of the skin, often associated with insulin resistance or malignancy. - This is a diffuse skin change and does not resemble the localized, nodular lesion described. *Atypical melanocytes* - The presence of **atypical melanocytes** in the epidermis and/or dermis is characteristic of **melanoma** or precursor lesions like dysplastic nevi. - Melanoma lesions typically show irregular borders, varied pigmentation, and rapid growth, which differ from the described lesion.
Question 32: A 21-year-old male college student is very anxious about having thyroid cancer as he found a lump in his neck a few days ago. He has also had diarrhea and a feeling of warmth on his face for 3 days now. His father and uncle both have been diagnosed with thyroid cancer. The lump is about 1 cm in diameter and is fixed and nontender on palpation. Physical examination is otherwise unremarkable. Ultrasound shows a non-cystic cold nodule that requires fine needle aspiration for diagnosis. Thyroid functions tests are normal, and his calcitonin level is 346 ug/ml. Which of the following genetic mutations would warrant thyroidectomy in this patient?
- A. A loss of function of PPARɣ
- B. MEN1 gene mutation
- C. Down expression of the Ras protooncogene
- D. RET gene mutation (Correct Answer)
- E. Activating mutation of the BRAF gene
Explanation: ***RET gene mutation*** - The patient's symptoms (neck lump, flushing, diarrhea, elevated calcitonin, family history of thyroid cancer) are highly suggestive of **medullary thyroid carcinoma (MTC)**. MTC is strongly associated with **activating germline mutations in the RET proto-oncogene**, which warrant prophylactic thyroidectomy. - An elevated **calcitonin level** is a key biochemical marker for MTC, and a positive family history, especially with features of MEN 2 syndrome, points towards a germline RET mutation. *A loss of function of PPARɣ* - **PPARɣ (Peroxisome Proliferator-Activated Receptor gamma)** loss of function is not directly associated with medullary thyroid carcinoma or the symptoms described. - Mutations in PPARG are occasionally seen in follicular thyroid carcinoma, but not MTC. *MEN1 gene mutation* - **MEN1 gene mutations** are associated with **Multiple Endocrine Neoplasia Type 1 (MEN 1)**, which includes parathyroid hyperplasia, pituitary adenomas, and pancreatic endocrine tumors, but generally **not medullary thyroid carcinoma**. - While MEN1 can cause endocrine tumors, it does not typically present with the significantly elevated calcitonin or the specific type of thyroid cancer seen in this patient. *Down expression of the Ras protooncogene* - **RAS gene mutations** (like HRAS, KRAS, NRAS) are commonly found in **follicular and papillary thyroid carcinomas**, but not in medullary thyroid carcinoma. - "Down expression" or reduced expression of a proto-oncogene would typically reduce its oncogenic potential, which is less likely to cause a rapidly growing, aggressively presenting tumor like MTC. *Activating mutation of the BRAF gene* - **BRAF V600E mutation** is the most common genetic alteration in **papillary thyroid carcinoma (PTC)**. BRAF is a serine/threonine kinase involved in the MAPK signaling pathway. - While PTC is a common thyroid cancer, the patient's presentation with flushing, diarrhea, and high calcitonin is classic for **medullary thyroid carcinoma**, not papillary thyroid carcinoma.
Question 33: A 12-year-old boy is brought in by his mother for a routine checkup. The patient’s mother says he is frequently fatigued and looks pale. She also claims that he has recently become “much quieter” than normal and is no longer interested in playing baseball with his friends. The patient’s mother believes it may just be “growing pains.” The patient has no significant medical history. He is the 90th percentile for height and weight and has been meeting all developmental milestones. The patient is afebrile, and his vital signs are within normal limits. Physical examination reveals several small bruises on the patient’s right arm and on both thighs. Laboratory findings are significant for the following: Sodium 140 mEq/L Potassium 4.2 mEq/L Chloride 101 mEq/L Bicarbonate 27 mEq/L BUN 16 mg/dL Creatinine 1.2 mg/dL Glucose (fasting) 111 mg/dL WBC 3,400/mm3 RBC 4.20 x 106/mm3 Hematocrit 22% Hemoglobin 7.1 g/dL Platelet count 109,000/mm3 A peripheral blood smear reveals myeloblasts. Which of the following is the next best step in the management of this patient?
- A. Packed red blood cell transfusion
- B. Administration of oral ferrous sulfate
- C. Chest radiograph
- D. Referral to social services
- E. Bone marrow biopsy (Correct Answer)
Explanation: ***Bone marrow biopsy*** - The patient's symptoms (fatigue, pallor, quiet demeanor, bruising), pancytopenia (low WBC, Hemoglobin, Platelets), and especially the presence of **myeloblasts on peripheral blood smear**, are highly suggestive of **acute leukemia**. - A **bone marrow biopsy** is crucial for confirming the diagnosis of leukemia, classifying its type, and guiding subsequent treatment. *Packed red blood cell transfusion* - While the patient has significant anemia (Hb 7.1 g/dL), a transfusion would address the symptom of anemia but not the underlying cause. - Without a definitive diagnosis, a transfusion is a supportive measure, not the next best diagnostic or management step in this scenario given the strong suspicion of leukemia. *Administration of oral ferrous sulfate* - The anemia presented is likely due to bone marrow failure from leukemia, not **iron deficiency**. - Treating with oral iron would be ineffective and delay the correct diagnosis and treatment of the underlying malignancy. *Chest radiograph* - A chest radiograph might be indicated later to assess for mediastinal involvement or infection, but it is not the immediate next step for diagnosing the suspected hematological malignancy. - The primary diagnostic concern here is the abnormal blood counts and myeloblasts, which point towards a bone marrow issue. *Referral to social services* - While the presence of bruises might raise suspicion for abuse in other contexts, the constellation of symptoms here (fatigue, pallor, pancytopenia with myeloblasts) strongly points to an underlying medical condition, specifically **acute leukemia**. - Focusing on a social work referral at this stage would delay critical medical diagnosis and intervention.
Question 34: A 62-year-old man comes to the physician because of a 2-month history of an itchy rash and a 7-kg (15-lb) weight loss. Physical examination shows multiple erythematous plaques on the arms, legs, and chest. There are palpable lymph nodes in the axillary and inguinal areas. A biopsy of a skin lesion shows aggregates of neoplastic cells within the epidermis. A peripheral blood smear is most likely to show which of the following findings in this patient?
- A. Giant cells with bilobed nuclei
- B. Plasma cells with intracytoplasmic inclusions
- C. Erythrocytes with basophilic nuclear remnants
- D. Myeloblasts with azurophilic granules
- E. CD4+ cells with cerebriform nuclei (Correct Answer)
Explanation: ***CD4+ cells with cerebriform nuclei*** - This clinical presentation, including an itchy rash, weight loss, erythematous plaques, palpable lymph nodes, and neoplastic cells in the epidermis, is highly suggestive of **Sézary syndrome**, a leukemic variant of **mycosis fungoides**. - On a peripheral blood smear, Sézary cells (malignant CD4+ T-lymphocytes) are characteristic, featuring large, atypical nuclei that are often described as **cerebriform** or "brain-like" due to their deep nuclear convolutions. *Giant cells with bilobed nuclei* - **Reed-Sternberg cells** are characterized by their large size and typical bilobed nuclei with prominent nucleoli ("owl's eye" appearance), which are pathognomonic for **Hodgkin lymphoma**. - While Hodgkin lymphoma can present with pruritus and lymphadenopathy, the skin biopsy showing neoplastic cells within the epidermis points away from Hodgkin lymphoma and towards a cutaneous T-cell lymphoma. *Plasma cells with intracytoplasmic inclusions* - **Plasma cells with intracytoplasmic inclusions** (e.g., Russell bodies or Mott cells) are seen in conditions involving reactive plasmacytosis or plasma cell dyscrasias like **multiple myeloma**, **Waldenstrom macroglobulinemia**, or **monoclonal gammopathy of undetermined significance (MGUS)**. - These conditions do not typically present with the described skin lesions of Sézary syndrome. *Erythrocytes with basophilic nuclear remnants* - **Erythrocytes with basophilic nuclear remnants**, known as **Howell-Jolly bodies**, are red blood cell inclusions that represent nuclear fragments. - They are typically seen in conditions of **hyposplenism** or **asplenism**, where the spleen's ability to remove these remnants is impaired. This finding is unrelated to the described neoplastic process. *Myeloblasts with azurophilic granules* - **Myeloblasts with azurophilic granules** are immature myeloid cells found in the bone marrow and peripheral blood in patients with **acute myeloid leukemia (AML)**. - While AML can cause weight loss and sometimes non-specific skin lesions (**leukemia cutis**), the specific description of neoplastic cells within the epidermis in this context is more consistent with a T-cell lymphoma than AML.
Question 35: A 10-year-old boy with trisomy 21 arrives for his annual check-up with his pediatrician. His parents explain that over the past week, he has been increasingly withdrawn and lethargic. On examination, lymph nodes appear enlarged around the left side of his neck; otherwise, there are no remarkable findings. The pediatrician orders some routine blood work. These are the results of his complete blood count: WBC 30.4 K/μL RBC 1.6 M/μL Hemoglobin 5.1 g/dL Hematocrit 15% MCV 71 fL MCH 19.5 pg MCHC 28 g/dL Platelets 270 K/μL Differential: Neutrophils 4% Lymphocytes 94% Monocytes 2% Peripheral smear demonstrates evidence of immature cells and the case is referred to hematopathology. On flow cytometry, the cells are found to be CALLA (CD10) negative. Which of the following diseases is most associated with these clinical and cytological findings?
- A. Precursor B-cell acute lymphoblastic leukemia/lymphoma
- B. Hairy cell leukemia
- C. Classic Hodgkin’s lymphoma
- D. Diffuse large B-cell lymphoma
- E. Precursor T-cell acute lymphoblastic leukemia/lymphoma (Correct Answer)
Explanation: ***Precursor T-cell acute lymphoblastic leukemia/lymphoma*** - The patient's **trisomy 21 (Down syndrome)** increases the risk for leukemia, and the CBC shows signs of **acute leukemia** (marked leukocytosis with lymphoblastic predominance and severe anemia). - **Enlarged lymph nodes**, particularly on one side of the neck (unilateral cervical lymphadenopathy), and the **immature cells** on peripheral smear, coupled with **CALLA (CD10) negativity**, strongly indicate a **T-cell lineage** for the ALL. - **CD10 (CALLA) is characteristically positive in precursor B-cell ALL** but **negative in T-cell ALL**, making this the key diagnostic feature distinguishing between B-ALL and T-ALL in this case. *Precursor B-cell acute lymphoblastic leukemia/lymphoma* - While this is the most common form of childhood ALL and is associated with Down syndrome, this diagnosis is unlikely due to the **CALLA (CD10) negativity**. - **CD10 is typically positive in precursor B-ALL**, making this immunophenotype inconsistent with B-cell lineage. - The presentation of **enlarged lymph nodes** is consistent with ALL, but the specific immunophenotype points away from B-cell lineage here. *Hairy cell leukemia* - This is a rare, **indolent B-cell leukemia** typically seen in middle-aged to older adults, not a child. - It is characterized by **pancytopenia** and abnormal "hairy" lymphocytes with cytoplasmic projections, which does not match the acute presentation or the CBC findings showing marked lymphocytosis. *Classic Hodgkin's lymphoma* - This lymphoma is characterized by **Reed-Sternberg cells** and typically presents with localized lymphadenopathy, but the CBC findings (marked leukocytosis with 94% immature lymphocytes) are not typical of Hodgkin's lymphoma. - It is a **lymphoma**, not a leukemia presenting with widespread immature cells in the blood. *Diffuse large B-cell lymphoma* - This is an aggressive **B-cell lymphoma**, primarily affecting adults, though it can occur in children. - It typically presents as a **mass lesion** and while it can have systemic symptoms, the **CBC findings with overwhelming immature cells in the peripheral blood** pointing to a leukemia are not characteristic of DLBCL.
Question 36: A 55-year-old man comes to the physician because of a 3-day history of decreased urine output, progressively worsening bilateral pedal edema, and fatigue. He has a 4-month history of persistent lower back pain. He has hypercholesterolemia and stable angina pectoris. Current medications include atorvastatin, aspirin, and ibuprofen. His pulse is 80/min, respirations are 16/min, and blood pressure is 150/100 mm Hg. Examination shows periorbital and pedal edema and pallor. There is tenderness of the lumbar spinal vertebrae. Straight leg raise test is negative. The remainder of the examination shows no abnormalities. Laboratory studies show: Hemoglobin 8.9 g/dl Serum Urea nitrogen 20 mg/dl Creatinine 2.4 mg/dl Calcium 11.2 mg/dl Alkaline phosphatase 140 U/L X-ray of the spine shows diffuse osteopenia and multiple lytic lesions. Which of the following is most likely to confirm the diagnosis?
- A. Bone marrow biopsy (Correct Answer)
- B. Parathyroid hormone levels
- C. Congo red stain of renal tissue
- D. Peripheral blood smear
- E. Skeletal survey
Explanation: ***Bone marrow biopsy*** - This patient presents with signs highly suggestive of **multiple myeloma**, including **anemia**, **renal insufficiency**, **hypercalcemia**, and **lytic bone lesions** and diffuse osteopenia. - A **bone marrow biopsy** is the most definitive test to confirm multiple myeloma by identifying an increased percentage of **plasma cells** and their clonality. *Parathyroid hormone levels* - While **hypercalcemia** is present, increased parathyroid hormone (PTH) levels would indicate **primary hyperparathyroidism**, which typically causes diffuse osteopenia but not multiple lytic lesions in this pattern. - In multiple myeloma, hypercalcemia results from **bone destruction** by plasma cells, leading to **suppressed PTH levels**. *Congo red stain of renal tissue* - A Congo red stain of renal tissue is used to diagnose **amyloidosis**, which can cause renal failure, proteinuria, and sometimes edema. - Although amyloidosis can be a complication of multiple myeloma, it is not the primary diagnostic test for the underlying myeloma itself, and this patient's presentation with prominent lytic lesions points more directly to myeloma. *Peripheral blood smear* - A peripheral blood smear might show **rouleaux formation** (RBCs stacked like coins) and occasionally **plasma cells**, which are suggestive of multiple myeloma. - However, these findings are not specific or reliably present in all cases, and a bone marrow biopsy is required for definitive diagnosis. *Skeletal survey* - A skeletal survey (X-ray series) is crucial for identifying and characterizing the **lytic bone lesions** and diffuse osteopenia, as seen in this patient. - While it provides strong evidence of bone involvement, it is an imaging study that supports the diagnosis but does not definitively confirm the underlying hematological malignancy like a bone marrow biopsy does.
Question 37: An investigator studying the molecular characteristics of various malignant cell lines collects tissue samples from several families with a known mutation in the TP53 tumor suppressor gene. Immunohistochemical testing performed on one of the cell samples stains positive for desmin. This sample was most likely obtained from which of the following neoplasms?
- A. Squamous cell carcinoma
- B. Rhabdomyosarcoma (Correct Answer)
- C. Prostate cancer
- D. Endometrial carcinoma
- E. Melanoma
Explanation: ***Rhabdomyosarcoma*** - **Desmin** is an intermediate filament present in **muscle cells**, and its positive staining is a definitive marker for tumors of muscle origin - A **rhabdomyosarcoma** is a malignant tumor of **skeletal muscle** differentiation, thus explaining the positive desmin staining. *Squamous cell carcinoma* - **Squamous cell carcinomas** are epithelial tumors that typically stain positive for **cytokeratin**, not desmin, as they originate from epithelial cells. - They are characterized by features such as **intercellular bridges** and **keratinization**. *Prostate cancer* - **Prostate cancer** is an adenocarcinoma, meaning it's derived from glandular epithelial cells, and would stain positive for markers like **PSA (prostate-specific antigen)**, not desmin. - This tumor type is characterized by glandular differentiation. *Endometrial carcinoma* - **Endometrial carcinomas** are adenocarcinomas of the uterine lining, derived from glandular epithelial cells, and would express **cytokeratins**, not desmin. - Histologically, they show glandular structures and atypical endometrial cells. *Melanoma* - **Melanomas** are malignant tumors of melanocytes and would stain positive for markers such as **S-100**, **HMB-45**, and **Mart-1**, not desmin. - These tumors originate from neural crest cells and are not muscle-derived.
Question 38: A 74-year-old retired female teacher is referred to the endocrinology clinic. She is very concerned about a large mass in her neck that has progressively enlarged over the past 2 weeks. She also reports a 15 pound weight loss over the last 3 months. She now has hoarseness and difficulty swallowing her food, giving her a sensation that food gets stuck in her windpipe when she swallows. There is no pain associated with swallowing. Her speech is monotonous. No other gait or language articulation problems are noted. Testing for cranial nerve lesions is unremarkable. On palpation, a large, fixed and non-tender mass in the thyroid is noted. Cervical lymph nodes are palpable bilaterally. The patient is urgently scheduled for an ultrasound-guided fine needle aspiration to guide management. Which of the following is the most likely gene mutation to be found in this mass?
- A. Activating mutation of the Ras protooncogene
- B. Inactivating mutation of the p53 tumor suppressor gene (Correct Answer)
- C. RET/PTC rearrangement
- D. BRAF mutation
- E. RET gene mutation
Explanation: ***Inactivating mutation of the p53 tumor suppressor gene*** - The patient's presentation with a **rapidly enlarging, fixed, non-tender thyroid mass**, *hoarseness*, *dysphagia*, *weight loss*, and *palpable cervical lymph nodes* is highly suggestive of **anaplastic thyroid carcinoma (ATC)**, an aggressive malignancy. - Inactivating mutations of the **p53 tumor suppressor gene** are frequently associated with the development and progression of ATC, contributing to its uncontrolled growth and poor prognosis. *Activating mutation of the Ras protooncogene* - **Ras mutations** are more commonly found in *follicular thyroid carcinoma* and *follicular variants of papillary thyroid carcinoma*. - While they can indicate malignancy, they are not typically the primary genetic driver for the highly aggressive features seen in anaplastic carcinoma. *RET/PTC rearrangement* - **RET/PTC rearrangements** are characteristic genetic alterations found in **papillary thyroid carcinoma (PTC)**. - PTC typically presents with a *slower growth rate* and *less aggressive features* compared to the rapid progression described in the patient. *BRAF mutation* - The **BRAF V600E mutation** is the most common genetic alteration in **papillary thyroid carcinoma (PTC)**, especially the conventional and tall-cell variants. - While it indicates a more aggressive subset of PTC, it is generally not the primary mutation associated with the extremely aggressive and rapidly progressing features of anaplastic thyroid carcinoma. *RET gene mutation* - **Germline RET mutations** are primarily associated with **medullary thyroid carcinoma (MTC)**, often occurring as part of Multiple Endocrine Neoplasia type 2 (MEN2). - The clinical presentation with a *rapidly growing, fixed mass* and *compressive symptoms* is less typical for MTC, which can also be aggressive but usually presents differently.
Question 39: A 58-year-old man presents with lower back pain that started a couple of weeks ago and is gradually increasing in severity. At present, he rates the intensity of the pain as 6/10. There is no radiation or associated paresthesias. There is no history of trauma. Past medical history is significant for aggressive squamous cell carcinoma of the right lung status post surgical resection followed by adjunct chemotherapy and radiation therapy that was completed 6 months ago. A technetium bone scan reveals metastatic lesions in the lumbar vertebrae at levels L2–L4. The physician explains to the patient that these are likely metastatic lesions from his primary lung cancer. Which of the following best describes the mechanism that most likely led to the development of these metastatic lesions?
- A. Transcoelomic
- B. Lymphatic spread
- C. Collagenase produced by cancer cells dissolves the basement membrane and aids in cellular invasion
- D. Hematogenous spread (Correct Answer)
- E. PTH (parathormone)-related protein production by tumor cells
Explanation: ***Hematogenous spread*** - Lung cancer frequently metastasizes to bone via the **hematogenous (bloodstream) route**, especially to the spine, pelvis, and long bones. - The rich vascular supply of the vertebrae makes them a common site for metastases from many primary cancers, including those of the lung. *Transcoelomic* - **Transcoelomic spread** occurs when tumor cells spread directly within body cavities, such as the peritoneal or pleural cavity. - This mechanism is typical for cancers of organs within these cavities, like ovarian cancer spreading within the peritoneum, and is not the primary route for lung cancer to distant bone. *Lymphatic spread* - **Lymphatic spread** involves tumor cells traveling through the lymphatic system to regional lymph nodes. - While lung cancer commonly spreads to mediastinal and hilar lymph nodes, it is usually not the direct mechanism for distant bone metastases, which typically involve the circulatory system. *Collagenase produced by cancer cells dissolves the basement membrane and aids in cellular invasion* - While **collagenase production** and **basement membrane degradation** are crucial steps in local tumor invasion and intravasation (entering blood or lymphatic vessels), they describe the *how* a cell invades, not the *route* of distant metastasis. - This mechanism facilitates the initial escape of cancer cells from the primary tumor but does not define the subsequent spread to distant sites like bone. *PTH (parathormone)-related protein production by tumor cells* - **PTH-related protein (PTHrP) production** by tumor cells can lead to **hypercalcemia of malignancy** due to its osteolytic effects. - While this is a common paraneoplastic syndrome associated with squamous cell carcinoma of the lung, it is a *consequence* or *effect* of the tumor and does not describe the *mechanism of metastasis* itself.
Question 40: A 62-year-old woman comes to the physician for evaluation of a mole on her forearm that has increased in size over the last several months. Physical examination shows a 9-mm skin lesion on the right forearm with irregular borders. An excisional biopsy is performed, and genetic analysis shows a mutation in the gene that encodes B-Raf. Which of the following cellular events most likely predisposed this patient to developing this skin lesion?
- A. Deamination of cytosine, guanine, and adenine nucleotides
- B. Relocation of a chromosomal segment onto a nonhomologous chromosome
- C. Formation of covalent bonds between adjacent pyrimidine bases (Correct Answer)
- D. Insufficient phosphorylation of p53
- E. Double-strand breaks in DNA molecules
Explanation: ***Formation of covalent bonds between adjacent pyrimidine bases*** - This describes **pyrimidine dimers**, typically **thymine dimers**, which are formed due to **UV radiation exposure**. - UV radiation is the primary environmental risk factor for **melanoma**, and the **B-Raf mutation** (common in melanoma) is often linked to these UV-induced DNA lesions. *Deamination of cytosine, guanine, and adenine nucleotides* - **Deamination** is a chemical alteration of DNA bases that can lead to mutations, but it is not the most direct or common mechanism for UV-induced melanoma. - While deamination can occur spontaneously or be induced by certain chemicals, it is not the primary event linked to **UV radiation** and **B-Raf mutations** in melanoma. *Relocation of a chromosomal segment onto a nonhomologous chromosome* - This describes a **translocation**, a type of chromosomal rearrangement. - While translocations can be associated with some cancers (e.g., leukemias, sarcomas), they are not the typical mechanism for initiating **melanoma** or directly causing **B-Raf mutations**. *Insufficient phosphorylation of p53* - **p53 phosphorylation** is crucial for its activation as a tumor suppressor protein, and insufficient phosphorylation would impair its function. - However, the direct cause of this specific melanoma with a **B-Raf mutation** is usually DNA damage (like pyrimidine dimers) rather than a primary defect in p53 phosphorylation. *Double-strand breaks in DNA molecules* - **Double-strand breaks (DSBs)** are highly deleterious DNA lesions that can lead to chromosomal rearrangements or cell death if not repaired. - While DSBs can be caused by various factors, including high-energy radiation, they are not the most common or characteristic DNA lesion specifically implicated in the initiation of **melanoma** due to UV exposure and subsequent **B-Raf mutation**.
Question 41: A 19-month-old girl is brought by her mother to the local walk-in clinic after noticing a mass protruding from her vagina. The mass had the appearance of "a bunch of grapes". She also says that she has been having a vaginal discharge for the past 6 months. Her family and personal history are not significant for malignancies or inherited disorders. The physical examination is unremarkable except for the presence of soft nodules protruding from the vaginal canal. A tissue sample is obtained for histologic evaluation. Several weeks later the patient returns to the walk-in clinic for a scheduled follow-up visit. The pathology report describes a polypoid mass beneath an epithelial surface with atypical stromal cells positive for polyclonal desmin. What is the most likely diagnosis in this patient?
- A. Squamous cell carcinoma (SCC)
- B. Verrucous carcinoma
- C. Sarcoma (Correct Answer)
- D. Adenocarcinoma
- E. Melanoma
Explanation: ***Sarcoma*** - The description of a **"bunch of grapes"** mass in a young girl, along with **atypical stromal cells** positive for **polyclonal desmin**, is highly characteristic of **embryonal rhabdomyosarcoma** (a type of sarcoma botryoides). - **Desmin positivity** indicates a muscle cell origin, and the **polypoid mass** is consistent with the gross appearance of this aggressive childhood tumor. *Squamous cell carcinoma (SCC)* - SCC of the vagina is extremely rare in a **19-month-old girl** and typically affects older women. - Histologically, SCC would show **dysplastic squamous epithelial cells** with **keratinization** or intercellular bridges, not atypical stromal cells positive for desmin. *Verrucous carcinoma* - This is a rare, well-differentiated variant of SCC, also typically occurring in **older individuals** and associated with HPV infection. - It presents as a **warty, exophytic lesion** with minimal cellular atypia, distinct from a "bunch of grapes" mass and desmin positivity. *Adenocarcinoma* - Vaginal adenocarcinoma can occur in young girls, particularly **clear cell adenocarcinoma** associated with **diethylstilbestrol (DES) exposure**; however, this patient has no such history. - Histology would show glandular differentiation and mucin production, not atypical stromal cells expressing desmin. *Melanoma* - Vaginal melanoma is very rare, typically presenting as a **pigmented lesion** in postmenopausal women. - Histopathology would reveal malignant melanocytes with **positive S-100 and HMB-45 staining**, not atypical stromal cells positive for desmin.
Question 42: A 26-year-old nulligravid woman presents to her gynecologist after noticing a lump in her right breast while showering. She states that she first noticed the lump approximately 2 weeks ago, when the mass was slightly tender to touch. Since then, the lump has gotten slightly smaller and is now non-tender. The patient is otherwise healthy. She does not take oral contraceptives. Her last menses was approximately 2 weeks ago. There is no family history of cancer. On exam, the patient's temperature is 98.3°F (36.8°C), blood pressure is 116/84 mmHg, pulse is 65/min, and respirations are 12/min. In her right breast, there is a small 1.5 cm mass that is mobile, well-circumscribed, and firm. Which of the following is most likely on histological examination of the mass?
- A. Large, pleomorphic cells with associated central necrosis and microcalcifications
- B. Cysts with “leaf-like” projections
- C. Terminal duct lobular units surrounded by dense stroma
- D. Hypercellular stroma with overgrowth of fibrous and glandular tissues (Correct Answer)
- E. Dilated glands with 2 cell layers present
Explanation: ***Hypercellular stroma with overgrowth of fibrous and glandular tissues*** - The clinical presentation of a **mobile, well-circumscribed, firm breast mass** in a young nulligravid woman, which slightly decreased in tenderness and size, is highly characteristic of a **fibroadenoma**. - Histologically, fibroadenomas are benign tumors composed of both **fibrous and glandular tissue**, with a characteristic **hypercellular stroma** surrounding compressed ducts. *Large, pleomorphic cells with associated central necrosis and microcalcifications* - This histological description is characteristic of **ductal carcinoma in situ (DCIS)** or **invasive ductal carcinoma (IDC)**, particularly the **comedo type DCIS**. - The patient's clinical presentation with a mobile, non-tender lump that improved and her young age make **malignancy less likely**. *Cysts with “leaf-like” projections* - This describes the histological appearance of a **phyllodes tumor**, which can be benign, borderline, or malignant. - While phylloides tumors can present as mobile masses, they tend to **grow rapidly** and often become quite large, unlike the description of the mass in this patient. *Terminal duct lobular units surrounded by dense stroma* - This description is characteristic of **fibrocystic changes** in the breast, a common benign condition. - While fibrocystic changes can cause lumps and tenderness, the presence of a distinct, mobile, well-circumscribed mass is more indicative of a **fibroadenoma**. *Dilated glands with 2 cell layers present* - This describes **sclerosing adenosis** or other types of **adenosis**, which are benign proliferative lesions within the breast. - While these can present as masses, the classic presentation of a fibroadenoma with its distinct encapsulation and mobility is a more precise fit.
Question 43: A 28-year-old patient presents to a medical office for a consultation regarding a mole on her nose that is increasing in size. She also complains of frequent headaches, which she associates with stress on the job. She works as a civil engineer and spends much of her time outside. Her past medical history is positive for bronchial asthma; nevertheless, her vitals are stable. The mole is 8 mm in diameter, has irregular borders, and is brown in color. A biopsy is performed and sent for genetic analysis. A mutation is found. A mutation in which gene is characteristic of this patient’s main diagnosis?
- A. DCC
- B. APC
- C. BRAF (Correct Answer)
- D. c-MYC
- E. BCL-2
Explanation: ***BRAF*** - The patient's presentation with an **enlarging mole** on the nose with **irregular borders** and significant sun exposure strongly suggests **melanoma**. - **BRAF mutations** are found in approximately 50% of melanomas and are a key target for therapy. *DCC* - The DCC (Deleted in Colorectal Carcinoma) gene is primarily associated with **colorectal cancer**. - While it plays a role in apoptosis and cellular differentiation, it is not a characteristic mutation for melanoma. *APC* - The APC (Adenomatous Polyposis Coli) gene is a **tumor suppressor gene** most famously linked to **familial adenomatous polyposis** and **colorectal cancer**. - Mutations in APC are not characteristic of melanoma. *c-MYC* - The c-MYC gene is an **oncogene** involved in cell growth, proliferation, and apoptosis, commonly amplified or mutated in various cancers like lymphomas and some solid tumors. - While important in cancer biology, c-MYC mutations are not a primary driver or characteristic mutation for melanoma. *BCL-2* - BCL-2 is an **anti-apoptotic gene** known for its role in preventing programmed cell death, and its overexpression is common in lymphomas (especially follicular lymphoma). - It is not a characteristic mutation associated with melanoma development or progression.
Question 44: A previously healthy 48-year-old man comes to the physician because of a 3-week history of progressively worsening jaundice, generalized itching, and epigastric discomfort. He also complains of nausea and loss of appetite. His stools have looked like clay for the past week. He has returned from a vacation in Thailand one week ago, where he got a new tattoo. He is sexually active with multiple partners and does not use protection. His vital signs are within normal limits. Examination shows jaundice and scleral icterus. Superficial excoriations are seen on all limbs. Abdominal examination shows no abnormalities. Serum studies show a fasting glucose level of 198 mg/dL, total bilirubin concentration of 10.6 mg/dL, direct bilirubin concentration of 9.8 mg/dl, and alkaline phosphatase activity of 450 U/L. Abdominal ultrasonography shows dilation of the biliary and pancreatic ducts and a 3-cm hypoechoic solid mass with irregular margins in the head of the pancreas. An elevation of which of the following serum findings is most specific for this patient's condition?
- A. Anti-HBc immunoglobulin M
- B. Alpha-fetoprotein
- C. Elevated anti-neutrophil cytoplasmic antibodies
- D. Glucagon
- E. Cancer antigen 19-9 (Correct Answer)
Explanation: ***Cancer antigen 19-9*** - The patient's symptoms (progressively worsening jaundice, epigastric discomfort, clay-colored stools, weight loss, nausea) and imaging findings (dilation of biliary and pancreatic ducts, hypoechoic solid mass in the pancreatic head) are highly suggestive of **pancreatic cancer**. - **CA 19-9** is a tumor marker that is elevated in most patients with pancreatic cancer and is used for diagnosis, monitoring treatment response, and detecting recurrence. *Anti-HBc immunoglobulin M* - **Anti-HBc IgM** indicates **acute hepatitis B infection**, which can cause jaundice but typically presents with elevated transaminases, and abdominal ultrasound would show liver inflammation, not a pancreatic mass or ductal dilation. - While unprotected sexual activity is a risk factor for hepatitis B, the clinical picture with an obstructed biliary system points away from acute viral hepatitis as the primary cause. *Alpha-fetoprotein* - **Alpha-fetoprotein (AFP)** is a tumor marker primarily associated with **hepatocellular carcinoma** and some germ cell tumors. - Although the patient has jaundice, the ultrasound findings of a pancreatic mass and dilated ducts are not consistent with hepatocellular carcinoma. *Elevated anti-neutrophil cytoplasmic antibodies* - **Anti-neutrophil cytoplasmic antibodies (ANCAs)** are associated with **autoimmune vasculitides** (e.g., GPA, MPA) and some inflammatory bowel diseases, not typically with obstructive jaundice due to a pancreatic mass. - There are no symptoms or signs to suggest a systemic vasculitis in this patient. *Glucagon* - **Glucagon** is a hormone involved in glucose regulation. While the patient has elevated fasting glucose, a specific elevation of glucagon itself is associated with a rare **glucagonoma**, which typically presents with a characteristic rash (necrolytic migratory erythema), diabetes, and weight loss, none of which are the primary presenting features here. - The elevated fasting glucose is more likely a paraneoplastic effect of pancreatic cancer, as the mass is compressing the bile ducts, and the patient has other features specific to pancreatic ductal adenocarcinoma.
Question 45: A 70-year-old retired police officer is being evaluated for fatigue. A peripheral smear shows extremely elevated numbers of immature myeloid cells, which are positive for myeloperoxidase and a translocation t(15,17). Which of the following statements is true regarding his condition?
- A. Myelodysplastic syndromes may give rise to the condition.
- B. This condition is also developed early in life in patients with Down syndrome.
- C. Philadelphia chromosome may be seen and indicates a poor prognosis.
- D. Auer rods are responsible for gum hyperplasia and bleeding.
- E. The patient can be treated with a vitamin A derivative. (Correct Answer)
Explanation: ***The patient can be treated with a vitamin A derivative.*** - The presence of **immature myeloid cells** positive for **myeloperoxidase (MPO)** and a **t(15;17) translocation** strongly indicates **Acute Promyelocytic Leukemia (APL)**. - APL is effectively treated with **all-trans retinoic acid (ATRA)**, which is a **vitamin A derivative**, as it induces differentiation of the promyelocytes. *Myelodysplastic syndromes may give rise to the condition.* - While myelodysplastic syndromes (MDS) can transform into other types of **acute myeloid leukemia (AML)**, they typically give rise to other subtypes of AML, not specifically APL, which has a distinct genetic translocation. - MDS would usually show a **dysplastic morphology** in multiple cell lines, which is not described as the primary feature here. *This condition is also developed early in life in patients with Down syndrome.* - **Down syndrome** patients have an increased risk of specific leukemias, particularly **Acute Megakaryoblastic Leukemia (AML M7)** in early childhood, and **Acute Lymphoblastic Leukemia (ALL)**. - APL, characterized by t(15;17), is not specifically associated with Down syndrome. *Philadelphia chromosome may be seen and indicates a poor prognosis.* - The **Philadelphia chromosome (t(9;22))** is characteristic of **Chronic Myeloid Leukemia (CML)** and some cases of **B-ALL**, not APL. - The t(15;17) translocation is the defining feature of APL, and Philadelphia chromosome is not seen in this condition. *Auer rods are responsible for gum hyperplasia and bleeding.* - **Auer rods** are indeed characteristic of AML, including APL, and are formed by abnormal fusion of primary granules. - However, **gum hyperplasia and bleeding** are more distinctly characteristic of **Acute Monocytic Leukemia (AML M5)** due to monocyte infiltration, rather than directly caused by Auer rods.
Question 46: A 63-year-old man comes to the physician because of a 2-month history of progressive fatigue. He also has shortness of breath and palpitations, which worsen on physical exertion and improve with rest. He has had intermittent constipation, low-grade fever, and generalized myalgia for the past 3 months. He has had a 10.4-kg (23-lb) weight loss over the past 4 months despite no change in appetite. His temperature is 37°C (98.6°F), pulse is 108/min, respirations are 16/min, and blood pressure is 130/78 mm Hg. Examination shows pale conjunctivae. His hemoglobin concentration is 9.1 g/dL, mean corpuscular volume is 70 μm3, and serum ferritin is 12 ng/mL. Test of the stool for occult blood is positive. Colonoscopy shows a 1.7-cm wide exophytic ulcer with irregular, bleeding edges in the ascending colon. Which of the following biopsy findings would have been the greatest predisposing factor for developing this patient's current condition?
- A. A pedunculated inflammatory polyp
- B. A villous adenomatous polyp (Correct Answer)
- C. A serrated hyperplastic polyp
- D. A submucosal lipomatous polyp
- E. A tubular adenomatous polyp
Explanation: ***A villous adenomatous polyp*** - Villous adenomas are **predisposed to malignant transformation** due to their large size, increased cellular atypia, and high-grade dysplasia. - The patient's presentation with **iron-deficiency anemia**, weight loss, and a bleeding colonic ulcer is highly suggestive of **colorectal adenocarcinoma**, which often arises from adenomatous polyps. *A pedunculated inflammatory polyp* - Inflammatory polyps are typically **non-neoplastic** and develop in response to chronic inflammation, such as in inflammatory bowel disease. - They have **minimal to no malignant potential** and are not a significant risk factor for colorectal cancer. *A serrated hyperplastic polyp* - Hyperplastic polyps are generally **benign** and have a very low risk of malignant transformation, especially if small and located in the rectosigmoid colon. - While serrated polyps (including sessile serrated adenomas) can progress to cancer via the **serrated pathway**, hyperplastic polyps specifically are largely considered harmless. *A submucosal lipomatous polyp* - Lipomas are **benign tumors** composed of mature adipose tissue that arise in the submucosa. - They are **non-neoplastic** and have no malignant potential, thus not contributing to cancer development. *A tubular adenomatous polyp* - Tubular adenomas are adenomatous polyps with malignant potential, but **villous adenomas have a higher risk** of progression to adenocarcinoma. - The presence of symptoms such as anemia and weight loss, along with the description of a bleeding ulcer, points to a more advanced lesion, which is more characteristic of a villous component or an already transformed malignancy.
Question 47: A 57-year-old man is brought to the emergency department by his wife 20 minutes after having had a seizure. He has had recurrent headaches and dizziness for the past 2 weeks. An MRI of the brain shows multiple, round, well-demarcated lesions in the brain parenchyma at the junction between gray and white matter. This patient's brain lesions are most likely comprised of cells that originate from which of the following organs?
- A. Kidney
- B. Skin
- C. Lung (Correct Answer)
- D. Thyroid
- E. Prostate
Explanation: ***Lung (Correct Answer)*** - **Lung cancer** is the most common cause of **brain metastases** in adults, accounting for approximately **50% of all cases** - The clinical presentation—seizure, headaches, dizziness, and **multiple, round, well-demarcated lesions at the gray-white matter junction**—is classic for metastatic lung cancer - Both **small cell and non-small cell lung cancers** have high propensity for hematogenous spread to the brain - The watershed areas at the gray-white junction are common sites due to lodging of tumor emboli in terminal arterioles *Kidney (Incorrect)* - **Renal cell carcinoma (RCC)** can metastasize to the brain but accounts for only **5-10% of brain metastases** - While RCC metastases can appear similar on imaging, lung cancer is statistically more likely given its higher prevalence - RCC metastases are often **highly vascular and may hemorrhage**, which is not mentioned in this case *Skin (Incorrect)* - **Melanoma** has the **highest propensity per case** to metastasize to the brain among all cancers - However, the **overall incidence of melanoma is much lower** than lung cancer, making it a less probable primary source - Melanoma brain metastases often present as **hemorrhagic lesions** and would typically have skin findings or history *Thyroid (Incorrect)* - **Thyroid cancer** rarely metastasizes to the brain (accounts for <1% of brain metastases) - Brain metastases from thyroid cancer typically occur in **advanced papillary or follicular carcinoma** or in **anaplastic thyroid cancer** - More common metastatic sites for thyroid cancer are lung and bone *Prostate (Incorrect)* - **Prostate cancer very rarely metastasizes to the brain** (<1% of cases) - Prostate cancer preferentially metastasizes to **bone (especially axial skeleton), lymph nodes, and liver** - Brain metastases from prostate cancer suggest extremely advanced, aggressive disease and are exceptionally uncommon
Question 48: A 55-year old man living in Midwest USA comes in complaining of painless hematuria for the past week. He denies dysuria but complains of fatigue and lethargy at work. He has lost about 9.0 kg (20.0 lb) in the past 6 months. He drinks 1–2 beers on the weekends over the past 10 years but denies smoking. He has worked at a plastic chemical plant for the past 30 years and has never been out of the country. His father died of a heart attack at age 62 and his mother is still alive and well. There is a distant history of pancreatic cancer, but he can not remember the specifics. His vitals are stable and his physical exam is unremarkable. Urinary analysis is positive for RBCs. A cystoscopy is performed and finds a pedunculated mass projecting into the bladder lumen. A biopsy shows malignant cells. Which of the following is the most concerning risk factor for this patient’s condition?
- A. Aromatic amine exposure (Correct Answer)
- B. Alcohol
- C. Vinyl chloride exposure
- D. Genetic predisposition
- E. Schistosoma haematobium infection
Explanation: ***Aromatic amine exposure*** - The patient's 30-year employment at a **plastic chemical plant** is a significant risk factor, as many chemicals used in such industries contain **aromatic amines**. - Exposure to **aromatic amines** is a well-established cause of **transitional cell carcinoma** of the bladder, which is consistent with the painless hematuria and the finding of a malignant bladder mass. *Alcohol* - While heavy alcohol consumption can contribute to various health issues, it is **not considered a direct or strong risk factor** for bladder cancer. - The patient's reported consumption of "1-2 beers on the weekends" over 10 years is relatively moderate and unlikely to be the primary cause of his severe presentation. *Vinyl chloride exposure* - **Vinyl chloride** exposure is primarily associated with **hepatic angiosarcoma** and, to a lesser extent, lung cancer and brain tumors. - It is **not a significant risk factor** for bladder cancer, differentiating it from the patient's presentation of a bladder mass. *Genetic predisposition* - While there can be a genetic component to some cancers, the familial history mentioned (father died of heart attack, distant history of pancreatic cancer) does **not specifically point to a strong genetic predisposition** for bladder cancer. - The powerful occupational exposure to chemicals is a much more direct and concerning risk factor in this case. *Schistosoma haematobium infection* - **Schistosoma haematobium** infection is a known cause of **squamous cell carcinoma** of the bladder, especially in endemic regions like parts of Africa and the Middle East. - The patient has **never been out of the country** and lives in the Midwest USA, making this infection highly unlikely.
Question 49: A 62-year-old woman presents to her primary care provider with anal bleeding. She reports a 4-month history of intermittent anal bleeding that was initially mild but has increased in severity over the past 2 weeks. She also reports having intermittent mucoid discharge from her anus. She denies any pain with defecation but does experience occasional constipation that has been increasing in frequency over the past month. Her past medical history is notable for hypertension and breast cancer status-post-mastectomy and radiation therapy. She takes enalapril. She has a 15-pack-year smoking history and drinks 3-4 glasses of wine per week. Her temperature is 98.4°F (36.9°C), blood pressure is 135/85 mmHg, pulse is 85/min, and respirations are 18/min. On exam, she appears pale but is pleasant and conversational. Digital rectal examination reveals a small mass within the anal canal. Anoscopy demonstrates an erythematous irregular mass arising from the mucosa proximal to the dentate line. Which of the following histologic findings is most likely to be seen in this patient’s lesion?
- A. Basal cell carcinoma
- B. Gastrointestinal stromal tumor
- C. Adenocarcinoma (Correct Answer)
- D. Basaloid carcinoma
- E. Squamous cell carcinoma
Explanation: ***Adenocarcinoma*** - The patient's presentation with **anal bleeding**, **mucoid discharge**, and an **irregular mass proximal to the dentate line** strongly suggests **anal adenocarcinoma**. - **Adenocarcinoma of the anus** arises from glandular tissue, often from the **anal glands** or as an extension from rectal adenocarcinoma, and is the **most common histology proximal to the dentate line** where columnar/glandular epithelium predominates. - Histologically, it shows **glandular architecture** with malignant columnar cells forming tubular or cribriform patterns, mucin production, and dysplastic features. - While the patient has smoking history (a risk factor for SCC), the **anatomical location above the dentate line** makes adenocarcinoma more likely than squamous cell carcinoma. *Squamous cell carcinoma* - **Squamous cell carcinoma (SCC)** is the most common type of anal cancer overall, but typically arises **at or below the dentate line** where squamous and transitional epithelium is present. - Risk factors include **smoking**, HPV infection, and immunosuppression. - Histologically shows nests of malignant squamous cells with **keratinization** and **intercellular bridges**. - The location **proximal to the dentate line** makes this less likely than adenocarcinoma. *Basaloid carcinoma* - **Basaloid carcinoma** (also known as cloacogenic carcinoma) is a variant of **squamous cell carcinoma** that arises from the transitional epithelium at or near the dentate line. - While it can occur in the anal canal, it is typically found **at the dentate line** in the transitional zone, not proximal to it. - It is considered part of the squamous cell carcinoma spectrum. *Basal cell carcinoma* - **Basal cell carcinoma** typically occurs on **sun-exposed skin** (e.g., face, neck) and is exceedingly rare in the anal canal, accounting for less than 1% of anal cancers. - Histologically presents with nests of **basaloid cells** with peripheral palisading, which is not characteristic of this patient's lesion location. *Gastrointestinal stromal tumor* - **Gastrointestinal stromal tumors (GISTs)** are mesenchymal tumors most commonly found in the stomach or small intestine, and are **exceedingly rare in the anus**. - Histologically characterized by **spindle-shaped** or epithelioid cells that stain positive for **CD117 (c-KIT)**, which would not be expected for a mucosal mass in this glandular epithelial location.
Question 50: A 72-year-old man comes to the physician because of several episodes of dark urine over the past 2 months. He has had a 6 kg (13.2-lb) weight loss over the past 3 months despite no changes in appetite. He has smoked a pack of cigarettes daily for 30 years. A CT scan shows a heterogeneous enhancing mass arising from the left renal pelvis. Pathologic examination of the lesion is most likely to show which of the following findings?
- A. Grayish-tan tumor comprised of primitive blastemal cells forming abortive glomeruli
- B. Bright yellow tumor comprised of polygonal cells filled with lipids and glycogen
- C. Ulcerating tumor comprised of glandular cells within mucinous material
- D. Tumor with central scar comprised of large eosinophilic cells with central nuclei
- E. Pedunculated tumor comprised of pleomorphic urothelial cells with severe nuclear atypia (Correct Answer)
Explanation: ***Pedunculated tumor comprised of pleomorphic urothelial cells with severe nuclear atypia*** - The patient's presentation with **dark urine** (hematuria), **weight loss**, and a **renal pelvis mass** in a 72-year-old chronic smoker is highly suggestive of **urothelial carcinoma** of the renal pelvis. - Urothelial carcinomas often present as **pedunculated masses** and are characterized histologically by **pleomorphic urothelial cells** with varying degrees of **nuclear atypia**, reflecting their origin from the transitional epithelium lining the renal pelvis. *Grayish-tan tumor comprised of primitive blastemal cells forming abortive glomeruli* - This description is characteristic of **Wilms tumor (nephroblastoma)**, which is a embryonal tumor predominantly affecting young children (typically <5 years old). - The patient's advanced age (72 years) makes Wilms tumor an extremely unlikely diagnosis. *Bright yellow tumor comprised of polygonal cells filled with lipids and glycogen* - This description is typical of **renal cell carcinoma (clear cell type)**, which originates from the renal cortex, not the renal pelvis. - While renal cell carcinoma can present with hematuria and weight loss, the CT finding of a mass "arising from the left renal pelvis" points away from a cortical origin. *Ulcerating tumor comprised of glandular cells within mucinous material* - This description is characteristic of **adenocarcinoma**, which can occur in various organs but is not typical for primary renal pelvis tumors. - While rarely, primary adenocarcinoma can arise in the renal pelvis, it is far less common than urothelial carcinoma and usually has a different histological appearance with glandular differentiation and mucin production. *Tumor with central scar comprised of large eosinophilic cells with central nuclei* - This description is consistent with **oncocytoma**, a benign renal tumor. - While oncocytomas can be large, they are usually asymptomatic or cause non-specific symptoms, and the patient's symptoms of significant weight loss and dark urine are more indicative of a malignant process.
Question 51: A 45-year-old African American male presents to his primary care physician complaining of difficulty swallowing that was initially limited to solids but has now progressed to liquids. Biopsy of the esophagus reveals dysplastic cells, but does not show evidence of glands or increased mucin. Which of the following most contributed to his condition?
- A. Gastroesophageal reflux disease
- B. Obesity
- C. Drinking extremely hot beverages
- D. Radiation exposure in the past 6 months
- E. Smoking (Correct Answer)
Explanation: ***Smoking*** - **Smoking** is the most significant risk factor for **squamous cell carcinoma** of the esophagus, which is strongly suggested by the biopsy findings of **dysplastic cells without glands or mucin**. - The combination of **progressive dysphagia** (solids to liquids) and smoking history in an **African American male** fits the classic demographic and presentation pattern for esophageal squamous cell carcinoma. *Gastroesophageal reflux disease* - **GERD** primarily leads to **esophageal adenocarcinoma** through **Barrett's esophagus**, which would show **glandular metaplasia** and **increased mucin production** on biopsy. - The biopsy explicitly states **absence of glands and mucin**, making GERD-related adenocarcinoma unlikely as the primary pathologic process. *Obesity* - **Obesity** increases risk of **esophageal adenocarcinoma** by worsening **GERD** and promoting **Barrett's esophagus** development. - Since the biopsy findings suggest **squamous cell carcinoma** rather than adenocarcinoma, obesity is not the most direct contributing factor in this case. *Drinking extremely hot beverages* - **Hot beverage consumption** is indeed a risk factor for **squamous cell carcinoma** of the esophagus, particularly in certain geographic regions. - However, **smoking** remains the more prevalent and significant risk factor globally, especially when combined with **alcohol use**, making it the primary contributor. *Radiation exposure in the past 6 months* - **Radiation exposure** can increase risk of esophageal cancer, including **squamous cell carcinoma**, but typically requires a **longer latency period** (years to decades). - A **6-month timeframe** is insufficient for radiation-induced carcinogenesis to manifest as advanced cancer with dysphagia and dysplastic changes.
Question 52: A 56-year-old woman presents to a physician for evaluation of a lump in her left breast. She noticed the lump last week while taking a shower. She says that the lump seemed to be getting larger, which worried her. The lump is not painful. The medical history is unremarkable. She has smoked cigarettes for the last 30 years. On examination, bilateral small nodules are present that are non-tender and immobile. A mammography confirms the masses and fine needle aspiration cytology of the lesions reveals malignant cells arranged in a row of cells. What is the most likely diagnosis?
- A. Fibroadenoma
- B. Mucinous carcinoma
- C. Inflammatory carcinoma
- D. Invasive lobular carcinoma (Correct Answer)
- E. Invasive ductal carcinoma
Explanation: ***Invasive lobular carcinoma*** - The classic presentation of **invasive lobular carcinoma** includes **bilateral, non-tender, immobile masses** and malignant cells arranged in a **single-file pattern** on FNA, often described as "**Indian files**". - This type of cancer frequently presents with subtle thickening or diffuse induration rather than well-defined masses due to its infiltrative growth pattern. *Fibroadenoma* - **Fibroadenomas** are typically **benign, mobile, well-defined** masses, often described as "rubbery" or "slippery," unlike the immobile nodules described. - While they can be firm, they do not show malignant cells on FNA or the classic "Indian file" arrangement. *Mucinous carcinoma* - **Mucinous carcinoma** is characterized by the presence of tumor cells floating in abundant **extracellular mucin**, which would be evident on FNA. - This typically presents as a **soft, gelatinous mass**, which doesn't align with the description of firm, immobile nodules. *Inflammatory carcinoma* - **Inflammatory carcinoma** presents with characteristic inflammatory signs like **redness, warmth, swelling, and peau d'orange** (orange peel skin appearance) due to dermal lymphatic invasion. - These prominent skin changes are not mentioned in the patient's presentation. *Invasive ductal carcinoma* - **Invasive ductal carcinoma** usually presents as a **solitary, firm, irregular mass** and on FNA typically shows malignant cells in **duct-like structures** or disorganized clusters, not characteristically in single-file lines. - While it is the most common type of breast cancer, the specific "Indian file" arrangement points more strongly to lobular carcinoma.
Question 53: A 60-year-old man presents to his physician as part of his routine annual medical check-up. He has no specific complaints but mentions that he has often experienced fatigue over the past few months. His past medical history is noncontributory. On physical examination, his temperature is 37.2°C (98.8°F), pulse rate is 84/min, blood pressure is 130/86 mm Hg, and respiratory rate is 18/min. On general examination, mild pallor is present. Palpation of the abdomen reveals splenomegaly, which extends 6.35 cm (2.5 in) below the left costal margin. There is no hepatomegaly. Laboratory studies show the following values: Hemoglobin 9.7 g/dL Total leukocyte count 30,000/mm3 Granulocytes 83% Lymphocytes 10% Eosinophils 5% Basophils 1% Monocytes 1% Platelet count 700,000/mm3 The physician orders a bone marrow biopsy analysis of hematopoietic cells. The report shows the presence of a t(9;22)(q34; q11) translocation. Which of the following is the most likely diagnosis?
- A. Chronic myeloid leukemia (Correct Answer)
- B. Transient myeloproliferative disorder
- C. Chronic myelomonocytic leukemia
- D. Chronic neutrophilic leukemia
- E. Myelodysplastic syndrome/myeloproliferative neoplasm, unclassifiable
Explanation: ***Chronic myeloid leukemia*** - The presence of **fatigue**, **splenomegaly**, **leukocytosis with a predominance of granulocytes**, **thrombocytosis**, and specifically the **t(9;22)(q34; q11) translocation (Philadelphia chromosome)** are classic findings for chronic myeloid leukemia (CML). - The **bcr-abl fusion gene** resulting from the t(9;22) translocation leads to uncontrolled tyrosine kinase activity, driving the myeloproliferation seen in CML. *Transient myeloproliferative disorder* - This is a condition seen almost exclusively in **neonates with Down syndrome** and typically resolves spontaneously. - The patient's age (60 years) and the specific translocation rule out this diagnosis. *Chronic myelomonocytic leukemia* - This is characterized by **monocytosis** (absolute monocyte count > 1 x 10^9/L and monocytes > 10% of WBCs) and features of both myelodysplastic and myeloproliferative disorders. - While there is leukocytosis, monocytes are only 1% of the differential, and the t(9;22) translocation is not characteristic of CMML. *Chronic neutrophilic leukemia* - This is a rare myeloproliferative neoplasm characterized by **sustained peripheral blood neutrophilia** and often mutations in the **CSF3R gene**. - While the patient has neutrophilia, the presence of the t(9;22) translocation is not associated with CNL. *Myelodysplastic syndrome/myeloproliferative neoplasm, unclassifiable* - This is a diagnosis of exclusion category used when a patient has features of both MDS and MPN but does not fit into a specific, well-defined entity. - Given the clear presence of the **Philadelphia chromosome**, the diagnostic criteria for **CML** are met, making a diagnosis of "unclassifiable" inappropriate.
Question 54: A 34-year-old woman visits an outpatient clinic with a complaint of pain in her left breast for the last few months. The pain worsens during her menstrual cycle and relieves once the cycle is over. She denies any nipple discharge, skins changes, warmth, erythema, or a palpable mass in the breast. Her family history is negative for breast, endometrial, and ovarian cancer. There is no palpable mass or any abnormality in the physical examination of her breast. A mammogram is ordered which shows a cluster of microcalcifications with a radiolucent center. A breast biopsy is also performed which reveals a lobulocentric proliferation of epithelium and myoepithelium. Which of the following is the most likely diagnosis?
- A. Intraductal papilloma
- B. Fibroadenoma
- C. Sclerosing adenosis (Correct Answer)
- D. Ductal hyperplasia without atypia
- E. Infiltrating ductal carcinoma
Explanation: ***Sclerosing adenosis*** - The combination of **cyclical mastalgia**, **microcalcifications with a radiolucent center** on mammography, and a biopsy showing **lobulocentric proliferation of epithelium and myoepithelium** is highly characteristic of sclerosing adenosis. - Sclerosing adenosis is a **benign proliferative lesion** of the breast that can mimic malignancy clinically and radiologically due to its firm consistency and calcifications. *Intraductal papilloma* - This typically presents with **bloody or serous nipple discharge** and is often associated with a mass near the nipple, which are not present in this case. - Histologically, it involves a papillary growth within a duct, not a lobulocentric proliferation. *Fibroadenoma* - This presents as a **well-circumscribed, palpable, mobile mass** that is typically rubbery and not usually associated with cyclical pain as the primary symptom. - Mammographically, it appears as a well-defined mass, often with coarse calcifications, but the specific **radiolucent center** in clustered microcalcifications is less typical. *Ductal hyperplasia without atypia* - While it can manifest as microcalcifications, it typically does not present with significant cyclical pain as the main symptom. - Histopathologically, it involves an increase in the number of **epithelial cells in the ducts** but without the lobulocentric proliferation of both epithelial and myoepithelial cells seen in sclerosing adenosis. *Infiltrating ductal carcinoma* - This is a **malignant condition** that should be considered with new breast pain and microcalcifications, but the absence of a palpable mass, skin changes, nipple discharge, and the specific biopsy findings make it less likely. - While it can present with microcalcifications, the histological finding of **lobulocentric proliferation of epithelium and myoepithelium** is inconsistent with invasive carcinoma.
Question 55: A 65-year-old man comes to the physician because he is worried about a mole on his right forearm. He has had the mole for several years, but it has grown in size in the past 3 months. Physical examination shows a hyperpigmented plaque with irregular borders and small area of ulceration. Histopathologic analysis of a full-thickness excisional biopsy confirms the diagnosis of malignant melanoma. Invasion of which of the following layers of skin carries the highest risk of mortality for this patient?
- A. Reticular dermis
- B. Papillary dermis
- C. Stratum basale
- D. Stratum corneum
- E. Hypodermis (Correct Answer)
Explanation: ***Hypodermis*** - Invasion into the **hypodermis (subcutaneous tissue)** indicates the deepest penetration of the melanoma, correlated with the **greatest tumor thickness** (Breslow depth). - Deeper invasion significantly increases the likelihood of **lymphatic and hematogenous spread**, leading to the highest risk of **metastasis** and mortality. - This represents the **worst prognosis** among the layers listed. *Stratum corneum* - The **stratum corneum** is the outermost, dead keratinized layer of the epidermis. - Melanoma cells limited to this layer would indicate **melanoma in situ** or a very superficial lesion. - This represents the most superficial involvement, carrying the **lowest risk of mortality** and metastasis. *Stratum basale* - The **stratum basale** is the deepest layer of the epidermis at the dermal-epidermal junction. - Melanoma confined to or near this level represents early invasion just beyond the basement membrane. - This level of invasion is still relatively superficial and is associated with a **better prognosis** than deeper dermal or subcutaneous invasion. *Papillary dermis* - Invasion into the **papillary dermis** signifies invasive melanoma but represents an early stage of dermal invasion. - The risk of distant metastasis and mortality is present but lower compared to invasion into deeper dermal layers or the hypodermis. *Reticular dermis* - Invasion into the **reticular dermis** indicates deeper penetration and a more advanced tumor with greater Breslow depth. - Metastatic risk is significantly increased compared to papillary dermis invasion but is still lower than invasion into the subcutaneous tissue (hypodermis).
Question 56: An 11-year-old boy who recently emigrated from Nigeria is brought to the physician for evaluation of jaw swelling. He has no history of serious illness and takes no medications. Examination shows a 5-cm solid mass located above the right mandible and significant cervical lymphadenopathy. A biopsy specimen of the mass shows sheets of lymphocytes with interspersed tingible body macrophages. Serology for Epstein-Barr virus is positive. Which of the following chromosomal translocations is most likely present in cells obtained from the tissue mass?
- A. t(8;14) (Correct Answer)
- B. t(12;21)
- C. t(11;22)
- D. t(15;17)
- E. t(11;14)
Explanation: ***t(8;14)*** - The constellation of **jaw swelling** in a child from **Nigeria**, positive **Epstein-Barr virus (EBV)** serology, and a biopsy showing a **"starry sky"** pattern (sheets of lymphocytes with interspersed tingible body macrophages) is classic for **endemic Burkitt lymphoma**. - **Burkitt lymphoma** is characterized by the **t(8;14) translocation**, which results in the constitutive activation of the **c-MYC oncogene** on chromosome 8 due to its proximity to the **immunoglobulin heavy chain locus** on chromosome 14. *t(12;21)* - This translocation is typically associated with **B-cell acute lymphoblastic leukemia (ALL)**, particularly in children. - While ALL can present with bone pain or cytopenias, it does not typically manifest as a localized **jaw mass** with a "starry sky" histology. *t(11;22)* - This translocation is characteristic of **Ewing sarcoma**, a **bone tumor** that can affect the jaw. - However, Ewing sarcoma would typically show small, round, blue cells on histology and would not be associated with **EBV infection** or the "starry sky" pattern. *t(15;17)* - This translocation is pathognomonic for **acute promyelocytic leukemia (APML)**, a subtype of acute myeloid leukemia. - APML presents with signs of bone marrow failure and disseminated intravascular coagulation, not with a localized head and neck mass. *t(11;14)* - This translocation is primarily associated with **mantle cell lymphoma**, a type of non-Hodgkin lymphoma that typically affects older adults. - Mantle cell lymphoma would have cyclin D1 overexpression, and usually does not present as a localized jaw mass in children, nor is it strongly linked to EBV in this clinical context.
Question 57: An 11-year-old boy presents to your clinic after 4 months of pain and swelling in his thigh. His mother states that at first she thought his condition was due to roughhousing, but it hasn’t gone away and now she’s concerned. You perform an X-ray that shows an ‘onion skin’ appearance on the diaphysis of the femur. You are concerned about a malignancy, so you perform a PET scan that reveals lung nodules. Which of the following is most associated with this disease?
- A. Defective mitochondrial DNA
- B. Nonsense mutation to DMD gene
- C. t(11;22) translocation (Correct Answer)
- D. t(9;22) translocation
- E. Rb loss of function mutation
Explanation: ***t(11;22) translocation*** - The clinical presentation, including the age of the patient (11-year-old boy), pain and swelling in the thigh, and the characteristic **"onion skin" appearance** on X-ray, are highly suggestive of **Ewing sarcoma** - **Ewing sarcoma** is strongly associated with the **t(11;22) chromosomal translocation**, leading to the fusion of the **EWSR1 and FLI1 genes** - This translocation is found in approximately **85-90% of Ewing sarcoma cases** and is the molecular hallmark of this aggressive pediatric bone malignancy *Defective mitochondrial DNA* - This is associated with mitochondrial disorders, which typically present with myopathies, encephalopathies, and other systemic issues, not bone tumors with an "onion skin" appearance - While sometimes involved in cancer pathogenesis, defective mitochondrial DNA is not the primary genetic hallmark of Ewing sarcoma *Nonsense mutation to DMD gene* - A nonsense mutation in the **DMD gene** causes **Duchenne muscular dystrophy**, a genetic disorder characterized by progressive muscle weakness and degeneration - This condition does not present with bone tumors, thigh pain from malignancy, or an "onion skin" periosteal reaction *t(9;22) translocation* - The **t(9;22) translocation**, also known as the **Philadelphia chromosome**, is characteristic of **chronic myeloid leukemia (CML)** and some cases of acute lymphoblastic leukemia (ALL) - This genetic abnormality is associated with hematologic malignancies, not bone sarcomas like Ewing sarcoma *Rb loss of function mutation* - A loss-of-function mutation in the **Rb (retinoblastoma) gene** is associated with **retinoblastoma** and an increased risk of other cancers such as osteosarcoma and small cell lung cancer - While osteosarcoma is a bone tumor, it typically presents with a "sunburst" or Codman's triangle appearance on X-ray, not the "onion skin" appearance seen in Ewing sarcoma
Question 58: A 19-year-old man comes to the physician for evaluation of night sweats, pruritus, and enlarging masses in his right axilla and supraclavicular area for 2 weeks. Physical examination shows painless, rubbery lymphadenopathy in the right axillary, supraclavicular, and submental regions. An excisional biopsy of an axillary node is performed. If present, which of the following features would be most concerning for a neoplastic process?
- A. Diffuse mitotic activity in secondary follicles
- B. Predominance of histiocytes in the medullary sinuses
- C. Preponderance of lymphocytes with a single immunoglobulin variable domain allele (Correct Answer)
- D. Positive staining of the paracortex for cluster of differentiation 8
- E. Polyclonal proliferation of lymphocytes with a single nucleus
Explanation: ***Preponderance of lymphocytes with a single immunoglobulin variable domain allele*** - A **monoclonal proliferation** of lymphocytes (i.e., a preponderance of lymphocytes with a single immunoglobulin variable domain allele) is a definitive indicator of a **lymphoid neoplasm**, such as lymphoma or leukemia. - This finding demonstrates that the lymphocytes are derived from a single clone, which is characteristic of cancer, unlike the diverse, polyclonal response seen in reactive conditions. *Diffuse mitotic activity in secondary follicles* - While increased **mitotic activity** can be seen in lymphomas, it is also a normal finding in **reactive lymphoid hyperplasia** within germinal centers, which are sites of active immune response. - The descriptor "diffuse" primarily points to spread, but in the context of secondary follicles, it would mostly suggest high metabolic and cell division rates that are not exclusively neoplastic. *Predominance of histiocytes in the medullary sinuses* - An increase in **histiocytes (macrophages)** in the medullary sinuses (sinus histiocytosis) is a common finding in **reactive lymph nodes**, indicating an increased immune response and filtration of antigens. - It is generally considered a benign condition and a sign of enhanced immune activity rather than malignancy. *Positive staining of the paracortex for cluster of differentiation 8* - The **paracortex** is the T-cell rich area of the lymph node, and **CD8+ T cells** are normal components of the immune response, particularly against viral infections and intracellular pathogens. - An increase in CD8+ T cells can be seen in various reactive conditions and does not, by itself, indicate a neoplastic process. *Polyclonal proliferation of lymphocytes with a single nucleus* - **Polyclonal proliferation** is characteristic of a **normal immune response** or reactive lymphoid hyperplasia, where various B and T cell clones respond to an antigen. - The phrase "single nucleus" is not a discriminating factor for malignancy versus benign conditions, as nearly all lymphocytes, whether neoplastic or not, possess a single nucleus.
Question 59: A 62-year-old man seeks evaluation at a local walk-in clinic for mid-low back pain of several weeks. He has tried different rehabilitation therapies and medications with no improvement. He was prescribed some pain medications and sent home last week, but the patient presents today with difficulty walking and worsening of his back pain. He was referred to the ER, where he was examined and found to have hypoesthesia from T12 to S4–S5, significant muscle weakness in both lower limbs, and reduced knee and ankle deep tendon reflexes. A hypotonic anal sphincter with conserved deep anal pressure was demonstrated on digital rectal examination, as well as a multinodular, asymmetric prostate. Imaging studies showed multiple sclerotic bone lesions along the spine. Subsequently, a prostate core biopsy was obtained which confirmed the diagnosis of prostate cancer. Which of the following characteristics would you expect in the specimen?
- A. Well-formed glands with an increase in interglandular stroma
- B. Fat invasion
- C. Prostatic intraepithelial neoplasia
- D. Small, closely-packed, well-formed glands
- E. Perineural invasion (Correct Answer)
Explanation: ***Perineural invasion*** - **Perineural invasion** is a common finding in prostate adenocarcinoma, indicating that cancer cells have invaded the nerves surrounding the prostatic glands. This feature is often associated with a higher Gleason score and increased likelihood of extraprostatic extension and metastasis. - While not visible on gross examination, its presence on biopsy can influence staging and treatment decisions for prostate cancer, particularly regarding the risk of recurrence and spread to other tissues. *Well-formed glands with an increase in interglandular stroma* - This description is more indicative of **benign prostatic hyperplasia (BPH)**, a non-cancerous enlargement of the prostate, characterized by an increase in both glandular and stromal components. - In BPH, the glands typically remain well-formed, and the stroma often proliferates, but these features do not represent malignancy. *Fat invasion* - **Fat invasion** is not a typical characteristic of prostate cancer within the prostate gland itself, as the prostate is not primarily composed of fat. - While prostate cancer can invade periprostatic fatty tissue if it extends beyond the prostatic capsule, fat invasion within the biopsy specimen from the prostate proper is not a diagnostic feature of adenocarcinoma. *Prostatic intraepithelial neoplasia* - **Prostatic intraepithelial neoplasia (PIN)** is a pre-malignant lesion where the prostatic ductal and acinar cells show cytologic atypia but remain confined within the basement membrane. - While PIN (especially high-grade PIN) can be associated with prostate cancer and may precede its development, it is not cancer itself and is not the definitive diagnosis in this case where prostate cancer has been confirmed. *Small, closely-packed, well-formed glands* - This description could represent a **low-grade prostate adenocarcinoma** (Gleason pattern 3), where the glands are still relatively well-formed but are more numerous and crowded than in benign tissue. - However, compared to perineural invasion, which is a more definitive sign of aggressive behavior and advanced disease in a patient presenting with metastatic features (sclerotic bone lesions, neurologic symptoms), this histological finding alone is less specific for the advanced cancer described.
Question 60: An otherwise healthy 66-year-old man comes to the physician for evaluation of rough skin over his forehead and the back of his hands. He has tried applying different types of moisturizers with no improvement. He has worked on a farm all his life. Physical examination shows two erythematous papules with a gritty texture and central scale over the left temple and three similar lesions over the dorsum of his hands. This patient's skin lesions increase his risk of developing a skin condition characterized by which of the following findings on histopathology?
- A. Intraepidermal acantholysis
- B. Noncaseating granulomas
- C. Atypical melanocytes
- D. Keratin pearls (Correct Answer)
- E. Basaloid cells
Explanation: ***Keratin pearls*** - The patient's description (rough, erythematous papules with gritty texture and central scale on sun-exposed areas) is characteristic of **actinic keratoses**, which are premalignant lesions for **squamous cell carcinoma (SCC)**. - **Squamous cell carcinoma** is histopathologically characterized by features like **keratin pearls** (whorls of keratinocytes) and atypical keratinocytes invading the dermis. *Intraepidermal acantholysis* - **Acantholysis** (loss of cohesion between keratinocytes) is a hallmark of **pemphigus vulgaris** and other pemphigus disorders, which present as blistering skin diseases, not gritty papules. - This finding is not associated with premalignant actinic keratoses or SCC. *Noncaseating granulomas* - **Noncaseating granulomas** are characteristic of **sarcoidosis**, a multisystem inflammatory disease that can affect the skin. - This finding is unrelated to sun-induced premalignant lesions or SCC. *Atypical melanocytes* - **Atypical melanocytes** are a key feature of **melanoma**, a highly malignant skin cancer arising from melanocytes. - While sun exposure is a risk factor for melanoma, the described lesions are more classic for actinic keratoses, leading to SCC, not melanoma. *Basaloid cells* - **Basaloid cells** forming peripheral palisading and nodular aggregates are characteristic of **basal cell carcinoma (BCC)**. - Although BCC is also a sun-induced skin cancer, actinic keratoses are primarily precursors to SCC, and the lesions described are more typical of SCC precursors.
Question 61: A 62-year-old woman presents to the clinic for a 2-month history of ‘fogginess’. She reports that for the last couple of months she feels like she has "lost a step" in her ability to think clearly, often forgetting where she parked her car or to lock the front door after leaving the house. She also feels that her mood has been low. On further questioning, she reports mild constipation and that she has had a bothersome, progressively worsening cough over the past couple of months, accompanied by 6.8 kg (15 lb) unintentional weight loss. She has a history of hypertension for which she takes amlodipine daily. She has smoked 1.5 packs of cigarettes per day for the last 40 years. Physical exam is unremarkable. Laboratory studies show: Na+ 138 mg/dL K+ 3.9 mg/dL Cl- 101 mg/dL HCO3- 24 mg/dL BUN 10 mg/dL Cr 0.6 mg/dL Glucose 86 mg/dL Ca2+ 13.6 mg/dL Mg2+ 1.9 mg/dL Parathyroid hormone (PTH) 2 pg/mL (10–65) 1,25-hydroxyvitamin D 15 pg/mL (20–45) Quantiferon-gold negative Which of the following best describes this patient's most likely underlying pathology?
- A. Toxicity (exogenous)
- B. Infectious
- C. Endocrine
- D. Inflammatory
- E. Neoplastic (Correct Answer)
Explanation: ***Neoplastic*** - The patient's presentation with **unexplained weight loss**, worsening cough, and **hypercalcemia** with **suppressed PTH** and low 1,25-hydroxyvitamin D is highly concerning for **paraneoplastic syndrome** due to malignancy, most likely lung cancer given her significant smoking history. - The cognitive 'fogginess' and low mood could be attributed to **hypercalcemia**, a common paraneoplastic manifestation. *Toxicity (exogenous)* - While exogenous toxins can cause neurological symptoms, there is **no clear exposure** history or laboratory findings (e.g., specific drug levels) to support this diagnosis. - The constellation of cough, weight loss, and hypercalcemia with suppressed PTH is not typical for common exogenous toxicities. *Infectious* - The patient's symptoms are chronic and progressive, rather than acute, and the **Quantiferon-gold test was negative**, ruling out tuberculosis. - There are no other objective signs of infection such as fever, elevated white blood cell count, or specific serological markers to suggest an infectious etiology. *Endocrine* - Although the patient has hypercalcemia (an endocrine issue), the **extremely low PTH** indicates that the parathyroid glands are not the primary source of the elevated calcium. This points away from primary hyperparathyroidism. - The overall presentation, including cough and weight loss, extends beyond a simple endocrine disorder and suggests a broader systemic process. *Inflammatory* - There are **no signs of systemic inflammation** such as fever, elevated CRP, elevated ESR, or specific autoantibodies in the provided data. - While some inflammatory conditions can cause constitutional symptoms, they do not typically present with this specific combination of hypercalcemia, suppressed PTH, and a persistent cough with weight loss.
Question 62: A 63-year-old man comes to the physician because of increasing generalized fatigue for 3 months. He is having more difficulty with keeping up with his activities of daily living and has lost 2.5 kg (5.5 lb) over the past month. He has hypertension and hyperlipidemia. He does not smoke and drinks two to three beers on weekends. His medications include lisinopril, hydrochlorothiazide, and atorvastatin. His temperature is 37.1°C (98.8°F), pulse is 85/min, respirations are 15/min, and blood pressure is 125/73 mm Hg. Examination shows pale conjunctivae. The remainder of the examination shows no abnormalities. His hematocrit is 27.3%, leukocyte count is 4500/mm3, and platelet count is 102,000/mm3. A peripheral blood smear shows numerous blast cells that stain positive for myeloperoxidase, CD33, and CD34. Which of the following is the most likely diagnosis?
- A. Non-Hodgkin lymphoma
- B. Acute myeloid leukemia (Correct Answer)
- C. Hairy cell leukemia
- D. Chronic lymphocytic leukemia
- E. Acute lymphoblastic leukemia
Explanation: ***Acute myeloid leukemia*** - The presence of **numerous blast cells** that stain positive for **myeloperoxidase (MPO)** and **CD33** is highly characteristic of **acute myeloid leukemia (AML)**. - The patient's symptoms of **fatigue**, **weight loss**, **pale conjunctivae (anemia)**, and **pancytopenia** (low hematocrit, leukopenia, thrombocytopenia) are consistent with bone marrow infiltration by leukemic blasts. *Non-Hodgkin lymphoma* - Characterized by **lymphadenopathy** and systemic 'B' symptoms (fever, night sweats, weight loss), which are not prominent features here. - While it can cause cytopenias, the presence of **myeloperoxidase-positive blasts** would point away from lymphoma, which involves lymphocytes. *Hairy cell leukemia* - Typically presents with **pancytopenia**, **splenomegaly**, and characteristic **hairy cells** on peripheral smear. - These cells are **CD103, CD123, and CD25 positive** and tartrate-resistant acid phosphatase (TRAP) positive, which differs from the findings in this case. *Chronic lymphocytic leukemia* - Characterized by an accumulation of **mature-appearing lymphocytes** (not blasts) in the blood, bone marrow, and lymph nodes. - These cells typically express **CD5 and CD20**, and **myeloperoxidase** would be negative. *Acute lymphoblastic leukemia* - Involves **lymphoblasts**, which are typically **MPO-negative** and express lymphoid markers like **CD10, CD19, and CD22**. - While it can present with similar symptoms and pancytopenia as AML, the **MPO positivity rules it out**.
Question 63: A 62-year-old man comes to the physician because of progressive fatigue and dyspnea on exertion for 3 months. During this time, he has also had increased straining during defecation and a 10-kg (22-lb) weight loss. He has no personal or family history of serious medical illness. Physical examination shows conjunctival pallor. Laboratory studies show microcytic anemia. Test of the stool for occult blood is positive. Colonoscopy shows an exophytic mass in the ascending colon. Pathologic examination of the mass shows a well-differentiated adenocarcinoma. A gain-of-function mutation in which of the following genes is most likely involved in the pathogenesis of this patient's condition?
- A. APC
- B. TP53
- C. MLH1
- D. KRAS (Correct Answer)
- E. DCC
Explanation: ***KRAS*** - A **gain-of-function mutation** in **KRAS** is a common early event in the development of colorectal adenocarcinoma, driving uncontrolled cell growth and proliferation. - This mutation is frequently found in **sporadic colorectal cancers**, particularly in the advanced stages of adenoma to carcinoma progression. *APC* - **APC** is a **tumor suppressor gene**, and mutations in it are typically **loss-of-function**, not gain-of-function. - While APC mutations are crucial early steps in the adenoma-carcinoma sequence, they lead to inactivation of the gene, not increased function. *TP53* - **TP53** is a **tumor suppressor gene** which, when mutated, usually involves **loss-of-function** or dominant-negative effects, impairing its ability to induce apoptosis or cell cycle arrest. - Mutations in TP53 are typically associated with **later stages** of colorectal cancer progression and tend to be loss-of-function, not gain-of-function. *MLH1* - **MLH1** is involved in **DNA mismatch repair**, and mutations here lead to **microsatellite instability** and are characteristic of hereditary nonpolyposis colorectal cancer (Lynch syndrome). - These are typically **loss-of-function mutations** that impair DNA repair, not gain-of-function mutations promoting oncogenesis directly through signaling pathways. *DCC* - **DCC** (**Deleted in Colorectal Carcinoma**) is a **tumor suppressor gene**, and its inactivation or loss is associated with colorectal cancer progression, particularly the transition from adenoma to carcinoma. - Mutations or deletions in DCC result in a **loss-of-function**, not a gain-of-function, contributing to tumor growth by failing to regulate cell differentiation and apoptosis.
Question 64: A 52-year-old man arrives to the clinic for arthritis and leg swelling. The patient reports that the joint pains began 8 months ago. He has tried acetaminophen and ibuprofen without significant improvement. He reports the leg swelling began within the past 2 months and has gotten progressively worse. The patient’s medical history is significant for diabetes. His medications include metformin and aspirin. The patient works as an accountant. He smokes cigars socially. The patient’s temperature is 99°F (37.2°C), blood pressure is 130/78 mmHg, pulse is 70/min, and respirations are 14/min with an oxygen saturation of 98% on room air. Physical examination notes a tan, overweight male with 2+ edema of bilateral lower extremities. Which of the following tumor markers is most likely to be associated with this patient’s condition?
- A. Alkaline phosphatase
- B. Chromogranin
- C. CA 19-9
- D. Carcinoembryonic antigen
- E. Alpha fetoprotein (Correct Answer)
Explanation: ***Alpha fetoprotein*** - The patient's presentation with **chronic arthritis**, **progressive bilateral leg edema**, and **diabetes** in an overweight patient raises clinical suspicion for **underlying liver disease**, potentially **cirrhosis** progressing to **hepatocellular carcinoma (HCC)**. - The combination of **arthritis** (suggesting possible iron deposition arthropathy) and **diabetes** may indicate **hemochromatosis**, a condition that leads to **cirrhosis** and significantly increases HCC risk. - The **bilateral lower extremity edema** suggests **portal hypertension** from cirrhosis or hypoalbuminemia from hepatic dysfunction. - **Alpha-fetoprotein (AFP)** is the most established and validated tumor marker for detecting and monitoring **hepatocellular carcinoma**, which develops in approximately 20-30% of patients with cirrhosis. *Alkaline phosphatase* - While **alkaline phosphatase (ALP)** can be elevated in liver disease including HCC, it is a **non-specific marker** that primarily indicates **cholestasis** or **bone disease**. - ALP is not a specific tumor marker and would not be the "most likely" marker associated with a suspected malignancy. *Chromogranin* - **Chromogranin A** is a tumor marker for **neuroendocrine tumors** (carcinoid syndrome, pheochromocytoma, gastrinomas). - The patient's clinical presentation does not suggest a neuroendocrine malignancy (no flushing, diarrhea, hypertensive episodes, or peptic ulcer disease). *CA 19-9* - **CA 19-9** is primarily a tumor marker for **pancreatic adenocarcinoma** and sometimes cholangiocarcinoma or gastric cancer. - The clinical presentation lacks features of pancreatic cancer (no jaundice, weight loss, abdominal pain, or obstructive symptoms). *Carcinoembryonic antigen* - **Carcinoembryonic antigen (CEA)** is most commonly associated with **colorectal cancer** and other adenocarcinomas (lung, breast, gastric). - CEA is not a specific or primary marker for HCC and does not fit this clinical picture as well as AFP.
Question 65: A 51-year-old woman comes to the physician because of a persistent cough and a 5-kg (11-lb) weight loss over the past 2 months. Yesterday, she coughed up bloody sputum. She does not smoke. Pulmonary examination shows decreased breath sounds over the right upper lobe. A CT scan of the chest shows a mass in the periphery of the right upper lobe. Histopathologic examination of a specimen obtained on CT-guided biopsy shows glandular cells with papillary components and signet ring cells that stain positive for mucin. An alteration in which of the following genes is most likely to have occurred in this patient?
- A. TP53
- B. SMAD4 (DPC4)
- C. APC
- D. MYCL1
- E. ALK (Correct Answer)
Explanation: ***ALK*** - The patient's presentation with **adenocarcinoma** (glandular cells, mucin, peripheral location) in a **non-smoker** suggests a higher likelihood of specific driver mutations, such as **ALK rearrangements**. - **ALK gene rearrangements** are characteristic oncogenic drivers in a subset of lung adenocarcinomas, particularly in younger patients and non-smokers. *TP53* - **TP53** is a tumor suppressor gene frequently mutated in many cancers, including lung cancer, but its mutation is not as specific to the clinical and histopathological findings of this patient's adenocarcinoma presenting in a non-smoker. - While common in lung cancer overall, **TP53 mutations** are more strongly associated with squamous cell carcinoma or small cell lung cancer, or with smoking-related adenocarcinoma. *SMAD4 (DPC4)* - **SMAD4** is a tumor suppressor gene primarily associated with **pancreatic cancer** and **colorectal cancer**, playing a key role in the TGF-β signaling pathway. - Its mutation is not a common or characteristic driver in lung adenocarcinoma, especially with the features described. *APC* - The **APC gene** is a tumor suppressor gene centrally involved in the **Wnt signaling pathway** and is primarily associated with **colorectal cancer**, particularly **familial adenomatous polyposis**. - APC mutations are not typically found as primary drivers in lung adenocarcinoma. *MYCL1* - **MYCL1 (L-MYC)** is an oncogene belonging to the MYC family, implicated in cell proliferation and apoptosis. - While MYC family genes can be amplified in various cancers, **MYCL1 amplification** is more characteristic of **small cell lung cancer**, not adenocarcinoma, and does not align with the glandular and papillary features described.
Question 66: A 6-year-old boy is brought to a primary care provider by his adoptive parents for evaluation of a 3-month history of jaw swelling. He has a travel history of recent immigration from equatorial Africa where his deceased mother was positive for HIV and died from related complications. On physical exam, extensive lymph node swelling on the left side of his jaw is noted. There is also an ulceration that appears to be infected. Fine needle biopsy of the lymph node yields a diagnosis of Burkitt’s lymphoma by the pathologist. Which of the following is most likely associated with the involvement of lymph nodes around his jaw?
- A. Ethnicity of the patient
- B. Close family member with HIV
- C. Gender of the patient
- D. Recent immigration from equatorial Africa (Correct Answer)
- E. Infected ulcer
Explanation: ***Recent immigration from equatorial Africa*** - **Endemic Burkitt's lymphoma**, common in equatorial Africa, typically manifests as a **jaw mass** in children and is strongly associated with **Epstein-Barr virus (EBV)**. - The patient's history of immigration from this region directly links to the presentation of Burkitt's lymphoma in his jaw. *Ethnicity of the patient* - While certain ethnic groups may have higher predispositions to specific diseases, ethnicity itself is not the primary determinant for the **endemic presentation of Burkitt's lymphoma** in the jaw. - The **geographical region** (equatorial Africa) is a more direct and stronger risk factor for this specific clinical picture. *Close family member with HIV* - HIV infection can increase the risk of **immunodeficiency-associated lymphomas**, but it doesn't specifically explain the characteristic **jaw involvement** seen in endemic Burkitt's lymphoma. - The mother's HIV status indicates a potential compromised immune system in the patient, which can be a predisposing factor for lymphomas in general, but not specifically for the jaw location of Burkitt's lymphoma. *Gender of the patient* - **Burkitt's lymphoma** does not show a significant predilection for one gender over the other to explain the specific jaw involvement. - The presentation is more tied to **geographic and immunological factors** than to the patient's gender. *Infected ulcer* - The infected ulcer is a **secondary complication** or a symptom that may arise from the rapidly growing tumor, indicating opportunistic infection, rather than the primary cause or association for the specific location of the lymphoma. - It doesn't explain why the lymphoma initially presented in the **jaw lymph nodes**.
Question 67: A 74-year-old man comes to the physician for evaluation of a skin lesion on his right arm. The lesion first appeared 3 months ago and has since been slowly enlarging. Physical examination shows a 1.5-centimeter, faintly erythematous, raised lesion with irregular borders on the dorsum of the right forearm. A biopsy specimen is obtained. If present, which of the following histopathological features would be most consistent with carcinoma in situ?
- A. Presence of epithelial cells in the dermis
- B. Pleomorphism of cells in the stratum corneum
- C. Increased nuclear to cytoplasmic ratio in the stratum spinosum
- D. Full-thickness basal to apical cell polarity
- E. Full-thickness nuclear atypia with intact basement membrane (Correct Answer)
Explanation: ***Full-thickness nuclear atypia with intact basement membrane*** - Carcinoma in situ (CIS) is characterized by **malignant changes confined to the epidermis** with **full-thickness involvement** of all viable epidermal layers. - The **basement membrane remains intact**, meaning there is no invasion into the dermis. - **Nuclear atypia, loss of maturation, and architectural disarray** extend from the basal layer to the superficial layers, but cancerous cells have not breached the basement membrane. - This describes **Bowen's disease** (squamous cell carcinoma in situ), which is consistent with the clinical presentation of a slowly enlarging erythematous plaque on sun-exposed skin in an elderly patient. *Presence of epithelial cells in the dermis* - The presence of **epithelial cells in the dermis** indicates **invasive squamous cell carcinoma**, as it signifies breach of the basement membrane. - Carcinoma in situ, by definition, is restricted to the **epidermis** and does not involve dermal invasion. *Pleomorphism of cells in the stratum corneum* - The **stratum corneum** consists of dead, anucleated keratinocytes, making nuclear **pleomorphism** impossible in this layer. - Malignant changes occur in the **viable layers of the epidermis** (stratum basale, spinosum, granulosum), not in the cornified layer. *Increased nuclear to cytoplasmic ratio in the stratum spinosum* - While an **increased nuclear-to-cytoplasmic ratio** is seen in carcinoma in situ, this option implies changes limited to the stratum spinosum only. - True carcinoma in situ requires **full-thickness** epidermal involvement, not changes confined to a single layer. - Changes limited to one layer would suggest **dysplasia** rather than carcinoma in situ. *Full-thickness basal to apical cell polarity* - This describes **normal epidermal architecture** with ordered maturation of keratinocytes from basal to superficial layers. - In carcinoma in situ, this **normal polarity is lost**, with architectural disarray and loss of orderly maturation throughout the epidermis.
Question 68: A 45-year-old woman presents to the emergency department after sustaining a gunshot wound to her shoulder. During the course of the physical exam, the physician notes her spleen is palpable 10 cm below the left costal margin. Additionally, radiography of her shoulder showed several 'punched-out' areas of lytic bone. While this was considered an incidental finding at the time, she was referred to her primary care physician for further workup. Subsequent biopsy of the spleen demonstrated that this patient’s splenomegaly was caused by an infiltrative process. Which of the following processes would most likely result in splenomegaly in this patient?
- A. Multiple myeloma (Correct Answer)
- B. Budd-Chiari syndrome
- C. Infectious mononucleosis
- D. Myelofibrosis
- E. Beta-thalassemia
Explanation: ***Multiple myeloma*** - **Multiple myeloma** is characterized by malignant plasma cell proliferation in the bone marrow, causing classic **"punched-out" lytic bone lesions** due to osteoclast-activating factors secreted by malignant plasma cells. - While splenomegaly is less common than in other hematologic malignancies, **plasma cell infiltration of the spleen** can occur, causing splenomegaly with an **infiltrative process on biopsy**. - The combination of **pathognomonic punched-out lytic bone lesions** + **infiltrative splenomegaly** is diagnostic of multiple myeloma with splenic involvement. - Additional features typically include **anemia**, **hypercalcemia**, **renal insufficiency**, and elevated serum protein with monoclonal spike on electrophoresis. *Myelofibrosis* - **Myelofibrosis** is a myeloproliferative neoplasm causing **massive splenomegaly** due to extramedullary hematopoiesis and does cause infiltrative changes in the spleen. - However, bone changes in myelofibrosis typically show **osteosclerosis** (increased bone density) or mixed sclerotic/lytic patterns, NOT the classic discrete "punched-out" lytic lesions described. - The punched-out lytic lesions are the key distinguishing feature pointing to multiple myeloma, not myelofibrosis. *Budd-Chiari syndrome* - **Budd-Chiari syndrome** involves hepatic venous outflow obstruction, leading to **hepatomegaly**, **ascites**, and congestive splenomegaly due to portal hypertension. - Splenomegaly is due to **passive congestion**, not an infiltrative process, and would not show infiltrative changes on biopsy. - Does not cause lytic bone lesions. *Beta-thalassemia* - **Beta-thalassemia** can cause splenomegaly due to extramedullary hematopoiesis and hemolysis, with bone changes from marrow expansion. - Bone changes show **widened medullary spaces** and "hair-on-end" appearance on skull X-ray, NOT discrete punched-out lytic lesions. - The primary features are severe **microcytic anemia** and abnormal hemoglobin patterns, not plasma cell infiltration. *Infectious mononucleosis* - **Infectious mononucleosis** (EBV infection) causes acute splenomegaly due to **lymphoid hyperplasia** and immune response. - This is a **self-limiting viral illness** that does not cause punched-out lytic bone lesions or chronic infiltrative splenomegaly. - Biopsy would show reactive lymphoid hyperplasia, not malignant infiltration.
Question 69: A 67-year-old man presents to the emergency department with increased fatigue. He states that he has been feeling very tired lately but today lost consciousness while walking up the stairs. He reports mild abdominal distension/discomfort, weight loss, a persistent cough, and multiple episodes of waking up drenched in sweat in the middle of the night. The patient does not see a primary care physician but admits to smoking 2 to 3 packs of cigarettes per day and drinking 1 to 3 alcoholic beverages per day. He recently traveled to Taiwan and Nicaragua. His temperature is 99.5°F (37.5°C), blood pressure is 177/98 mmHg, pulse is 100/min, respirations are 17/min, and oxygen saturation is 98% on room air. On physical exam, you note a fatigued appearing elderly man who is well-groomed. Cardiopulmonary exam reveals mild expiratory wheezes. Abdominal exam is notable for a non-pulsatile mass in the left upper quadrant. Laboratory values are ordered as seen below. Hemoglobin: 12 g/dL Hematocrit: 36% Leukocyte count: 105,500/mm^3 Platelet count: 197,000/mm^3 Serum: Na+: 139 mEq/L Cl-: 100 mEq/L K+: 4.3 mEq/L HCO3-: 25 mEq/L BUN: 20 mg/dL Glucose: 92 mg/dL Creatinine: 1.4 mg/dL Ca2+: 10.2 mg/dL Leukocyte alkaline phosphatase score: 25 (range 20 - 100) AST: 12 U/L ALT: 17 U/L Which of the following is the most likely diagnosis?
- A. Tuberculosis
- B. Leukemoid reaction
- C. Acute myelogenous leukemia
- D. Acute lymphoblastic leukemia
- E. Chronic myeloid leukemia (Correct Answer)
Explanation: ***Chronic myeloid leukemia*** - The patient presents with **fatigue, weight loss, night sweats, and a persistent cough**, which are common symptoms of CML. The **extreme leukocytosis (105,500/mm^3)**, **non-pulsatile LUQ mass (splenomegaly)**, and a **low-normal leukocyte alkaline phosphatase (LAP) score of 25** are highly indicative of CML. - CML characteristically shows a **low LAP score (typically <20)**, which distinguishes it from a leukemoid reaction. This patient's LAP of 25, while technically within the normal range (20-100), is at the lower end and consistent with CML. - CML is a myeloproliferative disorder characterized by the **Philadelphia chromosome (BCR-ABL fusion gene)**, leading to uncontrolled proliferation of myeloid cells. *Tuberculosis* - While **fatigue, weight loss, night sweats, and cough** can be present in tuberculosis, the **dramatically elevated leukocyte count** and **splenomegaly** are not characteristic findings of TB. - Tuberculosis would typically show a more prominent respiratory symptomology (e.g., hemoptysis) and imaging findings consistent with lung involvement, and its diagnosis would be confirmed by microbiologic studies. *Leukemoid reaction* - A leukemoid reaction is a **reactive leukocytosis (>50,000/mm^3)** often triggered by severe infection or inflammation, but it would present with an **elevated leukocyte alkaline phosphatase (LAP) score (typically >100)**, which contradicts the patient's low-normal LAP score of 25. - Unlike CML, a leukemoid reaction does not typically cause **splenomegaly** to the extent that it forms a palpable mass. *Acute myelogenous leukemia* - AML typically presents with **malignant myeloid blasts** in the peripheral blood (often >20%) and bone marrow, and patients are usually more acutely ill with symptoms related to **pancytopenia** (e.g., severe anemia, thrombocytopenia with bleeding), which are not present in this case. - While AML can cause leukocytosis, it is characterized by a **predominance of immature blast cells** rather than the mature granulocytes seen in CML. *Acute lymphoblastic leukemia* - ALL is primarily a disease of **lymphoid progenitor cells** and is more common in children, though it can occur in adults. It is characterized by the presence of **lymphoblasts** in the blood and bone marrow. - While it can cause fatigue and weight loss, the **extremely high leukocyte count composed primarily of mature myeloid cells** and **prominent splenomegaly** are inconsistent with ALL.
Question 70: A 9-year-old boy presents with polydipsia, polyuria, and a serum osmolality of 325 mOsm/L. A neurologic examination reveals bitemporal hemianopia. The lesion is believed to be derived from Rathke's pouch remnants. Which of the following is the most likely histologic finding?
- A. Lymphocytic infiltrate
- B. Cystic spaces (Correct Answer)
- C. Branching papillae
- D. Immune complex deposition
- E. Liquefactive necrosis
Explanation: ***Cystic spaces*** - The described symptoms (polydipsia, polyuria, bitemporal hemianopia) in a child, along with a lesion derived from **Rathke's pouch remnants**, strongly suggest **craniopharyngioma**. - Histologically, craniopharyngiomas are characterized by **cystic spaces** filled with thick, oily, "motor oil" like fluid rich in cholesterol crystals, along with adamantinomatous or papillary epithelial components. - The **adamantinomatous variant** (most common in children) features prominent cystic spaces, wet keratin, and calcifications. *Lymphocytic infiltrate* - While some tumors can have lymphocytic infiltrates, it is not a primary defining feature of **craniopharyngioma**. - **Lymphocytic infiltrates** are more characteristic of inflammatory or autoimmune conditions, or certain lymphoid neoplasms. *Branching papillae* - Although a **papillary variant** of craniopharyngioma exists (typically in adults), **branching papillae** are not the characteristic histologic finding, especially in a pediatric patient. - The adamantinomatous type (seen in children) is defined by **cystic spaces** with cholesterol crystals and wet keratin, not papillary architecture. - This pattern is more characteristic of tumors like **papillary thyroid carcinoma** or certain renal cell carcinomas. *Immune complex deposition* - **Immune complex deposition** is associated with autoimmune diseases or certain kidney disorders, such as glomerulonephritis. - It is not a pathologic hallmark of **craniopharyngioma**. *Liquefactive necrosis* - **Liquefactive necrosis** is a type of tissue death characterized by the dissolution of dead cells and formation of a viscous liquid mass. - While some tumors may undergo necrosis, it is not the primary or specific histological finding for diagnosing **craniopharyngioma**, which is more defined by its cystic and epithelial characteristics.
Question 71: A 38-year-old man presents with concerns after finding out that his father was recently diagnosed with colon cancer. Family history is only significant for his paternal grandfather who also had colon cancer. A screening colonoscopy is performed, and a polyp is found in the ascending (proximal) colon, which on biopsy shows adenocarcinoma. A mutation in a gene that is responsible for which of the following cellular functions is the most likely etiology of this patient’s cancer?
- A. DNA mismatch repair (Correct Answer)
- B. Signal transduction
- C. Cytoskeletal stability
- D. Inhibits progression from G1 to S phase
- E. Inhibitor of apoptosis
Explanation: ***DNA mismatch repair*** - The patient's presentation with **early-onset colon cancer** (38 years old), location in the **proximal colon** (ascending colon), and a **strong family history** of colon cancer in his father and paternal grandfather are highly suggestive of **Lynch syndrome (hereditary non-polyposis colorectal cancer or HNPCC)**. - Lynch syndrome is caused by inherited mutations in **DNA mismatch repair (MMR) genes**, such as *MLH1, MSH2, MSH6*, and *PMS2*, leading to microsatellite instability and an increased risk of various cancers, particularly colorectal and endometrial. *Signal transduction* - Mutations in **signal transduction genes (e.g., *KRAS*, *BRAF*)** are common in sporadic colorectal cancer and lead to constitutive activation of cell growth pathways through the RAS/MAPK signaling cascade. - While mutations in these genes are important in colorectal cancer pathogenesis, they typically do not explain the **familial aggregation, early onset, and proximal location** seen in this patient, which are hallmarks of Lynch syndrome. *Cytoskeletal stability* - Genes involved in cytoskeletal stability are crucial for cell structure and migration, but their primary dysfunction is not the direct cause of inherited colorectal cancer syndromes like Lynch syndrome. - While some advanced cancers may show changes in cytoskeletal proteins, this is not the fundamental genetic defect underlying this specific familial cancer presentation. *Inhibits progression from G1 to S phase* - Proteins that inhibit progression from G1 to S phase are typically **tumor suppressor genes**, such as **retinoblastoma protein (Rb)** or **p53**. - Loss of function in these genes promotes uncontrolled cell division, but mutations in *Rb* or *p53* are not the primary cause of Lynch syndrome; rather, it is characterized by defects in **DNA repair**. *Inhibitor of apoptosis* - Genes that inhibit apoptosis (programmed cell death) are often **oncogenes** (e.g., *BCL-2*) or genes that, when mutated, lead to resistance to apoptotic signals. - While resistance to apoptosis is a hallmark of cancer, the fundamental defect in Lynch syndrome is impaired **DNA repair**, not primarily a direct inhibition of apoptosis.
Question 72: A 71-year-old man comes to the physician for a routine health maintenance examination. He has occasional fatigue but otherwise feels well. He has a history of hypertension and type 2 diabetes mellitus. He is a retired chemist. His only medication is ramipril. His temperature is 37.8°C (100°F), pulse is 72/min, respirations are 18/min, and blood pressure is 130/70 mm Hg. Physical examination shows nontender cervical and axillary lymphadenopathy. The spleen is palpated 7 cm below the costal margin. Laboratory studies show a leukocyte count of 12,000/mm3 and a platelet count of 210,000/mm3. Further evaluation is most likely to show which of the following?
- A. Smudge cells (Correct Answer)
- B. Ringed sideroblasts
- C. Rouleaux formation
- D. Teardrop cells
- E. Polycythemia
Explanation: ***Smudge cells*** - The patient's presentation with **fatigue**, **lymphadenopathy**, **splenomegaly**, and a **leukocytosis** (12,000/mm³) is classic for **chronic lymphocytic leukemia (CLL)**. - **Smudge cells** (also known as Gumprecht shadows) are characteristic findings on a peripheral blood smear in CLL, resulting from the fragile lymphocytes being crushed during slide preparation. *Ringed sideroblasts* - **Ringed sideroblasts** are immature red blood cells with iron granules accumulated in a ring around the nucleus, seen in **myelodysplastic syndromes** and **sideroblastic anemia**. - This patient's symptoms and labs, particularly the significant lymphocytosis, do not support these conditions. *Rouleaux formation* - **Rouleaux formation** refers to red blood cells stacking up like coins, commonly seen in conditions with increased plasma proteins such as **multiple myeloma** or **macroglobulinemia**. - The clinical picture here, with prominent lymphadenopathy and splenomegaly, is not typical for these disorders. *Teardrop cells* - **Teardrop cells** (dacryocytes) are red blood cells with a characteristic teardrop shape, often associated with **myelofibrosis** due to their deformation as they squeeze through fibrotic marrow. - The patient's presentation lacks other key features of myelofibrosis, such as significant anemia, extremely high leukocyte counts, or symptoms of marrow failure. *Polycythemia* - **Polycythemia** refers to an abnormally high concentration of red blood cells (or hemoglobin) in the blood, often associated with conditions like **polycythemia vera**. - While fatigue can be a symptom, the patient's leukocyte count is elevated, not the erythrocyte count, and the presence of lymphadenopathy and splenomegaly points away from isolated polycythemia.
Question 73: A 44-year-old woman presents for her annual physical checkup. She says she first noticed a mass in her right breast while taking a shower 3 months ago, which has progressively increased in size. She denies any weight loss, fever, night sweats, discharge from or change in her nipples. Her family history is negative for breast, ovarian, and endometrial cancer. She is afebrile, and her vital signs are within normal limits. Physical examination reveals a smooth, multinodular, firm 5 cm x 5 cm mass in the right breast that is mobile and painless. The skin over the mass appears to be stretched and shiny without ulcerations, erythema, or vascular demarcation. On follow-up 6 weeks later, an interval ultrasound of the right breast reveals a well-circumscribed hypoechoic mass with some cystic components that now measures 8 cm x 7 cm. A core needle biopsy of the mass is performed. Which of the following diagnosis is most likely expected to be confirmed by the core needle biopsy in this patient?
- A. Fibroadenoma
- B. Breast abscess
- C. Fat necrosis
- D. Duct ectasia
- E. Phyllodes tumor (Correct Answer)
Explanation: ***Phyllodes tumor*** * The clinical presentation of a rapidly growing, large, **mobile, firm, and painless breast mass** in a middle-aged woman is highly suggestive of a phyllodes tumor. * Ultrasound findings of a **well-circumscribed hypoechoic mass with cystic components** are also characteristic, as is the significant interval increase in size. *Fibroadenoma* * While fibroadenomas are typically **mobile and painless**, they usually grow more slowly and rarely reach the large size (8 cm) observed in this patient. * Significant rapid growth and a multinodular appearance make fibroadenoma less likely, although phyllodes tumors can sometimes be mistaken for fibroadenomas on initial imaging. *Breast abscess* * A breast abscess typically presents with signs of **inflammation, pain, redness, warmth, and possibly fever**, which are absent in this case. * Ultrasound would show a fluid-filled collection with internal debris, often with surrounding inflammatory changes. *Fat necrosis* * Fat necrosis usually occurs after **trauma or surgery** to the breast and often presents as a firm, fixed mass that can mimic malignancy. * The absence of trauma history and the rapid, significant growth are inconsistent with fat necrosis. *Duct ectasia* * Duct ectasia commonly causes **nipple discharge**, subareolar masses, and sometimes nipple retraction. * The patient denies nipple discharge, and the mass characteristics do not align with typical duct ectasia.
Question 74: A 27-year-old man comes to the physician because of a 4-month history of recurrent episodes of headaches, palpitations, and sweating. He was adopted shortly after birth and does not know his biological parents. His pulse is 103/min and blood pressure is 160/105 mm Hg. Physical examination shows multiple soft, yellow papules on the tip of the tongue. There is a 2-cm, firm thyroid nodule. He has long and slender upper extremities, and his elbows and knees can be hyperextended. The most likely cause of this patient's condition is a mutation in which of the following genes?
- A. TSC2
- B. COL5A1
- C. RET (Correct Answer)
- D. MEN1
- E. FBN1
Explanation: ***Correct Option: RET*** - The patient's symptoms (headaches, palpitations, sweating, hypertension) point to a **pheochromocytoma**, and the thyroid nodule suggests **medullary thyroid carcinoma**. The marfanoid habitus (long, slender extremities, hyperextension) and mucosal neuromas (yellow papules on the tongue) are characteristic features of **Multiple Endocrine Neoplasia type 2B (MEN2B)**. - **MEN2B** is caused by a germline gain-of-function mutation in the **RET proto-oncogene**, which is involved in cell growth and differentiation. *Incorrect Option: TSC2* - Mutations in **TSC2** are associated with **tuberous sclerosis complex**, a neurocutaneous disorder characterized by **facial angiofibromas**, ash-leaf spots, shagreen patches, renal angiomyolipomas, and brain tubers. - The patient's presentation with pheochromocytoma, medullary thyroid cancer, and marfanoid features is not consistent with tuberous sclerosis. *Incorrect Option: COL5A1* - Mutations in **COL5A1** are associated with **Ehlers-Danlos syndrome (classical type)**, which is characterized by **skin hyperextensibility**, joint hypermobility, and tissue fragility. - While the patient exhibits joint hypermobility, the constellation of pheochromocytoma, medullary thyroid carcinoma, and mucosal neuromas is not a typical feature of Ehlers-Danlos syndrome. *Incorrect Option: MEN1* - Mutations in the **MEN1 gene** cause **Multiple Endocrine Neoplasia type 1 (MEN1)**, characterized by tumors of the **parathyroid glands** (leading to hyperparathyroidism), **pituitary gland**, and **pancreatic islet cells**. - The patient's presentation with medullary thyroid carcinoma and pheochromocytoma, along with mucosal neuromas and marfanoid features, is not consistent with MEN1. *Incorrect Option: FBN1* - Mutations in the **FBN1 gene** cause **Marfan syndrome**, characterized by **aortic root dilation**, ectopia lentis, and marfanoid body habitus (long limbs, joint hypermobility). - While the patient has a marfanoid habitus, the presence of pheochromocytoma, medullary thyroid carcinoma, and mucosal neuromas are not features of Marfan syndrome, differentiating it from MEN2B.
Question 75: A 15-year-old male presents to the emergency department with fever, malaise, and shortness of breath for 1 week. Further history reveals that the patient experiences swelling in his face in the morning that disappears as the day progresses. Physical exam reveals hepatosplenomegaly. A complete blood count shows WBC 84,000 cells/mL. Most of this patient's leukocytes are likely to express which of the following cell surface markers?
- A. CD20
- B. CD19 (Correct Answer)
- C. CD10
- D. CD16
- E. CD2
Explanation: ***CD19*** - The clinical picture of a 15-year-old male with **fever**, **malaise**, **shortness of breath**, **facial swelling** (periorbital edema), and **hepatosplenomegaly** with a **WBC of 84,000 cells/mL** is highly suggestive of **acute lymphoblastic leukemia (ALL)**. - **CD19** is a characteristic surface marker for **B-cell ALL**, which is the most common subtype of ALL in children and adolescents. *CD20* - **CD20** is also a B-cell marker, but its expression is usually seen in more mature B-cell lymphomas or leukemias, and less consistently or strongly in **precursor B-cell ALL** compared to CD19. - While some B-ALL cases can express CD20, **CD19** is a more universal and defining marker for the lineage of the leukemic blasts in this context. *CD10* - **CD10** (common acute lymphoblastic leukemia antigen or CALLA) is a cell surface marker that can be expressed by **precursor B-cell ALL**, and its presence often correlates with a favorable prognosis. - However, it is not expressed by all B-ALL cases and **CD19** is a more fundamental and consistently expressed pan-B-cell marker for these blasts. *CD16* - **CD16** (FcγRIII) is typically expressed on **natural killer (NK) cells**, neutrophils, macrophages, and some T-cells. - It is not a characteristic marker for **leukemic blasts** in **acute lymphoblastic leukemia**. *CD2* - **CD2** is a surface glycoprotein found on most **T-lymphocytes** and **NK cells**. - Its presence would indicate a **T-cell ALL**, which presents similarly but the most common form is B-cell ALL, for which CD19 is the definitive marker.
Question 76: A 58-year-old woman presents with a 2-week history of fever, fatigue, generalized weakness, and bleeding gums. Past medical history is significant for type 2 diabetes mellitus, managed with metformin. The patient is afebrile, and her vitals are within normal limits. On physical examination, she has bilateral cervical lymphadenopathy and hepatosplenomegaly. A complete blood count and peripheral blood smear reveal normocytic anemia and leukocytosis. A bone marrow biopsy is performed, which shows > 20 % myeloperoxidase positive myeloblasts with splinter-shaped structures in the cytosol. The patient is started on a vitamin A derivative. Which of the following chromosomal translocations is most likely responsible for this patient’s condition?
- A. t(9;22)
- B. t(15;17) (Correct Answer)
- C. t(14;18)
- D. t(11;14)
- E. t(8;14)
Explanation: ***t(15;17)*** * This translocation is pathognomonic for **acute promyelocytic leukemia (APML)**, a subtype of AML. * The presence of **myeloperoxidase (MPO) positive myeloblasts** with **splinter-shaped structures** (Auer rods), coupled with a response to a **vitamin A derivative (all-trans retinoic acid - ATRA)**, are classic features of APML. *t(9;22)* * This translocation, known as the **Philadelphia chromosome**, is characteristic of **chronic myeloid leukemia (CML)**, not AML. * CML typically presents with marked leukocytosis, a left shift, and often a very high white blood cell count, but not usually with Auer rods or responsiveness to ATRA. *t(14;18)* * This translocation is associated with **follicular lymphoma**, a **B-cell non-Hodgkin lymphoma**. * Follicular lymphoma is a lymphoid malignancy, entirely distinct from myeloid leukemias. *t(11;14)* * This translocation is highly characteristic of **mantle cell lymphoma**, another type of **B-cell non-Hodgkin lymphoma**. * Like follicular lymphoma, this is a lymphoid malignancy and does not involve myeloblasts or present with the clinical picture described. *t(8;14)* * This translocation is classically associated with **Burkitt lymphoma**, a highly aggressive **B-cell non-Hodgkin lymphoma**. * Burkitt lymphoma presents with different cytological features (e.g., starry sky appearance) and is not a myeloid leukemia.
Question 77: A 6-year-old girl is brought to the physician for pain and increasing swelling over her scalp for 1 month. She has not had any trauma to the area. There is no family or personal history of serious illness. Vital signs are within normal limits. Examination shows a 3-cm solitary, tender mass over the right parietal bone. X-ray of the skull shows a solitary osteolytic lesion. Laboratory studies show: Hemoglobin 10.9 g/dL Leukocyte count 7300/mm3 Serum Na+ 136 mEq/L K+ 3.7 mEq/L Cl- 103 mEq/L Ca2+ 9.1 mg/dL Glucose 71 mg/dL Which of the following is the most likely diagnosis?
- A. Giant-cell tumor of bone
- B. Langerhans cell histiocytosis (Correct Answer)
- C. Ewing sarcoma
- D. Multiple myeloma
- E. Aneurysmal bone cyst
Explanation: ***Langerhans cell histiocytosis*** - The presentation of a **solitary osteolytic skull lesion** in a child, especially with pain and swelling, is highly suggestive of **Langerhans cell histiocytosis (LCH)**. - LCH can manifest as **eosinophilic granuloma**, which is a localized form primarily affecting bone, often the skull, and commonly presents in children. *Giant-cell tumor of bone* - This tumor typically occurs in **young adults (20s-40s)**, not children, and most commonly affects the **epiphysis of long bones**, such as the distal femur or proximal tibia. - While it can be lytic, its demographic and usual location are inconsistent with this case. *Ewing sarcoma* - Ewing sarcoma also presents in children and young adults with bone pain and swelling, but it often involves the **diaphysis of long bones** or the pelvis. - Radiographically, it is classically described as an **"onion-skin" periosteal reaction** or a permeative lesion, which is not indicated here. *Multiple myeloma* - This is a malignancy of **plasma cells** almost exclusively seen in **older adults**, typically over 60 years of age. - It presents with widespread **punched-out lytic lesions** in the skull, vertebrae, and other bones, along with systemic symptoms like anemia and renal dysfunction. *Aneurysmal bone cyst* - An aneurysmal bone cyst is a benign, expansile, lytic bone lesion that can occur in children and often causes pain and swelling. - However, it typically presents as an **eccentric, expansile lesion** with a thin rim of periosteal new bone formation, and more often affects the metaphysis of long bones or vertebrae, rather than a purely lytic lesion in the parietal bone without trauma.
Question 78: A 72-year-old man goes to his primary care provider for a checkup after some blood work showed lymphocytosis 3 months ago. He says he has been feeling a bit more tired lately but doesn’t complain of any other symptoms. Past medical history is significant for hypertension and hyperlipidemia. He takes lisinopril, hydrochlorothiazide, and atorvastatin. Additionally, his right hip was replaced three years ago due to osteoarthritis. Family history is noncontributory. He drinks socially and does not smoke. Today, he has a heart rate of 95/min, respiratory rate of 17/min, blood pressure of 135/85 mm Hg, and temperature of 36.8°C (98.2°F). On physical exam, he looks well. His heartbeat has a regular rate and rhythm and lungs that are clear to auscultation bilaterally. Additionally, he has mild lymphadenopathy of his cervical lymph nodes. A complete blood count with differential shows the following: Leukocyte count 5,000/mm3 Red blood cell count 3.1 million/mm3 Hemoglobin 11.0 g/dL MCV 95 um3 MCH 29 pg/cell Platelet count 150,000/mm3 Neutrophils 40% Lymphocytes 40% Monocytes 5% A specimen is sent for flow cytometry that shows a population that is CD 5, 19, 20, 23 positive. Which of the following is the most likely diagnosis?
- A. Chronic lymphocytic leukemia (Correct Answer)
- B. Immune thrombocytopenic purpura
- C. Aplastic anemia
- D. Acute lymphoblastic leukemia
- E. Tuberculosis
Explanation: ***Chronic lymphocytic leukemia*** - The patient presents with mild **lymphadenopathy**, a **history of lymphocytosis**, and a **flow cytometry** showing cells positive for **CD5, CD19, CD20, and CD23**, which is pathognomonic for **CLL**. - While the total leukocyte count is within normal limits due to the absolute neutrophil decrease, the persistent lymphocytosis and characteristic immunophenotype are highly indicative of CLL. *Immune thrombocytopenic purpura* - This condition is characterized by **isolated thrombocytopenia** caused by autoantibody-mediated platelet destruction, which is not supported by the patient's normal platelet count (150,000/mm3). - While it can cause fatigue, it doesn't explain the lymphocytosis or the specific **CD marker profile**. *Aplastic anemia* - Aplastic anemia involves **pancytopenia** (decreased red blood cells, white blood cells, and platelets) due to bone marrow failure, which is not consistent with the patient's normal-range leukocyte and platelet counts. - The patient's presentation with lymphocytosis and lymphadenopathy further makes this diagnosis unlikely. *Acute lymphoblastic leukemia* - **ALL** typically presents with symptoms related to **bone marrow failure** (anemia, thrombocytopenia, infections) and often very **high blast counts** in the peripheral blood and bone marrow. - While it involves lymphocytes, the specific **CD5/19/20/23 co-expression** is characteristic of CLL, and ALL usually involves more aggressive symptoms and a different immunophenotype. *Tuberculosis* - **Tuberculosis** is an infectious disease that can cause **lymphadenopathy** and systemic symptoms like fatigue, but it is typically associated with a **caseating granulomatous inflammation** and is diagnosed via cultures or PCR rather than flow cytometry. - It would not explain the specific **B-cell lymphocytosis** with the described immunophenotype.
Question 79: A 49-year-old man with HIV comes to the physician because of a 1-month history of intermittent diarrhea and abdominal pain. Abdominal examination shows mild, diffuse tenderness throughout the lower quadrants. His CD4+ T-lymphocyte count is 180/mm3 (normal ≥ 500/mm3). Colonoscopy shows multiple hemorrhagic nodules in the rectum and descending colon. Polymerase chain reaction of the lesions is positive for HHV-8. Histologic examination of the lesions is most likely to show which of the following findings?
- A. Spindle-shaped cells with leukocytic infiltration (Correct Answer)
- B. Mucin-filled cell with peripheral nucleus
- C. Cords of atypical cells with extracellular mucin
- D. Enlarged cells with intranuclear inclusion bodies
- E. Polygonal cells with racket-shaped organelles
Explanation: ***Spindle-shaped cells with leukocytic infiltration*** - The presentation of an HIV-positive patient with a low CD4+ count, hemorrhagic nodules in the colon, and positive HHV-8 PCR is highly suggestive of **Kaposi sarcoma**. - Histologically, Kaposi sarcoma is characterized by proliferation of **spindle-shaped endothelial cells**, often forming slit-like vascular channels, and an inflammatory infiltrate rich in lymphocytes and plasma cells. *Mucin-filled cell with peripheral nucleus* - This describes a **signet ring cell**, which is characteristic of diffuse-type gastric carcinoma and other mucinous adenocarcinomas, not Kaposi sarcoma. - Signet ring cells contain a large **mucin vacuole** that pushes the nucleus to the periphery. *Cords of atypical cells with extracellular mucin* - This finding is typical of certain types of **adenocarcinoma**, particularly those with a mucinous component, such as mucinous colorectal carcinoma. - It does not align with the known histopathology of Kaposi sarcoma, which is a vascular tumor. *Enlarged cells with intranuclear inclusion bodies* - This description is characteristic of a **cytomegalovirus (CMV) infection**, particularly in immunocompromised patients. Inclusions are often described as "owl's eye" inclusions. - While CMV can cause gastrointestinal symptoms in HIV patients, the positive HHV-8 PCR points specifically to Kaposi sarcoma. *Polygonal cells with racket-shaped organelles* - This describes the characteristic cells of **Langerhans cell histiocytosis**, where the cells are Langerhans cells containing Birbeck granules (racket-shaped organelles). - This condition is a proliferative disorder of dendritic cells and does not fit the clinical or pathological findings of this case.
Question 80: A 7-year-old boy presents to his primary care physician for a general checkup. The patient has been feeling poorly for the past several weeks and has been losing weight. He states that he often feels weak and too tired to play with his friends. He is no longer interested in many recreational activities he used to be interested in. The patient's parents state that a few of their child's friends have been sick lately. His temperature is 102°F (38.9°C), blood pressure is 77/48 mmHg, pulse is 110/min, respirations are 24/min, and oxygen saturation is 98% on room air. On exam, you note a fatigued appearing child who has lost 10 pounds since his last appointment. Left upper quadrant tenderness and a mass is noted on abdominal exam. Which of the following best describes the most likely diagnosis?
- A. Smudge cells on peripheral smear
- B. TdT positive cells (Correct Answer)
- C. Infection sensitive to oseltamivir
- D. Auer rods on peripheral smear
- E. Parental mistreatment of the child
Explanation: ***TdT positive cells*** - This patient's symptoms, including **fever**, **weight loss**, **fatigue**, and **splenomegaly** (left upper quadrant tenderness and mass), are highly suggestive of **Acute Lymphoblastic Leukemia (ALL)**. - **Terminal deoxynucleotidyl transferase (TdT)** is a DNA polymerase found in immature lymphocytes (blasts) and is a key marker for diagnosing ALL. - ALL is the **most common childhood malignancy**, particularly prevalent in children aged 2-10 years. *Smudge cells on peripheral smear* - **Smudge cells** are characteristic of **Chronic Lymphocytic Leukemia (CLL)**, which predominantly affects older adults and is rare in children. - The clinical picture of rapid decline and significant systemic symptoms in a child is inconsistent with CLL. *Infection sensitive to oseltamivir* - Oseltamivir is an **antiviral medication for influenza**, and while the child has a fever, the profound **weight loss**, **fatigue**, and **abdominal mass** point towards a hematologic malignancy, not a typical viral infection. - Viral infections rarely present with such a significant abdominal mass or sustained constitutional symptoms for several weeks. *Auer rods on peripheral smear* - **Auer rods** are cytoplasmic inclusions pathognomonic for **Acute Myeloid Leukemia (AML)**. - While AML can occur in children, **ALL is far more common in this age group** (85% of childhood leukemias), and the presentation is highly classic for ALL, making TdT positivity the best diagnostic marker. *Parental mistreatment of the child* - While some symptoms (weight loss, fatigue) could potentially be seen in neglect, the presence of **fever**, **splenomegaly** (abdominal mass), and **hypotension** points strongly to a severe underlying medical condition. - Objective signs of systemic illness necessitate a thorough medical workup rather than suspicion of abuse.
Question 81: A 25-year-old man presents to his primary care provider complaining of scrotal swelling. He is a college student and plays basketball with his friends regularly. Two days ago, he sustained an injury close to his thigh. He does not have any significant past medical history. Today, his vitals are normal. A focused scrotal examination reveals a firm painless lump on the right testicle which is irregular and small. Ultrasound of the scrotum reveals a vascular 0.6 x 0.5 cm testicular mass. A pelvic lymph node exam is negative. He undergoes a radical orchiectomy and subsequent histopathological examination reveals sheets of small cuboidal cells, multinucleated cells, and large eosinophilic cells with pleomorphic nuclei consistent with choriocarcinoma. Which of the following tumor marker is most likely elevated in this patient?
- A. Placental alkaline phosphatase
- B. Prostate-specific antigen
- C. Carcinoembryonic antigen
- D. Testosterone
- E. Beta-human chorionic gonadotropin (Correct Answer)
Explanation: ***Beta-human chorionic gonadotropin*** - **Choriocarcinoma** is a rare and aggressive type of germ cell tumor that secretes **beta-human chorionic gonadotropin (β-hCG)**, which serves as a crucial tumor marker for diagnosis and monitoring. - The presence of multinucleated cells and large eosinophilic cells (syncytiotrophoblasts) in the histopathology is characteristic of choriocarcinoma, and these cells are responsible for β-hCG production. *Placental alkaline phosphatase* - **Placental alkaline phosphatase (PLAP)** is primarily associated with **seminoma**, another type of testicular germ cell tumor, but is not typically elevated in choriocarcinoma. - While PLAP can be detected in some non-seminomatous germ cell tumors, it is not the primary or most sensitive marker for choriocarcinoma. *Prostate-specific antigen* - **Prostate-specific antigen (PSA)** is a tumor marker used for the screening and monitoring of **prostate cancer** and is not associated with testicular germ cell tumors. - Testicular pathology would not lead to an elevation of PSA. *Carcinoembryonic antigen* - **Carcinoembryonic antigen (CEA)** is a tumor marker commonly associated with **colorectal cancer**, as well as other adenocarcinomas such as those of the lung, breast, and pancreas, but not testicular cancers. - Its elevation would not be expected in a patient with choriocarcinoma. *Testosterone* - **Testosterone** is the primary male sex hormone produced by the testicles and adrenal glands; its levels can be affected by testicular pathologies but it is **not a tumor marker** for choriocarcinoma. - While some testicular tumors can lead to hormonal imbalances, testosterone itself does not serve as a diagnostic or monitoring marker for testicular choriocarcinoma.
Question 82: A 55-year-old woman returns to her physician for a follow-up on the anemia that was detected last month. She received treatment for a nasopharyngeal infection 2 weeks ago. She was diagnosed with small cell lung cancer 2 years ago and was treated with combination chemotherapy. She was a 30-pack-year smoker and quit when she developed lung cancer. She has been a vegan for 2 years. The vital signs are within normal limits. Examination of the lungs, heart, abdomen, and extremities show no abnormalities. No lymphadenopathy is detected. The laboratory studies show the following: Hemoglobin 8.5 g/dL Mean corpuscular volume 105 μm3 Leukocyte count 4,500/mm3 Platelet count 160,000/mm3 An abdominal ultrasonography shows no organomegaly or other pathologic findings. A peripheral blood smear shows large and hypogranular platelets and neutrophils with hypo-segmented or ringed nuclei. No blasts are seen. A bone marrow aspiration shows hypercellularity. In addition, ring sideroblasts, hypogranulation, and hyposegmentation of granulocyte precursors, and megakaryocytes with disorganized nuclei are noted. Marrow myeloblasts are 4% in volume. Which of the following factors in this patient’s history most increased the risk of developing this condition?
- A. Tobacco smoking
- B. Chemotherapy (Correct Answer)
- C. Epstein-Barr virus infection
- D. Vegan diet
- E. Small cell lung cancer
Explanation: ***Chemotherapy*** - The patient's presentation with **macrocytic anemia**, **cytopenias**, and **dysplastic features** in the peripheral blood and bone marrow (e.g., ring sideroblasts, hypogranular neutrophils, disorganized megakaryocytes) strongly suggests **myelodysplastic syndrome (MDS)**. - Previous **chemotherapy** for small cell lung cancer is a significant risk factor for developing **therapy-related MDS (t-MDS)** due to its mutagenic effects on hematopoietic stem cells. *Tobacco smoking* - While **tobacco smoking** is a risk factor for various cancers, including lung cancer, and can contribute to other hematologic disorders, it is not the primary or most direct risk factor for this specific presentation of **myelodysplastic syndrome (MDS)** compared to prior chemotherapy. - MDS linked to smoking typically involves different genetic mutations than t-MDS, and the *cytotoxic effects of chemotherapy* are a more direct cause of the marrow dysplasia seen here. *Epstein-Barr virus infection* - **Epstein-Barr virus (EBV) infection** is associated with various lymphoproliferative disorders and certain cancers (e.g., Hodgkin lymphoma, nasopharyngeal carcinoma), but it is not a known direct cause or major risk factor for developing **myelodysplastic syndrome (MDS)**. - The patient's recent nasopharyngeal infection is likely unrelated to the underlying chronic marrow disorder. *Vegan diet* - A **vegan diet** can lead to **vitamin B12 deficiency**, which can cause **macrocytic anemia** and sometimes pancytopenia, mimicking some features of MDS (e.g., high MCV). - However, it does not explain the extensive **dysplastic features** observed in the peripheral smear and bone marrow (ring sideroblasts, hypo-segmented granulocytes, disorganized megakaryocytes) or the 4% marrow myeloblasts, which are characteristic of MDS and not typically found solely due to nutrient deficiencies. *Small cell lung cancer* - The **small cell lung cancer** itself is the primary disease that *necessitated* the chemotherapy, but it is not the direct causal factor for the development of the **myelodysplastic syndrome**. - It is the **treatment** for the cancer (chemotherapy) that induces genomic damage in hematopoietic stem cells, leading to therapy-related MDS.
Question 83: A 66-year-old man comes to the physician for a 3-month history of fatigue. He has hypertension and hyperlipidemia. He had a transient ischemic attack 3 years ago. He drinks 3 beers a day, and sometimes a couple more on social occasions. He currently takes aspirin, simvastatin, hydrochlorothiazide, and metoprolol. His temperature is 37.1°C (98.8°F), pulse is 78, respirations are 19/min, and oxygen saturation on room air is 97%. He is in no distress but shows marked pallor and has multiple pinpoint, red, nonblanching spots on his extremities. On palpation, his spleen is significantly enlarged. Laboratory studies show a hemoglobin of 8.0 g/dL, a leukocyte count of 80,000/mm3, and a platelet count of 34,000/mm3. A blood smear shows immature cells with large, prominent nucleoli and pink, elongated, needle-shaped cytoplasmic inclusions. Which of the following is the most likely diagnosis?
- A. Cirrhosis
- B. Acute lymphoblastic leukemia
- C. Chronic lymphocytic leukemia
- D. Myelodysplastic syndrome
- E. Acute myelogenous leukemia (Correct Answer)
Explanation: **Acute myelogenous leukemia** - The presence of **fatigue**, **marked pallor**, **splenomegaly**, **petechiae** (pinpoint, red, nonblanching spots), and **pancytopenia** (anemia, leukocytosis with immature forms, thrombocytopenia) are highly suggestive of acute leukemia. - The blood smear findings of **immature cells with large, prominent nucleoli** and **pink, elongated, needle-shaped cytoplasmic inclusions** (likely **Auer rods**) are pathognomonic for **acute myelogenous leukemia (AML)**. *Cirrhosis* - While **splenomegaly** and **pancytopenia** can occur in cirrhosis due to portal hypertension and hypersplenism, the specific blood smear findings of **immature cells** and **Auer rods** are not characteristic of cirrhosis. - The patient's alcohol intake could contribute to cirrhosis, but the hematological picture points definitively away from liver disease as the primary diagnosis. *Acute lymphoblastic leukemia* - Although acute lymphoblastic leukemia (ALL) presents with **fatigue**, **pallor**, and **pancytopenia**, the **immature cells** in ALL are lymphoblasts, which **lack Auer rods**. - The specific morphology described (large, prominent nucleoli, needle-shaped cytoplasmic inclusions) is inconsistent with ALL. *Chronic lymphocytic leukemia* - CLL typically presents with **lymphocytosis** (extremely high leukocyte count composed of mature-appearing lymphocytes) and often **splenomegaly**, but usually **without significant anemia or thrombocytopenia** at presentation. - The presence of **immature cells** and **Auer rods** is inconsistent with CLL, which involves mature B-lymphocytes. *Myelodysplastic syndrome* - MDS can cause **cytopenias** and may involve **immature blast forms**, but the blast count is typically less than 20% in the bone marrow (or periphery) and it does **not typically present with Auer rods** in circulating blasts. - The profound leukocytosis with highly immature cells and specific inclusions points beyond MDS to an acute leukemia.
Question 84: A 3-year-old boy is brought to the pediatrician by his parents because of excessive growth and a large tongue. His past medical-social history reveals that he is a product of non-consanguineous marriage to a 20-year-old primigravida. He was born at full term with a birth weight of 3.8 kg (8.4 lb) and length of 52 cm (20.5 in). His temperature is 37.0ºC (98.6°F), pulse is 90/min, and respirations are 22/min. Physical examination shows a mass coming out from his umbilicus and his head circumference is below average compared with children his age. On systemic examination, hepatomegaly is present. Asymptomatic hypoglycemia (36 mg/dL) is also detected, for which dextrose infusion is given. Which of the following is the most likely underlying mechanism that best explains the pathogenesis of this condition?
- A. Mutation in tumor suppressor gene on the long arm of chromosome 22
- B. Mutation in tumor suppressor gene on the long arm of chromosome 17
- C. Nondisjunction of chromosome 21
- D. Mutation in tumor suppressor gene on the short arm of chromosome 11 (Correct Answer)
- E. Mutation in tumor suppressor gene on the long arm of chromosome 11
Explanation: ***Mutation in tumor suppressor gene on the short arm of chromosome 11*** - The presented symptoms (excessive growth, macroglossia, umbilical mass/omphalocele, hepatomegaly, and hypoglycemia) in a 3-year-old boy are characteristic of **Beckwith-Wiedemann Syndrome (BWS)**. - BWS is a **genomic imprinting disorder** involving a cluster of imprinted genes on the **short arm of chromosome 11 (11p15.5)**, which includes the tumor suppressor gene *CDKN1C* and growth-promoting gene *IGF2*. - Loss of function of tumor suppressor genes and/or overexpression of growth factors in this region lead to the overgrowth phenotype and increased tumor risk (Wilms tumor, hepatoblastoma). *Mutation in tumor suppressor gene on the long arm of chromosome 22* - Mutations on the long arm of chromosome 22 are associated with **neurofibromatosis type 2 (NF2)** at 22q12 or deletions at 22q11.2 causing **DiGeorge syndrome** (developmental defects, not overgrowth). - The clinical features described, such as macrosomia, macroglossia, and omphalocele, do not align with disorders linked to chromosome 22q alterations. *Mutation in tumor suppressor gene on the long arm of chromosome 17* - A mutation in the tumor suppressor gene *TP53* on the short arm of chromosome 17 (17p13.1) is associated with **Li-Fraumeni syndrome**, which predisposes individuals to various cancers including sarcomas, breast cancer, and brain tumors. - This genetic alteration does not explain the characteristic features of BWS, such as overgrowth, macroglossia, omphalocele, or neonatal hypoglycemia. *Nondisjunction of chromosome 21* - **Nondisjunction of chromosome 21** leads to **Down syndrome (Trisomy 21)**, characterized by distinct facial features, intellectual disability, hypotonia, and congenital heart defects. - This condition does not present with the excessive growth, macroglossia, omphalocele, or hepatomegaly seen in this patient; rather, Down syndrome is associated with growth retardation. *Mutation in tumor suppressor gene on the long arm of chromosome 11* - While chromosome 11 is involved in BWS, the critical region for this syndrome is on the **short arm (11p15.5)**, not the long arm. - Alterations on the long arm of chromosome 11 (11q) are linked to other genetic disorders, such as certain forms of leukemia (MLL gene rearrangements) or ataxia-telangiectasia, which do not match the presented clinical picture.
Question 85: An 82-year-old man presents with painless swelling of the neck for the past week. He reports no recent fever, night sweats, or weight loss. He has no significant medical history, and his only medication is daily aspirin. His temperature is 36.8℃ (98.2℉). On physical examination, there are several non-tender lymph nodes, each averaging 2 cm in diameter, which are palpable in the right anterior cervical triangle. No other palpable lymphadenopathy is noted. The remainder of the physical exam is unremarkable. Laboratory studies show the following: Hemoglobin 10 g/dL Leukocyte count 8000/mm3 with a normal differential Platelet count 250,000/mm3 Erythrocyte sedimentation rate 30 mm/h An excisional biopsy of a cervical lymph node reveals the presence of Reed-Sternberg (RS) cells. Computed tomography (CT) scans and positron emission tomography (PET) scans reveal no mediastinal mass or signs of additional disease. Which of the following aspects most strongly indicates a good prognosis for this patient?
- A. Erythrocyte sedimentation rate (ESR)
- B. Leukocyte count and differential
- C. Absence of B symptoms
- D. Stage of the disease (Correct Answer)
- E. Hemoglobin level
Explanation: ***Stage of the disease*** - The **stage of Hodgkin lymphoma** is the most significant prognostic factor, with **earlier stages (I and II)** having a much better prognosis than advanced stages (III and IV). The prompt indicates **no mediastinal mass or additional disease**, suggesting an early stage. - Absence of widespread disease in CT and PET scans is a critical indicator of **localized disease**, which is associated with higher cure rates. *Absence of B symptoms* - While the **absence of B symptoms** (fever, night sweats, weight loss) is a favorable prognostic indicator, it is secondary to the overall disease stage in predicting long-term outcomes in Hodgkin lymphoma. - The patient's lack of B symptoms is positive, but the *extent of disease spread* (stage) remains the primary determinant of prognosis. *Erythrocyte sedimentation rate (ESR)* - An **elevated ESR** (30 mm/h in this case) is a known adverse prognostic factor in Hodgkin lymphoma, indicating systemic inflammation. - While important, it is a **secondary indicator** and does not outweigh the significance of disease stage in determining prognosis. *Hemoglobin level* - A **hemoglobin level below 10.5 g/dL** is an adverse prognostic factor in Hodgkin lymphoma according to the International Prognostic Score, and this patient's hemoglobin is 10 g/dL. - This factor suggests a potentially **worse prognosis**, making it an incorrect answer for "good prognosis." *Leukocyte count and differential* - An **elevated leukocyte count** (above 15,000/mm³) and a **lymphopenia** (absolute lymphocyte count less than 600/mm³ or less than 8% of the white cell count) are adverse prognostic factors in Hodgkin lymphoma. - This patient has a normal leukocyte count and differential (8000/mm³ with normal differential), which is **neutral to good** but less impactful than the disease stage.
Question 86: A 69-year-old woman comes to the physician because of lower back pain and right-sided chest pain for the past month. The pain is aggravated by movement. Over the past 2 months, she has had increasing fatigue. Her mother died of breast cancer. She has hypertension and reflux disease. Current medications include metoprolol and omeprazole. Vital signs are within normal limits. Examination shows full muscle strength. There is tenderness to palpation over the lower spine and the right lateral chest. The remainder of the examination shows no abnormalities. Laboratory studies show: Hemoglobin 9.5 g/dL Leukocyte count 7,300/mm3 Platelet count 230,000/mm3 Serum Na+ 137 mEq/L K+ 3.5 mEq/L Creatinine 1.3 mg/dL An ECG shows no evidence of ischemia. An x-ray of the chest shows lytic lesions in 2 ribs. Blood smear shows aggregations of erythrocytes. Protein electrophoresis of the serum with immunofixation shows an M-protein spike. This patient's condition is most likely associated with which of the following findings?
- A. Urinary tract infection (Correct Answer)
- B. Leukemic hiatus
- C. Splenomegaly
- D. Richter's transformation
- E. Autoimmune hemolytic anemia
Explanation: ***Urinary tract infection*** - Patients with **multiple myeloma** are at **increased risk of bacterial infections**, particularly **urinary tract infections** and infections with **encapsulated organisms** (e.g., *Streptococcus pneumoniae*, *Haemophilus influenzae*). - This susceptibility results from **hypogammaglobulinemia** (decreased normal immunoglobulins despite elevated M-protein), **impaired cell-mediated immunity**, and **renal dysfunction**. - Her symptoms of **bone pain** (back, chest), **fatigue**, **anemia** (Hgb 9.5 g/dL), **lytic bone lesions** on X-ray, **rouleaux formation** on blood smear, **elevated creatinine**, and **M-protein spike** on serum protein electrophoresis are classic features of **multiple myeloma**. *Leukemic hiatus* - This refers to the absence of intermediate myeloid maturation forms in peripheral blood, characteristic of **acute myeloid leukemia (AML)**, not plasma cell disorders. - The patient's presentation with **M-protein spike** and **lytic bone lesions** points to a **plasma cell neoplasm** (multiple myeloma), not a myeloid malignancy. *Splenomegaly* - Splenomegaly is **uncommon** in multiple myeloma as plasma cells primarily infiltrate the bone marrow. - It is more characteristic of **myeloproliferative neoplasms**, **chronic myeloid leukemia**, or **lymphomas**, which do not fit this clinical picture. *Richter's transformation* - This describes the transformation of **chronic lymphocytic leukemia (CLL)** into a more aggressive lymphoma, typically **diffuse large B-cell lymphoma**. - This patient's findings (lytic lesions, M-protein spike, rouleaux formation) are diagnostic of **multiple myeloma**, not CLL, making Richter's transformation irrelevant. *Autoimmune hemolytic anemia* - This condition involves **destruction of red blood cells** by autoantibodies, typically presenting with **spherocytes** on blood smear and a **positive direct Coombs test**. - The anemia in this patient is more likely due to **bone marrow infiltration** by plasma cells, **renal insufficiency** (causing decreased erythropoietin), and **chronic disease**. - The blood smear shows **rouleaux formation** (stacked erythrocytes due to elevated proteins), which is characteristic of multiple myeloma, not spherocytes seen in hemolytic anemia.
Question 87: A 63-year-old male is accompanied by his wife to his primary care doctor complaining of shortness of breath. He reports a seven-month history of progressively worsening dyspnea and a dry non-productive cough. He has also lost 15 pounds over the same time despite no change in diet. Additionally, over the past week, his wife has noticed that the patient appears confused and disoriented. His past medical history is notable for stable angina, hypertension, hyperlipidemia, and diabetes mellitus. He currently takes aspirin, metoprolol, lisinopril, atorvastatin, metformin, and glyburide. He has smoked 1 pack of cigarettes per day for 30 years and previously worked as a mechanic at a shipyard. Physical examination reveals no wheezes, rales, or rhonchi with slightly decreased aeration in the left lower lung field. Mucus membranes are moist with normal skin turgor and capillary refill. Laboratory analysis reveals the following: Na 121 mEq/L K 3.4 mEq/L Cl 96 mEq/L HCO3 23 mEq/L Cr 1.1 mg/dl BUN 17 mg/dl A biopsy of the responsible lesions will most likely demonstrate which of the following findings?
- A. Anaplastic pleomorphic giant cells
- B. Pleomorphic cells arising from the alveolar lining with disruption of the alveolar architecture
- C. Sheets of large pleomorphic cells containing keratin and intercellular bridges
- D. Undifferentiated small round blue cells (Correct Answer)
- E. Sheets of epithelial cells with papillary fragments, necrosis, and psammoma bodies
Explanation: ***Undifferentiated small round blue cells*** - The patient's history of heavy smoking, shipyard work (exposure to **asbestos**), progressive dyspnea, weight loss, and hyponatremia point towards **small cell lung carcinoma (SCLC)** with possible paraneoplastic **SIADH** causing confusion. - **SCLC** is characterized histologically by sheets of **small, round, blue cells** with scant cytoplasm, fine chromatin, and absent or inconspicuous nucleoli. *Anaplastic pleomorphic giant cells* - This description is more consistent with **large cell carcinoma**, an undifferentiated lung cancer that lacks the specific features of adenocarcinoma, squamous cell carcinoma, or small cell carcinoma. - Large cell carcinoma does not typically present with the same paraneoplastic syndromes (like SIADH) as SCLC, nor the characteristic "small blue cell" morphology. *Pleomorphic cells arising from the alveolar lining with disruption of the alveolar architecture* - This description suggests **adenocarcinoma**, which typically arises from the **glandular cells** of the lung and may disrupt normal alveolar structures. - While adenocarcinoma can cause dyspnea and weight loss, it is less strongly associated with heavy smoking than SCLC and does not commonly present with **SIADH** and confusion in this manner. *Sheets of large pleomorphic cells containing keratin and intercellular bridges* - This biopsy finding is characteristic of **squamous cell carcinoma**, which is often associated with a strong smoking history and can be centrally located. - However, squamous cell carcinoma less frequently leads to paraneoplastic SIADH, and the classic description for SCLC is "small blue cells," not large pleomorphic cells with keratin. *Sheets of epithelial cells with papillary fragments, necrosis, and psammoma bodies* - This pathology description is included as a distractor, though **psammoma bodies are NOT characteristic of lung cancer** and are typically seen in papillary thyroid carcinoma, serous ovarian carcinoma, and meningioma. - While the patient has asbestos exposure raising concern for **mesothelioma**, this tumor typically shows epithelioid or sarcomatoid patterns without psammoma bodies, and the clinical presentation with **SIADH** and hyponatremia strongly favors SCLC over mesothelioma.
Question 88: A 65-year-old man comes to the physician for a routine health maintenance examination. He has a strong family history of colon cancer. A screening colonoscopy shows a 4 mm polyp in the upper sigmoid colon. Which of the following findings on biopsy is associated with the lowest potential for malignant transformation into colorectal carcinoma?
- A. Branching tubules embedded in lamina propria
- B. Tree-like branching of muscularis mucosa
- C. Regenerating epithelium with inflammatory infiltrate
- D. Hyperplastic epithelium at the base of crypts (Correct Answer)
- E. Finger-like projections with a fibrovascular core
Explanation: ***Hyperplastic epithelium at the base of crypts*** - This description corresponds to a **hyperplastic polyp**, which is the classic **benign colonic polyp** with **negligible malignant potential**. - Hyperplastic polyps are characterized by a **serrated (saw-toothed) architecture** with delayed maturation of epithelial cells in the lower third of the colonic crypt. - These polyps are **non-neoplastic** and represent the polyp type with the **lowest risk of malignant transformation** in traditional classification. - Note: Sessile serrated adenomas/polyps (SSA/Ps) are a distinct entity with malignant potential, but traditional small hyperplastic polyps are considered benign. *Branching tubules embedded in lamina propria* - This morphology is characteristic of a **tubular adenoma**, which is a **neoplastic polyp** with definite malignant potential. - Tubular adenomas have approximately **5% risk of malignancy** when small (<1 cm), but this increases with size and degree of dysplasia. - These are **precancerous lesions** that require surveillance. *Tree-like branching of muscularis mucosa* - This description suggests a **villous growth pattern** characteristic of adenomas with villous architecture. - **Villous adenomas** have a **higher risk of malignant transformation** (up to 40%) compared to pure tubular adenomas. - The villous architecture indicates greater neoplastic potential. *Regenerating epithelium with inflammatory infiltrate* - This describes an **inflammatory (pseudo)polyp**, which arises from cycles of **inflammation and repair** in inflammatory bowel disease or other mucosal injury. - **Inflammatory polyps** are **non-neoplastic** and have **no direct malignant potential** themselves. - However, hyperplastic polyps are the traditional answer for "lowest malignant potential" polyp in screening contexts, as inflammatory polyps are typically associated with underlying inflammatory conditions rather than routine screening findings. *Finger-like projections with a fibrovascular core* - This is the classic histological description of a **villous adenoma**, showing finger-like projections of epithelium covering fibrovascular cores. - **Villous adenomas** have the **highest malignant potential** among adenomatous polyps, with up to **40% risk of harboring carcinoma** depending on size. - They often contain high-grade dysplasia and are at significant risk for progression to adenocarcinoma.
Question 89: A 56-year-old man presents to his physician’s office with a sudden increase in urinary frequency. During the past month, he has observed that he needs more frequent bathroom breaks. This is quite unusual as he hasn’t been consuming extra fluids. He reports feeling generally unwell over the past 2 months. He has lost over 7 kg (15.4 lb) of weight and has also been feeling progressively fatigued by the end of the day. He also has a persistent cough and on a couple of occasions, he noticed blood streaks on his napkin. In addition to all of this, he has been feeling weak with frequent muscle cramps during the day. He has never been diagnosed with any medical condition in the past. He doesn’t drink but has smoked 2 packs of cigarettes daily for the last 25 years. Prior to his appointment, he took a couple of tests. The results are given below: Hemoglobin (Hb) 13.1 g/dL Serum creatinine 0.8 mg/dL Serum urea 13 mg/dL Serum sodium 129 mEq/L Serum potassium 3.2 mEq/L His chest X-ray shows a central nodule with some hilar thickening. The physician recommends a biopsy of the nodule. Which of the following histological patterns is the nodule most likely to exhibit?
- A. Glandular cells, positive for mucin
- B. Squamous cells with keratin pearls
- C. Kulchitsky cells with hyperchromatic nuclei (Correct Answer)
- D. Papillary epithelial cells with Psammoma bodies
- E. Pleomorphic giant cells
Explanation: ***Kulchitsky cells with hyperchromatic nuclei*** - This patient presents with **hyponatremia** and **hypokalemia**, indicative of **syndrome of inappropriate antidiuretic hormone (SIADH)** and **ectopic ACTH production**, respectively. These paraneoplastic syndromes are commonly associated with **small cell lung carcinoma (SCLC)**, which arises from **Kulchitsky cells** (neuroendocrine cells) and features **hyperchromatic nuclei**. - The patient's significant **smoking history**, weight loss, fatigue, persistent cough with hemoptysis, and chest X-ray findings of a **central nodule with hilar thickening** are all highly suggestive of SCLC. *Glandular cells, positive for mucin* - This description is characteristic of **adenocarcinoma**, which typically presents as a **peripheral lung nodule** and is not as strongly associated with paraneoplastic syndromes like SIADH and ectopic ACTH production. - While adenocarcinoma can cause weight loss and cough, the specific paraneoplastic endocrinopathies and central mass with hilar thickening deviate from its most common presentation. *Squamous cells with keratin pearls* - This defines **squamous cell carcinoma**, which is also strongly linked to smoking and often forms **central masses** with potential cavitation. - However, squamous cell carcinoma is more commonly associated with paraneoplastic **hypercalcemia (due to PTHrP production)**, rather than the hyponatremia and hypokalemia seen in this patient. *Papillary epithelial cells with Psammoma bodies* - This histological pattern is characteristic of **papillary thyroid carcinoma** or **mesothelioma** (in the lungs), not typically primary lung cancer. - It is not associated with the paraneoplastic syndromes of SIADH or ectopic ACTH production that are key to this patient's presentation. *Pleomorphic giant cells* - This finding is characteristic of **large cell carcinoma**, a diagnosis of exclusion in non-small cell lung cancer. - While it can be centrally or peripherally located and linked to smoking, it is less commonly associated with the specific combination of paraneoplastic syndromes (SIADH and ectopic ACTH) seen in this case compared to SCLC.
Question 90: A 45-year-old male reports several years of asbestos exposure while working in the construction industry. He reports smoking 2 packs of cigarettes per day for over 20 years. Smoking and asbestos exposure increase the incidence of which of the following diseases?
- A. Emphysema
- B. Malignant pulmonary mesothelioma
- C. Multiple myeloma
- D. Bronchogenic carcinoma (Correct Answer)
- E. Chronic bronchitis
Explanation: ***Bronchogenic carcinoma*** - **Smoking** is the leading cause of **bronchogenic carcinoma**, and **asbestos exposure** significantly *multiplies* its risk, rather than simply adding to it. - This synergistic effect means that smokers exposed to asbestos have a **much higher incidence** of lung cancer compared to those with either exposure alone. *Emphysema* - Primarily linked to **smoking** and chronic exposure to irritants, but asbestos exposure does not significantly increase its incidence. - While both smoking and asbestos can cause pulmonary issues, their primary mechanisms for emphysema are distinct. *Malignant pulmonary mesothelioma* - **Malignant mesothelioma** is strongly associated with **asbestos exposure**, but its incidence is *not significantly increased* by smoking. - Smoking is a risk factor for lung cancer, but not a primary risk factor for mesothelioma itself. *Multiple myeloma* - This is a **hematologic malignancy** (cancer of plasma cells) and has no established link with either **smoking** or **asbestos exposure**. - Its risk factors are largely genetic and related to other environmental factors, but not directly linked to respiratory toxins. *Chronic bronchitis* - **Chronic bronchitis** is primarily caused by **smoking** and exposure to environmental pollutants. - While asbestos exposure can cause lung damage, it doesn't directly or significantly increase the incidence of chronic bronchitis.
Question 91: A 51-year-old man presents to the emergency department with an episode of syncope. He was at a local farmer's market when he fainted while picking produce. He rapidly returned to his baseline mental status and did not hit his head. The patient has a past medical history of diabetes and hypertension but is not currently taking any medications. His temperature is 97.5°F (36.4°C), blood pressure is 173/101 mmHg, pulse is 82/min, respirations are 14/min, and oxygen saturation is 98% on room air. Physical exam is notable for clear breath sounds and a S4 heart sound. Rectal exam reveals a firm and nodular prostate that is non-tender and a fecal-occult sample that is negative for blood. Which of the following is this patient's presentation most concerning for?
- A. Prostatitis
- B. Prostate abscess
- C. Benign prostatic hyperplasia
- D. Prostate cancer (Correct Answer)
- E. Normal physical exam
Explanation: ***Prostate cancer*** - A **firm**, **nodular**, and non-tender prostate on digital rectal examination is highly suspicious for prostate cancer, particularly in a 51-year-old male. - The patient's presentation with **syncope** could indirectly be related to a paraneoplastic syndrome in advanced prostate cancer, although this is less common. *Prostatitis* - Prostatitis typically presents with **perineal pain**, **dysuria**, and **fever**, none of which are noted in this patient. - The prostate would usually be **tender** and boggy, not firm and nodular. *Prostate abscess* - A prostate abscess is characterized by **severe pain**, **fever**, **chills**, and urinary symptoms, which are absent in this case. - The prostate would be exquisitely **tender** and potentially fluctuant on examination. *Benign prostatic hyperplasia* - While BPH can cause urinary symptoms, it typically results in a **smooth**, enlarged, and rubbery prostate, not a firm and nodular one. - It is not associated with syncope or the specific prostate findings described. *Normal physical exam* - A **firm** and **nodular** prostate on rectal exam is an abnormal finding that warrants further investigation, especially given the patient's age. - While other findings may be normal, the prostate exam is highly concerning for pathology.
Question 92: A 67-year-old man comes to the physician because of urinary frequency, dysuria, and blood in his urine. He has also had a 4.5-kg (10-lb) weight loss over the past 3 months and has been feeling more fatigued than usual. He smoked one pack of cigarettes daily for 40 years but quit 2 years ago. A urinalysis shows 3+ blood. Cystoscopy shows an irregular mass on the bladder wall; a biopsy is taken. Which of the following histologic findings would indicate the worst survival prognosis?
- A. Disordered urothelium lined with papillary fronds
- B. Dysplastic cells extending into the lamina propria
- C. Infiltrating nests of cells with squamous differentiation
- D. Nests of atypical cells in the urothelium
- E. Tubular glands with mucin secretions (Correct Answer)
Explanation: ***Tubular glands with mucin secretions*** - The presence of **tubular glands with mucin secretions** indicates a diagnosis of **adenocarcinoma of the bladder**. - Bladder adenocarcinoma is a rare and aggressive form of bladder cancer with a **significantly worse prognosis** compared to urothelial carcinoma, comprising <2% of bladder cancers and often presenting at advanced stages with limited treatment options. *Dysplastic cells extending into the lamina propria* - This description refers to **high-grade urothelial carcinoma** that has invaded the **lamina propria** (stage T1). - While it's an invasive cancer with significant risk, it generally has a better prognosis than adenocarcinoma when treated appropriately. *Disordered urothelium lined with papillary fronds* - This suggests a **papillary urothelial neoplasm**, which could be low-grade or high-grade. - Early-stage papillary tumors generally have a favorable prognosis, especially low-grade variants. *Nests of atypical cells in the urothelium* - This finding describes **carcinoma in situ (CIS)**, a high-grade, flat, non-invasive form of urothelial carcinoma. - Although it has a high risk of progression to invasive cancer, it does not inherently indicate a worse prognosis than invasive adenocarcinoma at the time of diagnosis. *Infiltrating nests of cells with squamous differentiation* - This describes **squamous cell carcinoma of the bladder**, which accounts for 3-5% of bladder cancers. - While aggressive and often associated with chronic irritation or schistosomiasis, it generally has a better prognosis than adenocarcinoma when detected and treated early.
Question 93: A 74-year-old man with a history of encephalomyelitis, ataxia, and nystagmus has a new diagnosis of small cell carcinoma of the lung (T2, N1, M0) is admitted to the hospital due to painless loss of vision in his right eye. A full workup reveals optic neuritis and uveitis in the affected eye. Which of the following antibodies is most likely to be present in the serum of the patient?
- A. Anti-amphiphysin
- B. Anti-Yo
- C. Anti-Hu (Correct Answer)
- D. Anti-CV2 (CRMP5)
- E. Anti-Ri
Explanation: ***Anti-Hu*** - This antibody is strongly associated with **paraneoplastic syndromes** in **small cell lung cancer (SCLC)**, often presenting with **encephalomyelitis**, **ataxia**, and **optic neuritis/uveitis**, as described in the patient. - Anti-Hu antibodies target neuronal proteins, leading to a wide range of neurological deficits, and the presence of SCLC makes this the most likely antibody. *Anti-amphiphysin* - This antibody is typically associated with **stiff-person syndrome**, which presents with muscle rigidity and spasms, and less commonly with paraneoplastic encephalomyelitis. - While it can be associated with breast cancer or SCLC, the patient's specific presentation (encephalomyelitis, ataxia, optic neuritis) is not a classical feature. *Anti-Yo* - **Anti-Yo (Purkinje cell cytoplasmic antibody)** is primarily associated with **paraneoplastic cerebellar degeneration**, leading to severe ataxia, often in the context of gynecological or breast cancers. - Although the patient has ataxia, the extensive involvement including encephalomyelitis and optic neuritis without a predominant cerebellar syndrome makes anti-Yo less likely. *Anti-CV2 (CRMP5)* - **Anti-CV2/CRMP5** antibodies are associated with **paraneoplastic encephalomyelitis**, **optic neuropathy**, and chorea, and are commonly seen in SCLC. - While plausible given the symptoms, anti-Hu is historically the most frequently identified antibody in SCLC patients presenting with this breadth of neurological and visual symptoms. *Anti-Ri* - **Anti-Ri (ANNA-2)** antibodies are classically associated with **opsoclonus-myoclonus syndrome**, characterized by chaotic eye movements and myoclonus, often linked to SCLC or breast cancer. - The patient's symptom of **nystagmus** could be a feature of opsoclonus-myoclonus syndrome, but the more dominant presentation of encephalomyelitis, ataxia, and optic neuritis points away from a primary opsoclonus-myoclonus syndrome.
Question 94: A 60-year-old woman is brought to the emergency department by ambulance after suffering a generalized tonic-clonic seizure. The seizure lasted 2 minutes, followed by a short period of unresponsiveness and loud breathing. Her blood pressure is 130/80 mm Hg, the heart rate is 76/min, and the respiratory rate is 15/min and regular. On physical examination, the patient is confused but follows commands and cannot recall recent events. The patient does not present with any other neurological deficits. T1/T2 MRI of the brain demonstrates a hypointense, contrast-enhancing mass within the right frontal lobe, surrounded by significant cerebral edema. Which of the following would you expect in the tissue surrounding the described lesion?
- A. Loss of endothelial tight junctions (Correct Answer)
- B. Replacement of interstitial fluid with cerebrospinal fluid (CSF)
- C. Increased intracellular concentrations of osmolytes
- D. Upregulation of aquaporin-4
- E. Increased interstitial fluid low in protein
Explanation: ***Loss of endothelial tight junctions*** - The presence of a **contrast-enhancing mass** with surrounding edema suggests **vasogenic edema**, which is caused by the disruption of the **blood-brain barrier (BBB)**. - This disruption primarily involves the **loss of tight junctions** between endothelial cells, allowing plasma proteins and fluid to leak into the interstitial space. *Replacement of interstitial fluid with cerebrospinal fluid (CSF)* - **CSF** is produced by the choroid plexus and flows through the ventricular system and subarachnoid space; it does not replace interstitial fluid within the brain parenchyma. - While disruptions can occur, the primary mechanism of edema in this context is leakage from blood vessels, not direct replacement by CSF. *Increased intracellular concentrations of osmolytes* - This describes the mechanism of **cytotoxic edema**, where intracellular swelling occurs due to **cellular dysfunction** (e.g., ischemia) and the accumulation of osmolytes within cells. - However, the patient's MRI findings of a **contrast-enhancing mass** and significant surrounding edema are more consistent with **vasogenic edema**, which is extracellular. *Upregulation of aquaporin-4* - **Aquaporin-4** channels are involved in water transport and are primarily associated with the development of **cytotoxic edema** or hydrocephalic edema by facilitating water movement across cell membranes. - In **vasogenic edema**, the primary issue is the **breakdown of the BBB** and leakage of fluid and proteins, rather than altered aquaporin expression as the initial cause. *Increased interstitial fluid low in protein* - While there is **increased interstitial fluid**, the fluid in **vasogenic edema** is typically **rich in protein** (plasma proteins) because the **blood-brain barrier** is compromised. - Fluid that is **low in protein** is characteristic of **hydrocephalic edema**, where CSF transudates into the periventricular white matter due to increased ventricular pressure.
Question 95: A 61-year-old man comes to the physician because of a 2-month history of a cough productive of clear mucoid sputum. He has smoked one pack of cigarettes daily for 33 years. Physical examination shows no abnormalities. Chest x-ray shows a 2-cm solid nodule in the periphery of the lower left lobe. A bronchial biopsy of the mass shows numerous mucin-filled epithelial cells lining the alveolar basement membrane. The cells have prominent nucleoli, coarse chromatin, and some cells have multiple nuclei. Which of the following is the most likely diagnosis?
- A. Endobronchial tuberculosis
- B. Pulmonary hamartoma
- C. Small cell carcinoma
- D. Carcinoid tumor
- E. Adenocarcinoma in situ (Correct Answer)
Explanation: ***Adenocarcinoma in situ*** - The presence of **mucin-filled epithelial cells** lining the **alveolar basement membrane** (**lepidic growth pattern**) is characteristic of adenocarcinoma in situ. - **Prominent nucleoli**, **coarse chromatin**, and **multinucleated cells** suggest malignancy, and the nodule's peripheral location is typical for adenocarcinomas. *Endobronchial tuberculosis* - While it can cause a productive cough and lung nodules, the biopsy findings of **mucin-filled epithelial cells** and specific cytological features of malignancy are inconsistent with tuberculosis. - Tuberculosis usually shows **granulomas**, **caseation necrosis**, or acid-fast bacilli on biopsy. *Pulmonary hamartoma* - A hamartoma is a **benign tumor** composed of disorganized mature tissues, typically containing **cartilage**, fat, and connective tissue. - It would not show the distinct **mucin-filled epithelial cells** or the malignant cytological features described. *Small cell carcinoma* - Small cell carcinoma typically presents as a **central mass** and is characterized by small, **undifferentiated cells** with scant cytoplasm and high nuclear-to-cytoplasmic ratio. - It does not exhibit the **mucin production** or the lepidic growth pattern seen in this case. *Carcinoid tumor* - Carcinoid tumors are **neuroendocrine tumors** that typically display nests or cords of uniform, small cells with "salt-and-pepper" chromatin. - They are usually located centrally and do not show the **mucin-filled epithelial cells** or the aggressive cytological features described.
Question 96: A 62-year-old man comes to the physician because of a growth on his penis that has been gradually increasing in size over the last year. He was diagnosed with HIV 10 years ago. He has been divorced for 25 years and has had “at least 30 sexual partners” since. Physical examination shows a nontender 2.5-cm ulcerated lesion with an erythematous base on the dorsum of the glans. There is firm left inguinal lymphadenopathy. A biopsy of the lesion shows small uniform basophilic cells with central necrosis that invade into the corpus cavernosum. This patient's condition is most likely associated with which of the following pathogens?
- A. Chlamydia trachomatis
- B. Haemophilus ducreyi
- C. Epstein-Barr virus
- D. Human papillomavirus (Correct Answer)
- E. Neisseria gonorrhoeae
Explanation: ***Human papillomavirus*** - The description of a slowly growing, ulcerated penile lesion with inguinal lymphadenopathy in an HIV-positive man with multiple sexual partners is highly suggestive of **penile squamous cell carcinoma**, which is strongly associated with **human papillomavirus (HPV)** infection. - The biopsy findings of "small uniform basophilic cells with central necrosis invading into the corpus cavernosum" are consistent with a poorly differentiated squamous cell carcinoma, often linked to high-risk HPV types. *Chlamydia trachomatis* - This pathogen causes **urethritis**, **cervicitis**, and **lymphogranuloma venereum**, which presents with painful lymphadenopathy and anogenital ulcers, but typically not a slowly growing, ulcerated mass like the one described. - The histological description does not fit the typical presentation of complications from *Chlamydia trachomatis* infection. *Haemophilus ducreyi* - This bacterium is the cause of **chancroid**, which presents as painful, ragged ulcers with tender inguinal lymphadenopathy. - While it causes ulcers and lymphadenopathy, the clinical presentation and biopsy findings of a chronic, slowly enlarging, infiltrative lesion are not typical of chancroid. *Epstein-Barr virus* - While Epstein-Barr virus (EBV) is associated with several cancers, including **nasopharyngeal carcinoma**, **Burkitt lymphoma**, and **post-transplant lymphoproliferative disorder**, it is not a known cause of penile squamous cell carcinoma. - The clinical and histological features do not align with EBV-associated malignancies. *Neisseria gonorrhoeae* - This bacterium primarily causes **urethritis**, **cervicitis**, and **disseminated gonococcal infection**. - It does not cause chronic, slowly enlarging ulcerated lesions on the penis that progress to squamous cell carcinoma.
Question 97: A 61-year-old man comes to the physician because of a 6-month history of epigastric pain and a 9-kg (20-lb) weight loss. He feels full and bloated even after eating small portions of food. His hemoglobin concentration is 9.5 g/dL with a mean corpuscular volume of 78 μm3. Test of the stool for occult blood is positive. Esophagogastroduodenoscopy shows a 2-cm raised lesion with central ulceration on the lesser curvature of the stomach. Histologic examination of a gastric biopsy specimen from the lesion is most likely to show which of the following?
- A. Mucin-filled round cells
- B. Gland-forming cuboidal cells (Correct Answer)
- C. Neutrophilic infiltration with pit abscesses
- D. Lymphocytic aggregates with noncaseating granulomas
- E. Foveolar and smooth muscle hyperplasia
Explanation: ***Gland-forming cuboidal cells*** - The patient's symptoms (epigastric pain, weight loss, early satiety, anemia, and positive occult blood in stool) along with the endoscopic finding of a raised, ulcerated lesion on the lesser curvature are highly suggestive of **gastric adenocarcinoma**. - Gastric adenocarcinoma is characterized histologically by **malignant glandular proliferation** with cuboidal or columnar cells forming irregular glands, often with varying degrees of differentiation. *Mucin-filled round cells* - This description is characteristic of **signet-ring cell carcinoma**, a specific poorly differentiated subtype of gastric adenocarcinoma. - While signet-ring cells are a type of gastric cancer, the more general and common histological pattern for gastric adenocarcinoma involves **glandular formation** by cuboidal or columnar cells, making the gland-forming option a broader and typically more direct answer for gastric adenocarcinoma unless specified as diffuse type. *Neutrophilic infiltration with pit abscesses* - This histological pattern is indicative of **acute gastritis** or **H. pylori infection**. - While *H. pylori* is a risk factor for gastric cancer, these findings are not consistent with a malignant tumor presenting with significant weight loss and a mass. *Lymphocytic aggregates with noncaseating granulomas* - This finding is characteristic of **Crohn's disease** or other **granulomatous conditions**, not gastric cancer. - Noncaseating granulomas are not typically seen in gastric adenocarcinoma. *Foveolar and smooth muscle hyperplasia* - This describes a **hyperplastic gastric polyp** or a **Menetrier's disease**-like pattern (giant rugal hypertrophy). - While these conditions can be associated with gastric symptoms, they are not typically malignant lesions causing significant weight loss and a distinct ulcerated mass, as seen in this patient.
Question 98: A 59-year-old Caucasian man presents with a one-month history of left flank fullness and pain. The patient has stable angina, which is controlled with medications including atorvastatin, metoprolol, and aspirin. His vital signs are within normal limits. BMI is 32 kg/m2. Clinical examination reveals a 10 x 10-cm palpable mass in the left flank. Testicular examination indicates left varicocele. Laboratory parameters are as follows: Urine Blood 3+ WBC none RBC 65/hpf without dysmorphic features Abdominal CT scan confirms the presence of a large solid mass originating in the left kidney with impingement on the left renal vein. Based on the most likely diagnosis, which of the following is considered a risk factor in this patient?
- A. Obesity (Correct Answer)
- B. Varicocele
- C. Atorvastatin
- D. Lynch syndrome
- E. Caucasian race
Explanation: ***Obesity*** - This patient's **BMI of 32 kg/m2** indicates **obesity**, which is a well-established risk factor for **renal cell carcinoma (RCC)**, the most likely diagnosis given the clinical presentation (flank mass, hematuria, varicocele, and CT findings). - Obesity is thought to increase RCC risk due to associated hormonal changes, such as increased **estrogen** and **insulin-like growth factor 1 (IGF-1)**, and chronic inflammation. *Varicocele* - While a **left varicocele** is a clinical finding often associated with **renal cell carcinoma**, particularly on the left side due to impingement on the left renal vein, it is a **symptom/sign** of the disease, not a risk factor for its development. - The varicocele develops because the tumor obstructs the **left renal vein**, leading to retrograde flow and dilation of the **gonadal vein**. *Atorvastatin* - **Atorvastatin**, a statin used to treat hyperlipidemia and prevent cardiovascular disease, has **no known association** with an increased risk of renal cell carcinoma. - Some studies even suggest a potential **protective effect** of statins against certain cancers, but this is not definitively established for RCC, and certainly not a risk factor. *Lynch syndrome* - **Lynch syndrome** (hereditary nonpolyposis colorectal cancer) is primarily associated with an increased risk of **colorectal cancer**, **endometrial cancer**, and other gastrointestinal/genitourinary cancers, but **not renal cell carcinoma**. - Renal cell carcinoma is more commonly linked to other genetic syndromes like **Von Hippel-Lindau disease** or **hereditary papillary renal carcinoma**. *Caucasian race* - While there are some **racial disparities** in certain cancer incidences, the **Caucasian race itself is not considered a primary modifiable risk factor** for renal cell carcinoma. - **African Americans** may have a slightly higher risk for RCC, but this is often attributed to socioeconomic factors and comorbidities rather than race as an independent biological risk factor.
Question 99: A 69-year-old man comes to the physician because of a 4-month history of progressive fatigue, cough, shortness of breath, and a 6.6-kg (14.5-lb) weight loss. For the past week, he has had blood-tinged sputum. He is a retired demolition foreman. There is dullness to percussion and decreased breath sounds over the left lung base. A CT scan of the chest shows a left-sided pleural effusion and circumferential pleural thickening with calcifications on the left hemithorax. Pathologic examination of a biopsy specimen of the thickened tissue is most likely to show which of the following findings?
- A. Keratin-producing large polygonal cells with intercellular bridges
- B. Calretinin-positive polygonal cells with numerous long surface microvilli (Correct Answer)
- C. Napsin-positive cells in an acinar growth pattern with intracytoplasmic mucin
- D. Synaptophysin-positive dark blue cells with hyperchromatic nuclei and scarce cytoplasm
- E. Large polygonal cells with prominent nucleoli and abundant pale cytoplasm
Explanation: ***Calretinin-positive polygonal cells with numerous long surface microvilli*** - The patient's history of **demolition work (asbestos exposure)**, progressive fatigue, weight loss, cough, shortness of breath, blood-tinged sputum, and imaging showing **pleural effusion** and **circumferential pleural thickening with calcifications** are highly suggestive of **mesothelioma**. - **Mesothelioma** typically presents with **calretinin positivity** on immunohistochemistry and electron microscopy reveals **long, slender microvilli** on the surface of polygonal or spindle-shaped tumor cells. *Keratin-producing large polygonal cells with intercellular bridges* - This description is characteristic of **squamous cell carcinoma**, which is often associated with smoking but less directly with asbestos exposure in the presented manner. - While squamous cell carcinoma can involve the lung, the specific pleural findings and asbestos exposure history point away from this diagnosis. *Napsin-positive cells in an acinar growth pattern with intracytoplasmic mucin* - This describes **adenocarcinoma**, which is positive for **napsin A** and typically presents with an acinar growth pattern and mucin production. - While asbestos exposure increases the risk of lung adenocarcinoma, the clinical and radiological presentation (especially circumferential pleural thickening) is more classic for mesothelioma. *Synaptophysin-positive dark blue cells with hyperchromatic nuclei and scarce cytoplasm* - This morphology and immunohistochemical marker (synaptophysin) are characteristic of **small cell carcinoma**, a highly aggressive neuroendocrine tumor. - Small cell carcinoma is strongly linked to smoking but less so directly to asbestos, and its typical presentation differs from the described pleural involvement. *Large polygonal cells with prominent nucleoli and abundant pale cytoplasm* - This description is vague but could represent various types of **large cell carcinoma**. - Without more specific immunohistochemical markers or architectural patterns, it's a less precise diagnosis compared to the strong evidence for mesothelioma.
Question 100: A 57-year-old woman with a long-standing history of liver cirrhosis presents to her primary care provider with a complaint of unintended weight loss of 8.2 kg (18.0 lb) within the last month. She has a history of intermittent right upper quadrant pain in her abdomen with decreased appetite for a few years and occasional shortness of breath. The past medical history is significant for hepatitis E infection during her first pregnancy when she was 28 years old, and a history of blood transfusion after an accident 25 years ago. She drinks about 2–3 pints of beer every week on average and does not use tobacco. The vital signs include: blood pressure 110/68 mm Hg, pulse rate 82/min, respiratory rate 11/min, and temperature 37.7 °C (99.9°F). The physical exam is normal except for moderate icterus and tender hepatomegaly. The blood tests show mild anemia with decreased iron stores. Serum electrolytes, blood sugar, and renal function are normal. The chest X-ray is normal. An ultrasound of the abdomen revealed a mass in the liver, which was confirmed with a biopsy to be hepatocellular carcinoma. Which of the following is the strongest causative factor that can be linked to her diagnosis?
- A. Shortness of breath
- B. Hemochromatosis
- C. History of blood transfusion (Correct Answer)
- D. History of hepatitis E
- E. History of alcohol consumption
Explanation: ***History of blood transfusion*** - Blood transfusions before **1992** were a significant risk factor for **hepatitis C virus (HCV)** transmission, which is a major cause of chronic hepatitis, cirrhosis, and hepatocellular carcinoma. - Given the patient's age and history of transfusion 25 years ago, it is highly probable she acquired HCV, leading to her current diagnosis. *Shortness of breath* - While shortness of breath can be associated with advanced liver disease (e.g., **hepatopulmonary syndrome**), it is a symptom, not a direct causative factor for hepatocellular carcinoma. - There is no direct causal link between experiencing shortness of breath and the development of liver cancer. *Hemochromatosis* - **Hemochromatosis** is a genetic disorder causing **iron overload**, which can lead to cirrhosis and hepatocellular carcinoma. - However, the patient's blood tests show **decreased iron stores** (mild anemia with decreased iron), ruling out hemochromatosis as a causative factor. *History of hepatitis E* - **Hepatitis E virus (HEV)** typically causes **acute, self-limiting hepatitis** and is rarely associated with chronic liver disease or hepatocellular carcinoma, especially in immunocompetent individuals. - Chronic HEV infection primarily occurs in **immunocompromised patients** or in certain genotypes, which is not suggested by the patient's history. *History of alcohol consumption* - While excessive **alcohol consumption** is a well-known risk factor for cirrhosis and hepatocellular carcinoma, the patient's reported intake of **2-3 pints of beer per week** is considered moderate and unlikely to be the primary cause of her long-standing liver cirrhosis. - This level of alcohol consumption would typically not lead to significant **alcoholic liver disease** over time.
Question 101: A 75-year-old male presents to his primary care physician complaining of epigastric pain. He has developed progressively worsening epigastric pain, heartburn, and nausea over the past five months. The pain does not change with meals and is not positional. He also reports that he is rarely hungry and has lost ten pounds. The patient immigrated from Japan two years ago to live with his son in the United States. He worked as a fisherman and dock worker for most of his life. His past medical history is notable for gout and gastroesophageal reflux disease. He takes allopurinol and cimetidine. He has a 30 pack-year smoking history and drinks 1-2 alcoholic beverages per day. Physical examination reveals mild epigastric tenderness to palpation and a hard lymph node near his left shoulder. Which of the following substances is most strongly associated with this patient’s condition?
- A. Asbestos
- B. Vinyl chloride
- C. Aflatoxin
- D. Naphthalene
- E. Nitrosamine (Correct Answer)
Explanation: ***Nitrosamine*** - This patient presents with **epigastric pain**, **heartburn**, **nausea**, **anorexia**, and **weight loss**, suggestive of **gastric adenocarcinoma**. His history of being from Japan and his occupation as a fisherman, along with a hard lymph node near his left shoulder (likely a **Virchow node**), further support this diagnosis. **Nitrosamines** are potent carcinogens found in cured and pickled foods, which are common in the traditional Japanese diet. - **Nitrosamines** are directly linked to an increased risk of developing **gastric cancer**. *Asbestos* - **Asbestos** exposure is primarily associated with **mesothelioma** and **lung cancer**, not gastric adenocarcinoma. - While previous occupations involving exposure to various toxins are relevant, his symptoms and specific demographic/lifestyle factors point away from asbestos as the primary culprit for this gastric presentation. *Vinyl chloride* - **Vinyl chloride** exposure is strongly linked to **hepatic angiosarcoma**, a rare liver cancer. - It is not associated with gastric adenocarcinoma. *Aflatoxin* - **Aflatoxins**, produced by certain molds, are powerful **hepatocarcinogens** and are primarily associated with **hepatocellular carcinoma**. - They are typically found in contaminated grains and nuts, and are not a direct risk factor for gastric cancer. *Naphthalene* - **Naphthalene** is a component of mothballs and is associated with **hemolytic anemia** (in individuals with G6PD deficiency) and, in chronic high-dose exposure, irritation of the respiratory tract, not gastric cancer. - It does not have a known association with gastric adenocarcinoma.
Question 102: A 52-year-old woman comes to the physician because of a 1-month history of mild fever, fatigue, and shortness of breath. She has no history of serious medical illness and takes no medications. Cardiopulmonary examination shows a mid-diastolic plopping sound heard best at the apex and bilateral rales at the base of the lungs. Echocardiography shows a pedunculated, heterogeneous mass in the left atrium. A biopsy of the mass shows clusters of mesenchymal cells surrounded by gelatinous material. Further evaluation of this patient is most likely to show which of the following?
- A. Malignant pleural effusion
- B. Axillary lymphadenopathy
- C. Increased S100 protein serum concentration
- D. Increased IL-6 serum concentration (Correct Answer)
- E. Ash-leaf skin lesions
Explanation: ***Increased IL-6 serum concentration*** - This patient's presentation with **fever**, **fatigue**, **shortness of breath**, and a **pedunculated left atrial mass** on echocardiography is highly suggestive of a **cardiac myxoma**. - **Cardiac myxomas** are known to secrete various cytokines, including **IL-6**, which can cause constitutional symptoms such as fever, fatigue, and weight loss. *Malignant pleural effusion* - While pleural effusions can cause shortness of breath, a **malignant pleural effusion** is usually associated with an underlying malignancy, and the described cardiac mass is benign. - The patient's symptoms are more directly attributable to the **obstructive effects** and **cytokine secretion** of the left atrial myxoma. *Axillary lymphadenopathy* - **Axillary lymphadenopathy** would suggest an infection or malignancy in the upper extremity or breast, which is not supported by the patient's presentation focusing on cardiac and systemic symptoms related to an atrial mass. - Myxomas do not typically metastasize or cause regional lymph node involvement. *Increased S100 protein serum concentration* - **S100 protein** is a marker primarily associated with **melanoma** and **neural crest tumors**. - It is not a characteristic finding in patients with **cardiac myxomas**. *Ash-leaf skin lesions* - **Ash-leaf spots** are hypopigmented macules characteristic of **tuberous sclerosis**, a genetic disorder. - This condition is not related to **cardiac myxomas** and would present with different neurological and dermatological findings.
Question 103: A 3-year-old girl is brought to the physician by her parents due to observations of rapid, random, horizontal and vertical eye movements along with occasional jerking movements of her limbs and head. CT scan reveals an abdominal mass that crosses the midline. Further work-up reveals elevated 24-hour urinary homovanillic acid and vanillylmandelic acid. Neuroblastoma is suspected. Which of the following diseases pathologically originates from the same type of cells as Neuroblastoma?
- A. Pilocytic astrocytoma
- B. Craniopharyngioma
- C. Medulloblastoma
- D. Hirschsprung disease (Correct Answer)
- E. Retinoblastoma
Explanation: ***Hirschsprung disease*** - Both **neuroblastoma** and **Hirschsprung disease** originate from neural crest cells. Neuroblastomas arise from the adrenal medulla or sympathetic ganglia, while Hirschsprung disease results from failed neural crest cell migration to the distal colon, leading to an **aganglionic segment**. - The shared embryological origin from the **neural crest** explains their occasional coexistence or shared genetic predispositions. *Pilocytic astrocytoma* - This tumor originates from **astrocytes**, which are glial cells derived from the **neuroectoderm** (specifically the neural tube). - It is distinct from the neural crest cells that give rise to neuroblastoma. *Craniopharyngioma* - This tumor is derived from remnants of **Rathke's pouch**, an embryonic invagination of the stomodeum (oral ectoderm). - It is not related to neural crest cells. *Medulloblastoma* - This highly malignant brain tumor arises from primitive neuroectodermal cells in the **cerebellum**. - While also part of the neuroectoderm, its specific origin is distinct from the neural crest cells that form neuroblastomas. *Retinoblastoma* - This pediatric eye cancer originates from immature **retinal cells** (retinoblasts), which are part of the **neuroectoderm** (specifically the optic vesicle). - Its cellular origin is different from the neural crest lineage of neuroblastoma.
Question 104: A 40-year-old man comes to the physician because of a 1-month history of a painless lump on his neck. Two years ago, he underwent surgery for treatment-resistant hypertension, episodic headaches, and palpitations. Physical examination shows a firm, irregular swelling on the right side of the neck. Ultrasonography of the thyroid gland shows a 2-cm nodule with irregular margins and microcalcifications in the right thyroid lobe. Further evaluation of this patient is most likely to show increased serum concentration of which of the following substances?
- A. Thyroid-stimulating hormone
- B. Gastrin
- C. Parathyroid hormone
- D. Metanephrines
- E. Calcitonin (Correct Answer)
Explanation: ***Calcitonin*** - The patient's history of treatment-resistant **hypertension**, episodic **headaches**, and **palpitations**, for which he underwent surgery 2 years ago, is highly suggestive of a prior **pheochromocytoma**. - The neck lump with a **thyroid nodule** showing **irregular margins** and **microcalcifications** in a patient with a history of pheochromocytoma points to **Medullary Thyroid Carcinoma (MTC)**, often part of **Multiple Endocrine Neoplasia type 2A (MEN2A)**, which is characterized by elevated **calcitonin**. *Thyroid-stimulating hormone* - **TSH** levels are typically normal or suppressed in differentiated thyroid cancers (papillary or follicular carcinoma) but would be elevated in primary hypothyroidism. - MTC is a neuroendocrine tumor of the parafollicular C cells and does not generally affect TSH production, as it is not a differentiated thyroid cancer. *Gastrin* - Elevated **gastrin** levels are typically associated with **Zollinger-Ellison syndrome**, often caused by a **gastrinoma**, which is a feature of **MEN1**, not MEN2A. - Gastrinomas do not present with thyroid masses or pheochromocytoma. *Parathyroid hormone* - While **primary hyperparathyroidism** (due to parathyroid adenoma or hyperplasia) is also a component of **MEN2A**, the primary endocrine marker for **medullary thyroid carcinoma** itself is calcitonin, not PTH. - Elevated PTH would be expected if the patient also had hyperparathyroidism, but calcitonin directly indicates MTC. *Metanephrines* - **Metanephrines** (metanephrine and normetanephrine) are elevated in patients with **pheochromocytoma**, which the patient likely had in the past (hence the surgery for hypertension, headaches, and palpitations). - However, the current presentation focuses on a new thyroid nodule, and calcitonin is the primary marker for **medullary thyroid carcinoma**, which develops in a significant proportion of patients with MEN2A.
Question 105: A 75-year-old woman comes to the physician because of a 3-month history of involuntary weight loss and a painless lump on her neck. Physical examination shows a firm, irregular swelling on the right side of the neck. Ultrasonography of the thyroid gland shows a 2-cm nodule with irregular margins and microcalcifications in the right thyroid lobe. A biopsy of the thyroid nodule is performed. Which of the following changes would be most consistent with anaplasia?
- A. Negative staining of tumor cells for thyroglobulin (Correct Answer)
- B. Disorganized proliferation of mature thyroid cells
- C. Increased expression of thyroid transcription factor-1
- D. Replacement of thyroid cells by normal squamous epithelium
- E. Reduced number of functional thyroid cells
Explanation: ***Negative staining of tumor cells for thyroglobulin*** - Anaplastic thyroid carcinoma is characterized by extreme **dedifferentiation**, losing most of the features of normal thyroid cells, including the ability to produce **thyroglobulin**. - Therefore, **negative or weak staining for thyroglobulin** (a marker of thyroid differentiation) in a highly malignant thyroid tumor is consistent with anaplasia. *Disorganized proliferation of mature thyroid cells* - This description is more consistent with a **benign tumor** or hyperplastic nodule where cells retain their mature characteristics but grow abnormally. - In contrast, anaplastic carcinomas involve highly **undifferentiated cells** that bear little resemblance to mature thyroid cells. *Increased expression of thyroid transcription factor-1* - **Thyroid transcription factor-1 (TTF-1)** is a nuclear protein expressed in various thyroid neoplasms, including well-differentiated carcinomas. - While TTF-1 expression can occur in anaplastic carcinoma, it is usually **lost or significantly reduced** due to dedifferentiation, making increased expression inconsistent with anaplasia. *Replacement of thyroid cells by normal squamous epithelium* - This describes **squamous metaplasia**, a common finding in chronic inflammation or conditions like Hashimoto's thyroiditis, but it isn't anaplasia. - Anaplastic carcinoma involves **malignant transformation** of thyroid cells into highly pleomorphic, undifferentiated cells, not replacement by normal non-thyroid cells. *Reduced number of functional thyroid cells* - While anaplastic carcinomas replace normal thyroid tissue, leading to a reduced number of functional cells, this is a **consequence** of the disease, not a defining characteristic of anaplasia itself. - Anaplasia refers to the **histological appearance** of highly undifferentiated, malignant cells, rather than simply a reduction in functional cell count.
Question 106: A 44-year-old man comes to the physician because of fatigue and increased straining during defecation for 3 months. During this time, he has lost 5 kg (12 lb) despite no change in appetite. He has a family history of colon cancer in his maternal uncle and maternal grandfather. His mother died of ovarian cancer at the age of 46. Physical examination shows conjunctival pallor. His hemoglobin concentration is 11.2 g/dL, hematocrit is 34%, and mean corpuscular volume is 76 μm3. Colonoscopy shows an exophytic mass in the ascending colon. Pathologic examination of the resected mass shows a poorly differentiated adenocarcinoma. Genetic analysis shows a mutation in the MSH2 gene. Which of the following is the most likely diagnosis?
- A. Familial adenomatous polyposis
- B. Peutz-Jeghers syndrome
- C. Turcot syndrome
- D. Lynch syndrome (Correct Answer)
- E. Gardner syndrome
Explanation: ***Lynch syndrome*** - The patient's **poorly differentiated adenocarcinoma** in the ascending colon, coupled with the **family history of colon and ovarian cancer** (early onset, diverse cancer types), and the **MSH2 gene mutation**, strongly indicates Lynch syndrome (hereditary nonpolyposis colorectal cancer). - **Lynch syndrome** is caused by germline mutations in **DNA mismatch repair (MMR) genes** (e.g., MSH2, MLH1, MSH6, PMS2), leading to an increased risk of colorectal, ovarian, endometrial, and other cancers, often at a younger age and predominantly in the **right colon**. *Familial adenomatous polyposis* - This syndrome is characterized by the development of **hundreds to thousands of colorectal adenomatous polyps** during adolescence or early adulthood, a feature not mentioned in the patient's presentation. - It is caused by a germline mutation in the **APC gene**, not MSH2, leading to an almost 100% lifetime risk of colorectal cancer if untreated. *Peutz-Jeghers syndrome* - This syndrome is characterized by **hamartomatous polyps** throughout the gastrointestinal tract and **mucocutaneous melanin pigmentation** (dark spots on lips, buccal mucosa, fingers/toes). - It is associated with mutations in the **STK11 gene** and an increased risk of various cancers, but the clinical presentation and genetic mutation do not match. *Turcot syndrome* - Turcot syndrome is a rare condition characterized by the coexistence of **colorectal polyposis** (either FAP-like or Lynch-like) and **central nervous system tumors** (e.g., medulloblastoma, glioblastoma). - While it can involve MMR gene mutations in some cases, the prominent feature of CNS tumors is absent in this patient's history. *Gardner syndrome* - This is a subtype of FAP, characterized by colorectal polyps along with **extra-intestinal manifestations** such as **osteomas** (especially in the mandible or skull), **epidermoid cysts**, and **desmoid tumors**. - Like FAP, it is caused by mutations in the **APC gene**, and the characteristic extra-intestinal features are not described in the patient.
Question 107: A 32-year-old woman presents to her primary care physician for an annual checkup. She reports that she has been feeling well and has no medical concerns. Her past medical history is significant for childhood asthma but she has not experienced any symptoms since she was a teenager. Physical exam reveals a 1-centimeter hard mobile mass in the left upper outer quadrant of her breast. A mammogram was performed and demonstrated calcifications within the mass so a biopsy was obtained. The biopsy shows acinar proliferation with intralobular fibrosis. Which of the following conditions is most likely affecting this patient?
- A. Sclerosing adenosis (Correct Answer)
- B. Fibroadenoma
- C. Cystic hyperplasia
- D. Invasive lobular carcinoma
- E. Infiltrating ductal carcinoma
Explanation: ***Sclerosing adenosis*** - This condition is characterized by **acinar proliferation with intralobular fibrosis**, which exactly matches the biopsy findings mentioned in the vignette. - Sclerosing adenosis can present as a palpable mass with **calcifications on mammography**, mimicking carcinoma, necessitating biopsy for definitive diagnosis. *Fibroadenoma* - Characterized by proliferation of both **stromal and epithelial elements**, often forming well-circumscribed, mobile masses. - While it can present as a mobile mass, the specific histological finding of "acinar proliferation with intralobular fibrosis" is not the primary descriptive characteristic of a fibroadenoma. *Cystic hyperplasia* - This term, often used interchangeably with **fibrocystic changes**, involves the formation of cysts and an increase in fibrous tissue. - While it can involve hyperplasia, it doesn't typically describe the distinct pattern of "acinar proliferation with intralobular fibrosis" as seen in sclerosing adenosis. *Invasive lobular carcinoma* - This carcinoma is characterized by its **infiltrative growth pattern** often in single file lines, and typically does not form a well-defined mass. - While it can present with calcifications, the absence of overt malignant features and the specific benign histological description rule out this diagnosis. *Infiltrating ductal carcinoma* - The most common type of breast cancer, characterized by **malignant epithelial cells infiltrating the stroma**. - The biopsy findings described ("acinar proliferation with intralobular fibrosis") are features of a benign process, not a malignant one.
Question 108: A 70-year-old man presents to the physician with a 1-month history of severe fatigue. During this time, he has unintentionally lost 2 kg (4.4 lb). Currently, he takes no medications other than aspirin for occasional knee pain. He does not smoke or drink alcohol. His vital signs are within the normal range. On physical examination, the conjunctivae are pale. Petechiae are present on the distal lower extremities and on the soft and hard palates. Palpation reveals bilateral painless cervical lymphadenopathy. Examination of the lungs, heart, and abdomen shows no abnormalities. Which of the following factors in this patient’s history or laboratory findings would most likely indicate a good prognosis?
- A. Leukocyte count > 100,000/mm3
- B. History of myelodysplastic syndrome
- C. Philadelphia chromosome
- D. Prior treatment with cytotoxic agents
- E. Translocation t(15;17) (Correct Answer)
Explanation: ***Translocation t(15;17)*** - This translocation is characteristic of **acute promyelocytic leukemia (APL)**. - APL is highly sensitive to **all-trans retinoic acid (ATRA)** and **arsenic trioxide**, leading to high remission rates and a significantly better prognosis compared to other AML subtypes. *Leukocyte count > 100,000/mm3* - An extremely high white blood cell count in acute leukemia, especially **AML**, is generally associated with a **worse prognosis**. - It indicates a large disease burden and increased risk of complications like **leukostasis** and disseminated intravascular coagulation (DIC). *History of myelodysplastic syndrome* - Myelodysplastic syndromes (MDS) often transform into **secondary acute myeloid leukemia (sAML)**. - AML arising from MDS typically has a **poor prognosis** due to higher rates of unfavorable cytogenetics and resistance to standard chemotherapy. *Philadelphia chromosome* - The **Philadelphia chromosome (t(9;22))** is typically associated with **chronic myeloid leukemia (CML)** and some types of acute lymphoblastic leukemia (ALL). - Its presence in AML is rare but is associated with an **adverse prognosis** due to its underlying genetic instability. *Prior treatment with cytotoxic agents* - Prior exposure to cytotoxic agents (e.g., chemotherapy for another cancer) can lead to **therapy-related AML (tAML)**. - tAML generally has a **very poor prognosis**, often characterized by unfavorable cytogenetics and multidrug resistance.
Question 109: A 5-year-old boy presents to his pediatrician with weakness. His father observed that his son seemed less energetic at daycare and kindergarten classes. He was becoming easily fatigued from mild play. His temperature is 98°F (37°C), blood pressure is 90/60 mmHg, pulse is 100/min, and respirations are 20/min. Physical exam reveals pale conjunctiva, poor skin turgor and capillary refill, and cervical and axillary lymphadenopathy with assorted bruises throughout his body. A complete blood count reveals the following: Leukocyte count: 3,000/mm^3 Segmented neutrophils: 30% Bands: 5% Eosinophils: 5% Basophils: 10% Lymphocytes: 40% Monocytes: 10% Hemoglobin: 7.1 g/dL Hematocrit: 22% Platelet count: 50,000/mm^3 The most specific diagnostic assessment would most likely show which of the following?
- A. Bone marrow biopsy with ≥ 20% lymphoblasts (Correct Answer)
- B. Fluorescence in situ hybridization analysis with 9:22 translocation
- C. Peripheral blood smear with > 50% lymphoblasts
- D. Flow cytometry with positive terminal deoxynucleotidyl transferase staining
- E. Fluorescence in situ hybridization analysis with 12:21 translocation
Explanation: ***Bone marrow biopsy with ≥ 20% lymphoblasts*** - The patient's symptoms (weakness, fatigue, pallor, bruising, lymphadenopathy) and blood counts (anemia, thrombocytopenia, leukopenia with relative lymphocytosis) are highly suggestive of **Acute Lymphoblastic Leukemia (ALL)**. - The most specific diagnostic assessment for ALL involves a **bone marrow biopsy** showing **≥20% lymphoblasts** per WHO 2016 classification, confirming the abnormal proliferation of immature lymphoid cells. - This is the **gold standard** for diagnosing ALL and distinguishes it from other hematologic disorders. *Fluorescence in situ hybridization analysis with 9:22 translocation* - The **Philadelphia chromosome (t[9;22])** is characteristic of **Chronic Myeloid Leukemia (CML)**, which is rare in children and presents differently. - While t(9;22) can occur in 3-5% of childhood ALL and indicates poor prognosis, it is a **prognostic marker**, not the primary diagnostic criterion for ALL itself. *Peripheral blood smear with > 50% lymphoblasts* - While lymphoblasts can be seen in the peripheral blood in ALL, a specific percentage threshold in peripheral blood is **not a diagnostic criterion** for ALL. - The peripheral blood smear can be suggestive, but the **bone marrow blast percentage is the gold standard** for definitive diagnosis. *Flow cytometry with positive terminal deoxynucleotidyl transferase staining* - **Terminal deoxynucleotidyl transferase (TdT)** is a nuclear enzyme expressed in pre-B and pre-T lymphoblasts and is an important marker for ALL. - Flow cytometry with positive TdT staining helps **characterize and classify the blasts** but does not quantify the blast percentage required for diagnosis, which is provided by the bone marrow biopsy. *Fluorescence in situ hybridization analysis with 12:21 translocation* - The **t(12;21) [ETV6-RUNX1] translocation** is the most common cytogenetic abnormality in childhood B-cell ALL (20-25% of cases) and is associated with favorable prognosis. - While its presence is relevant for risk stratification and treatment planning, the primary diagnostic criterion for ALL is the **percentage of lymphoblasts in the bone marrow**.
Question 110: A 10-year-old boy is brought by his mother to his pediatrician for "skin growths." His mother reports that she started noticing small lumps arising from the patient's lips and eyelids several months ago. She also notes that he seems to suffer from frequent constipation and appears "weaker" than many of his peers. The boy's past medical history is unremarkable. His father and paternal grandmother have a history of medullary thyroid carcinoma. His height and weight are in the 85th and 45th percentiles, respectively. His temperature is 99°F (37.1°C), blood pressure is 110/65 mmHg, pulse is 90/min, and respirations are 18/min. On examination, he has an elongated face with protruding lips. There are numerous sessile painless nodules on the patient's lips, tongue, and eyelids. This patient's condition is most strongly associated with a mutation in which of the following genes?
- A. NF1
- B. MEN1
- C. RET (Correct Answer)
- D. NF2
- E. c-KIT
Explanation: ***RET*** - The constellation of **skin growths** on the lips and eyelids (neuromas), **constipation** (ganglioneuromatosis), and a family history of **medullary thyroid carcinoma** (MTC) strongly suggests **Multiple Endocrine Neoplasia type 2B (MEN2B)**. - MEN2B is caused by a germline mutation in the **RET proto-oncogene**, which is a receptor tyrosine kinase involved in cell growth and differentiation. *NF1* - Mutations in the **NF1 gene** cause **Neurofibromatosis type 1**, characterized by **café-au-lait spots**, neurofibromas (subcutaneous, not typically mucosal), iris Lisch nodules, and optic pathway gliomas. - While it involves skin growths (neurofibromas), the specific mucosal neuromas, elongated facies, and family history of MTC are not typical features. *MEN1* - **MEN1 syndrome** is caused by mutations in the **MEN1 gene** and is associated with tumors of the **parathyroid**, **anterior pituitary**, and **pancreatic islet cells** (the 3 Ps). - This patient's presentation of mucosal neuromas and medullary thyroid carcinoma is not characteristic of MEN1. *NF2* - Mutations in the **NF2 gene** cause **Neurofibromatosis type 2**, classically characterized by **bilateral vestibular schwannomas**, meningiomas, and ependymomas. - Skin manifestations are less prominent and different from what is described, and MTC is not associated. *c-KIT* - Mutations in the **c-KIT gene** are primarily associated with **gastrointestinal stromal tumors (GIST)** and certain types of mastocytosis. - It is not linked to the constellation of mucosal neuromas, elongated facies, or medullary thyroid carcinoma seen in this patient.
Question 111: A 55-year-old man presents to the emergency department because of an excruciating headache that started suddenly after he got home from work. He also reports having double vision. Specifically, in the last week he almost got into two car accidents with vehicles that "came out of nowhere" while he was trying to merge on the highway. Physical examination is notable for ptosis of the left eye, which is also inferiorly and laterally deviated. The patient is treated emergently and then started on a hormone replacement in order to avoid life-threatening post-treatment complications. The patient's current presentation was associated with a pathologic process that existed for several months prior to this event. Which of the following symptoms could this patient have experienced as part of that pre-existing pathology?
- A. Kidney stones
- B. Hyperkalemia
- C. Increased hat size (Correct Answer)
- D. Gastric ulcers
- E. Hypoglycemia
Explanation: ***Increased hat size*** - The emergent treatment and subsequent hormone replacement for a life-threatening post-treatment complication, along with double vision and an excruciating headache, suggests a diagnosis of **pituitary apoplexy**. - Pituitary apoplexy is often due to an acute hemorrhage or infarction within a pre-existing pituitary adenoma. A large adenoma can cause symptoms like **increased hat size** due to the progressive growth of facial bones and skull, a hallmark of **acromegaly** if the adenoma secretes growth hormone. *Kidney stones* - While a pituitary adenoma secreting **ACTH** (Cushing's disease) can lead to **hypercalciuria** and kidney stones, this specific symptom is not as directly indicative of a pre-existing pathology that would explain the acute presentation and subsequent hormone replacement. - Kidney stones are not a primary or direct symptom of a pituitary adenoma in the way that acromegaly-related changes are. *Hyperkalemia* - Hyperkalemia is typically associated with conditions like **adrenal insufficiency** or **renal failure**, not directly with the pre-existing pituitary pathology leading to apoplexy. - Insufficiency of mineralocorticoids (e.g., in adrenal crisis, which can be a complication of pituitary apoplexy due to ACTH deficiency) causes **hyponatremia** and **hyperkalemia**, but this would be a consequence of the acute event and not a pre-existing symptom of the adenoma itself. *Gastric ulcers* - Although conditions like **Zollinger-Ellison syndrome** (due to a **gastrinoma**) involve ulcers, and **MEN1 syndrome** can include pituitary adenomas and gastrinomas, gastric ulcers are not a direct or common pre-existing symptom of a pituitary adenoma itself. - Additionally, **Cushing's syndrome** (which can be caused by an ACTH-secreting pituitary adenoma) can be associated with an increased risk of peptic ulcers due to high cortisol levels, but it's not a primary or specific finding. *Hypoglycemia* - Hypoglycemia can occur with **adrenal insufficiency** or **growth hormone deficiency**, both of which can be consequences of pituitary dysfunction, particularly if the adenoma destroys normal pituitary tissue or after apoplexy. - However, hypoglycemia is often an acute or late symptom of hormonal deficiencies, rather than a prominent pre-existing symptom of the growing adenoma prior to the acute event, especially compared to the chronic changes of acromegaly.
Question 112: A 3-year-old boy was brought in by his parents for undescended testes. The physical examination showed an absence of the left testis in the scrotum. Inguinal swelling was noted on the left side and was surgically corrected. Which of the following conditions will most likely occur in the later stages of his life?
- A. Epididymitis
- B. Testicular cancer (Correct Answer)
- C. Varicocele
- D. Torsion testis
- E. Spermatocele
Explanation: ***Testicular cancer*** - Undescended testes (**cryptorchidism**) are a major risk factor for developing **testicular cancer**, even after surgical correction (**orchidopexy**). - The risk is higher for both the undescended and the contralateral descended testicle, suggesting a potential underlying developmental abnormality. *Epididymitis* - **Epididymitis** is an inflammation of the **epididymis**, usually caused by bacterial infection, and is not a common long-term complication of surgically corrected undescended testes. - While it can cause scrotal pain and swelling, it is not directly linked to the history of cryptorchidism in this context. *Varicocele* - A **varicocele** is an enlargement of veins within the **spermatic cord**, often compared to a "bag of worms," and is a common cause of **male infertility**. - It is not typically associated with a history of undescended testes, and its development is independent of whether the testis was surgically brought into the scrotum. *Torsion testis* - **Testicular torsion** is a surgical emergency involving the twisting of the **spermatic cord**, which cuts off the blood supply to the testicle. - While it can occur in individuals with undescended testes, surgical correction does not significantly increase the lifetime risk beyond the general population, and it is a sudden event rather than a long-term consequence. *Spermatocele* - A **spermatocele** is a benign, sperm-containing cyst that develops in the **epididymis**, usually causing a painless lump above the testicle. - These cysts are generally not a long-term complication of undescended testes or their surgical correction.
Question 113: A 65-year-old man presents to his primary care provider with excessive fatigue, weight loss, and multiple small bruises on his arms and abdomen. These symptoms started several months ago. He reports worsening fatigue and a 20-pound (9 kg) weight loss in the past month. Past medical history is significant for an asymptomatic lymphocytosis noted 6 months ago on a yearly physical. On review of systems, he denies chest pain, difficulty breathing, swelling in the extremities, or change in bowel habits. Vitals include: temperature 37.0°C (98.6°F), blood pressure 110/75 mm Hg, pulse 99/min, respirations 20/min, and oxygen saturation 91% on room air. On physical exam, the patient is listless. The cardiac exam is normal. Lungs are clear to auscultation. The abdominal exam is significant for mild splenomegaly. Scleral icterus is present and there is prominent generalized non-tender lymphadenopathy. Which of the following laboratory findings is best associated with this patient’s condition?
- A. Decreased serum ferritin
- B. Codocytes on peripheral blood smear
- C. Increased serum complement
- D. Degmacytes on peripheral blood smear
- E. Positive direct Coombs test (Correct Answer)
Explanation: ***Positive direct Coombs test*** - The patient's symptoms, including **fatigue**, **weight loss**, **bruising**, **splenomegaly**, **lymphadenopathy**, and prior **lymphocytosis**, are highly suggestive of **chronic lymphocytic leukemia (CLL)**. - CLL can be complicated by **autoimmune hemolytic anemia (AIHA)**, which is indicated by **scleral icterus** and rapid onset fatigue, and confirmed by a **positive direct Coombs test**. *Decreased serum ferritin* - **Decreased serum ferritin** is indicative of **iron deficiency anemia**. While anemia can cause fatigue, the presence of **scleral icterus** and prominent **lymphocytosis** suggests a hemolytic component rather than iron deficiency. - Furthermore, the clinical picture is more consistent with a lymphoproliferative disorder like CLL, which can cause anemia through AIHA or bone marrow infiltration, not primarily iron deficiency. *Codocytes on peripheral blood smear* - **Codocytes**, also known as **target cells**, are typically seen in conditions like **thalassemia**, **sickle cell anemia**, and **liver disease**, or after **splenectomy**. - While liver involvement could explain scleral icterus and bruising, it does not fully explain the severe **lymphocytosis** and **lymphadenopathy** seen in this patient. *Increased serum complement* - **Increased serum complement levels** are generally associated with **acute inflammatory processes** or specific infections. - In autoimmune hemolytic anemia, complement can be consumed, leading to **decreased** rather than increased levels, especially in cases mediated by complement-fixing antibodies. *Degmacytes on peripheral blood smear* - **Degmacytes**, or **bite cells**, are red blood cells from which a portion of the membrane has been removed by macrophages, typically seen in conditions like **G6PD deficiency** or when there is **oxidative stress**. - While hemolytic anemia can be part of this patient's presentation, **G6PD deficiency** does not typically cause **lymphadenopathy** or prior **lymphocytosis**, making it less likely than AIHA secondary to CLL.
Question 114: A 55-year-old man presents with severe fatigue and fever. His past medical history is significant for a recent history of mononucleosis from which he fully recovered 8 weeks ago. On physical examination, the patient seems pale. A chest radiograph shows multiple enlarged mediastinal lymph nodes. A biopsy of one of the enlarged mediastinal lymph nodes is performed and shows the presence of multinucleated cells with an 'owl-eye' appearance in a hypocellular background. Which of the following is the most likely diagnosis in this patient?
- A. Extranodal marginal zone lymphoma
- B. Classical Hodgkin lymphoma (Correct Answer)
- C. Diffuse large B cell lymphoma
- D. Nodular lymphocyte-predominant lymphoma
- E. Follicular lymphoma
Explanation: ***Classical Hodgkin lymphoma*** - The presence of **Reed-Sternberg cells** with their characteristic **'owl-eye' appearance** in a hypocellular background is pathognomonic for **Classical Hodgkin lymphoma**. - The patient's presentation with **fatigue**, **fever**, **pale appearance**, and **enlarged mediastinal lymph nodes** is highly suggestive of this diagnosis, particularly given the recent **mononucleosis**, which is associated with Epstein-Barr virus (EBV) and can precede Hodgkin lymphoma development. *Extranodal marginal zone lymphoma* - This lymphoma typically arises in **mucosa-associated lymphoid tissue (MALT)**, often in the stomach in association with *H. pylori* infection. - It is characterized by **small B cells** and **lymphoplasmacytic differentiation**, not Reed-Sternberg cells. *Diffuse large B cell lymphoma* - This is an **aggressive non-Hodgkin lymphoma** characterized by a proliferation of **large B cells**. - While it can present with B symptoms and lymphadenopathy, the presence of **Reed-Sternberg cells** on biopsy rules out DLBCL. *Nodular lymphocyte-predominant lymphoma* - This is a rare type of Hodgkin lymphoma characterized by **lymphocyte-predominant (LP) cells** (popcorn cells), which are different from the classic Reed-Sternberg cells. - It typically presents with **peripheral lymphadenopathy** and has a more indolent course than classical Hodgkin lymphoma. *Follicular lymphoma* - Follicular lymphoma is an **indolent non-Hodgkin lymphoma** characterized by a **follicular growth pattern** and composed of centrocytes and centroblasts. - It does not feature the **Reed-Sternberg cells** with an 'owl-eye' appearance.
Question 115: A 60-year-old woman presents to the dermatologist with a lesion on her lower eyelid. She noticed it a month ago and looked like a pimple. She says that it has been bleeding lately with minimal trauma which alarmed her. She says the lesion has not grown in size and is not associated with pain or pruritus. No significant past medical history. Physical examination reveals a 0.5 cm lesion that has a pearly appearance with telangiectasia and central ulceration and curled borders. The lesion is biopsied. Histopathology reveals peripheral palisading cells with large, hyperchromatic nuclei and a high nuclear: cytoplasmic ratio. Which of the following mechanisms best describes the most common mode of spread of this patient’s neoplasm?
- A. Hematogenous spread
- B. Lymphatic spread
- C. Local invasion via collagenase (Correct Answer)
- D. Does not spread (tumor is typically benign)
- E. Seeding
Explanation: ***Local invasion via collagenase*** - The patient's clinical presentation (pearly papule with telangiectasias, central ulceration, and rolled borders on the lower eyelid) and histological findings (peripheral **palisading cells** with large, hyperchromatic nuclei) are classic for **basal cell carcinoma (BCC)**. - **BCC** is known for its **slow growth** and tendency for local tissue destruction through **collagenase-mediated invasion**, rarely metastasizing. *Hematogenous spread* - **Hematogenous spread** is characteristic of many aggressive cancers, such as melanoma or renal cell carcinoma, which directly enter the bloodstream. - While possible in very rare, advanced cases of **BCC**, it is not the **most common** or typical mode of spread for this type of neoplasm. *Lymphatic spread* - **Lymphatic spread** is common for many carcinomas, like squamous cell carcinoma or breast cancer, where tumor cells invade lymphatic vessels and travel to regional lymph nodes. - **Basal cell carcinoma** rarely metastasizes via the lymphatic system; its primary mode of invasion is local. *Does not spread (tumor is typically benign)* - While **basal cell carcinoma** grows slowly and rarely metastasizes, it is a **malignant neoplasm** that can cause significant local tissue destruction if left untreated. - Referring to it as "typically benign" is incorrect, as its invasive growth pattern can lead to substantial morbidity. *Seeding* - **Seeding** (or transcoelomic spread) involves tumor cells detaching from the primary site and implanting onto a different surface within a body cavity (e.g., peritoneal carcinomatosis from ovarian cancer). - This mechanism is not applicable to **basal cell carcinoma**, which originates from the epidermis and primarily invades adjacent dermal and subcutaneous tissues.
Question 116: A 70-year-old man presents for a routine checkup. He says that he recently completely lost hearing in both ears and has been having occasional flare-ups of osteoarthritis in his hands and hips. Past medical history is significant for hypertension diagnosed 25 years ago that is well controlled. Family history is significant for his brother, who recently died from prostate cancer. The patient's blood pressure is 126/84 mm Hg. Laboratory findings are significant for an alkaline phosphatase level that is more than 3 times the upper limit. Right upper quadrant ultrasound and non-contrast computed tomography of the abdomen and pelvis reveal no significant abnormalities. Which of the following is the most likely complication of this patient’s condition?
- A. Pulmonary metastasis
- B. Hypoparathyroidism
- C. Cushing syndrome
- D. Osteosarcoma (Correct Answer)
- E. Osteoid osteoma
Explanation: ***Osteosarcoma*** * The patient's presentation with **complete hearing loss**, **high alkaline phosphatase** (ALP) without other organ involvement, and **osteoarthritis** in weight-bearing joints suggests **Paget's disease of bone**. * **Osteosarcoma** is a well-known, albeit rare, complication of long-standing Paget's disease, particularly in older patients, accounting for about 1% of cases where it undergoes sarcomatous degeneration. *Pulmonary metastasis* * While prostate cancer (family history) can lead to pulmonary metastases, there is no evidence of this in the patient's presentation or imaging, and the elevated **alkaline phosphatase** points to a bone turnover issue, not necessarily active malignancy with metastasis. * The high ALP in this context is likely bone-specific and not related to metastatic prostate cancer, as the patient's prostate cancer status is unknown and there are no signs of primary tumor. *Hypoparathyroidism* * **Hypoparathyroidism** is characterized by **low calcium** and **low parathyroid hormone (PTH)** levels, which are not suggested by the clinical picture or the elevated ALP; ALP elevation is typically inversely related to hypoparathyroidism. * Symptoms would include **tetany**, muscle cramps, and paresthesias, which are not present in this patient's history. *Cushing syndrome* * **Cushing syndrome** involves excessive **cortisol**, causing symptoms like central obesity, moon facies, and proximal muscle weakness, which are absent in this patient. * It does **not explain the hearing loss** or the isolated, markedly elevated alkaline phosphatase related to bone activity. *Osteoid osteoma* * **Osteoid osteoma** is a benign bone tumor typically presenting in younger individuals with localized pain that is relieved by NSAIDs. It does not cause widespread bone remodeling, hearing loss, or a markedly elevated alkaline phosphatase. * It is a **solitary lesion** and does not explain the systemic symptoms or the high ALP noted.
Question 117: A 34-year-old woman presents to her primary care physician for a routine check-up. She complains that she is not feeling her normal self, but has no specific complaints. After a routine examination, the physician orders a full thyroid workup, including TSH, T3, and free T4. He also refers her directly to an oncologist for an initial consultation. Which type of lymphadenopathy was most likely present during the physical examination that made the primary care physician react this way?
- A. Generalized painful lymphadenopathy
- B. Localized painful lymphadenopathy
- C. Reactive lymphadenitis
- D. Localized painless lymphadenopathy (Correct Answer)
- E. Generalized painless lymphadenopathy
Explanation: ***Localized painless lymphadenopathy*** - The physician's immediate referral to an oncologist suggests a high suspicion of **malignancy**, which is often indicated by **painless, localized lymphadenopathy**. - While the patient has diffuse, non-specific symptoms, the specific finding that led to an urgent oncology referral was likely a **firm, non-tender lymph node** in a particular region. *Generalized painful lymphadenopathy* - **Painful lymphadenopathy** typically indicates an **inflammatory** or **infectious process**, rather than a malignancy requiring immediate oncology consultation. - While generalized findings could prompt further investigation, sudden, **widespread pain** often points away from primary malignancy. *Localized painful lymphadenopathy* - **Localized pain** in a lymph node is usually a sign of **acute inflammation or infection** in the drainage area. - This presentation is less concerning for an urgent cancer diagnosis compared to a painless, firm node. *Reactive lymphadenitis* - **Reactive lymphadenitis** is characterized by enlarged, often **tender lymph nodes** in response to local infection or inflammation. - It would not typically prompt an immediate cancer referral unless there were other concerning features. *Generalized painless lymphadenopathy* - While certain malignancies can cause **generalized painless lymphadenopathy** (e.g., lymphomas), the question emphasizes a specific finding in the physical exam that prompted the rapid referral to an oncologist. - **Localized painless lymphadenopathy**, especially in areas like the supraclavicular or axillary regions, is often a more direct and concerning sign of malignancy.
Question 118: A 43-year-old man comes to the physician because of weight loss and swelling on the left side of his neck. Physical examination shows a firm, enlarged left upper cervical lymph node that is immobile. Immunohistochemical testing performed on a biopsy specimen from the lymph node stains positive for cytokeratin. Which of the following is the most likely site of the primary neoplasm in this patient?
- A. Nerve sheath
- B. Bone
- C. Muscle
- D. Skin
- E. Nasopharynx (Correct Answer)
Explanation: ***Nasopharynx*** - A **firm, enlarged, immobile cervical lymph node** in the upper neck (Level II) with **cytokeratin positivity** indicates metastatic carcinoma of epithelial origin. - **Nasopharyngeal carcinoma** classically presents with **cervical lymphadenopathy as the initial manifestation** in up to 90% of cases, often before other symptoms develop. - The **left upper cervical location** is characteristic of nasopharyngeal primary tumors, which have a strong predilection for Level II nodal metastasis. - **Weight loss** suggests systemic disease consistent with advanced carcinoma. - Nasopharyngeal carcinoma is **cytokeratin-positive** (epithelial origin) and frequently presents with isolated neck mass **without nasal symptoms** in early stages. *Skin* - While cutaneous squamous cell carcinoma can metastasize to cervical nodes, it would require a **visible primary skin lesion** on the head, neck, or scalp, which would be evident on physical examination. - Skin primaries more commonly metastasize to **posterior cervical nodes (Level V)** from scalp lesions, not upper anterior cervical nodes. - This presentation is **far less common** than mucosal head and neck primaries for isolated cervical metastasis. *Nerve sheath* - Nerve sheath tumors such as **schwannomas** or **neurofibromas** are of mesenchymal origin and stain positive for **S-100 protein**, not cytokeratin. - These tumors are typically **benign and mobile**, not firm and immobile like metastatic carcinoma. *Bone* - Primary bone tumors (e.g., osteosarcoma) do not express **cytokeratin** and would not present with isolated cervical lymphadenopathy. - Bone tumors would show characteristic imaging findings and typically metastasize to lungs, not regional lymph nodes. *Muscle* - Muscle-derived tumors such as **rhabdomyosarcoma** or **leiomyosarcoma** are mesenchymal in origin. - These tumors stain positive for **desmin** and **actin**, not cytokeratin, which is specific to epithelial cells.
Question 119: A 13-year-old boy is brought to the physician because of a 4-month history of worsening dizziness, nausea, and feeling clumsy. An MRI of the brain shows a well-demarcated, 4-cm cystic mass in the posterior fossa. The patient undergoes complete surgical resection of the mass. Pathologic examination of the surgical specimen shows parallel bundles of cells with eosinophilic, corkscrew-like processes. Which of the following is the most likely diagnosis?
- A. Pinealoma
- B. Medulloblastoma
- C. Pilocytic astrocytoma (Correct Answer)
- D. Craniopharyngioma
- E. Ependymoma
Explanation: **Pilocytic astrocytoma** - The clinical presentation of **posterior fossa symptoms** (dizziness, nausea, clumsiness) in a child, coupled with an **MRI showing a cystic mass**, is highly suggestive of pilocytic astrocytoma. - Histologically, this tumor is characterized by **Rosenthal fibers** (eosinophilic, corkscrew-like processes) and **bipolar cells arranged in parallel bundles**. *Pinealoma* - Pinealomas typically present with symptoms related to compression of the **aqueduct of Sylvius** (hydrocephalus) or the **superior colliculus** (Parinaud's syndrome), such as impaired upward gaze. - They are located in the **pineal region**, not the posterior fossa, and their histology is distinct from the described features. *Medulloblastoma* - Medulloblastomas are common **posterior fossa tumors** in children, often presenting with similar symptoms. - However, they are typically **solid, poorly demarcated** masses on imaging, and their histology reveals **small, round blue cells** with **Homer-Wright rosettes**, not Rosenthal fibers. *Craniopharyngioma* - Craniopharyngiomas are typically located in the **suprasellar region**, causing symptoms like **visual field defects** (bitemporal hemianopsia) and **endocrine dysfunction**. - While they can be cystic, their location and characteristic histology (e.g., **wet keratin**, calcifications) differentiate them from the given case. *Ependymoma* - Ependymomas commonly arise from the **ventricular system**, especially the **fourth ventricle** in children, and can cause hydrocephalus and posterior fossa symptoms. - Histologically, they are characterized by **perivascular pseudorosettes** and true rosettes, lacking the described corkscrew-like processes.
Question 120: A 58-year-old woman with HIV infection is brought to the emergency department because of a 2-week history of headaches, blurred vision, and confusion. Her current medications include antiretroviral therapy and trimethoprim-sulfamethoxazole. Neurological examination shows ataxia and memory impairment. Her CD4+ T-lymphocyte count is 90/μL. Cerebrospinal fluid analysis shows lymphocytic predominant pleocytosis, and PCR is positive for Epstein-Barr virus DNA. An MRI of the brain with contrast shows a solitary, weakly ring-enhancing lesion with well-defined borders involving the corpus callosum. Which of the following is the most likely diagnosis?
- A. Glioblastoma multiforme
- B. Cerebral toxoplasmosis
- C. Primary cerebral lymphoma (Correct Answer)
- D. Progressive multifocal leukoencephalopathy
- E. AIDS dementia
Explanation: ***Primary cerebral lymphoma*** - The combination of **HIV infection** with a very low **CD4 count (<100/μL)**, **weakly ring-enhancing solitary lesion** in the corpus callosum, Epstein-Barr virus (EBV) DNA in CSF, and typical neurological symptoms points strongly to **primary cerebral lymphoma (PCL)**. - PCL is a common **AIDS-defining illness** and is highly associated with **EBV infection** in immunocompromised individuals. *Glioblastoma multiforme* - While GBM is a primary brain tumor, it typically presents with a **strongly and irregularly enhancing lesion**, often with a **necrotic center**, rather than a solitary, weakly enhancing lesion. - GBM is not directly associated with **HIV infection** or **EBV DNA in CSF**, which are key features in this case. *Cerebral toxoplasmosis* - Cerebral toxoplasmosis typically presents with **multiple ring-enhancing lesions**, often in the **basal ganglia**, rather than a solitary lesion as described. - Diagnosis is usually confirmed by **serology for *Toxoplasma gondii*** and a positive response to empiric anti-toxoplasma therapy, not EBV DNA in CSF. *Progressive multifocal leukoencephalopathy* - PML is characterized by **non-enhancing white matter lesions** on MRI, rather than a ring-enhancing lesion. - It is caused by the **JC virus**, not EBV, and typically presents with **rapidly progressive neurological deficits** without mass effect. *AIDS dementia* - AIDS dementia complex (now HIV-associated neurocognitive disorder) presents as **diffuse cerebral atrophy** and **white matter changes** on MRI, without focal or ring-enhancing lesions. - It is a diagnosis of exclusion in HIV patients with cognitive decline, and the presence of a focal lesion with mass effect points to another etiology.
Question 121: An obese 63-year-old man comes to the physician because of 3 episodes of red urine over the past week. He has also had recurrent headaches and intermittent blurry vision during the past month. He has benign prostatic hyperplasia. He works as an attendant at a gas station. The patient has smoked one pack of cigarettes daily for the last 40 years. He does not drink alcohol. Current medications include tamsulosin. His temperature is 37.4°C (99.4°F), pulse is 90/min, and blood pressure is 152/95 mm Hg. Examination shows a flushed face. Cardiopulmonary examination shows no abnormalities. The abdomen is soft and non-tender. Digital rectal examination shows an enlarged prostate with no nodules. Urinalysis shows: Blood 3+ Glucose negative Protein negative WBC 1-2/hpf RBC 40-45/hpf RBC casts none Which of the following is the most likely diagnosis?
- A. Nephrolithiasis
- B. Renal cell carcinoma (Correct Answer)
- C. Transitional cell bladder carcinoma
- D. IgA nephropathy
- E. Renal oncocytoma
Explanation: ***Correct: Renal cell carcinoma*** - This patient presents with **painless gross hematuria**, a common initial symptom of renal cell carcinoma, especially concerning in a long-term **smoker** with hypertension. - The constellation of **headaches, blurry vision, and flushed face** could indicate paraneoplastic syndromes associated with RCC, such as **erythrocytosis (polycythemia)** causing facial flushing and hyperviscosity symptoms, or **hypertension due to renin secretion** by the tumor. - RCC is strongly associated with **smoking** (major risk factor) and **obesity**. *Incorrect: Nephrolithiasis* - While nephrolithiasis can cause hematuria, it is typically associated with **severe, colicky flank pain** radiating to the groin, which is absent in this patient. - The patient's other symptoms like headaches, blurry vision, and flushed face are not characteristic of nephrolithiasis. *Incorrect: Transitional cell bladder carcinoma* - Bladder cancer often presents with **painless gross hematuria**, similar to RCC. - However, the additional symptoms of **headaches, blurry vision, flushed face, and hypertension in a long-term smoker** point more strongly towards a renal mass with **paraneoplastic effects** (polycythemia, renin secretion) rather than solely bladder involvement. - Urothelial carcinoma is also associated with smoking but does not typically cause these systemic paraneoplastic manifestations. *Incorrect: IgA nephropathy* - IgA nephropathy is characterized by recurrent episodes of **gross hematuria**, often following an upper respiratory or gastrointestinal infection (synpharyngitic hematuria). - Urinalysis would typically show **dysmorphic RBCs and RBC casts** (indicating glomerular bleeding), which are **absent** here. - The non-glomerular hematuria pattern (no casts, no proteinuria) argues against this diagnosis. *Incorrect: Renal oncocytoma* - Renal oncocytomas are **benign renal tumors** that are often asymptomatic and discovered incidentally on imaging. - While they can cause hematuria, they are **rarely associated with systemic symptoms** like headaches, blurry vision, hypertension, or flushed face. - Unlike RCC, oncocytomas do **not produce paraneoplastic syndromes** (no erythropoietin or renin secretion).
Question 122: A 40-year-old male presents to his primary care physician for a regularly scheduled check-up. Physical examination reveals nontender cervical lymphadenopathy. A biopsy of the lymph node reveals aggregates of follicular architecture, and cytogenic analysis shows a t(14;18) translocation. The protein most likely responsible for the patient’s condition does which of the following:
- A. Regulates passage through the cell cycle
- B. Activates DNA repair proteins
- C. Regulates cell growth through signal transduction
- D. Inhibits apoptosis (Correct Answer)
- E. Provides mitotic cytoskeleton
Explanation: ***Inhibits apoptosis*** - The t(14;18) translocation is characteristic of **follicular lymphoma** and leads to the overexpression of the **BCL-2 protein**. - **BCL-2** is an anti-apoptotic protein that prevents programmed cell death, allowing abnormal cells to accumulate. *Regulates passage through the cell cycle* - Proteins involved in **cell cycle regulation** (e.g., p53, Rb) control progression through different phases, but BCL-2's primary role is in cell survival, not direct cell cycle progression. - Dysregulation of cell cycle proteins is seen in many cancers, but the specific BCL-2 translocation primarily affects apoptosis. *Activates DNA repair proteins* - **DNA repair proteins** (e.g., ATM, BRCA1/2) are crucial for maintaining genomic integrity and correcting DNA damage. - While important in cancer development, their activation is not the direct function of the BCL-2 protein overexpressed due to the t(14;18) translocation. *Regulates cell growth through signal transduction* - **Signal transduction pathways** often involve growth factors and their receptors (e.g., RTKs) that regulate cell proliferation and differentiation. - While BCL-2 indirectly impacts cell numbers by preventing apoptosis, its direct role is not in initiating or participating in growth-promoting signal transduction cascades. *Provides mitotic cytoskeleton* - The **mitotic cytoskeleton**, composed of microtubules, is essential for chromosome segregation during cell division. - Proteins like tubulin are the primary components, and BCL-2 has no direct role in forming or organizing these structures.
Question 123: A 67-year-old man presents to the emergency department with altered mental status. The patient is non-verbal at baseline, but his caretakers at the nursing home noticed he was particularly somnolent recently. The patient has a past medical history of diabetes and Alzheimer dementia. His temperature is 99.7°F (37.6°C), blood pressure is 157/98 mmHg, pulse is 150/min, respirations are 16/min, and oxygen saturation is 98% on room air. Laboratory values are obtained and shown below. Hemoglobin: 9 g/dL Hematocrit: 33% Leukocyte count: 8,500/mm^3 with normal differential Platelet count: 197,000/mm^3 Serum: Na+: 139 mEq/L Cl-: 102 mEq/L K+: 4.3 mEq/L HCO3-: 25 mEq/L BUN: 37 mg/dL Glucose: 99 mg/dL Creatinine: 2.4 mg/dL Ca2+: 12.2 mg/dL The patient has lost 20 pounds over the past month. His parathyroid hormone is within normal limits, and his urinary calcium is increased. Physical exam demonstrates discomfort when the patient's lower back and extremities are palpated. Which of the following is the most accurate diagnostic test for this patient's underlying diagnosis?
- A. Peripheral blood smear
- B. Urine protein levels
- C. Bone marrow biopsy (Correct Answer)
- D. Radiograph of the lumbar spine
- E. Urine, blood, and cerebrospinal fluid cultures
Explanation: **Bone marrow biopsy** - The patient presents with **hypercalcemia**, **elevated creatinine** (acute kidney injury), **anemia**, **weight loss**, and bony pain, which are classic features of **multiple myeloma**; a bone marrow biopsy is crucial for diagnosis and staging by identifying plasma cell infiltration. - Identification of > **10% clonal plasma cells** in the bone marrow confirms the diagnosis of multiple myeloma in patients with myeloma-defining events (e.g., hypercalcemia, renal failure, anemia, bone lesions). *Peripheral blood smear* - While a peripheral blood smear might show **rouleaux formation** in multiple myeloma due to increased plasma proteins, it is not specific or diagnostic as rouleaux can be seen in other conditions like inflammation. - It does not quantify the percentage of **clonal plasma cells**, which is essential for diagnosing multiple myeloma. *Urine protein levels* - **Urine protein electrophoresis (UPEP)** and **immunofixation** are important for detecting Bence-Jones proteinuria (clonal free light chains) which supports the diagnosis of multiple myeloma, but quantifying general urine protein levels (e.g., with a 24-hour collection) is not as specific or diagnostic. - While **elevated urine protein** is expected in multiple myeloma due to light chain excretion, it doesn't provide definitive evidence of plasma cell dyscrasia or bone marrow involvement. *Radiograph of the lumbar spine* - **Skeletal surveys** (including radiographs) are used to identify **lytic bone lesions** characteristic of multiple myeloma, which contribute to pain and hypercalcemia. - Although important for identifying bone involvement, radiographs are not the most accurate diagnostic test for the underlying disease itself, as they do not directly evaluate the presence of **clonal plasma cells**. *Urine, blood, and cerebrospinal fluid cultures* - These cultures are primarily used to diagnose **infections**, which can cause altered mental status and fever. - While infection is a consideration, the constellation of hypercalcemia, renal failure, anemia, and bone pain points strongly toward multiple myeloma, making cultures less likely to reveal the primary underlying diagnosis.
Question 124: A 1-year-old boy is brought to the physician for the evaluation of swelling around the eyelids. He was born at term after an uncomplicated pregnancy. He is at the 95th percentile for weight and 60th percentile for length. His blood pressure is 130/86 mm Hg. Physical examination shows an empty scrotal sac and a left-sided abdominal mass. Ophthalmologic examination shows no abnormalities. Urinalysis shows a proteinuria of 3+ and fatty casts. Abdominal ultrasound shows a hypervascular mass at the upper pole of the kidney. Which of the following best describes the pathogenesis of this patient's disease?
- A. Inhibition of hypoxia-inducible factor 1α
- B. Increased expression of insulin-like growth factor 2
- C. Deficiency of 17α-hydroxylase
- D. Loss of function of zinc finger transcription factor
- E. Deletion of the WT1 gene on chromosome 11 (Correct Answer)
Explanation: ***Deletion of the WT1 gene on chromosome 11*** - This patient presents with the classic features of **Denys-Drash syndrome**: **gonadal dysgenesis** (**empty scrotal sac**), **renal disease** (**nephrotic syndrome** with proteinuria and fatty casts, hypertension), and **Wilms tumor**. - **Denys-Drash syndrome** is caused by a **germline mutation** (often deletion) in the **WT1 tumor suppressor gene** located on **chromosome 11p13**. The WT1 gene encodes a zinc finger transcription factor critical for genitourinary development. *Inhibition of hypoxia-inducible factor 1α* - This is linked to some rare forms of **renal cell carcinoma**, particularly those associated with **VHL disease**, but not directly to **Wilms tumor** or the specific constellation of symptoms seen here. - **HIF-1α** typically promotes angiogenesis and cell survival under hypoxic conditions, and its inhibition would generally not lead to tumor formation in this context. *Increased expression of insulin-like growth factor 2* - **IGF-2 overexpression** is associated with **Beckwith-Wiedemann syndrome**, which also involves an increased risk of **Wilms tumor**, as well as other features like **macroglossia** and **hemihypertrophy**. - While both conditions are linked to Wilms tumor and chromosome 11, the presence of **gonadal dysgenesis** and significant **renal disease** (nephrotic syndrome) strongly points to **Denys-Drash syndrome** rather than Beckwith-Wiedemann, which is a separate pathogenetic mechanism (often involving epigenetic changes in the 11p15.5 region). *Deficiency of 17α-hydroxylase* - This enzyme deficiency leads to **congenital adrenal hyperplasia** with features like **hypertension** and **gonadal dysgenesis** (due to impaired sex steroid synthesis) but *does not* cause **renal tumors** or **nephrotic syndrome**. - The elevated blood pressure in 17α-hydroxylase deficiency is due to accumulation of mineralocorticoid precursors, distinct from the renal pathology here. *Loss of function of zinc finger transcription factor* - While the **WT1 gene** does encode a **zinc finger transcription factor**, this answer is too vague and non-specific. Multiple genes encode zinc finger transcription factors involved in various developmental and disease processes. - The **correct and specific answer** is the **deletion of the WT1 gene on chromosome 11**, which precisely identifies the pathogenetic mechanism of Denys-Drash syndrome rather than using a generic functional description.
Question 125: A 6-year-old boy is brought to the physician by his parents because of right lower extremity weakness, worsening headaches, abdominal pain, dark urine, and a 5-kg (11-lb) weight loss for the past 2 months. His teachers report that he has not been paying attention in class and his grades have been worsening. He has a history of infantile seizures. Physical examination shows a palpable abdominal mass and left costovertebral angle tenderness. Neurological exam shows decreased strength of the right lower limb. He has several acne-like angiofibromas around the nose and cheeks. Further evaluation is most likely to show which of the following?
- A. Subependymal giant cell astrocytoma
- B. Vestibular schwannoma
- C. Pheochromocytoma
- D. Lisch nodules
- E. Renal angiomyolipomas (Correct Answer)
Explanation: ***Renal angiomyolipomas*** - The patient's presentation of **infantile seizures**, **facial angiofibromas (adenoma sebaceum)**, and multiple organ system involvement strongly indicates **tuberous sclerosis complex (TSC)**. - The **palpable abdominal mass**, **costovertebral angle tenderness**, and **dark urine (hematuria)** are key findings pointing to renal pathology. - **Renal angiomyolipomas** occur in approximately **80% of TSC patients** and are the most common renal manifestation of the disease. - These benign tumors contain blood vessels, smooth muscle, and fat, and can cause flank pain, hematuria, and palpable masses, all present in this patient. - Given the prominent renal symptoms, further evaluation with imaging (CT or ultrasound) would most likely reveal renal angiomyolipomas. *Subependymal giant cell astrocytoma* - While **subependymal giant cell astrocytomas (SEGAs)** are indeed associated with TSC and could explain the neurological symptoms (headaches, weakness), they occur in only **10-20% of TSC patients**. - The question asks what further evaluation is **most likely** to show - the prominent renal findings (palpable mass, CVA tenderness, hematuria) make renal imaging the most likely next step, which would reveal angiomyolipomas. - SEGAs are a valid TSC manifestation but less likely than renal angiomyolipomas given the clinical presentation emphasizing renal symptoms. *Vestibular schwannoma* - **Vestibular schwannomas** are associated with **Neurofibromatosis type 2 (NF2)**, not tuberous sclerosis. - These tumors typically present with hearing loss, tinnitus, and balance problems, none of which are described in this patient. - The facial angiofibromas and infantile seizures clearly point to TSC, not NF2. *Lisch nodules* - **Lisch nodules** are iris hamartomas pathognomonic for **Neurofibromatosis type 1 (NF1)**. - NF1 presents with café-au-lait spots, neurofibromas, and optic gliomas, not facial angiofibromas or the pattern seen here. - This patient's constellation of findings is diagnostic of TSC, not NF1. *Pheochromocytoma* - **Pheochromocytomas** cause episodic hypertension, palpitations, headaches, and sweating due to catecholamine excess. - While associated with genetic syndromes (MEN2, NF1, VHL), they are not a typical feature of tuberous sclerosis. - The patient's symptoms and physical findings do not suggest pheochromocytoma, and there is no mention of hypertensive episodes or associated symptoms.
Question 126: An 11-month-old boy presents with a scaly erythematous rash on his back for the past 2 days. No significant past medical history. Family history is significant for the fact that the patient’s parents are first-degree cousins. In addition, his older sibling had similar symptoms and was diagnosed with a rare unknown skin disorder. On physical examination, whitish granulomatous plaques are present in the oral mucosa, which exhibit a tendency to ulcerate, as well as a scaly erythematous rash on his back. A complete blood count reveals that the patient is anemic. A plain radiograph of the skull shows lytic bone lesions. Which of the following immunohistochemical markers, if positive, would confirm the diagnosis in this patient?
- A. CD30
- B. CD1a (Correct Answer)
- C. CD15
- D. CD21
- E. CD40L
Explanation: ***CD1a*** - The constellation of **scaly erythematous rash**, **oral granulomatous plaques**, **lytic bone lesions**, and **anemia** in an infant, especially with a history of **consanguinity** and an affected sibling, strongly suggests **Langerhans cell histiocytosis (LCH)**. - **CD1a** is a classic and definitive **immunohistochemical marker** for Langerhans cells, which are the neoplastic cells in LCH. *CD30* - **CD30** is typically associated with **anaplastic large cell lymphoma** and **Hodgkin lymphoma**, and is not a marker for Langerhans cell histiocytosis. - While some skin lesions can be present in these lymphomas, the overall clinical picture, particularly the lytic bone lesions and oral plaques, is inconsistent with CD30-positive lymphomas. *CD15* - **CD15** is primarily a marker for **neutrophils** and is also expressed in **Reed-Sternberg cells** of Hodgkin lymphoma. - It does not characterize Langerhans cells and would not confirm the diagnosis of Langerhans cell histiocytosis. *CD21* - **CD21** is a marker for **B-lymphocytes**, follicular dendritic cells, and some epithelial cells, involved in complement receptor function. - It is not expressed on Langerhans cells and is not relevant to the diagnosis of Langerhans cell histiocytosis. *CD40L (CD154)* - **CD40L (CD154)** is a **T-cell surface protein** crucial for T-cell help to B cells and macrophage activation. Its deficiency causes **X-linked hyper-IgM syndrome**. - It is not a marker used for the direct diagnosis of Langerhans cell histiocytosis.
Question 127: A 32-year-old man visits his family physician for 10 months of persistent left flank pain, weight loss, and fatigue. Also, he has had hematuria a couple of times in the last month. His mother was diagnosed and treated for a pheochromocytoma when she was 36 years old, and his father died at 45 years due to myocardial infarction. His personal medical history is not relevant. He does not smoke and used to be a varsity athlete in high school and university. Physical examination shows temporal wasting, pale mucous membranes and palms, a palpable mass in the left flank, and a varicocele that does not reduce upon recumbency. His family physician sends the patient to the emergency department for an abdominal computed tomography (CT) scan, which shows a complex left renal mass and a hemangioblastoma in T10. A biopsy of the renal mass is ordered by the oncology team, which demonstrates compact cells with prominent nucleoli, eosinophilic cytoplasm within a network of a small and thin-walled vasculature. What is the most likely type of tumor in this patient?
- A. Collecting duct carcinoma
- B. Clear-cell carcinoma (Correct Answer)
- C. Oncocytic carcinoma
- D. Papillary carcinoma
- E. Chromophobe carcinoma
Explanation: ***Clear-cell carcinoma*** - This patient's presentation with a **renal mass**, hemangioblastoma, a family history of **pheochromocytoma** (his mother), and an early death of his father (likely from heart disease associated with pheochromocytoma) is highly suggestive of **Von Hippel-Lindau (VHL) syndrome**. **Clear cell renal cell carcinoma** is the most common renal tumor associated with VHL syndrome. - The biopsy description of **compact cells with prominent nucleoli**, **eosinophilic cytoplasm**, and a **network of small and thin-walled vasculature** is characteristic of clear cell renal cell carcinoma. *Collecting duct carcinoma* - This is a rare and aggressive subtype of **renal cell carcinoma** that typically presents with a mass in the renal medulla, often with central necrosis. - Its histological features involve atypical cells arranged in **tubules or ducts**, which does not match the description of compact cells with eosinophilic cytoplasm. *Oncocytic carcinoma* - **Oncocytic carcinoma** is a rare and generally benign tumor. It is characterized histologically by cells with abundant, granular eosinophilic cytoplasm. - While it has eosinophilic cytoplasm, it lacks the prominent nucleoli and compact cell arrangement seen in the biopsy, and it is not typically associated with VHL syndrome. *Papillary carcinoma* - **Papillary carcinoma** is characterized by cells arranged in papillary formations or tubular structures. It is generally associated with different genetic syndromes (e.g., hereditary papillary renal carcinoma). - The histological description provided, particularly the "compact cells" and vasculature, does not fit the typical papillary architecture. *Chromophobe carcinoma* - **Chromophobe carcinoma** is characterized by large cells with distinct cell borders and pale, flocculent cytoplasm. It typically has a good prognosis. - This type of carcinoma is generally not associated with VHL syndrome and its histological features do not align with the biopsy description of compact cells with eosinophilic cytoplasm and prominent nucleoli.
Question 128: A 72-year-old male visits his gastroenterologist for a check-up one year following resection of a 2-cm malignant lesion in his sigmoid colon. Serum levels of which of the following can be used in this patient to test for cancer recurrence?
- A. Gamma glutamyl transferase
- B. Cancer antigen 125 (CA-125)
- C. Alpha-fetoprotein
- D. Carcinoembryonic antigen (Correct Answer)
- E. CA-19-9 tumor marker
Explanation: ***Carcinoembryonic antigen*** - **Carcinoembryonic antigen (CEA)** is the most widely used **tumor marker** for monitoring **colorectal cancer recurrence** after surgical resection. - Elevated or rising levels of CEA in a patient previously treated for colorectal cancer suggest a high probability of **disease recurrence** or metastasis. *Gamma glutamyl transferase* - **Gamma glutamyl transferase (GGT)** is an enzyme primarily found in the liver and kidneys, and its elevation is typically indicative of **hepatobiliary disease** or **alcohol abuse**. - It is not a specific marker for colorectal cancer and would not be used to monitor for recurrence. *Cancer antigen 125 (CA-125)* - **CA-125** is a tumor marker primarily associated with **ovarian cancer** and is used for monitoring its progression and recurrence. - It does not have a role in the surveillance of colorectal cancer. *Alpha-fetoprotein* - **Alpha-fetoprotein (AFP)** is a primary tumor marker for **hepatocellular carcinoma** (liver cancer) and **germ cell tumors**. - It is not used for monitoring colorectal cancer recurrence. *CA-19-9 tumor marker* - **CA-19-9** is primarily associated with **pancreatic cancer** and can also be elevated in some gastrointestinal cancers, but it is not the preferred marker for colorectal cancer surveillance. - **CEA** is the standard and most reliable marker for **colorectal cancer recurrence**.
Question 129: A 15-year-old girl comes to the physician because of a sore throat and subjective fevers for the past 2 weeks. She has been feeling lethargic and is unable to attend school. She has a history of multiple episodes of streptococcal pharyngitis treated with amoxicillin. She immigrated with her family to the United States from China 10 years ago. She appears thin. Her temperature is 37.8°C (100°F), pulse is 97/min, and blood pressure is 90/60 mm Hg. Examination shows pharyngeal erythema and enlarged tonsils with exudates and palatal petechiae. There is cervical lymphadenopathy. The spleen is palpated 2 cm below the left costal margin. Her hemoglobin concentration is 12 g/dL, leukocyte count is 14,100/mm3 with 54% lymphocytes (12% atypical lymphocytes), and platelet count is 280,000/mm3. A heterophile agglutination test is positive. The underlying cause of this patient's symptoms is most likely to increase the risk of which of the following conditions?
- A. Kaposi sarcoma
- B. Glomerulonephritis
- C. Pneumonia
- D. Nasopharyngeal carcinoma (Correct Answer)
- E. Necrotizing retinitis
Explanation: ***Nasopharyngeal carcinoma*** - The patient's symptoms (sore throat, fatigue, pharyngeal erythema, enlarged tonsils with exudates, palatal petechiae, cervical lymphadenopathy, splenomegaly, atypical lymphocytosis, and positive heterophile agglutination test) are classic for **infectious mononucleosis**, caused by the **Epstein-Barr virus (EBV)**. - EBV infection is a significant risk factor for developing **nasopharyngeal carcinoma**, especially in individuals of Chinese descent, making this the most likely long-term complication. *Kaposi sarcoma* - **Kaposi sarcoma** is associated with **human herpesvirus 8 (HHV-8)**, not EBV. - It is typically seen in immunocompromised individuals, such as those with HIV/AIDS, or in specific endemic regions. *Glomerulonephritis* - **Glomerulonephritis** can be a complication of **Streptococcus pyogenes infections** (post-streptococcal glomerulonephritis) or other autoimmune diseases, but it is not directly linked to EBV infection. - The patient's history of streptococcal pharyngitis is relevant for this, but her current presentation points to EBV. *Pneumonia* - While pneumonia can occur as a secondary complication in severely ill patients with infectious mononucleosis, it is not a direct long-term increased risk associated with the underlying EBV infection itself. - EBV primarily affects lymphoid tissues. *Necrotizing retinitis* - **Necrotizing retinitis** is most commonly associated with **cytomegalovirus (CMV)** infection, particularly in immunocompromised patients (e.g., HIV/AIDS). - It is not a typical complication or long-term risk of EBV infection.
Question 130: A 9-year-old boy is brought to the physician for evaluation of 2 months of progressive clumsiness, falls, and increased urinary frequency. Physical examination shows bilateral temporal visual field loss. An MRI of the head shows a small calcified suprasellar mass. The patient undergoes surgery with complete removal of the mass. Pathological examination of the specimen shows a lobular tumor composed of cysts filled with oily, brownish-yellow fluid. This mass is most likely derived from which of the following structures?
- A. Arachnoid cells
- B. Ventricular ependyma
- C. Lactotroph cells
- D. Rathke pouch (Correct Answer)
- E. Astroglial cells
Explanation: ***Rathke pouch*** - The combination of **suprasellar mass**, visual field deficits (bitemporal hemianopsia due to optic chiasm compression), **calcification**, and cystic components filled with **oily, brownish-yellow fluid** in a child points strongly to a **craniopharyngioma**. - **Craniopharyngiomas** are benign tumors derived from remnants of **Rathke's pouch**, which is an embryonic evagination of the stomodeum that gives rise to the anterior pituitary. *Arachnoid cells* - Tumors arising from **arachnoid cells** are typically **meningiomas**, which are more common in adults and usually present as dural-based masses, often without significant cystic components. - While meningiomas can calcify, their characteristic histology (whorled patterns, psammoma bodies) and typical presentation differ from craniopharyngiomas. *Ventricular ependyma* - Tumors derived from **ependyma** are **ependymomas**, which typically arise within the ventricles of the brain or spinal cord. - They are less common in the suprasellar region and their characteristic cystic or fluid content is usually not described as oily and brownish-yellow. *Lactotroph cells* - **Lactotroph cells** are found in the **anterior pituitary gland**, and tumors arising from them are **prolactinomas**. - While prolactinomas can present with visual field defects due to suprasellar extension, they are typically solid pituitary adenomas, rarely calcified, and do not contain oily, brownish-yellow fluid. *Astroglial cells* - Tumors originating from **astroglial cells** include **astrocytomas** and **glioblastomas**, which are highly variable in presentation but are typically solid or have pseudocystic areas, not an oily, brownish-yellow fluid-filled cyst. - While some astrocytomas can calcify, their microscopic appearance and characteristic fluid content are different from what is described.
Question 131: A previously healthy 75-year-old woman comes to the physician because of fatigue and decreasing exercise tolerance over the past 6 weeks. She also has intermittent episodes of dizziness. She has never smoked and does not drink alcohol. She takes a daily multivitamin. She appears pale. Physical examination shows a smooth liver that is palpable 1 cm below the costal margin. The spleen is not palpable. Laboratory studies show: Hemoglobin 9.8 g/dL MCV 104 fL Reticulocyte count 0.2 % Folate 21 ng/mL (N = 2–20) Vitamin B12 789 pg/mL (N = 200–900) A peripheral blood smear shows anisocytosis and bone marrow aspirate shows ringed sideroblasts. This patient is most likely to develop which of the following?
- A. Hairy cell leukemia
- B. Chronic lymphocytic leukemia
- C. Burkitt lymphoma
- D. Acute myelocytic leukemia (Correct Answer)
- E. Sézary syndrome
Explanation: ***Acute myelocytic leukemia*** - The presence of **fatigue**, **anemia** (Hb 9.8 g/dL), **macrocytosis** (MCV 104 fL), **low reticulocyte count** (0.2%), and specifically **ringed sideroblasts** in the bone marrow aspirate points to a myelodysplastic syndrome (MDS) with ringed sideroblasts. - A significant portion of patients with **myelodysplastic syndromes** (MDS), especially those with ringed sideroblasts, are at an elevated risk of transforming to **acute myelocytic leukemia (AML)**, making this the most likely future complication. *Hairy cell leukemia* - This typically presents with **splenomegaly**, **pancytopenia**, and characteristic **'hairy' lymphocytes** on peripheral smear, none of which are described here. - The patient's presentation with **ringed sideroblasts** is not a feature of hairy cell leukemia. *Chronic lymphocytic leukemia* - Characterized by **lymphocytosis** (>5000 clonal B lymphocytes/µL), often with **lymphadenopathy** and **splenomegaly**, and typically presenting in older adults. - The current findings of **macrocytic anemia** and **ringed sideroblasts** do not align with the typical features of CLL. *Burkitt lymphoma* - This is an aggressive B-cell lymphoma often associated with specific **translocations (e.g., t(8;14))** and rapidly growing tumors, especially in endemic regions. - The patient's signs of **anemia** and **ringed sideroblasts** are not suggestive of Burkitt lymphoma. *Sézary syndrome* - This is a **leukemic variant of cutaneous T-cell lymphoma**, characterized by generalized erythroderma, lymphadenopathy, and circulating malignant T-cells (Sézary cells). - The patient's anemic presentation and **ringed sideroblasts** are not consistent with Sézary syndrome.
Question 132: A 52-year-old man is brought to the emergency department because of headaches, vertigo, and changes to his personality for the past few weeks. He was diagnosed with HIV 14 years ago and was started on antiretroviral therapy at that time. Medical records from one month ago indicate that he followed his medication schedule inconsistently. Since then, he has been regularly taking his antiretroviral medications and trimethoprim-sulfamethoxazole. His vital signs are within normal limits. Neurological examination shows ataxia and apathy. Mini-Mental State Examination score is 15/30. Laboratory studies show: Hemoglobin 12.5 g/dL Leukocyte count 8400/mm3 Segmented neutrophils 80% Eosinophils 1% Lymphocytes 17% Monocytes 2% CD4+ T-lymphocytes 90/μL Platelet count 328,000/mm3 An MRI of the brain with contrast shows a solitary ring-enhancing lesion involving the corpus callosum and measuring 4.5 cm in diameter. A lumbar puncture with subsequent cerebrospinal fluid analysis shows slight pleocytosis, and PCR is positive for Epstein-Barr virus DNA. Which of the following is the most likely diagnosis?
- A. CNS lymphoma (Correct Answer)
- B. AIDS dementia
- C. Glioblastoma
- D. Bacterial brain abscess
- E. Progressive multifocal leukoencephalopathy
Explanation: ***CNS lymphoma*** - The patient's **immunosuppressed state (CD4 count 90/µL)** and the **solitary ring-enhancing lesion in the corpus callosum** are highly suggestive of CNS lymphoma. - The **positive Epstein-Barr virus (EBV) DNA in CSF** is a strong indicator, as primary CNS lymphoma in HIV-positive patients is often associated with EBV infection. *AIDS dementia* - Characterized by **widespread cortical atrophy** and demyelination rather than a solitary, well-defined mass. - While associated with cognitive decline, it doesn't typically present with a **mass lesion** or **EBV DNA in CSF**. *Glioblastoma* - More commonly presents as an **irregularly enhancing mass** in immunocompetent individuals and is less common in HIV patients with low CD4 counts. - **EBV DNA in CSF** is not a feature of glioblastoma. *Bacterial brain abscess* - Usually presents with **fever, seizures, and focal neurological deficits**, and often multiple lesions. - There is no mention of fever or a clear source of bacterial infection, and **EBV DNA in CSF** is not typical. *Progressive multifocal leukoencephalopathy* - Typically presents with **non-enhancing white matter lesions** without mass effect. - Caused by the **JC virus (JCV)**, not EBV, and does not show ring enhancement.
Question 133: A 67-year-old woman comes to the physician because of a 9-month history of progressive fatigue. Examination shows pallor. Her hemoglobin concentration is 8.9 g/dL, mean corpuscular volume is 75 μm3, and serum ferritin is 9 ng/mL. Test of the stool for occult blood is positive. Colonoscopy shows an irregular, bleeding 3-cm exophytic ulcer in the right colon. Which of the following lesions is the greatest risk factor for this patient's condition?
- A. Serrated hyperplastic polyp
- B. Villous adenomatous polyp (Correct Answer)
- C. Pedunculated inflammatory polyp
- D. Submucosal lipomatous polyp
- E. Tubular adenomatous polyp
Explanation: ***Villous adenomatous polyp*** - The patient presents with **iron deficiency anemia** (low hemoglobin, low MCV, low ferritin) and **GI bleeding** (positive occult blood, bleeding exophytic ulcer), indicating a **colon malignancy**. - **Villous adenomas** have the highest malignant potential among polyps, with a progression rate to adenocarcinoma of around 30-70%, making them the greatest risk factor for the patient's condition. *Serrated hyperplastic polyp* - While **sessile serrated adenomas** (SSAs) can have malignant potential, **hyperplastic polyps** are generally considered benign and have little to no risk of progressing to adenocarcinoma. - The patient's presentation with an **irregular, bleeding ulcer** is more indicative of an advanced lesion than a typical hyperplastic polyp. *Pedunculated inflammatory polyp* - **Inflammatory polyps** are benign mucosal projections resulting from chronic inflammation, such as inflammatory bowel disease, and have **no malignant potential**. - They are distinct from adenomatous polyps, which are true neoplastic growths with varying degrees of dysplasia. *Submucosal lipomatous polyp* - **Lipomatous polyps** are benign, non-epithelial lesions composed of mature adipose tissue, typically found in the submucosa. - They are **non-neoplastic** and carry no malignant potential, thus not contributing to the risk of colorectal cancer. *Tubular adenomatous polyp* - **Tubular adenomas** are common but have a lower malignant potential (about 5-10% lifetime risk) compared to villous adenomas. - While they can progress to adenocarcinoma, the **villous component** is a stronger predictor of malignancy and is more consistent with a large, bleeding exophytic ulcer described in the right colon.
Question 134: A 53-year-old woman comes to the emergency department because of blurry vision, headache, and multiple episodes of nosebleeds over the last few weeks. During this time, she has also been itching a lot, especially after getting ready for work in the mornings. She has had an 8-kg (17.6-lb) weight loss and increasing fatigue during the past 6 months. Her temperature is 37.8°C (100.0°F), pulse is 80/min, respirations are 15/min, and blood pressure is 158/90 mm Hg. Physical examination shows no lesions or evidence of trauma in the nasal cavity. Her face, palms, nail beds, oral mucosa, and conjunctiva appear red. Abdominal examination shows splenomegaly. Her hemoglobin concentration is 19 g/dL, hematocrit is 58%, platelets are 450,000/μL, and erythropoietin level is below normal. A peripheral blood smear shows RBC precursor cells. Which of the following is the most likely underlying cause of this patient's condition?
- A. Stress erythrocytosis
- B. Increased intracranial pressure
- C. Mutated JAK2 gene (Correct Answer)
- D. Megakaryocyte proliferation
- E. Renal cell carcinoma
Explanation: ***Mutated JAK2 gene*** - The patient's symptoms, including **elevated hemoglobin and hematocrit**, **splenomegaly**, **pruritus after showering (aquagenic pruritus)**, and **low erythropoietin levels**, are highly suggestive of **polycythemia vera (PV)**. - **Polycythemia vera** is a chronic myeloproliferative neoplasm characterized by uncontrolled production of red blood cells, often due to a **JAK2 V617F mutation**, leading to constitutive activation of the JAK-STAT pathway independent of erythropoietin. *Stress erythrocytosis* - **Stress erythrocytosis** (or relative polycythemia) is characterized by an elevated hematocrit due to **decreased plasma volume**, not an actual increase in red blood cell mass. - It would not explain the associated symptoms like **splenomegaly**, **pruritus**, or the presence of **RBC precursor cells** in the peripheral smear, which indicate increased erythropoiesis. *Increased intracranial pressure* - **Increased intracranial pressure** can cause headache and blurry vision (due to papilledema), but does not explain the **systemic symptoms** like pruritus, splenomegaly, weight loss, or the specific hematological findings (high hemoglobin, low erythropoietin). - The nosebleeds are more likely related to abnormal platelet function or vessel distension in the context of PV. *Megakaryocyte proliferation* - While **megakaryocyte proliferation** is a feature of **myeloproliferative neoplasms**, particularly **essential thrombocythemia** and **primary myelofibrosis**, it is not the primary underlying cause that explains the entire clinical picture for PV. - In PV, panmyelosis (proliferation of all myeloid lineages, including megakaryocytes) occurs, but the **JAK2 mutation** is the driving oncogenic event leading to this proliferation. *Renal cell carcinoma* - **Renal cell carcinoma** can cause **secondary polycythemia** by secreting erythropoietin, which would lead to **elevated erythropoietin levels**. - This patient has **below-normal erythropoietin levels**, ruling out erythropoietin-producing tumors as the cause of her polycythemia.
Question 135: A 73-year-old man is brought to the emergency department because of fever and a productive cough for 2 days. He has had increasing fatigue and dyspnea for the past 2 weeks. During this time he has lost 3 kg (6.6 lb). He received chemotherapy for myelodysplastic syndrome (MDS) 1 year ago. He is currently on supportive treatment and regular blood transfusions. He does not smoke or drink alcohol. The vital signs include: temperature 38.5℃ (101.3℉), pulse 93/min, respiratory rate 18/min, and blood pressure 110/65 mm Hg. He has petechiae distally on the lower extremities and several purpura on the trunk and extremities. Several enlarged lymph nodes are detected in the axillary and cervical regions on both sides. On auscultation of the lungs, crackles are heard in the left lower lobe area. Physical examination of the heart and abdomen shows no abnormalities. The laboratory studies show the following: Hemoglobin 9 g/dL Mean corpuscular volume 95 μm3 Leukocyte count 18,000/mm3 Platelet count 40,000/mm3 Prothrombin time 11 sec (INR = 1) Based on these findings, this patient is most likely to have developed which of the following?
- A. Non-cardiogenic pulmonary edema
- B. Acute myeloid leukemia (Correct Answer)
- C. Disseminated intravascular coagulation
- D. Small cell lung cancer
- E. Burkitt lymphoma
Explanation: ***Acute myeloid leukemia*** - The patient's history of **myelodysplastic syndrome (MDS)**, combined with the current presentation of **fever**, **fatigue**, **dyspnea**, significant **weight loss**, **generalized lymphadenopathy**, **petechiae**, **purpura**, and dramatically altered blood counts (**leukocytosis**, **thrombocytopenia**, **anemia**), is highly suggestive of progression from MDS to **acute myeloid leukemia (AML)**. - The elevated **white blood cell count (18,000/mm3)** with anemia and thrombocytopenia, along with systemic symptoms and a history of a pre-leukemic condition, points directly to a clonal proliferation of myeloid blasts, which is the hallmark of AML. *Non-cardiogenic pulmonary edema* - While the patient has dyspnea and crackles, **non-cardiogenic pulmonary edema** is a symptom or complication, not an underlying primary diagnosis that explains the constellation of other systemic findings like lymphadenopathy, petechiae, weight loss, and the specific blood count abnormalities. - Pulmonary edema can be a complication of severe sepsis or acute respiratory distress syndrome, but it does not account for the **malignant hematological picture**. *Disseminated intravascular coagulation* - **Disseminated intravascular coagulation (DIC)** is a possibility given the petechiae and purpura, indicating a coagulopathy, and it can be a complication of severe infection or malignancy. - However, the patient's **PT/INR is normal**, and while his platelet count is low, DIC would typically also involve deranged coagulation times (prolonged PT/INR and aPTT) to a greater extent, and the overarching clinical picture with lymphadenopathy and history of MDS points to an underlying hematological malignancy as the primary issue rather than DIC as the sole diagnosis. *Small cell lung cancer* - **Small cell lung cancer** could cause weight loss and fatigue, and potentially paraneoplastic syndromes leading to certain hematological changes, but would not typically present with such pronounced **generalized lymphadenopathy** and the specific **pancytopenia-like picture** (anemia, thrombocytopenia with leukocytosis) without a clear lung mass or primary respiratory symptoms beyond crackles. - The history of MDS transitioning to leukemia is a much more direct and likely explanation for the presenting signs and symptoms. *Burkitt lymphoma* - **Burkitt lymphoma** is a high-grade B-cell lymphoma that can cause lymphadenopathy and systemic symptoms, but it typically presents with distinct patterns of involvement (e.g., jaw mass in endemic form, abdominal involvement in sporadic form) and less commonly transitions directly from MDS. - While it can manifest with bone marrow involvement, the particular blood count abnormalities and the history of **MDS progressing to acute leukemia** makes AML a far more probable diagnosis.
Question 136: A 34-year-old man comes to the physician because of a 3-week history of left testicular swelling. He has no pain. He underwent a left inguinal hernia repair as a child. He takes no medications. He appears healthy. His vital signs are within normal limits. Examination shows an enlarged, nontender left testicle. When the patient is asked to cough, there is no bulge present in the scrotum. When a light is held behind the scrotum, it does not shine through. There is no inguinal lymphadenopathy. Laboratory studies show: Hemoglobin 14.5 g/dL Leukocyte count 8,800/mm3 Platelet count 345,000/mm3 Serum Glucose 88 mg/dL Creatinine 0.8 mg/dL Total bilirubin 0.7 mg/dL Alkaline phosphatase 35 U/L AST 15 U/L ALT 14 U/L Lactate dehydrogenase 60 U/L β-Human chorionic gonadotropin 80 mIU/mL (N < 5) α-Fetoprotein 6 ng/mL (N < 10) Which of the following is the most likely diagnosis?
- A. Seminoma (Correct Answer)
- B. Leydig cell tumor
- C. Choriocarcinoma
- D. Spermatocele of testis
- E. Yolk sac tumor
Explanation: **Seminoma** - The elevated **beta-human chorionic gonadotropin (β-hCG)** in the presence of a normal alpha-fetoprotein (α-FP) is highly suggestive of seminoma, especially in a painless testicular mass in a young man. - While AFP is typically not elevated in pure seminomas, β-hCG can be mildly to moderately elevated in approximately 10-30% of cases, consistent with this presentation. *Leydig cell tumor* - These tumors often produce androgens or estrogens, leading to symptoms like **precocious puberty** in boys or **gynecomastia** in adult men, which are not described. - Serum tumor markers like β-hCG and α-FP are typically **not elevated** in Leydig cell tumors. *Choriocarcinoma* - This highly aggressive germ cell tumor is characterized by **markedly elevated β-hCG levels**, often much higher than 80 mIU/mL, and can also elevate α-FP. - Given the relatively mild β-hCG elevation and normal α-FP, choriocarcinoma is less likely. *Spermatocele of testis* - A spermatocele is a **benign cyst** that typically transilluminates (light shines through), which is absent in this case. - Tumor markers like β-hCG and α-FP would be **normal** in a spermatocele, ruling it out. *Yolk sac tumor* - Yolk sac tumors are characterized by **elevated alpha-fetoprotein (α-FP)** levels, which are normal in this patient. - While they can also elevate β-hCG in some cases, the defining marker, α-FP, is not elevated here.
Question 137: A 52-year-old female was found upon mammography to have branching calcifications in the right lower breast. Physical exam revealed a palpable nodularity in the same location. A tissue biopsy was taken from the lesion, and the pathology report diagnosed the lesion as comedocarcinoma. Which of the following histological findings is most likely present in the lesion?
- A. Disordered glandular cells invading the ductal basement membrane
- B. Pleomorphic cells surrounding areas of comedonecrosis (Correct Answer)
- C. Extensive lymphocytic infiltrate
- D. Halo cells in epidermal tissue
- E. Orderly rows of cells surrounding lobules
Explanation: ***Pleomorphic cells surrounding areas of comedonecrosis*** - **Comedocarcinoma** specifically refers to a high-grade subtype of **ductal carcinoma in situ (DCIS)** characterized by **central necrosis (comedonecrosis)** surrounded by **pleomorphic epithelial cells**. - The presence of branching calcifications on mammography is also a classic sign often associated with **comedonecrosis** within the ducts. *Disordered glandular cells invading the ductal basement membrane* - This description is characteristic of **invasive ductal carcinoma**, where malignant cells breach the basement membrane and infiltrate surrounding tissues, which is not stated in the diagnosis of comedocarcinoma. - Comedocarcinoma is a form of **carcinoma in situ**, meaning the cancerous cells are confined within the ductal system and have not yet invaded the basement membrane. *Extensive lymphocytic infiltrate* - While immune cell infiltrates can be seen in various cancers, an **extensive lymphocytic infiltrate** is more characteristic of conditions like **medullary carcinoma** of the breast or specific immune responses, not a defining feature of comedocarcinoma. - It does not directly relate to the characteristic histological appearance of **comedonecrosis** and **pleomorphic cells** seen in comedocarcinoma. *Halo cells in epidermal tissue* - **Halo cells** (koilocytes) are characteristic of **human papillomavirus (HPV) infection** and are found in **cervical or anal squamous lesions**, not typically in breast tissue. - This finding is completely unrelated to breast pathology and specifically to comedocarcinoma. *Orderly rows of cells surrounding lobules* - This description is more indicative of **lobular carcinoma in situ (LCIS)** or some benign proliferative lesions, where cellular architecture tends to maintain some order. - **Comedocarcinoma** involves disordered, pleomorphic cells within ducts, often with central necrosis, and does not form orderly rows surrounding lobules.
Question 138: A 76-year-old woman is brought to the physician because of lesions on her left arm. She first noticed them 3 months ago and they have grown larger since that time. She has not had any pain or pruritus in the area. She has a history of invasive ductal carcinoma of the left breast, which was treated with mastectomy and radiation therapy 27 years ago. Since that time, she has had lymphedema of the left arm. Physical examination shows extensive edema of the left arm. There are four coalescing, firm, purple-blue nodules on the left lateral axillary region and swelling of the surrounding skin. Which of the following is the most likely diagnosis?
- A. Thrombophlebitis
- B. Cellulitis
- C. Melanoma
- D. Angiosarcoma (Correct Answer)
- E. Kaposi sarcoma
Explanation: ***Angiosarcoma*** - The presence of **firm, purple-blue nodules** in a patient with **chronic lymphedema** following **mastectomy and radiation** for breast cancer is highly suggestive of **angiosarcoma (Stewart-Treves syndrome)**. - This rare but aggressive vascular malignancy often presents as skin lesions in the setting of long-standing lymphedema, particularly in the upper extremity after breast cancer treatment. *Thrombophlebitis* - Typically presents with **erythema**, **tenderness**, and **pain** along the course of a superficial vein, which is not described here. - The lesions would likely blanch with pressure and feel more like a cord or streak, rather than firm, discrete nodules. *Cellulitis* - Would present with **warmth**, **tenderness**, **erythema with ill-defined borders**, and often **fever**, none of which are mentioned. - While lymphedema is a risk factor for cellulitis, the description of discrete, firm, purple-blue nodules growing over time is not characteristic. *Melanoma* - Although melanoma can present as a dark lesion, it often has **irregular borders**, **asymmetry**, and **color variegation**, and is typically associated with UV exposure. - While it can be nodular, the specific context of chronic lymphedema and the description of purple-blue lesions are more indicative of a vascular tumor. *Kaposi sarcoma* - Characterized by **purple-brown skin lesions** and is primarily associated with **HIV infection** or **immunosuppression**, neither of which is indicated in this patient. - While it is a vascular tumor, the unique presentation in the context of chronic lymphedema post-breast cancer therapy makes angiosarcoma a more fitting diagnosis.
Question 139: A 12-year-old boy is brought to the emergency department after he vomited and said he was having double vision in school. He also says that he has been experiencing morning headaches, nausea, and dizziness over the last month. He has no past medical history and is not taking any medications. Physical exam reveals a broad-based gait, dysmetria on finger-to-nose testing, and nystagmus. Both serum and urine toxicology are negative, and radiography reveals a solid mass in the midline cerebellum that enhances after contrast administration. Biopsy of this lesion reveals cells of primitive neuroectodermal origin. Which of the following would most likely be seen on histology of this lesion?
- A. Rosettes with small blue cells (Correct Answer)
- B. Rosenthal fibers
- C. Tooth enamel-like calcification
- D. Foamy cells and high vascularity
- E. Perivascular pseudorosettes
Explanation: ***Rosettes with small blue cells*** - The description of a **midline cerebellar mass** in a child, presenting with signs of **increased intracranial pressure (headaches, vomiting, double vision)** and **cerebellar dysfunction (broad-based gait, dysmetria, nystagmus)**, is classic for **medulloblastoma**. - **Medulloblastomas** are primitive neuroectodermal tumors (PNETs) known for their distinctive histology of **small, round, blue cells** forming **Homer-Wright rosettes**. *Rosenthal fibers* - **Rosenthal fibers** are eosinophilic, corkscrew-shaped structures that are characteristic histological features of **pilocytic astrocytomas**. - While pilocytic astrocytomas can be cerebellar and common in children, the question describes a "solid mass of primitive neuroectodermal origin" rather than the typical cystic lesion with mural nodule associated with pilocytic astrocytomas, and the aggressive presentation points away from pilocytic astrocytoma. *Tooth enamel-like calcification* - **Tooth enamel-like calcification** is a pathognomonic feature of **craniopharyngiomas**, which are typically supratentorial (in the sellar region) and cause symptoms related to pituitary dysfunction and optic chiasm compression, not cerebellar dysfunction. - The location and symptoms provided in the vignette do not match the typical presentation of a craniopharyngioma. *Foamy cells and high vascularity* - **Foamy cells and high vascularity** are characteristic features of **hemangioblastomas**, which are typically seen in adults, often associated with **von Hippel-Lindau disease**, and are more commonly located in the cerebellum. - However, the patient's age (12-year-old) and the description of cells of "primitive neuroectodermal origin" do not align with the typical presentation or origin of hemangioblastomas. *Perivascular pseudorosettes* - **Perivascular pseudorosettes** are the classic histological finding in **ependymomas**, another common pediatric brain tumor. - While ependymomas can occur in the posterior fossa, they typically arise from the floor of the fourth ventricle and are not described as having primitive neuroectodermal origin in the same way medulloblastomas are, and the specific rosettes formed by medulloblastomas are Homer-Wright rosettes.
Question 140: A 34-year-old man presents to the office for evaluation of a lesion on his upper arm that appeared a few months ago and has not healed. The patient appears healthful but has a history of cardiovascular disease. He states that his friend at the industrial ammunition factory where he works told him he should "get it looked at." The patient admits to some nausea, vomiting, and diarrhea over the past year, but he states that he "feels fine now." On physical examination, the lesion is an erythematous, scaly, ulcerated plaque on the flexor surface of his upper arm. The rest of the exam is within normal limits. What is the most likely diagnosis?
- A. Squamous cell carcinoma (SCC) (Correct Answer)
- B. Erythema multiforme
- C. Actinic keratosis
- D. Erysipelas
- E. Contact dermatitis
Explanation: ***Squamous cell carcinoma (SCC)*** - The patient's occupational exposure to chemicals at an **ammunition factory**, along with chronic non-healing, **ulcerated, scaly plaque**, raises suspicion for SCC, particularly **arsenic-induced SCC**. - His history of vague **gastrointestinal symptoms** (nausea, vomiting, diarrhea) over the past year is also consistent with **chronic arsenic exposure**, which is a known carcinogen. *Erythema multiforme* - This is an **acute, self-limiting hypersensitivity reaction** to medications or infections, characterized by target lesions, not a chronic, non-healing ulcerated plaque. - It would not typically present with a history of chronic GI symptoms related to occupational exposure. *Actinic keratosis* - This is a **precancerous lesion** caused by chronic sun exposure, typically presenting as a rough, scaly patch on sun-exposed areas. - While it has malignant potential to transform into SCC, the description of an **ulcerated, non-healing lesion** with a history of probable chemical exposure makes SCC a more likely *current* diagnosis. *Erysipelas* - Erysipelas is a **superficial bacterial infection** of the skin characterized by a rapidly spreading, bright red, well-demarcated, and painful rash, often accompanied by fever and systemic symptoms. - It would not manifest as a chronic, non-healing ulcerated plaque over several months. *Contact dermatitis* - This is an **inflammatory skin reaction** due to direct contact with an allergen or irritant, typically presenting as an itchy, erythematous rash with vesicles or papules. - It would not typically result in a chronic, ulcerated, non-healing plaque and is not associated with the systemic symptoms or occupational exposure history presented.
Question 141: A 28-year-old man presents with a 3-day history of cough and fever. He says that he recently became a factory worker in a huge plant that is involved in the polyvinyl chloride (PVC) polymerization process. Because he has heard about occupational diseases specifically related to this particular industry, he asks the physician whether his new job is associated with any serious conditions. His physician mentions that polyvinyl chloride is a known chemical carcinogen and that workers who have been exposed to it are known to be at increased risk of developing a particular type of cancer. Which of the following cancers is the physician most likely talking about?
- A. Bronchogenic carcinoma
- B. Adenocarcinoma of the small intestine
- C. Hepatic angiosarcoma (Correct Answer)
- D. Malignant lymphoma
- E. Urothelial carcinoma
Explanation: ***Hepatic angiosarcoma*** - Exposure to **polyvinyl chloride (PVC)**, especially in the polymerization process, is a well-established occupational risk factor for **hepatic angiosarcoma**. - This knowledge is crucial for understanding the **carcinogenic potential** of specific industrial chemicals and conducting appropriate occupational health screenings. *Bronchogenic carcinoma* - While various occupational exposures (e.g., asbestos, radon) can cause **bronchogenic carcinoma**, PVC polymerization is not primarily linked to this malignancy. - This diagnosis is more commonly associated with chronic inhalation of **pulmonary irritants** and smoking. *Adenocarcinoma of the small intestine* - This is a very rare primary malignancy of the gastrointestinal tract and it is not typically associated with **polyvinyl chloride exposure**. - Its risk factors are generally related to chronic inflammatory conditions of the bowel, such as **Crohn's disease**, or certain genetic syndromes. *Malignant lymphoma* - Various chemical exposures can increase the risk of lymphoma, but **polyvinyl chloride exposure** is not a primary or well-established risk factor for its development. - Lymphomas are a diverse group of cancers often linked to immune system dysfunction, viral infections (e.g., EBV), or certain genetic predispositions. *Urothelial carcinoma* - This cancer is primarily associated with exposure to **aromatic amines** and **cigarette smoking**, which are known bladder carcinogens. - There is no strong evidence linking **polyvinyl chloride exposure** to an increased risk of urothelial carcinoma.
Question 142: A 47-year-old woman comes to the physician because of a 2-month history of a lump on her neck and a 1-week history of hoarseness. Examination shows a 3-cm, firm, non-tender nodule on the anterior neck. Further evaluation confirms a thyroid malignancy, and she undergoes thyroidectomy. Histopathologic examination of the surgical specimen shows lymphatic invasion. Genetic analysis shows an activating mutation in the RET/PTC genes. Microscopic examination of the surgical specimen is most likely to also show which of the following?
- A. Pleomorphic giant cells with numerous atypical mitotic figures
- B. Cuboidal cells arranged spherically around colloid lakes
- C. Hyperplastic epithelium with colloid scalloping
- D. Calcified spherules and large oval cells with empty-appearing nuclei (Correct Answer)
- E. Sheets of polygonal cells surrounding amyloid deposition
Explanation: ***Calcified spherules and large oval cells with empty-appearing nuclei*** - The presence of an **activating mutation in RET/PTC genes**, **lymphatic invasion**, and a new neck lump with hoarseness (suggesting nerve involvement) are highly characteristic of **papillary thyroid carcinoma**. - Microscopic features of papillary thyroid carcinoma include **Psammoma bodies (calcified spherules)**, **Orphan Annie eye nuclei (large oval cells with empty-appearing nuclei)**, and nuclear grooves. *Pleomorphic giant cells with numerous atypical mitotic figures* - This description typically refers to **anaplastic thyroid carcinoma**, a highly aggressive and undifferentiated tumor. - While anaplastic carcinoma can present with rapid growth and hoarseness, it is less commonly associated with a **RET/PTC mutation** (BRAF mutations are more common) and typically has a much poorer prognosis, often presenting with a rapidly enlarging mass rather than a 2-month history suggestive of a more indolent tumor. *Cuboidal cells arranged spherically around colloid lakes* - This morphology is characteristic of **follicular thyroid carcinoma** or **follicular adenoma**. - While follicular tumors can have RET/PTC mutations in some variants, the classic features described (empty-appearing nuclei and psammoma bodies) are absent here. *Hyperplastic epithelium with colloid scalloping* - This describes the histologic features seen in **Graves' disease** or **diffuse toxic goiter**, a benign condition. - It is not indicative of malignancy, and the patient's presentation with a solitary nodule and hoarseness points to a malignant process. *Sheets of polygonal cells surrounding amyloid deposition* - This is the classic microscopic appearance of **medullary thyroid carcinoma**. - Medullary thyroid carcinoma is also associated with **RET mutations**, but these are typically **germline or somatic RET point mutations** (e.g., RET M918T), not RET/PTC rearrangements, and it arises from parafollicular C cells, producing calcitonin, not thyroid hormones.
Question 143: A 70-year-old man comes to the physician because of a painless skin lesion on his neck for the past 5 months. The lesion has gradually become darker in color and is often pruritic. He has a similar lesion on the back. He is a retired landscaper. He has smoked half a pack of cigarettes daily for 45 years. Physical examination shows a 0.9-cm hyperpigmented papule on the neck with a greasy, wax-like, and stuck-on appearance. Histopathologic examination is most likely to show which of the following?
- A. Nests of melanocytes at the base of rete ridges and the dermis
- B. Fibroblast proliferation with small, benign dermal growth
- C. S100-positive epithelioid cells with fine granules in the cytoplasm
- D. Koilocytes in the granular cell layer of the epidermis
- E. Immature keratinocytes with small keratin-filled cysts (Correct Answer)
Explanation: ***Immature keratinocytes with small keratin-filled cysts*** - The clinical presentation of a **hyperpigmented papule** with a **greasy, wax-like, and stuck-on appearance** is highly characteristic of a **seborrheic keratosis**. - Histopathologically, seborrheic keratoses are characterized by a proliferation of **immature keratinocytes** and often contain **horn cysts** (small keratin-filled cysts) and pseudo-horn cysts. *Nests of melanocytes at the base of rete ridges and the dermis* - This description is characteristic of a **melanocytic nevus** (mole) or potentially a melanoma, especially if there are nests of atypical melanocytes in the dermis. - While seborrheic keratoses can be hyperpigmented, their clinical appearance is distinct from melanocytic lesions, lacking features like irregular borders or rapid changes. *Fibroblast proliferation with small, benign dermal growth* - This histological finding is more consistent with a **dermatofibroma** (fibrous histiocytoma), which presents as a firm, often pigmented nodule that may dimple inward when compressed. - Dermatofibromas do not typically have the **greasy, stuck-on appearance** seen in seborrheic keratoses. *S100-positive epithelioid cells with fine granules in the cytoplasm* - **S100 positivity** is a marker for neural crest-derived cells, including melanocytes and Schwann cells. Epithelioid cells with fine granules could be seen in conditions like **granular cell tumor**, which stains positive for S100 protein. - A granular cell tumor usually presents as a solitary, firm nodule and does not typically have the classic "greasy, stuck-on" appearance of a seborrheic keratosis. *Koilocytes in the granular cell layer of the epidermis* - **Koilocytes** are characteristic of **human papillomavirus (HPV) infection**, leading to conditions like common warts (verruca vulgaris) or genital warts (condyloma acuminatum). - Warts typically have a rough, verrucous surface and do not present with the greasy, wax-like texture of a seborrheic keratosis.
Question 144: A 2-year-old boy is brought to the physician with complaints of gingival growth in the lower jaw with associated pain for the past few weeks. He has no history of trauma or any other significant medical conditions. His temperature is 37.0°C (98.6°F), pulse is 92/min, and respiratory rate is 24/min. On extraoral examination, a swelling of 4 cm x 2 cm is present on the left lower jaw. On intraoral examination, a diffuse erythematous swelling covered with necrotic slough is present on the gingiva. Computed tomography (CT) scan of the head shows multiple soft tissue density lesions involving mandibular, maxillary, left occipital, and temporal regions. Which of the following findings, if present, would be the most specific indicator of the disease in this patient?
- A. Birbeck granules (Correct Answer)
- B. Starry sky appearance
- C. Auer rods
- D. Owl's eye inclusions
- E. Reed-Sternberg cells
Explanation: ***Birbeck granules*** - The clinical presentation, including multifocal bone lesions (mandibular, maxillary, occipital, temporal) and gingival swelling in a 2-year-old boy, is highly suggestive of **Langerhans cell histiocytosis (LCH)**. - **Birbeck granules** are characteristic rod- or tennis racket-shaped cytoplasmic organelles found specifically in Langerhans cells and are considered the **pathognomonic microscopic finding** for LCH. *Starry sky appearance* - This refers to the microscopic appearance of a high-grade lymphoma, most famously **Burkitt lymphoma**, where dark tumor cells are interspersed with pale macrophages. - While Burkitt lymphoma can cause jaw lesions, the multifocal bone involvement described in this case, particularly in multiple distant sites, makes LCH a more fitting diagnosis. *Auer rods* - These are **azurophilic, needle-like cytoplasmic inclusions** found in the cytoplasm of myeloid blasts in patients with **acute myeloid leukemia (AML)**. - AML can present with gingival infiltration and bone lesions, but Auer rods are specific for myeloid leukemias, not the histiocytic proliferation suggested by the widespread bone involvement. *Owl's eye inclusions* - These refer to the characteristic appearance of **cytomegalovirus (CMV)**-infected cells, exhibiting an enlarged nucleus with a central basophilic inclusion body surrounded by a clear halo. - CMV infection does not typically cause multifocal bone lesions or gingival growth in this manner. *Reed-Sternberg cells* - These are large, multinucleated cells with prominent nucleoli that are characteristic of **Hodgkin lymphoma**. - Hodgkin lymphoma predominantly affects lymph nodes and rarely presents with widespread lytic bone lesions and gingival involvement as the primary manifestation in this age group.
Question 145: A 45-year-old man comes to the physician for the evaluation of difficulty swallowing that has worsened over the past year. He also reports some hoarseness and generalized bone, muscle, and joint pain. During the past six months, he has had progressive constipation and two episodes of kidney stones. He also reports recurrent episodes of throbbing headaches, diaphoresis, and palpitations. He does not smoke or drink alcohol. He takes no medications. His vital signs are within normal limits. Physical examination and an ECG show no abnormalities. Laboratory studies show calcium concentration of 12 mg/dL, phosphorus concentration of 2 mg/dL, alkaline phosphatase concentration of 100 U/L, and calcitonin concentration of 11 pg/mL (N < 8.8). Ultrasonography of the neck shows hypoechoic thyroid lesions with irregular margins and microcalcifications. Which of the following is the most likely underlying cause of this patient's condition?
- A. Altered RET proto-oncogene expression (Correct Answer)
- B. Deleted VHL gene
- C. Disrupted menin protein function
- D. Exposure to ionizing radiation
- E. Mutated NF1 gene
Explanation: ***Altered RET proto-oncogene expression*** - This patient's symptoms are highly suggestive of **multiple endocrine neoplasia type 2A (MEN2A)**, which is caused by gain-of-function mutations in the **RET proto-oncogene**. - **MEN2A** typically presents with **medullary thyroid carcinoma** (hypoechoic thyroid lesions, elevated calcitonin), **pheochromocytoma** (throbbing headaches, diaphoresis, palpitations), and **primary hyperparathyroidism** (hypercalcemia, hypophosphatemia, bone/muscle/joint pain, kidney stones). *Deleted VHL gene* - A deleted **VHL gene** is associated with **Von Hippel-Lindau disease**, characterized by **retinal and cerebellar hemangioblastomas**, **renal cell carcinoma**, and **pheochromocytoma**. - While pheochromocytoma is present, the thyroid and parathyroid findings are not consistent with VHL disease. *Disrupted menin protein function* - Disrupted **menin protein function** is characteristic of **multiple endocrine neoplasia type 1 (MEN1)**, which includes **pituitary tumors**, **parathyroid adenomas** (leading to hyperparathyroidism), and **pancreatic endocrine tumors**. - Although primary hyperparathyroidism is present, the thyroid carcinoma is medullary (not follicular/papillary) and the specific symptoms point more toward MEN2A. *Exposure to ionizing radiation* - Exposure to **ionizing radiation** is a risk factor for **papillary and follicular thyroid carcinomas**, but not typically **medullary thyroid carcinoma**. - It also does not explain the concurrent **pheochromocytoma** and **hyperparathyroidism**. *Mutated NF1 gene* - A mutated **NF1 gene** is responsible for **neurofibromatosis type 1**, which manifests with **café-au-lait spots**, **neurofibromas**, **optic gliomas**, and sometimes **pheochromocytoma**. - There are no cutaneous or neurological findings of neurofibromatosis in this patient, and the prominent medullary thyroid carcinoma and hyperparathyroidism are not features of NF1.
Question 146: A previously healthy 68-year-old woman is brought to the emergency department because of a 3-day history of nausea, anorexia, polyuria, and confusion. Her only medication is acetaminophen, which she takes daily for back pain that started 6 weeks ago. Physical examination shows conjunctival pallor. She is oriented to person but not to time or place. Laboratory studies show a hemoglobin concentration of 9.3 g/dL, a serum calcium concentration of 13.8 mg/dL, and a serum creatinine concentration of 2.1 mg/dL. Her erythrocyte sedimentation rate is 65 mm/h. Which of the following is the most likely underlying cause of this patient's condition?
- A. Overproliferation of plasma cells (Correct Answer)
- B. Decreased renal excretion of calcium
- C. Excessive intake of calcium
- D. Ectopic release of PTHrP
- E. Excess PTH secretion from parathyroid glands
Explanation: ***Overproliferation of plasma cells*** - The patient's symptoms (nausea, anorexia, polyuria, confusion, back pain, anemia, hypercalcemia, acute kidney injury, and elevated ESR) are classic features of **multiple myeloma** (CRAB — Calcium elevation, Renal insufficiency, Anemia, Bone lesions). - Multiple myeloma is characterized by the **malignant proliferation of plasma cells** in the bone marrow, leading to skeletal destruction (causing back pain and hypercalcemia), renal damage, and anemia. *Decreased renal excretion of calcium* - While **renal insufficiency** (creatinine 2.1 mg/dL) contributes to hypercalcemia by impairing calcium excretion, it is typically a **consequence** of the underlying disease rather than the primary cause of hypercalcemia, especially with such a high calcium level. - The elevated calcium itself can worsen kidney function, creating a **vicious cycle**, but an underlying cause for hypercalcemia is still needed. *Excessive intake of calcium* - This typically occurs with **calcium and vitamin D supplementation** (milk-alkali syndrome) and is not suggested by the patient's history, as her only medication is acetaminophen. - Her current symptoms are too severe and multi-systemic to be explained solely by dietary calcium excess without other contributing factors. *Ectopic release of PTHrP* - **Parathyroid hormone-related peptide (PTHrP)** is secreted by various solid tumors (e.g., squamous cell carcinoma of the lung, renal cell carcinoma) and causes humoral hypercalcemia of malignancy. - While it causes hypercalcemia, the prominent **bone pain and anemia** in this patient are more characteristic of multiple myeloma than a solid tumor secreting PTHrP. *Excess PTH secretion from parathyroid glands* - This describes **primary hyperparathyroidism**, which causes hypercalcemia and can lead to bone pain and renal stones. - However, primary hyperparathyroidism is typically associated with **normal or elevated PTH levels**, and it does not usually cause the degree of anemia or elevated ESR seen in this case.
Question 147: A 58-year-old woman presents to a physician with a painless swelling behind her right ear, which she noticed 1 month ago. She has no other complaint nor does she have any specific medical condition. On physical examination, her vital signs are stable. An examination of the right post-auricular area shows enlarged lymph nodes, which are non-tender and rubbery in consistency, with normal overlying skin. A detailed general examination reveals the presence of one enlarged axillary lymph node on the left side with similar features. Complete blood counts are within normal limits but atypical lymphocytes are present on the peripheral blood smear. The patient’s serum lactate dehydrogenase level is slightly elevated. Excisional biopsy of the lymph node is performed and histopathological examination of the tissue yields a diagnosis of follicular lymphoma. Further cytogenetic studies reveal that the condition is associated with overexpression of the BCL-2 gene. Which of the following cytogenetic abnormalities is most likely to be present?
- A. t(3;14)(q27;q32)
- B. t(11;18)(q21;q21)
- C. t(8;14)(q24;q32)
- D. t(11;14)(q13;q32)
- E. t(14;18)(q32;q21) (Correct Answer)
Explanation: ***t(14;18)(q32;q21)*** - This translocation is the **hallmark of follicular lymphoma**, present in approximately **85-90% of cases**. - The **BCL-2 gene** on chromosome **18q21** is translocated to the **immunoglobulin heavy chain (IGH) locus** on chromosome **14q32**, leading to **BCL-2 overexpression**. - BCL-2 is an **anti-apoptotic protein** that promotes **B-cell survival** by inhibiting programmed cell death, resulting in accumulation of malignant lymphocytes. *t(3;14)(q27;q32)* - This translocation involves the **BCL6 gene** on chromosome **3q27** and the immunoglobulin heavy chain locus on chromosome **14q32**. - It is more commonly associated with **diffuse large B-cell lymphoma (DLBCL)** and occasionally seen in follicular lymphomas with transformation. - BCL6 rearrangements promote lymphomagenesis through dysregulation of germinal center B-cell differentiation, but this is **not the mechanism** in primary follicular lymphoma with BCL-2 overexpression. *t(11;18)(q21;q21)* - This translocation is characteristic of **extranodal marginal zone lymphoma** of mucosa-associated lymphoid tissue (**MALT lymphoma**). - It results in the **API2-MALT1 fusion gene**, which activates NF-κB signaling. - This is distinct from the BCL-2 overexpression mechanism seen in follicular lymphoma. *t(8;14)(q24;q32)* - This translocation is the **hallmark of Burkitt lymphoma**, leading to **MYC gene overexpression**. - The **MYC oncogene** on chromosome **8q24** is juxtaposed to the immunoglobulin heavy chain locus on chromosome **14q32**. - MYC overexpression drives aggressive cell proliferation through dysregulation of cell cycle control, which is different from the anti-apoptotic mechanism of BCL-2 in follicular lymphoma. *t(11;14)(q13;q32)* - This translocation is the **hallmark of mantle cell lymphoma**, leading to **cyclin D1 (CCND1) overexpression**. - The **CCND1 gene** on chromosome **11q13** is translocated to the immunoglobulin heavy chain locus on chromosome **14q32**. - Cyclin D1 overexpression promotes cell cycle progression from G1 to S phase, which is a different pathogenic mechanism from BCL-2-mediated inhibition of apoptosis in follicular lymphoma.
Question 148: A 33-year-old woman comes to the physician 1 week after noticing a lump in her right breast. Fifteen years ago, she was diagnosed with osteosarcoma of her left distal femur. Her father died of an adrenocortical carcinoma at the age of 41 years. Examination shows a 2-cm, firm, immobile mass in the lower outer quadrant of the right breast. A core needle biopsy of the mass shows adenocarcinoma. Genetic analysis in this patient is most likely to show a defect in which of the following genes?
- A. BRCA1
- B. KRAS
- C. TP53 (Correct Answer)
- D. Rb
- E. PTEN
Explanation: ***TP53*** - This patient's presentation with **early-onset breast cancer**, a history of **osteosarcoma** at a young age, and a father's death from **adrenocortical carcinoma** at 41 years strongly suggests **Li-Fraumeni syndrome**. - Li-Fraumeni syndrome is an autosomal dominant disorder caused by a germline mutation in the **tumor suppressor gene TP53**, increasing the risk for multiple primary cancers at a young age. *BRCA1* - While **BRCA1 mutations** are associated with an increased risk of breast and ovarian cancer, they are not typically linked to osteosarcoma or adrenocortical carcinoma. - The constellation of cancers in this patient is more indicative of Li-Fraumeni syndrome than solely a BRCA1-related cancer syndrome. *KRAS* - **KRAS** is an oncogene commonly mutated in several cancers, including pancreatic, colorectal, and lung cancer, but is not primarily associated with either Li-Fraumeni syndrome or the specific tumors seen in this family history. - Mutations in KRAS are typically somatic mutations acquired during a person's lifetime, not germline mutations causing inherited cancer syndromes like the one suggested here. *Rb* - Mutations in the **retinoblastoma (Rb) gene** are associated with retinoblastoma and an increased risk of osteosarcoma, but not typically with adrenocortical carcinoma or breast cancer as part of a classic inherited syndrome. - The combination of breast cancer, osteosarcoma, and adrenocortical carcinoma points more specifically to TP53. *PTEN* - **PTEN mutations** are associated with Cowden syndrome, which increases the risk for breast cancer, thyroid cancer, and endometrial cancer, along with benign growths. - However, Cowden syndrome does not typically include osteosarcoma or adrenocortical carcinoma as prominent features, making PTEN less likely than TP53 for this specific family history.
Question 149: A 30-year-old boxer seeks evaluation by his physician after he noticed swelling at the angle of his jaw a few days ago. He recalls a recent boxing match when he was punched in his face. He says that his jaw is very painful. On examination, a firm mass is palpated, measuring 4 x 4 cm. An ultrasound was performed, which shows a thin, encapsulated, well-circumscribed, predominantly solid mass with occasional cystic areas. The mass is surgically excised, after which he develops a hoarse voice for a few days, but recovers within 1 week. The histopathologic evaluation of the surgical specimen reports a pseudocapsule with a hypocellular stromal component consisting of a myxoid background and cartilage arranged in clusters and a hypercellular epithelial component with cells arranged in sheets and trabeculae. From which of the following structures did the mass most likely arise?
- A. Salivary duct
- B. Thyroid
- C. Parotid gland (Correct Answer)
- D. Minor salivary gland
- E. Seventh cranial nerve
Explanation: ***Parotid gland*** - The location of the mass at the **angle of the jaw** is highly suggestive of the parotid gland, as the superficial lobe often extends into this region. - The histopathological findings of a **pseudocapsule**, hypocellular stromal component with **myxoid background and cartilage**, and a hypercellular epithelial component are classic features of a **pleomorphic adenoma**, which is the most common tumor of the parotid gland. - The temporary **hoarseness** after surgery suggests inadvertent injury to the **recurrent laryngeal nerve**, which can occur if the surgical dissection extends deeper into the neck near the carotid sheath. Note that the **facial nerve (CN VII)** runs through the parotid gland and is at risk during parotidectomy, but facial nerve injury typically causes facial weakness rather than voice changes. *Salivary duct* - While salivary ducts are present within salivary glands, a tumor arising directly from a salivary duct rather than the gland parenchyma would likely present with very different histological features, such as those of a **ductal papilloma** or **adenocarcinoma, salivary duct type**. - The complex **stromal and epithelial components** with cartilage described are characteristic of a pleomorphic adenoma, which originates from both epithelial and mesenchymal elements of the gland, not solely the duct. *Thyroid* - The thyroid gland is located in the **anterior neck**, inferior to the laryngeal prominence (Adam's apple), not at the **angle of the jaw**. - Tumors of the thyroid gland, such as papillary or follicular carcinoma, would have distinct histological features and would not typically present with the described myxoid and cartilaginous stromal components. *Minor salivary gland* - Minor salivary glands are numerous and widely distributed in the oral cavity and upper aerodigestive tract, but a mass of this size (4 x 4 cm) at the **angle of the jaw** specifically points to one of the major salivary glands. - While pleomorphic adenomas can arise in minor salivary glands (most commonly in the palate), their presentation as a large mass at the angle of the jaw is far less common than their occurrence in the parotid gland. *Seventh cranial nerve* - The seventh cranial nerve (facial nerve) passes through the parotid gland but does not itself give rise to tumors with the described histological features. - Tumors involving the facial nerve are typically **schwannomas** or **neurofibromas**, which originate from Schwann cells and would show different microscopic characteristics such as Antoni A and B patterns, not the mixed epithelial-mesenchymal features of pleomorphic adenoma.
Question 150: A 62-year-old woman presents to her primary care physician because of fever, fatigue, and shortness of breath. She has noticed that she has a number of bruises, but she attributes this to a hike she went on 1 week ago. She has diabetes and hypertension well controlled on medication and previously had an abdominal surgery but doesn’t remember why. On physical exam, she has some lumps in her neck and a palpable liver edge. Peripheral blood smear shows white blood cells with peroxidase positive eosinophilic cytoplasmic inclusions. The abnormal protein most likely seen in this disease normally has which of the following functions?
- A. Binding to anti-apoptotic factors
- B. Binding as cofactor to kinases
- C. Inhibiting pro-apoptotic factors
- D. Recruiting histone acetylase proteins (Correct Answer)
- E. Interacting with IL-3 receptor
Explanation: ***Recruiting histone acetylase proteins*** - The clinical presentation with **fever, fatigue, shortness of breath, bruising**, and **hepatomegaly** along with a **peripheral blood smear showing white blood cells with peroxidase-positive eosinophilic cytoplasmic inclusions** strongly suggests **Acute Promyelocytic Leukemia (APL)**. - APL is characterized by a **chromosomal translocation t(15;17)**, which fuses the **PML (promyelocytic leukemia)** gene with the **RARα (retinoic acid receptor alpha)** gene. The **PML-RARα fusion protein** acts as an **abnormal transcriptional repressor**, recruiting histone deacetylase (HDAC) proteins and forming a complex that blocks gene expression essential for myeloid differentiation, while the **normal RARα protein** (which is being asked about in the question "abnormal protein most likely seen in this disease normally has which of the following functions") normally **recruits histone acetylase proteins** to promote gene transcription crucial for cellular differentiation. *Binding to anti-apoptotic factors* - While a protein's function might involve apoptosis regulation, the **PML-RARα fusion protein**'s primary mechanism in APL is related to **transcriptional repression** and **differentiation block**, not directly binding to anti-apoptotic factors in its normal state. - The normal function of **RARα** is to promote differentiation, and its dysregulation in APL leads to apoptosis resistance due to the block in differentiation and subsequent proliferation, rather than directly binding anti-apoptotic factors. *Binding as cofactor to kinases* - **RARα** is a nuclear receptor and a **ligand-activated transcription factor**, not typically known for directly binding as a cofactor to kinases in its normal physiological role. - Its main function involves **DNA binding** and interaction with co-activator/co-repressor complexes to regulate gene expression. *Inhibiting pro-apoptotic factors* - The normal **RARα protein** is involved in promoting cellular differentiation, and its dysregulation in APL leads to a block in differentiation, which can contribute to the accumulation of immature cells that resist apoptosis. - However, its normal function is not described as directly **inhibiting pro-apoptotic factors**; rather, its absence or altered function in APL leads to an environment that less efficiently triggers apoptosis in undifferentiated cells. *Interacting with IL-3 receptor* - The **IL-3 receptor** is a cell surface receptor involved in cytokine signaling that promotes the growth and differentiation of hematopoietic cells. - **RARα** is a nuclear receptor located within the cell and primarily interacts with **DNA** and **transcriptional co-regulators**, not with cell surface receptors like the IL-3 receptor.
Question 151: A 45-year-old woman is found to have multiple masses in her liver while performing abdominal ultrasonography for recurrent right upper quadrant abdominal pain. Biopsy of one of the masses discloses large plates of adenoma cells, which are larger than normal hepatocytes and contain glycogen and lipid. Regular septa, portal tracts, and bile ductules are absent. Which of the following is associated with this patient's condition?
- A. Polyvinyl chloride
- B. Smoking
- C. Carbon tetrachloride
- D. Oral contraceptive pills (Correct Answer)
- E. Aflatoxin
Explanation: ***Oral contraceptive pills*** - The description of **large plates of adenoma cells** containing **glycogen and lipid**, along with the absence of normal liver architecture (septa, portal tracts, bile ductules), points to a **hepatic adenoma**. - **Hepatic adenomas** are strongly associated with **oral contraceptive pill (OCP)** use, especially in women aged 35-50. *Polyvinyl chloride* - Exposure to **polyvinyl chloride (PVC)** is mainly linked to **angiosarcoma of the liver**, a rare and aggressive vascular tumor, not hepatic adenomas. - PVC exposure is typically found in occupational settings, which is not mentioned in this patient's history. *Smoking* - **Smoking** is a risk factor for various cancers, including hepatocellular carcinoma (HCC), but it is **not directly associated** with the development of **hepatic adenomas**. - While smoking can contribute to overall disease burden, it does not fit the specific liver tumor characteristics described. *Carbon tetrachloride* - Exposure to **carbon tetrachloride** is known to cause severe **hepatotoxicity**, leading to centrolobular necrosis and potentially cirrhosis. - It is an industrial solvent and is not primarily linked to the formation of **hepatic adenomas**. *Aflatoxin* - **Aflatoxin** exposure, primarily from contaminated food products (e.g., peanuts, corn), is a well-established risk factor for **hepatocellular carcinoma (HCC)**, especially in endemic areas. - It is not associated with the development of benign **hepatic adenomas**, which have different histopathological features and risk factors.
Question 152: A 21-year-old female presents to the family physician with 3 weeks of headaches, sweating, and palpitations. Her BP was 160/125 mmHg, and a 24-hour urine test revealed elevated vanillylmandelic acid (VMA) and normetanephrine. Past medical history is notable for bilateral retinal hemangioblastomas, and family history is significant for three generations (patient, mother, and maternal grandfather) with similar symptoms. Genetic analysis revealed a mutation of a gene on chromosome 3p. Which of the following is the patient at risk of developing?
- A. Osteosarcoma
- B. Breast cancer
- C. Retinoblastoma
- D. Clear cell renal cell carcinoma (Correct Answer)
- E. Ovarian cancer
Explanation: ***Clear cell renal cell carcinoma*** - The patient's symptoms (headaches, sweating, palpitations, hypertension) along with elevated **VMA** and **normetanephrine** suggest a **pheochromocytoma**. - The combination of **bilateral retinal hemangioblastomas**, a family history of similar symptoms across generations, and a **mutation on chromosome 3p** points to **Von Hippel-Lindau (VHL) disease**. Individuals with VHL are at a high risk of developing **clear cell renal cell carcinoma**. *Osteosarcoma* - Osteosarcoma is a primary malignant bone tumor, not typically associated with VHL disease. - Its risk factors include genetic conditions like **Li-Fraumeni syndrome** and **hereditary retinoblastoma**, which do not match the clinical presentation. *Breast cancer* - Breast cancer is a common malignancy but is not directly linked to VHL disease. - Genetic predispositions for breast cancer include mutations in **BRCA1** and **BRCA2** genes, which are different from the VHL gene. *Retinoblastoma* - Retinoblastoma is a childhood eye cancer caused by mutations in the **RB1 gene** on **chromosome 13q14**. - While this patient has retinal hemangioblastomas, these are distinct from retinoblastoma and are characteristic of VHL disease. *Ovarian cancer* - Ovarian cancer is a gynecological malignancy, and its common genetic associations include **BRCA1** and **BRCA2** mutations. - It is not a known component tumor type of VHL syndrome.
Question 153: A 50-year-old woman presents to the outpatient clinic because of a swollen and enlarged right breast. Clinical examination shows no evidence of mass or axillary lymphadenopathy. There is no history of trauma or inflammation. Her past medical and surgical history is positive for breast augmentation with a textured implant 15 years ago. Magnetic resonance imaging (MRI) shows an accumulation of fluid around the right breast implant with intact implant integrity. Which of the following is the most appropriate next step in the management?
- A. Chemotherapy
- B. Mastectomy
- C. Surgical replacement of textured implant with a smooth implant
- D. Mammogram
- E. Cytological analysis for CD30 and ALK (Correct Answer)
Explanation: ***Cytological analysis for CD30 and ALK*** - The presentation of a **swollen and enlarged breast** with an **accumulation of fluid around a textured breast implant**, particularly 15 years after implantation, is highly suggestive of **Breast Implant-Associated Anaplastic Large Cell Lymphoma (BIA-ALCL)**. - **Cytological analysis of the periprosthetic fluid** for **CD30** (a surface marker expressed by BIA-ALCL cells) and **ALK** (typically negative in BIA-ALCL) is crucial for diagnosis. *Chemotherapy* - This is a treatment, not a diagnostic step, and is not the initial appropriate action for a suspected periprosthetic fluid accumulation without a definitive diagnosis. - The specific type of chemotherapy would also depend on the confirmed diagnosis and staging of the lymphoma, if present. *Mastectomy* - While mastectomy might be part of the treatment for advanced BIA-ALCL, it is an aggressive surgical intervention and not the initial diagnostic step in this scenario. - A definitive diagnosis is required before considering such a radical procedure. *Surgical replacement of textured implant with a smooth implant* - This option addresses the implant itself but does not diagnose or treat the underlying cause of the fluid accumulation, especially if it is indeed BIA-ALCL. - Surgical intervention might be part of the treatment, but only after a diagnosis is confirmed. *Mammogram* - A mammogram is primarily used to detect breast masses and calcifications indicative of breast cancer, not typically for evaluating periprosthetic fluid or lymphoma. - While imaging is useful, an MRI has already been performed, and the key diagnostic step now is to analyze the fluid.
Question 154: A 55-year-old woman presents with symptoms of rectal bleeding and pruritus in the perianal region. She works as a real estate agent and has a history of gastroesophageal reflux disease (GERD). On physical examination, her spleen and liver are enlarged. A blood smear reveals teardrop red blood cells (RBCs), and a leucoerythroblastic picture with the presence of nucleated RBC precursors and immature myeloid cells. A complete blood count shows a normocytic anemia. The physician explains that her condition is due to a JAK2 mutation in one of her chromosomes. What is a characteristic bone marrow aspirate of this condition?
- A. Hypocellular bone marrow
- B. Hypercellular with numerous abnormal megakaryocytes (Correct Answer)
- C. Hypercellular bone marrow with fibrosis in later stages
- D. Ringed sideroblasts and < 20% of myeloblasts
- E. Fibrous tissue with sclerotic spicules in later stages
Explanation: ***Hypercellular with numerous abnormal megakaryocytes*** - **Primary myelofibrosis (PMF)**, driven by a **JAK2 mutation**, presents with characteristic bone marrow findings that evolve over time. - In the **early (prefibrotic) phase**, bone marrow aspirate shows **hypercellularity** with increased proliferation of all three myeloid lineages. - The hallmark feature is the presence of **abnormal, dysplastic megakaryocytes** which are enlarged, hyperchromatic, with cloud-like or irregularly lobulated nuclei, often appearing in clusters. - These megakaryocytes are key to the diagnosis and are visible on aspirate in early disease before significant fibrosis develops. *Hypocellular bone marrow* - This is characteristic of **aplastic anemia** or hypoplastic myelodysplastic syndromes, not PMF. - PMF is a **myeloproliferative neoplasm** characterized by increased hematopoietic cell proliferation, resulting in hypercellularity. *Hypercellular bone marrow with fibrosis in later stages* - While PMF does progress to **reticulin and collagen fibrosis** in later stages, this option combines features from different disease phases. - The question asks for characteristic aspirate findings, and **fibrosis makes aspiration difficult** (often resulting in a "dry tap"). - Early aspirate shows hypercellularity with megakaryocyte abnormalities before extensive fibrosis develops. *Ringed sideroblasts and < 20% of myeloblasts* - This description is characteristic of **myelodysplastic syndromes (MDS)**, specifically MDS with ring sideroblasts. - Ringed sideroblasts are not a feature of PMF, and the clinical presentation with **teardrop RBCs, marked splenomegaly, and JAK2 mutation** points to PMF, not MDS. *Fibrous tissue with sclerotic spicules in later stages* - **Reticulin and collagen fibrosis** is indeed a hallmark of PMF, but this develops in **later stages** of the disease. - In advanced PMF, the bone marrow shows extensive fibrosis with osteosclerosis, making aspiration nearly impossible ("dry tap"). - The characteristic aspirate findings refer to the **early phase** when aspiration is still possible and shows the hypercellular, megakaryocyte-rich picture.
Question 155: A 52-year-old Caucasian man presents to the clinic for evaluation of a mole on his back that he finds concerning. He states that his wife noticed the lesion and believes that it has been getting larger. On inspection, the lesion is 10 mm in diameter with irregular borders. A biopsy is performed. Pathology reveals abnormal melanocytes forming nests at the dermo-epidermal junction and discohesive cell growth into the epidermis. What is the most likely diagnosis?
- A. Desmoplastic melanoma
- B. Lentigo maligna melanoma
- C. Superficial spreading melanoma (Correct Answer)
- D. Nodular melanoma
- E. Acral lentiginous melanoma
Explanation: ***Superficial spreading melanoma*** - This is the **most common type of melanoma**, accounting for 70% of cases, and typically presents with a **radial growth phase** showing irregular borders and enlarging size. - Histopathology revealing **nests of abnormal melanocytes at the dermo-epidermal junction** and **discohesive cell growth into the epidermis** (pagetoid spread) is characteristic of superficial spreading melanoma. *Desmoplastic melanoma* - Characterized by **fibrous stroma** and often **neural invasion**, with a less pigmented appearance, which is not described. - Typically presents as a firm, often amelanotic nodule, and can be more aggressive. *Lentigo maligna melanoma* - Primarily found in **chronically sun-damaged areas** of the elderly, often on the face, and begins as a flat, tan-brown macule that slowly enlarges. - Histologically, it shows **atypical melanocytes along the basal layer** of a thinned epidermis, not necessarily forming nests or extensive discohesive growth into the epidermis early on. *Nodular melanoma* - This type of melanoma has a **vertical growth phase from the outset**, appearing as a rapidly growing, dark, elevated lesion without a significant preceding radial growth phase. - Histologically, it involves a substantial dermal component with **minimal or absent intraepidermal radial growth**. *Acral lentiginous melanoma* - Occurs on the **palms, soles, or under the nails (subungual)**, and is less associated with sun exposure, often presenting as a dark, spreading lesion. - Its histological features involve **lentiginous proliferation of atypical melanocytes** along the dermo-epidermal junction with spread into the rete ridges in an acral distribution.
Question 156: A 55-year-old man comes to the physician for a routine health visit. He feels well except for occasional left-sided abdominal discomfort and left shoulder pain. He has smoked 1 pack of cigarettes daily for 20 years. He does not drink alcohol. His pulse is 85/min and his blood pressure is 130/70 mmHg. Examination shows a soft, nontender abdomen. The spleen is palpated 5 cm below the costal margin. There is no lymphadenopathy present. The remainder of the examination shows no abnormalities. Laboratory studies show: Hemoglobin 12.2 g/dL Hematocrit 36 % Leukocyte count 34,000/mm3 Platelet count 450,000/mm3 Cytogenetic testing of his blood cells is pending. Further evaluation of this patient is most likely to show which of the following findings?
- A. Autoimmune hemolytic anemia
- B. Elevated serum β2 microglobulin
- C. Elevated serum calcium
- D. Decreased basophil count
- E. Low leukocyte alkaline phosphatase score (Correct Answer)
Explanation: ***Low leukocyte alkaline phosphatase score*** - The patient's presentation with **splenomegaly**, **leukocytosis** (34,000/mm³), and a normal hemoglobin/platelet count, strongly suggests a **myeloproliferative neoplasm**, specifically **chronic myeloid leukemia (CML)**. - A **low leukocyte alkaline phosphatase (LAP) score** is a classic diagnostic feature of CML, as the neutrophils in CML have decreased LAP activity. *Autoimmune hemolytic anemia* - This condition is characterized by **anemia** and signs of **hemolysis**, such as elevated reticulocytes and lactate dehydrogenase, which are not described. - While anemia is present, the primary issue indicated by the high leukocyte count and splenomegaly is a myeloproliferative disorder, not solely autoimmune hemolysis. *Elevated serum β2 microglobulin* - Elevated **β2 microglobulin** is a marker of **lymphocytic proliferation** and is commonly seen in conditions like **multiple myeloma** or **lymphoma**. - The patient's dominant features of **marked leukocytosis** and **splenomegaly** are more consistent with a myeloid disorder than a lymphoid one. *Elevated serum calcium* - **Hypercalcemia** is a common complication of **multiple myeloma** or certain **carcinomas** due to bone destruction or paraneoplastic syndromes. - The patient's symptoms and lab findings (especially high leukocyte count and splenomegaly) do not point to these conditions. *Decreased basophil count* - In conditions like **CML**, an **elevated basophil count** is often observed, which contradicts the option of a decreased basophil count. - Other myeloproliferative neoplasms can also have varying basophil counts, but a decrease is not a hallmark.
Question 157: A 35-year-old male presents to his physician with the complaint of fatigue and weakness for six months. His physician orders a CBC which demonstrates anemia and thrombocytopenia. During the subsequent work up, a bone marrow biopsy is performed which ultimately leads to the diagnosis of acute promyelocytic leukemia. Which of the following translocations and fusion genes would be present in this patient?
- A. t(15;17) - PML/RARalpha (Correct Answer)
- B. t(9;22) - PML/RARalpha
- C. t(9;22) - BCR/Abl1
- D. t(14;18) - PML/RARalpha
- E. t(8;14) - BCR/Abl1
Explanation: ***t(15;17) - PML/RARalpha*** - **Acute Promyelocytic Leukemia (APL)** is uniquely characterized by the **t(15;17) translocation**, which fuses the **PML (promyelocytic leukemia)** gene on chromosome 15 with the **RARalpha (retinoic acid receptor alpha)** gene on chromosome 17. - This specific genetic alteration is crucial for diagnosis and dictates treatment with **all-trans retinoic acid (ATRA)**, which targets the aberrant RARalpha fusion protein. *t(9;22) - PML/RARalpha* - The **t(9;22) translocation** is associated with **Chronic Myeloid Leukemia (CML)**, forming the **BCR-ABL1 fusion gene**, not PML/RARalpha. - This option incorrectly pairs the translocation with a fusion gene specific to APL. *t(9;22) - BCR/Abl1* - While **t(9;22)** and the **BCR/Abl1 fusion gene** are correctly paired, this is the hallmark of **Chronic Myeloid Leukemia (CML)**, not acute promyelocytic leukemia. - CML typically presents with a different clinical picture and bone marrow findings than APL, primarily **leukocytosis with a left shift** and **basophilia**. *t(14;18) - PML/RARalpha* - The **t(14;18) translocation** is characteristic of **follicular lymphoma**, not any form of acute leukemia. - It results in the overexpression of the **BCL-2 gene**, promoting cell survival, and is not associated with the PML/RARalpha fusion. *t(8;14) - BCR/Abl1* - The **t(8;14) translocation** is associated with **Burkitt lymphoma**, leading to the translocation of the **MYC oncogene** close to immunoglobulin heavy chain enhancers. - This option also incorrectly pairs the translocation with the **BCR/Abl1 fusion gene**, which is characteristic of CML, and is not relevant to APL.
Question 158: A 70-year-old man is brought to the emergency department by his wife because of lethargy, confusion, and nausea for the past 2 days. He has previously been healthy and has no past medical history. His only medications are a daily multivitamin and acetaminophen, which he takes daily for hip pain. Vital signs are within normal limits. He is disoriented to place and time but recognizes his wife. The remainder of his physical examination shows no abnormalities. Laboratory studies show a hemoglobin concentration of 9.1 g/dL, a serum calcium concentration of 14.7 mg/dL, and a serum creatinine of 2.2 mg/dL (previously 0.9 mg/dL). Which of the following is the most likely underlying mechanism of this patient's condition?
- A. Increased serum levels of 1,25-hydroxyvitamin D
- B. Excessive consumption of calcium
- C. Excess PTH secretion from parathyroid glands
- D. Ectopic PTHrP release
- E. Overproliferation of plasma cells (Correct Answer)
Explanation: ***Overproliferation of plasma cells*** - The patient presents with **hypercalcemia** (14.7 mg/dL), acute **kidney injury** (creatinine 2.2 mg/dL from 0.9 mg/dL), and **anemia** (hemoglobin 9.1 g/dL). These three findings, especially in an elderly patient, strongly suggest **multiple myeloma**, which is characterized by the overproliferation of plasma cells in the bone marrow. - The overproliferation of plasma cells in multiple myeloma leads to the production of **osteoclast-activating factors**, resulting in increased bone resorption and subsequent hypercalcemia. *Increased serum levels of 1,25-hydroxyvitamin D* - While **elevated vitamin D levels** can cause hypercalcemia, it typically occurs due to excessive supplementation or granulomatous diseases (e.g., sarcoidosis). There is no history of either in this patient. - This mechanism would not explain the accompanying **anemia** or **acute kidney injury** (beyond what hypercalcemia itself might induce), which are prominent features here. *Excessive consumption of calcium* - **Milk-alkali syndrome**, caused by excessive intake of calcium and absorbable alkali, can lead to hypercalcemia, metabolic alkalosis, and renal insufficiency. - However, the patient's history does not indicate excessive calcium intake, and this etiology would not typically explain significant **anemia**. *Excess PTH secretion from parathyroid glands* - **Primary hyperparathyroidism** results in increased PTH, leading to hypercalcemia and often low or normal phosphate. While it can cause kidney stones and bone issues, it does not typically cause **anemia** or the rapid progression of kidney injury seen here. - The patient's creatinine has doubled in a short period, which is more suggestive of an acute insult or a systemic disease like myeloma, rather than chronic changes from primary hyperparathyroidism. *Ectopic PTHrP release* - **Parathyroid hormone-related protein (PTHrP)** can be ectopically secreted by various malignancies (e.g., squamous cell carcinoma of the lung, renal cell carcinoma), leading to **humoral hypercalcemia of malignancy**. - While this can cause **hypercalcemia** and related kidney issues, it typically does not directly cause **anemia** in the same way as multiple myeloma, where **bone marrow infiltration** by plasma cells directly suppresses hematopoiesis. The constellation of hypercalcemia, anemia, and acute kidney injury points more specifically to multiple myeloma.
Question 159: A 93-year-old woman is brought to the physician because of a purple area on her right arm that has been growing for one month. She has not had any pain or itching of the area. She has hyperlipidemia, a history of basal cell carcinoma treated with Mohs surgery 2 years ago, and a history of invasive ductal carcinoma of the right breast treated with radical mastectomy 57 years ago. She has had chronic lymphedema of the right upper extremity since the mastectomy. Her only medication is simvastatin. She lives in an assisted living facility. She is content with her living arrangement but feels guilty that she is dependent on others. Vital signs are within normal limits. Physical examination shows extensive edema of the right arm. Skin exam of the proximal upper right extremity shows three coalescing, 0.5–1.0 cm heterogeneous, purple-colored plaques with associated ulceration. Which of the following is the most likely diagnosis?
- A. Lymphangiosarcoma (Correct Answer)
- B. Cellulitis
- C. Thrombophlebitis
- D. Kaposi sarcoma
- E. Lichen planus
Explanation: ***Lymphangiosarcoma*** - This patient presents with a **purple area** with **ulceration** on an arm affected by chronic **lymphedema** following a mastectomy. This constellation of findings is highly suggestive of **Stewart-Treves syndrome**, which is a rare but aggressive form of angiosarcoma (lymphangiosarcoma) arising in the setting of chronic lymphedema. - The history of **radical mastectomy 57 years ago** with subsequent **chronic right upper extremity lymphedema** strongly predisposes to this condition, especially given the lack of pain or itching and the progressive nature of the lesion. *Cellulitis* - Characterized by **erythema**, **warmth**, **pain**, and **tenderness**, often with fever and systemic symptoms, none of which are described. - While lymphedema is a risk factor for cellulitis, the description of a **purple, ulcerated plaque** with a duration of one month is inconsistent with acute bacterial infection. *Thrombophlebitis* - Typically presents with **pain**, **tenderness**, **erythema**, and a palpable cord-like vein along the course of a superficial vein, which is not described. - The lesion described is a spreading, **ulcerated plaque**, not a discrete inflamed vein. *Kaposi sarcoma* - While it can present with **purple lesions**, Kaposi sarcoma is typically associated with **immunosuppression** (e.g., HIV infection) or certain endemic regions, neither of which is mentioned. - The strong association with **chronic lymphedema** in this case makes lymphangiosarcoma a more specific diagnosis. *Lichen planus* - A chronic inflammatory condition characterized by **pruritic, purple, polygonal, planar papules and plaques (the 6 Ps)**, often with fine white lines (Wickham's striae). - It does not typically present as a growing, **ulcerated purple plaque** in the setting of chronic lymphedema, and itching is a prominent symptom.
Question 160: A 53-year-old woman presents to her primary care physician in order to discuss the results of a biopsy. Two weeks ago, her mammogram revealed the presence of suspicious calcifications in her right breast, and she subsequently underwent biopsy of these lesions. Histology of the lesions revealed poorly cohesive cells growing in sheets with a nuclear to cytoplasmic ratio of 1:1. Furthermore, these cells were found to undergo invasion into the surrounding tissues. Given these findings, the patient is referred to an oncologist for further evaluation. Upon further imaging, the patient is found to have no lymph node adenopathy and no distant site metastases. Which of the following would most properly describe the lesions found in this patient?
- A. Low grade and high stage
- B. Low grade and low stage
- C. High grade and high stage
- D. High grade and low stage (Correct Answer)
- E. High grade and no stage
Explanation: ***High grade and low stage*** - The description of **poorly cohesive cells** growing in sheets and invading surrounding tissues indicates **high-grade** malignancy, suggesting aggressive cellular features and rapid growth. - The absence of lymph node adenopathy and distant metastases signifies a **low stage** of cancer, indicating that the disease is localized. *Low grade and high stage* - This option is incorrect because the cellular description points to a **high-grade** tumor, not low grade. - While there are no distant metastases, a tumor invading surrounding tissues is not considered low grade in terms of cellular aggressiveness. *Low grade and low stage* - This option is incorrect because the histological findings of **poorly cohesive cells** and **invasion** are characteristic of a **high-grade** tumor. - A low-grade tumor would typically have well-differentiated cells with minimal anaplasia and less aggressive behavior. *High grade and high stage* - This option is incorrect because, despite the tumor being **high grade** (aggressive cellular features), the absence of lymph node involvement and distant metastases indicates a **low stage**. - A high stage would imply spread to regional lymph nodes or distant sites. *High grade and no stage* - This option is incorrect because all cancers receive a stage, even if it's stage 0 or stage I, based on the extent of the disease (TNM classification). - The tumor, despite being **high grade**, can be accurately staged as **low stage** given the lack of spread.
Question 161: A 51-year-old woman presents with the following significant and unintentional weight loss. She denies any personal history of blood clots in her past, but she says that her mother has also had to be treated for pulmonary embolism in the recent past. She also mentions that she had been struggling with her weight, so she was initially content with losing the weight, but her daughter convinced her to come to the office to be checked out. Her past medical history is significant for preeclampsia, hypertension, polycystic ovarian syndrome, and hypercholesterolemia. She currently smokes 1 pack of cigarettes per day, drinks a glass of wine per day, and she currently denies any illicit drug use, although she has a remote past of injection drug use with heroin. The vital signs include: temperature 36.7°C (98.0°F), blood pressure 126/74 mm Hg, heart rate 111/min and irregular, and respiratory rate 17/min. On physical examination, her pulses are bounding and complexion is pale, but breath sounds remain clear. Oxygen saturation was initially 91% on room air and electrocardiogram (ECG) showed atrial fibrillation. Upon further discussion with the patient, her physician discovers that she is having some cognitive difficulty. Her leukocyte count is elevated to 128,000/mm3, and she has elevated lactate dehydrogenase (LDH), uric acid, and B-12 levels. A BCR-ABL translocation is present, as evidenced by the Philadelphia chromosome. What is the most likely diagnosis for this patient?
- A. Chronic lymphocytic leukemia
- B. Hairy cell leukemia
- C. Chronic myelogenous leukemia (Correct Answer)
- D. Acute lymphocytic leukemia
- E. Acute myelogenous leukemia
Explanation: ***Chronic myelogenous leukemia*** - The presence of a **Philadelphia chromosome (BCR-ABL translocation)** is the hallmark genetic abnormality for **chronic myelogenous leukemia (CML)**. - **Marked leukocytosis** (128,000/mm3) with elevated **LDH, uric acid**, and **B-12 levels** are characteristic findings in CML due to high cell turnover. *Chronic lymphocytic leukemia* - This condition is typically associated with **lymphocytosis** rather than such a high total leukocyte count, and it lacks the **Philadelphia chromosome**. - Patients often experience **generalized lymphadenopathy** and **hepatosplenomegaly**, which are not explicitly mentioned as primary findings. *Hairy cell leukemia* - Characterized by **pancytopenia**, **splenomegaly**, and **"hairy" lymphocytes** on blood smear, none of which are described. - It is not associated with the **Philadelphia chromosome** or such extreme leukocytosis. *Acute lymphocytic leukemia* - Presents with a rapid onset, often with symptoms like **bone pain**, **fevers**, and **bleeding**, along with immature lymphocytes (blasts). - While it can present with high white blood cell counts, the presence of the **Philadelphia chromosome** in this context points more specifically to CML. *Acute myelogenous leukemia* - Characterized by the presence of at least **20% myeloblasts** in the bone marrow or peripheral blood. - While it can manifest with high leukocyte counts, the defining feature of a **Philadelphia chromosome** is not typical, and it generally has a more acute presentation.
Question 162: A 75-year-old man presents to the physician with a complaint of persistent back pain. The patient states that the pain has been constant and occurs throughout the day. He says that he has also been experiencing greater fatigue when carrying out his daily activities. On review of systems, the patient notes that he lost more than 10 pounds in the past month despite maintaining his usual diet and exercising less often due to his fatigue. Physical exam is notable for a systolic murmur at the right sternal border, mild crackles at the bases of both lungs, and tenderness to palpation of his lumbar spine. Laboratory values are below: Serum: Na+: 141 mEq/L Cl-: 101 mEq/L K+: 4.2 mEq/L HCO3-: 23 mEq/L BUN: 20 mg/dL Glucose: 101 mg/dL Creatinine: 1.6 mg/dL Ca2+: 12.8 mg/dL A peripheral blood smear is ordered for the patient’s work-up. Which of the following would be the most likely finding on peripheral blood smear?
- A. Rouleaux formation (Correct Answer)
- B. Schistocytes
- C. Atypical lymphocytes
- D. Target cells
- E. Echinocytes
Explanation: ***Rouleaux formation*** - The patient's symptoms (persistent back pain, fatigue, weight loss, elevated calcium) are highly suggestive of **multiple myeloma**. - **Rouleaux formation** (stacking of red blood cells like coins) is a classic finding in multiple myeloma due to increased plasma proteins (monoclonal paraproteins) reducing the zeta potential between RBCs. *Schistocytes* - **Schistocytes** are fragmented red blood cells, typically seen in **microangiopathic hemolytic anemias** (e.g., TTP, HUS, DIC) or mechanical destruction (e.g., prosthetic heart valves). - This patient's presentation does not suggest a hemolytic process or microangiopathy. *Atypical lymphocytes* - **Atypical lymphocytes** are typically associated with **viral infections** (e.g., infectious mononucleosis, CMV) or some lymphoproliferative disorders. - The clinical picture of bone pain, hypercalcemia, and weight loss does not align with a primary diagnosis indicated by atypical lymphocytes. *Target cells* - **Target cells** (codocytes) are red blood cells with a central darkly stained area and an outer rim of hemoglobin, often seen in **liver disease**, **thalassemia**, and **iron deficiency anemia**. - While anemia can be present in multiple myeloma, target cells are not a primary and specific peripheral smear finding for this condition, and hypercalcemia is not characteristic of these disorders. *Echinocytes* - **Echinocytes** (burr cells) are red blood cells with evenly spaced spicules, often indicative of **uremia**, pyruvate kinase deficiency, or artifact. - While the patient has elevated creatinine, the presence of rouleaux formation in the context of hypercalcemia and bone pain points more strongly to multiple myeloma.
Question 163: A 70-year-old man presents to a medical office with painful micturition for 2 weeks. He denies any other symptoms. The past medical history is unremarkable. He has been a smoker most of his life, smoking approx. 1 pack of cigarettes every day. The physical examination is benign. A urinalysis shows an abundance of red blood cells. A cystoscopy is performed, which reveals a slightly erythematous area measuring 1.5 x 1 cm on the bladder mucosa. A biopsy is obtained and microscopic evaluation shows cells with an increased nuclear: cytoplasmic ratio and marked hyperchromatism involving the full thickness of the epithelium, but above the basement membrane. Which of the following best describes the biopsy findings?
- A. Microinvasion
- B. Urothelial metaplasia
- C. Urothelial carcinoma-in-situ (Correct Answer)
- D. Urothelial hyperplasia
- E. Reactive atypia
Explanation: ***Urothelial carcinoma-in-situ*** - The biopsy findings of cells with an increased **nuclear:cytoplasmic ratio**, **marked hyperchromatism**, and involvement of the **full thickness of the epithelium** but *above the basement membrane* are classic for **carcinoma-in-situ (CIS)**. - This represents a **high-grade dysplasia** confined to the epithelium, without invasion into the underlying stroma. *Microinvasion* - **Microinvasion** would involve the malignant cells breaching the **basement membrane** and entering the lamina propria. - The description explicitly states the changes are *above the basement membrane*, ruling out invasion. *Urothelial metaplasia* - **Urothelial metaplasia** involves the replacement of normal urothelium with another epithelial type, such as squamous or glandular epithelium. - While it can be a precursor to malignancy, it does not typically show the **severe cytologic atypia** and **full-thickness involvement** described. *Urothelial hyperplasia* - **Urothelial hyperplasia** is characterized by an increase in the number of layers of urothelial cells, but the cells themselves retain a relatively **benign appearance** with minimal atypia. - It lacks the prominent **cytologic abnormalities** (increased N:C ratio, hyperchromasia) seen in this biopsy. *Reactive atypia* - **Reactive atypia** (or inflammatory atypia) involves cellular changes due to inflammation or irritation, such as mild nuclear enlargement and irregular contours. - However, reactive changes generally do not exhibit the **marked cytologic abnormalities** and **full-thickness involvement** characteristic of high-grade dysplasia or CIS.
Question 164: A 66-year-old woman presents to the emergency department with abdominal pain. Her symptoms began when she was eating dinner. She has a past medical history of obesity, constipation, intravenous drug use, and diabetes. The patient is instructed to be nil per os and is transferred to the surgical floor. Three days later she had a cholecystectomy and is recovering on the surgical floor. Her laboratory values are ordered as seen below. Hemoglobin: 11 g/dL Hematocrit: 33% Leukocyte count: 8,500/mm^3 with normal differential Platelet count: 197,000/mm^3 Serum: Na+: 139 mEq/L Cl-: 100 mEq/L K+: 4.3 mEq/L HCO3-: 25 mEq/L BUN: 20 mg/dL Glucose: 99 mg/dL Creatinine: 1.1 mg/dL Ca2+: 10.5 mg/dL Alkaline phosphatase: 533 U/L GGT: 50 U/L AST: 22 U/L ALT: 20 U/L The patient is currently asymptomatic and states that she feels well. Which of the following is associated with this patient's underlying condition?
- A. Repeat gastrointestinal tract obstruction
- B. Blastic and lytic skeletal lesions (Correct Answer)
- C. Qualitative bone defect
- D. Reemergence of a hepatitis infection
- E. Monoclonal plasma cell replication
Explanation: ***Blastic and lytic skeletal lesions*** - The patient's **markedly elevated alkaline phosphatase** (533 U/L) with **normal liver enzymes** (AST, ALT) and **relatively normal GGT** indicates a **bone source** of the elevated alkaline phosphatase. - This laboratory pattern, in an asymptomatic elderly patient with normal calcium, is highly suggestive of **Paget's disease of bone**. - **Paget's disease** is characterized by abnormal bone remodeling with three phases: initial osteolytic phase, mixed lytic-blastic phase, and final osteoblastic phase, resulting in **both blastic and lytic skeletal lesions** on imaging. - The disease features disorganized bone remodeling with increased osteoclastic resorption followed by excessive osteoblastic activity, producing the characteristic mixed lytic-blastic pattern. *Repeat gastrointestinal tract obstruction* - While the patient had abdominal pain requiring cholecystectomy, there is no association between **Paget's disease** and recurrent gastrointestinal obstruction. - Paget's disease primarily affects bone and does not cause mechanical GI complications. *Qualitative bone defect* - **Qualitative bone defects** refer to abnormalities in bone matrix composition, such as **osteomalacia** (defective mineralization) or **osteogenesis imperfecta** (defective collagen). - **Paget's disease** is a **quantitative** disorder of bone remodeling with excessive, disorganized bone turnover, not a qualitative defect in bone matrix composition. - The bone formed in Paget's disease is structurally abnormal but has normal mineral and collagen composition. *Reemergence of a hepatitis infection* - There is no clinical or laboratory evidence of hepatitis reactivation. - The patient's **liver enzymes** (ALT 20, AST 22) are completely normal, excluding active hepatitis. - While the patient has a history of IV drug use (risk factor for hepatitis), this is unrelated to the current isolated elevation of alkaline phosphatase from bone. *Monoclonal plasma cell replication* - **Multiple myeloma** (characterized by monoclonal plasma cell proliferation) can present with hypercalcemia and lytic bone lesions. - However, alkaline phosphatase is typically **normal or low** in multiple myeloma because it causes purely lytic lesions without osteoblastic activity. - This patient's **markedly elevated alkaline phosphatase** (533 U/L) rules out multiple myeloma and points to a condition with increased osteoblastic activity like Paget's disease.
Question 165: A 56-year-old woman, gravida 3, para 3, comes to the physician because her left breast has become larger, hot, and itchy over the past 2 months. The patient felt a small lump in her left breast 1 year ago but did not seek medical attention at that time. She has hypertension and hyperlipidemia. Menarche was at the age of 11 years and menopause at the age of 46 years. Her mother died of breast cancer at the age of 45 years. The patient does not smoke or drink alcohol. Current medications include labetalol, simvastatin, and daily low-dose aspirin. She is 170 cm (5 ft 7 in) tall and weighs 78 kg (172 lb); BMI is 27 kg/m2. Her temperature is 37.7°C (99.9°F), pulse is 78/min, and blood pressure is 138/88 mm Hg. Examination shows large dense breasts. There is widespread erythema and edematous skin plaques over a breast mass in the left breast. The left breast is tender to touch and left-sided axillary lymphadenopathy is noted. Which of the following is the most likely diagnosis?
- A. Paget's disease of the breast
- B. Inflammatory breast cancer (Correct Answer)
- C. Mastitis
- D. Breast fibroadenoma
- E. Breast abscess
Explanation: ***Inflammatory breast cancer*** - The rapid onset of a **hot, itchy, and enlarged breast** with widespread **erythema and edematous skin plaques** (peau d'orange appearance) covering a breast mass, along with **axillary lymphadenopathy** and a history of a growing lump, are classic signs of inflammatory breast cancer. - Inflammatory breast cancer is an aggressive form of breast cancer characterized by cancer cells blocking lymph vessels in the skin of the breast, leading to these distinctive inflammatory symptoms. *Paget's disease of the breast* - Typically presents as a **red, scaly, patchy rash** resembling eczema on the nipple and areola, sometimes with itching or burning. - While it is a type of breast cancer, it usually does not cause the diffuse breast enlargement, warmth, and widespread edematous plaques seen in this case. *Mastitis* - Although it causes a **hot, red, and painful breast** and can be accompanied by fever, mastitis is typically associated with **lactation** and presents more acutely. - The presence of a long-standing "small lump" that has grown and the specific "peau d'orange" skin changes make mastitis less likely than cancer. *Breast fibroadenoma* - Fibroadenomas are **benign, solid lumps** that are typically **painless, movable, and rubbery**. - They do not cause diffuse breast enlargement, heat, itching, skin changes like erythema and edema, or axillary lymphadenopathy. *Breast abscess* - A breast abscess is a **localized collection of pus** within the breast, often following mastitis, characterized by severe localized pain, redness, swelling, and sometimes a fluctuant mass. - While it causes warmth and tenderness, the **widespread edematous plaques** and diffuse nature of the skin changes, coupled with a history of a growing lump, are more indicative of inflammatory breast cancer.
Question 166: A 58-year-old lifeguard develops squamous cell carcinoma of the skin on his forehead. Which of the following most likely preceded the development of this carcinoma?
- A. Dermatophyte infection
- B. Hamartomatous lesion of sebaceous glands
- C. Dry, scaly, hyperkeratotic papule (Correct Answer)
- D. A single, large pink patch
- E. UVC exposure
Explanation: ***Dry, scaly, hyperkeratotic papule*** - This description is characteristic of an **actinic keratosis**, a common **precursor lesion** to cutaneous **squamous cell carcinoma (SCC)**, especially in sun-exposed areas like the forehead of a lifeguard. - Actinic keratoses arise from chronic **UV radiation exposure** and represent **atypical epidermal keratinocytes**. *Dermatophyte infection* - A **dermatophyte infection** (e.g., ringworm) is a **fungal infection** of the skin, hair, or nails. - It does not typically progress to squamous cell carcinoma; rather, it causes inflammatory and scaling lesions. *Hamartomatous lesion of sebaceous glands* - A **hamartoma** is a benign, localized malformation of mature cells and tissues that occurs in normal configuration but in an abnormal quantity or arrangement. - A hamartomatous lesion of sebaceous glands is generally known as a **sebaceous nevus** (Nevus sebaceous of Jadassohn), which is present at birth and, while it carries a small risk of developing secondary tumors (including basal cell carcinoma, but less commonly SCC), it is not described as a "dry, scaly, hyperkeratotic papule" and is less common as a direct precursor in adults. *A single, large pink patch* - A **single, large pink patch** could describe various benign or malignant skin conditions, such as a **superficial basal cell carcinoma** or a form of **eczema**, but it is not specific for a precursor to SCC. - **Bowen's disease** (SCC in situ) can appear as a pink or reddish scaly patch, but the description "dry, scaly, hyperkeratotic papule" is more fitting for **actinic keratosis**, a more common antecedent lesion. *UVC exposure* - While **UV radiation** (specifically UVA and UVB) is a primary risk factor for SCC, **UVC radiation** is mostly blocked by the ozone layer and does not typically reach the Earth's surface or cause skin cancer in humans from environmental exposure. - The question asks for what most likely *preceded* the carcinoma in terms of a physical lesion, not the type of radiation that caused it.
Question 167: A 40-year-old woman presents to her primary care physician complaining of a several-month history of episodic sweating and heart racing. Her husband noticed that she becomes pale during these episodes. She also has progressive episodic pounding headaches which are not relieved by paracetamol. Her family history is negative for hypertension, endocrinopathies, or tumors. Vital signs reveal a blood pressure of 220/120 mm Hg, temperature (normal) and pulse of 110/min. Fundus examination reveals hypertensive retinal changes. This patient condition is most likely due to neoplasm arising from which of the following?
- A. Extra-adrenal chromaffin cells
- B. Zona glomerulosa
- C. Zona fasciculata
- D. Adrenal chromaffin cells (Correct Answer)
- E. Zona reticularis
Explanation: **Adrenal chromaffin cells** - The patient's symptoms of **episodic sweating, heart racing, pallor, pounding headaches**, and **severe hypertension** are classic for a **pheochromocytoma**. - A pheochromocytoma is a **neuroendocrine tumor** arising from the **chromaffin cells** of the **adrenal medulla**, which produce and release excess catecholamines. *Extra-adrenal chromaffin cells* - While pheochromocytomas can arise from **extra-adrenal chromaffin cells** (paragangliomas), the adrenal medulla is the most common site (approximately 80-85% of cases). - The symptoms are identical, but without imaging or further biochemical localization, the adrenal origin is statistically more likely. *Zona glomerulosa* - The **zona glomerulosa** of the adrenal cortex produces **mineralocorticoids**, primarily **aldosterone**. - Tumors of the zona glomerulosa (aldosteronomas) cause **primary hyperaldosteronism**, characterized by hypertension, hypokalemia, and metabolic alkalosis, but not the episodic symptoms described. *Zona fasciculata* - The **zona fasciculata** of the adrenal cortex produces **glucocorticoids**, primarily **cortisol**. - Tumors of the zona fasciculata cause **Cushing's syndrome**, characterized by central obesity, moon facies, striae, and hypertension, which are not consistent with the episodic symptoms presented. *Zona reticularis* - The **zona reticularis** of the adrenal cortex produces **androgen precursors**. - Tumors or hyperplasia of the zona reticularis can lead to hyperandrogenism, causing virilization symptoms, which are not present in this patient.
Question 168: A 32-year-old G0P0 African American woman presents to the physician with complaints of heavy menstrual bleeding as well as menstrual bleeding in between her periods. She also reports feeling fatigued and having bizarre cravings for ice and chalk. Despite heavy bleeding, she does not report any pain with menstruation. Physical examination is notable for an enlarged, asymmetrical, firm uterus with multiple palpable, non-tender masses. Biopsy confirms the diagnosis of a benign condition. Which of the following histological characteristics would most likely be seen on biopsy in this patient?
- A. Whorled pattern of smooth muscle bundles with well-defined borders (Correct Answer)
- B. Granulosa cells scattered around collections of eosinophilic fluid
- C. Laminated, concentric spherules with dystrophic calcification
- D. Presence of endometrial glands and stroma in the myometrium
- E. Clustered pleomorphic, hyperchromatic smooth muscle cells with extensive mitosis
Explanation: ***Whorled pattern of smooth muscle bundles with well-defined borders*** - The patient's symptoms (heavy and intermenstrual bleeding, enlarged, asymmetrical, firm uterus with palpable masses, fatigue, and **pica** due to **iron deficiency anemia**) are classic for **uterine leiomyomas** (fibroids). - Leiomyomas are benign tumors composed of **smooth muscle cells** arranged in a **whorled pattern** with distinct borders, differentiating them from the surrounding myometrium. *Granulosa cells scattered around collections of eosinophilic fluid* - This histological description is characteristic of a **granulosa cell tumor of the ovary**, which is a malignant tumor. - Granulosa cell tumors often present with symptoms related to **estrogen production**, such as abnormal uterine bleeding, but the uterine examination would not show an enlarged, firm, and asymmetrical uterus with palpable masses. *Laminated, concentric spherules with dystrophic calcification* - This describes **psammoma bodies**, which are often seen in conditions like **papillary thyroid carcinoma**, **meningiomas**, **ovarian serous cystadenocarcinomas**, and **papillary renal cell carcinoma**. - They are not associated with uterine findings described in this patient. *Presence of endometrial glands and stroma in the myometrium* - This is the histological hallmark of **adenomyosis**, a condition where endometrial tissue infiltrates the myometrium. - While adenomyosis can cause heavy menstrual bleeding and an enlarged uterus, it typically causes a **globular, symmetrically enlarged uterus** that is often **tender**, and severe **dysmenorrhea** (painful periods), which is notably absent in this patient. *Clustered pleomorphic, hyperchromatic smooth muscle cells with extensive mitosis* - This description is highly suggestive of a **leiomyosarcoma**, which is a malignant tumor of smooth muscle. - The question explicitly states that the biopsy confirms a **benign condition**, ruling out malignancy.
Question 169: A 54-year-old woman comes to the physician because of an ulcer on her left ankle for 6 years. She has had multiple ulcers over her left lower extremity during this period that have subsided with wound care and dressing. She has type 2 diabetes mellitus and gastroesophageal reflux disease. Current medications include metformin, sitagliptin, and omeprazole. She appears anxious. She is 162 cm (5 ft 4 in) tall and weighs 89 kg (196 lb); BMI is 34 kg/m2. Vital signs are within normal limits. Examination shows a 7.5-cm (3-in) ulcer with elevated, indurated margins and a necrotic floor above the left medial malleolus. There are multiple dilated, tortuous veins along the left lower extremity. There is 2+ pretibial edema of the lower extremities bilaterally. The skin around the left ankle appears darker than the right and there are multiple excoriation marks. Cardiopulmonary examination shows no abnormalities. Which of the following is the most appropriate next step in management of this patient's current condition?
- A. Trendelenburg test
- B. Punch biopsy (Correct Answer)
- C. Digital subtraction angiography
- D. Perthes test
- E. CT scan of the left leg
Explanation: ***Punch biopsy*** - A 6-year history of a non-healing **ulcer with elevated, indurated margins and a necrotic floor** is highly suspicious for **Marjolin's ulcer**, a type of squamous cell carcinoma arising in chronic wounds. - A **punch biopsy** is the most appropriate next step to obtain a tissue diagnosis and confirm or rule out malignancy. *Trendelenburg test* - The Trendelenburg test assesses **venous valve competence** in superficial veins. - While this patient has signs of **venous insufficiency** (dilated veins, edema, skin changes), the primary concern is the non-healing, suspicious ulcer, for which biopsy is more urgent. *Digital subtraction angiography* - Digital subtraction angiography is used to visualize **arterial blood flow** and diagnose peripheral artery disease. - Although the patient has diabetes, there are no classic signs of significant arterial insufficiency (e.g., claudication, cold limb, diminished pulses), and the ulcer characteristics are more suggestive of malignancy or venous etiology. *Perthes test* - The Perthes test evaluates the **patency of deep veins** and the function of communicating veins by assessing changes in superficial venous distension after exercise with a tourniquet. - Similar to the Trendelenburg test, it focuses on venous hemodynamics, which is secondary to the suspicion of malignancy in a chronic, non-healing ulcer. *CT scan of the left leg* - A CT scan can assess the **extent of soft tissue destruction or bone involvement** if malignancy is suspected or confirmed. - However, it is not the initial diagnostic step for determining the nature of the ulcer itself; a **tissue biopsy** is required for definitive diagnosis.
Question 170: A 44-year-old woman presents to the outpatient infectious disease clinic. She has a known history of HIV, well-controlled on HAART for the past 8 years. She currently has no additional significant medical conditions. She feels well and a physical examination is within normal limits. She denies any current tobacco use, alcohol use, or illicit drug use, although she has a history of heroin use (injection). Her vital signs include: temperature, 36.7°C (98.0°F); blood pressure, 126/74 mm Hg; heart rate, 87/min; and respiratory rate, 17/min. She has no complaints and is up to date on all of her vaccinations and preventative care. Which of the following malignancies can be seen and is often associated with AIDS?
- A. Thymomas
- B. Kaposi’s sarcoma (Correct Answer)
- C. Colonic adenocarcinoma
- D. Malignant melanoma
- E. Secondary osteosarcoma
Explanation: **Kaposi’s sarcoma** - **Kaposi's sarcoma (KS)** is a highly characteristic malignancy associated with **AIDS**, caused by **Human Herpesvirus 8 (HHV-8)**, and often presents with skin lesions, though it can affect internal organs. - Although the patient's HIV is well-controlled, her history of HIV infection places her at significant risk for **AIDS-defining malignancies** like KS, even with a stable immune status. *Thymomas* - **Thymomas** are rare tumors of the **thymus gland** and are not typically associated with HIV or AIDS. - Their pathogenesis is distinct, often linked to autoimmune conditions like **myasthenia gravis**, not immunodeficiency. *Colonic adenocarcinoma* - While **colonic adenocarcinoma** can occur in individuals with HIV, it is not considered an **AIDS-defining malignancy** and its incidence is not disproportionately elevated compared to the general population in the same way as KS. - Risk factors for colonic adenocarcinoma are generally linked to age, diet, and genetic predispositions, not directly to HIV infection. *Malignant melanoma* - **Malignant melanoma** is a skin cancer linked to **UV radiation exposure** and genetic factors, not directly nor significantly to HIV or AIDS. - Although immunosuppression can potentially increase the risk of certain cancers, melanoma is not specifically an **AIDS-defining malignancy**. *Secondary osteosarcoma* - **Osteosarcoma** is a primary **malignancy of bone**, typically seen in adolescents and young adults, and secondary osteosarcoma refers to one that develops after radiation or in conditions like Paget's disease. - There is no established direct link between HIV/AIDS and an increased risk of developing **osteosarcoma**.
Question 171: A 70-year-old man is at his dermatologist’s office for the treatment of a severely pruritic erythroderma with scaling on his buttocks that has been slowly progressing over the past two weeks. The patient works as a truck driver and has a history of hypertension treated with enalapril. The patient reports having tried an over-the-counter cream on the rash without improvement. The vital signs are within normal range. On physical exam, he has multiple confluent and well-demarcated pink patches on his buttocks and legs with some scaling and enlarged inguinal lymph nodes. The dermatologist orders a skin biopsy that reveals Pautrier microabscesses. What is the most likely diagnosis?
- A. Atopic dermatitis
- B. Kaposi sarcoma
- C. Lichen planus
- D. Psoriasis
- E. Mycosis fungoides (Correct Answer)
Explanation: ***Mycosis fungoides*** - The presence of **severely pruritic erythroderma** with **scaling**, progressing over weeks, and **enlarged regional lymph nodes** is highly suggestive of cutaneous T-cell lymphoma, specifically mycosis fungoides. - The definitive diagnostic finding is **Pautrier microabscesses** on skin biopsy, which are collections of atypical T lymphocytes in the epidermis, pathognomonic for mycosis fungoides. *Atopic dermatitis* - While it can cause **pruritic and scaly erythematous patches**, it typically presents earlier in life, often with a history of allergies or asthma, which are not mentioned. - **Pautrier microabscesses** are not a feature of atopic dermatitis; histology would show spongiosis and inflammation. *Kaposi sarcoma* - This condition presents as **violaceous plaques, patches, or nodules**, often in immunocompromised individuals, and is caused by HHV-8. - Histologically, it shows **spindle cells** and **vascular proliferation**, not Pautrier microabscesses. *Lichen planus* - Characterized by **pruritic, polygonal, planar, purple papules and plaques** (the 6 Ps), often with Wickham's striae. - Biopsy would reveal a **band-like lymphocytic infiltrate** at the dermoepidermal junction, not Pautrier microabscesses. *Psoriasis* - Typically presents as **well-demarcated erythematous plaques with silvery scales**, often on extensor surfaces. - While it can cause erythroderma, **Pautrier microabscesses** are not characteristic; histology shows **acanthosis**, **parakeratosis**, and **Munro microabscesses** (neutrophils in the stratum corneum).
Question 172: A 37-year-old woman, G1P0, visits her gynecologist's office for a routine prenatal checkup. During her quadruple screening test, her alpha-fetoprotein, β-hCG, and pregnancy-associated plasma protein were all decreased. There is also evidence of increased nuchal translucency on the scanning of the male fetus. A confirmatory test indicates signs of a genetic syndrome. The woman is counseled that her child will most likely have a severe intellectual disability. Physical features of this condition include polydactyly, cleft palate, micrognathia and clenched fists. This genetic condition also affects the formation of the brain and can lead to stillbirth. Most babies do not survive beyond the first year of life. Which of the following is responsible for this type of genetic syndrome?
- A. Nondisjunction of chromosomes (Correct Answer)
- B. Genomic imprinting
- C. Error in metabolism
- D. In utero infections
- E. Autosomal dominant genes
Explanation: ***Nondisjunction of chromosomes*** - The combination of **decreased alpha-fetoprotein, β-hCG, and PAPP-A**, **increased nuchal translucency**, and the described physical features (polydactyly, cleft palate, micrognathia, clenched fists) strongly points to **trisomy 13 (Patau syndrome)**. - Trisomy 13 is caused by **nondisjunction** during meiosis, where chromosomes fail to separate properly, resulting in an extra copy of chromosome 13 in the fetus. - Classic features include holoprosencephaly, severe intellectual disability, polydactyly, and the characteristic facial abnormalities described. *Genomic imprinting* - **Genomic imprinting** refers to epigenetic modifications that cause genes to be expressed only from the allele inherited from a specific parent (e.g., Prader-Willi or Angelman syndromes). - This mechanism typically involves altered gene expression, not the presence of an entire extra chromosome, and does not explain the widespread structural anomalies observed here. *Error in metabolism* - **Errors in metabolism** are genetic disorders that cause a deficiency or absence of specific enzymes, leading to the accumulation of toxic substances or impaired production of essential compounds (e.g., PKU, MPS). - While metabolic disorders can cause severe intellectual disability, they typically do not present with the specific constellation of visible congenital abnormalities and abnormal screening markers seen in this case. *In utero infections* - **In utero infections** (e.g., TORCH infections like toxoplasmosis, rubella, CMV) can cause congenital anomalies, intellectual disability, and increased nuchal translucency. - However, the specific pattern of quadruple screen results (all decreased markers) is highly characteristic of chromosomal abnormalities like trisomy 13, rather than infections. *Autosomal dominant genes* - **Autosomal dominant genes** cause disorders when a single copy of a mutated gene is sufficient to cause the disease (e.g., Huntington's disease, Marfan syndrome). - While these can cause genetic syndromes, the severe, multiorgan structural anomalies described, coupled with the specific prenatal screening profile, are not typically characteristic of a single autosomal dominant gene mutation but rather a gross chromosomal abnormality.
Question 173: A 35-year-old woman comes to the physician because of a 2-month history of vaginal bleeding after intercourse. Menarche occurred at the age of 13 years and menses occur at regular 28-day intervals. Gynecologic examination shows an irregular lesion at the cervical os. Histological evaluation of a cervical biopsy specimen obtained on colposcopy confirms a diagnosis of in-situ cervical cancer. This cancer is most likely derived from which of the following types of cells?
- A. Simple cuboidal epithelium
- B. Non-keratinized stratified squamous epithelium (Correct Answer)
- C. Ciliated simple columnar epithelium
- D. Keratinized stratified squamous epithelium
- E. Simple columnar epithelium with tubular glands
Explanation: ***Non-keratinized stratified squamous epithelium*** - The **cervical os** (ectocervix) is normally lined by **non-keratinized stratified squamous epithelium**. **Cervical cancer**, whether in situ or invasive, almost always arises from this type of epithelium. - The **transformation zone**, where the squamous epithelium meets the columnar epithelium, is particularly vulnerable to HPV infection and subsequent dysplastic changes. *Simple cuboidal epithelium* - This type of epithelium is typically found in structures like the **kidney tubules** and some glands, not the cervix. - Cervical cancer is not derived from simple cuboidal epithelium. *Ciliated simple columnar epithelium* - This epithelium lines the **fallopian tubes** and parts of the **endocervix**, but it is not the primary site for the development of most cervical cancers. - Adenocarcinoma of the cervix arises from columnar cells, but squamous cell carcinoma (the most common type) originates from squamous cells. *Keratinized stratified squamous epithelium* - **Keratinized stratified squamous epithelium** is found on the external skin and in the vagina, providing protection against abrasion and desiccation. - This type of epithelium is **not typically found on the cervix**, and cervical cancer does not originate from keratinized epithelium. *Simple columnar epithelium with tubular glands* - The **endocervix** is lined by **simple columnar epithelium** with tubular glands, which produce mucus. - While adenocarcinoma of the cervix can arise from these cells, the most common type of cervical cancer (**squamous cell carcinoma**) originates from the squamous epithelium of the ectocervix.
Question 174: A 32-year-old man presents to the emergency room for a generalized tonic-clonic seizure. After stabilizing the patient, a full radiologic evaluation reveals multiple contrast-enhancing lesions in the brain, lungs, and liver. According to his wife, he lost several pounds in the last few months. The medical history is relevant for cryptorchidism, with abdominal testes that were surgically transferred to the scrotum just before he turned 1-year old. His lab investigation reveals: α-fetoprotein: 9 ng/mL (normal values < 10 ng/mL) Human chorionic gonadotropin: 1,895 IU/L (normal values < 0.5 IU/L) Which of the following microscopic features best describes the lesions seen in this patient's imaging study?
- A. Germ cells with well-defined borders, central nuclei, prominent nucleoli, and clear cytoplasm
- B. Mixture of primitive neuroectoderm, loose mesenchyme, and primitive glandular structures
- C. Intimate association of syncytiotrophoblast and cytotrophoblast cells (Correct Answer)
- D. Glomerulus-like structure with a mesoderm core, a central capillary, and lined with germ cells
- E. Cells with hyaline-like globules
Explanation: ***Intimate association of syncytiotrophoblast and cytotrophoblast cells*** - The combination of a **generalized tonic-clonic seizure** (suggesting brain metastasis), **multiple contrast-enhancing lesions** in brain, lungs, and liver, weight loss, history of **cryptorchidism**, and significantly **elevated human chorionic gonadotropin (hCG)** (1,895 IU/L, normal < 0.5 IU/L) despite normal AFP, is highly indicative of a **choriocarcinoma**. - **Choriocarcinomas** are characterized microscopically by an intimate admixture of **syncytiotrophoblast** and **cytotrophoblast cells** lacking chorionic villi. These tumors are highly aggressive and prone to widespread metastasis, particularly to the lungs, brain, and liver. *Germ cells with well-defined borders, central nuclei, prominent nucleoli, and clear cytoplasm* - This description is characteristic of **seminoma**, the most common germ cell tumor. - While seminomas can spread, the extremely high hCG levels without elevated AFP and the rapid, widespread metastasis depicted are more typical of choriocarcinoma. *Mixture of primitive neuroectoderm, loose mesenchyme, and primitive glandular structures* - This description refers to the microscopic features of an **immature teratoma**. - While immature teratomas can arise from germ cells, they typically do not produce such high levels of hCG, and their metastatic pattern is often different. *Glomerulus-like structure with a mesoderm core, a central capillary, and lined with germ cells* - This is the classic description of a **Schiller-Duval body**, which is pathognomonic for a **yolk sac tumor** (also known as endodermal sinus tumor). - Yolk sac tumors are associated with elevated **alpha-fetoprotein (AFP)**, which is normal in this patient. *Cells with hyaline-like globules* - The presence of **hyaline-like globules** (containing AFP and/or alpha-1-antitrypsin) is also a feature seen in **yolk sac tumors**. - As mentioned, the normal AFP level in this patient makes a yolk sac tumor less likely.
Question 175: A 65-year-old man presents with complaints of weakness and swollen gums for the past 3 weeks. He also says he cut his finger while cooking, and the bleeding took more than 10 minutes to stop. He has a family history of diabetes mellitus type 2 and prostate cancer. Current medications are multivitamin. His blood pressure is 122/67 mm Hg, the respiratory rate is 13/min, and the temperature is 36.7°C (98.0°F). On physical examination, the patient seems pale and lethargic. On cardiac exam, a pulmonary valve flow murmur is heard. There is significant hepatosplenomegaly present, and several oral mucosal petechiae in the oral cavity are noted. Gum hypertrophy is also present. A peripheral blood smear reveals myeloperoxidase-positive cells and Auer Rods. A bone marrow biopsy shows > 30% of blast cells. Which of the following chromosomal abnormalities is associated with this patient’s most likely diagnosis?
- A. t(9;22)
- B. JAK2 mutation
- C. t(11;14)
- D. t(15;17) (Correct Answer)
- E. t(8;14)
Explanation: ***t(15;17)*** - The presence of **myeloperoxidase-positive cells**, **Auer rods**, and **gum hypertrophy** indicates acute promyelocytic leukemia (APML), a subtype of acute myeloid leukemia (AML). - APML is strongly associated with the **t(15;17) translocation**, which involves the **PML** and **RARα** genes. *t(9;22)* - The **t(9;22) translocation** (Philadelphia chromosome) is characteristic of **chronic myeloid leukemia (CML)**, which typically presents with a high white blood cell count and often with a more chronic course, not the acute features seen here. - While CML can have splenomegaly, it's less likely to present with rapidly progressive bleeding, gum hypertrophy, and a high blast percentage in the bone marrow. *JAK2 mutation* - **JAK2 mutations** are commonly found in **myeloproliferative neoplasms (MPNs)** such as polycythemia vera, essential thrombocythemia, and primary myelofibrosis. - MPNs usually present with different clinical features and laboratory findings than those indicative of acute leukemia, like the absence of a high blast count and Auer rods. *t(11;14)* - The **t(11;14) translocation** is characteristic of **mantle cell lymphoma**, a type of non-Hodgkin lymphoma. - While mantle cell lymphoma can present with lymphadenopathy and splenomegaly, it does not typically manifest with Auer rods, myeloperoxidase-positive blasts, or the acute signs of bone marrow failure seen in this patient. *t(8;14)* - The **t(8;14) translocation** is the hallmark of **Burkitt lymphoma**, which is a highly aggressive B-cell lymphoma. - Burkitt lymphoma typically presents with rapidly growing masses, often extranodal, and while it can involve the bone marrow, it does not show myeloperoxidase-positive blasts or Auer rods.
Question 176: A 60-year-old man presents to your office because he noticed a "weird patch" on the floor of his mouth. He states that he noticed it a few months ago, but did not report it because it did not hurt. However, he is concerned because it has not regressed and seems to have changed in shape. On examination, you notice the patient has poor dentition and he admits to using chewing tobacco daily. The patch on the floor of his mouth is red with irregular borders. Which of the following would be an appropriate way to counsel this patient on his current condition?
- A. This lesion is closely associated with chronic Hepatitis C infection.
- B. This lesion necessitates biopsy. (Correct Answer)
- C. Tobacco use is not a risk factor.
- D. This lesion carries no increased risk of cancer.
- E. This lesion is due to an infection.
Explanation: ***This lesion necessitates biopsy.*** - The description of a **red patch** (erythroplakia) with **irregular borders** on the floor of the mouth, especially in a chronic **chewing tobacco user**, is highly suspicious for **dysplasia or squamous cell carcinoma**. - **Biopsy** is essential for definitive diagnosis and to rule out malignancy, which is crucial given the high-risk features and continued tobacco use. *This lesion is closely associated with chronic Hepatitis C infection.* - While chronic **Hepatitis C** can be associated with certain oral lesions like **lichen planus**, it is not a direct or strong association for an isolated, evolving red patch like the one described. - The primary risk factors here are **tobacco use** and the **morphology** of the lesion itself, not chronic viral infection. *Tobacco use is not a risk factor.* - This statement is incorrect; **chewing tobacco use** is a major **risk factor** for oral cancers, particularly **squamous cell carcinoma**, which can present as erythroplakia. - The patient's history directly points to a significant behavioral risk factor for this type of lesion. *This lesion carries no increased risk of cancer.* - The lesion described, especially its presentation as **erythroplakia** (red patch) and its **tendency not to regress** but instead to change shape in a tobacco user, carries a **very high risk of being cancerous or precancerous**. - **Erythroplakia** has a higher malignant transformation rate than leukoplakia. *This lesion is due to an infection.* - While some oral lesions can be infectious (e.g., fungal, viral), the description of a **red patch with irregular borders** that is progressive, combined with **chewing tobacco use**, is much more indicative of **dysplasia or malignancy** rather than a simple infection. - There are no other signs of infection such as fever, pus, or acute inflammation.
Question 177: A 47-year-old female comes to the emergency department because of increasing back pain for the past 2 weeks. She is unable to perform her daily chores. One month ago, she fell and hurt her back while working outside in the garden. The pain subsided with over-the-counter acetaminophen. She underwent a left mastectomy 1 year ago for breast cancer. She has type 2 diabetes mellitus. Current medications include metformin, sitagliptin, and a multivitamin. She appears uncomfortable. Her temperature is 38.9°C (102.0°F), pulse is 101/min, and blood pressure is 110/80 mm Hg. Examination of the back shows thoracic vertebral tenderness. She has mild stiffness on neck flexion. Muscle strength is decreased in the lower extremities. Deep tendon reflexes are 2+ bilaterally. Sensation to pain, fine touch, temperature, and proprioception is intact. Her hemoglobin concentration is 13.1 g/dL and leukocyte count is 19,300/mm3. Which of the following is the most appropriate next step in management?
- A. MRI of the spine (Correct Answer)
- B. Vancomycin and nafcillin therapy
- C. Serum protein electrophoresis
- D. Methylprednisone therapy
- E. X-rays of the spine
Explanation: ***MRI of the spine*** - The patient presents with **back pain, fever, leukocytosis**, and a history of **breast cancer**, which raises suspicion for **spinal metastasis** or **spinal infection (e.g., discitis, osteomyelitis)**, both requiring urgent imaging. - Given the neurological deficits noted (decreased muscle strength in lower extremities), an **MRI is crucial** to assess for **spinal cord compression** and guide immediate surgical or medical intervention. *Vancomycin and nafcillin therapy* - While the patient has signs suggestive of infection (fever, leukocytosis, elevated pulse, vertebral tenderness), starting broad-spectrum antibiotics empirically **without definitive diagnosis** or imaging is not the most appropriate first step. - An **MRI of the spine** is needed to confirm the presence of infection, identify the location, and rule out other serious etiologies like spinal metastasis before initiating targeted antimicrobial therapy. *Serum protein electrophoresis* - **Serum protein electrophoresis (SPEP)** is used to detect and quantify monoclonal proteins, primarily in the diagnosis and monitoring of **multiple myeloma**. - While back pain can be a symptom of multiple myeloma, the patient's acute presentation with fever, leukocytosis, and neurological deficits makes **spinal cord compression** or **infection** more pressing concerns that require immediate anatomical imaging. *Methylprednisone therapy* - **Corticosteroids** like methylprednisone can reduce inflammation and swelling, potentially alleviating symptoms in cases of acute spinal cord compression due to inflammation or tumor. - However, steroids can also **mask symptoms of infection** and are generally **contraindicated in infectious processes** unless absolutely necessary (e.g., severe spinal cord compression from epidural abscess where benefits outweigh risks), and should only be considered after an MRI and diagnosis. *X-rays of the spine* - **Plain X-rays** are **poor at visualizing soft tissue structures** like the spinal cord, nerve roots, or early tumor infiltration and infection (e.g., discitis, osteomyelitis). - They have **limited sensitivity** for detecting early lesions, making them less suitable for evaluating acute neurological deficits or suspected cord compression, where an **MRI is superior**.
Question 178: A previously healthy 61-year-old man comes to the physician because of a 3-month history of intermittent fever, easy fatiguability, and a 4.4-kg (9.7-lb) weight loss. Physical examination shows conjunctival pallor. The spleen is palpated 5 cm below the left costal margin. Laboratory studies show a leukocyte count of 75,300/mm3 with increased basophils, a platelet count of 455,000/mm3, and a decreased leukocyte alkaline phosphatase score. A peripheral blood smear shows increased numbers of promyelocytes, myelocytes, and metamyelocytes. Which of the following is the most likely diagnosis?
- A. Chronic myeloid leukemia (Correct Answer)
- B. Acute promyelocytic leukemia
- C. Essential thrombocythemia
- D. Chronic lymphocytic leukemia
- E. Leukemoid reaction
Explanation: ***Chronic myeloid leukemia*** - The combination of **leukocytosis (75,300/mm3)**, **splenomegaly**, **increased basophils**, and a **low leukocyte alkaline phosphatase (LAP) score** is highly characteristic of CML - The presence of immature myeloid forms (promyelocytes, myelocytes, metamyelocytes) on peripheral smear, referred to as a **"left shift"**, further supports this diagnosis - CML is typically associated with the **Philadelphia chromosome [t(9;22)]** resulting in the BCR-ABL fusion gene *Acute promyelocytic leukemia* - This acute leukemia is characterized by a high number of **abnormal promyelocytes** with prominent Auer rods and is associated with the **t(15;17)** chromosomal translocation - It typically presents with severe **cytopenias** (not leukocytosis) and a high risk of **disseminated intravascular coagulation (DIC)**, which are not described here - The chronic course and marked leukocytosis make this diagnosis unlikely *Essential thrombocythemia* - This myeloproliferative neoplasm primarily involves **excessive platelet production**, leading to consistently high platelet counts (typically >450,000/mm3) - While this patient has mild thrombocytosis, the prominently elevated **white blood cell count** (75,300/mm3) with myeloid left shift and **splenomegaly** point to a different myeloproliferative disorder *Chronic lymphocytic leukemia* - CLL is characterized by a proliferation of mature **B lymphocytes**, resulting in **lymphocytosis** with small, mature lymphocytes on peripheral smear - The peripheral smear in this case shows increased **immature myeloid forms** (not lymphocytes), making CLL incompatible with this presentation - CLL typically has a normal or elevated LAP score *Leukemoid reaction* - A leukemoid reaction is a reactive (non-malignant) process causing marked leukocytosis, usually in response to severe infection, inflammation, or malignancy - It is characterized by a **normal or elevated LAP score**, which is the key distinguishing feature from CML - The **decreased LAP score** in this patient makes a leukemoid reaction unlikely and strongly supports a diagnosis of CML
Question 179: A 24-year-old man comes to the physician because of 2 episodes of bleeding from the rectum over the past month. The patient’s father died of colon cancer at the age of 42. The patient has no history of any serious illness and takes no medications. He does not smoke. His vital signs are within normal limits. Physical examination shows a small hard mass over the right mandible that is nontender and fixed to the underlying bone. A similarly hard and painless 5 × 5 mass is palpated over the rectus abdominis muscle. On examination of the rectum, a polypoid mass is palpated at fingertip. Proctosigmoidoscopy shows numerous polyps. Which of the following best explains these findings?
- A. Familial polyposis of the colon
- B. Peutz-Jeghers syndrome
- C. Turcot’s syndrome
- D. Gardner’s syndrome (Correct Answer)
- E. Lynch’s syndrome
Explanation: ***Gardner's syndrome*** - This syndrome is a variant of **familial adenomatous polyposis (FAP)**, characterized by numerous **colonic polyps** (leading to rectal bleeding) in conjunction with **extra-intestinal manifestations**. - The extra-intestinal features described, such as **osteomas** (small hard mass over the mandible) and **desmoid tumors** (painless 5 × 5 mass over the rectus abdominis muscle), are classic findings of Gardner's syndrome. The family history of colon cancer further supports this diagnosis. *Familial polyposis of the colon* - Familial adenomatous polyposis (FAP) primarily involves the development of **hundreds to thousands of adenomatous colonic polyps**, leading to a high risk of colorectal cancer. - While it explains the rectal polyps and family history, it does **not account for the extra-intestinal manifestations** like osteomas and desmoid tumors, which are key to Gardner's syndrome. *Peutz-Jeghers syndrome* - This syndrome is characterized by **hamartomatous polyps** throughout the gastrointestinal tract and **mucocutaneous hyperpigmentation** (dark spots) on the lips, buccal mucosa, and digits. - The patient's presentation does not include hamartomatous polyps or mucocutaneous pigmentation. *Turcot's syndrome* - Turcot's syndrome is a rare condition involving the co-occurrence of **colorectal polyps** (often adenomatous) and **central nervous system (CNS) tumors**, such as medulloblastoma or glioblastoma. - The patient presents with osteomas and desmoid tumors, which are not CNS manifestations central to Turcot's syndrome. *Lynch's syndrome* - Lynch syndrome (hereditary nonpolyposis colorectal cancer, HNPCC) is characterized by an increased risk of developing **colorectal cancer** and other cancers (e.g., endometrial, ovarian) due to defects in **DNA mismatch repair genes**. - It typically involves fewer polyps than FAP and does not present with the specific extra-intestinal symptoms like osteomas or desmoid tumors seen in this patient.
Question 180: A 53-year-old female visits her physician with watery diarrhea and episodic flushing. The patient reports that she is often short of breath, and a pulmonary exam reveals bilateral wheezing. A CT scan shows a mass in the terminal ileum. 24-hour urine collection shows abnormally elevated 5-hydroxyindoleacetic acid (HIAA) levels. Ultrasound demonstrates a tricuspid valve with signs of fibrosis with a normal mitral valve. A metastatic disease to which organ is most commonly associated with the patient's syndrome?
- A. Liver (Correct Answer)
- B. Pancreas
- C. Kidney
- D. Brain
- E. Lung
Explanation: ***Liver*** - The combination of **watery diarrhea**, **episodic flushing**, **bilateral wheezing**, a **terminal ileum mass**, elevated **5-HIAA**, and **tricuspid valve fibrosis** points to **carcinoid syndrome**. This syndrome typically occurs when neuroendocrine tumors, often originating in the gut, metastasize to the liver. - The **liver** is usually the site of metastasis that allows hormones like **serotonin** (metabolized to 5-HIAA) to bypass hepatic metabolism and enter systemic circulation, causing the characteristic symptoms. *Pancreas* - While neuroendocrine tumors can originate in the **pancreas**, **metastasis to the liver** is still the most common scenario for systemic symptoms in carcinoid syndrome. - Pancreatic neuroendocrine tumors (PNETs) primarily produce other hormones (e.g., insulin, glucagon, VIP), and the classic carcinoid syndrome with flushing and wheezing from serotonin is less typical unless **liver metastases** are present. *Kidney* - **Kidney** metastasis from neuroendocrine tumors is less common than liver involvement and would not typically explain the systemic symptoms of **carcinoid syndrome** due to bypass of first-pass metabolism. - While some neuroendocrine tumors can metastasize to the kidney, it is not the most common organ associated with systemic carcinoid features. *Brain* - **Brain** metastases from neuroendocrine tumors, while possible, are less frequent than liver metastases and rarely cause the systemic symptoms of **carcinoid syndrome**. - **Serotonin** does not readily cross the blood-brain barrier in significant amounts systemically to cause brain-specific symptoms related to its peripheral overproduction. *Lung* - **Primary lung carcinoid tumors** can cause carcinoid syndrome without liver metastasis, but the presence of a **terminal ileum mass** in this case strongly suggests a gut origin. - When lung metastases occur from a gut primary, they are usually a consequence of widespread disease, and the **liver** is still the primary site enabling systemic symptom onset due to its role in metabolizing gut hormones.
Question 181: A 14-year-old boy presents to his pediatrician with a 5-day history of abdominal pain and bloody stool. He denies having a fever and says that he has not experienced any other symptoms associated with the abdominal pain. He has no past medical history and does not take any medications or supplements. His family history is significant for a grandfather who developed Alzheimer disease at age 80 and a cousin who died at age 21 from colon cancer. Physical exam is unremarkable. Based on clinical suspicion a colonoscopy is obtained showing hundreds of small polyps in the colon. A mutation of a gene on which of the following chromosomes is most likely responsible for this patient's symptoms?
- A. 5 (Correct Answer)
- B. 7
- C. X
- D. 17
- E. 19
Explanation: ***Correct: Chromosome 5*** - The patient's presentation with hundreds of small colon polyps on colonoscopy strongly suggests **Familial Adenomatous Polyposis (FAP)** - FAP is an **autosomal dominant** disorder caused by a mutation in the **adenomatous polyposis coli (APC) gene**, which is located on **chromosome 5 (5q21-q22)** - The family history of a cousin dying at age 21 from colon cancer supports this diagnosis *Incorrect: Chromosome 7* - Mutations on chromosome 7 are not typically associated with FAP or extensive colonic polyposis - While other genetic conditions are linked to chromosome 7 (e.g., cystic fibrosis), they do not present with this specific phenotype *Incorrect: Chromosome X* - Mutations on the X chromosome cause **X-linked disorders**, affecting males disproportionately - Hereditary colorectal cancer syndromes are generally autosomal, not X-linked *Incorrect: Chromosome 17* - Chromosome 17 is associated with several genetic conditions, including **Neurofibromatosis type 1 (NF1)** and mutations in **TP53 (Li-Fraumeni syndrome)** - While Li-Fraumeni syndrome increases cancer risk, it typically presents with a broader spectrum of cancers and not primarily with hundreds of colonic polyps in adolescence *Incorrect: Chromosome 19* - Chromosome 19 contains genes linked to various conditions, but not typically to FAP or other hereditary polyposis syndromes of the colon - For instance, **myotonic dystrophy type 1** is linked to chromosome 19, which does not involve extensive colonic polyps
Question 182: A 72-year-old and his caregiver present for a follow-up after a transthoracic needle biopsy of one of the large lesions in his chest was reported as non-small cell carcinoma of the lung. Previously, a chest CT revealed numerous nodules in the lungs bilaterally. The chest CT was ordered after the patient experienced a persistent cough with hemoptysis and a history of multiple episodes of pneumonia over the past year. The patient has a history of dementia and is a poor historian. The caregiver states that the patient has no history of smoking and that he was a lawyer before he retired, 10 years ago. The caregiver can only provide a limited medical history, but states that the patient sees another doctor “to monitor his prostate”. Which of the following is true regarding the pathogenesis of the nodules seen in this patient?
- A. Proliferation of cells that contain glands that produce mucin (Correct Answer)
- B. Tumors seeded via the pulmonary arteries
- C. Infection of the lung parenchyma with a gram-negative bacteria grown on charcoal yeast agar
- D. Aspergillus infection leading to a formation of a 'fungus ball'
- E. Malignant transformation of neuroendocrine cells
Explanation: ***Proliferation of cells that contain glands that produce mucin*** - This describes **adenocarcinoma**, the most common subtype of non-small cell lung carcinoma (NSCLC), which was confirmed by the **transthoracic needle biopsy**. - Adenocarcinoma is characterized by **glandular differentiation** and **mucin production**, and is the **most common lung cancer in non-smokers**. - The presentation of **numerous bilateral nodules** is consistent with **primary lung adenocarcinoma with intrapulmonary metastases** (spread within the lungs via lymphatics or hematogenous routes). Adenocarcinoma has a propensity for early hematogenous spread. - The persistent cough, hemoptysis, and recurrent pneumonias are all consistent with advanced lung adenocarcinoma. *Malignant transformation of neuroendocrine cells* - This describes **small cell lung carcinoma** or **neuroendocrine tumors** (carcinoid tumors, large cell neuroendocrine carcinoma). - The biopsy explicitly reported **non-small cell carcinoma**, which rules out small cell lung cancer. - While large cell neuroendocrine carcinoma is technically classified under NSCLC, the classic description of neuroendocrine transformation typically refers to small cell carcinoma. *Tumors seeded via the pulmonary arteries* - This describes **hematogenous metastases** to the lungs from an extrapulmonary primary tumor. - However, the biopsy showed **non-small cell carcinoma of the lung**, not metastatic carcinoma from another organ (such as prostate, breast, colon, etc.). - If these were metastases from prostate cancer, the pathology report would indicate **metastatic prostatic adenocarcinoma**, not primary lung carcinoma. Pathologists can distinguish lung primary from metastases using morphology and immunohistochemistry. - While the patient "monitors his prostate," this likely refers to benign prostatic hyperplasia or PSA surveillance, not active prostate cancer. *Infection of the lung parenchyma with a gram-negative bacteria grown on charcoal yeast agar* - This describes **Legionella pneumophila**, which causes Legionnaires' disease and is grown on buffered charcoal yeast extract (BCYE) agar. - This is an **infectious process**, not a neoplastic one. The biopsy confirmed **malignancy** (non-small cell carcinoma), definitively ruling out infection as the cause of the nodules. *Aspergillus infection leading to a formation of a 'fungus ball'* - An **aspergilloma** (fungus ball) is a saprophytic colonization of **pre-existing lung cavities** (from TB, sarcoidosis, etc.) by *Aspergillus* species. - This is an **infectious/fungal process**, not malignancy. The biopsy showed **non-small cell carcinoma**, confirming a neoplastic process. - Aspergillomas typically present as a **single cavity with a mobile mass**, not numerous bilateral nodules.
Question 183: An 82-year-old man is brought to the emergency department after he was found down by his daughter. On presentation, he is alert and oriented with no obvious signs of trauma. He says that he felt lightheaded shortly before passing out and that he has been feeling extremely fatigued over the last few weeks. He has a known diagnosis of colorectal adenocarcinoma and had it surgically removed 2 months ago; however, recently he has been feeling increasingly short of breath. He has a 60-pack-year smoking history and drinks 2-3 beers a night. He worked as an insulation technician and shipyard laborer for 40 years prior to retiring at age 65. Radiographs reveal approximately a dozen new nodules scattered throughout his lungs bilaterally. Biopsy of these lesions would most likely reveal which of the following?
- A. Pleomorphic giant cells
- B. Small dark blue cells that stain for chromogranin
- C. Flat cells with keratin pearls and intercellular bridges
- D. Psammoma bodies
- E. Mucin-producing glandular structures (Correct Answer)
Explanation: ***Mucin-producing glandular structures*** - The patient has a history of **colorectal adenocarcinoma**, and the numerous new lung nodules suggest **metastatic spread** from the primary tumor. - **Adenocarcinoma of the colon** is characterized by the formation of glands that typically produce mucin. *Pleomorphic giant cells* - This description is characteristic of **undifferentiated giant cell carcinoma**, a rare and aggressive subtype of **lung cancer**. - While lung cancer is possible given the patient's smoking and occupational history, the history of colorectal adenocarcinoma and findings of multiple nodules strongly point towards metastasis rather than a primary lung tumor of this specific subtype. *Small dark blue cells that stain for chromogranin* - These features describe **small cell carcinoma**, a type of neuroendocrine tumor often found in the lungs, strongly associated with smoking. - However, the patient's primary diagnosis of **colorectal adenocarcinoma** makes metastatic colorectal cancer to the lung a more direct and probable explanation for the new lung nodules. *Flat cells with keratin pearls and intercellular bridges* - This is the histological description of **squamous cell carcinoma**, which can occur in the lung and is also strongly associated with smoking and occupational exposures. - While possible as a new primary lung cancer, the established diagnosis of **colorectal adenocarcinoma** and the pattern of multiple nodules make metastatic disease more likely. *Psammoma bodies* - These concentric calcifications are characteristic of several tumors, including **papillary thyroid carcinoma**, **meningiomas**, and **serous ovarian adenocarcinoma**. - They are not typically associated with **colorectal adenocarcinoma** or its common metastatic presentations.
Question 184: A 16-year-old boy is brought to the physician because of a lesion that has been growing on his jaw over the past several months. He recently immigrated to the USA from Kenya with his family. Physical examination shows a 3-cm solid mass located above the left mandible. There is cervical lymphadenopathy. Biopsy of the mass shows sheets of lymphocytes and interspersed reactive histiocytes with abundant, clear cytoplasm and phagocytosed debris. Which of the following mechanisms is most likely directly responsible for the malignant transformation of this patient's cells?
- A. Defect in DNA repair
- B. Impairment of receptor function
- C. Inhibition of cell cycle arrest
- D. Integration of viral DNA (Correct Answer)
- E. Activation of transcription
Explanation: **Integration of viral DNA** - The clinical presentation (rapidly growing jaw mass in a young boy from Kenya) and histological findings (sheets of lymphocytes, "starry sky" appearance due to macrophages) are classic for **endemic Burkitt lymphoma**. - Endemic Burkitt lymphoma is strongly associated with **Epstein-Barr virus (EBV)** infection. EBV DNA integrates into the host cell genome, promoting the characteristic **t(8;14) translocation** of *MYC* oncogene, leading to its overexpression and uncontrolled cell proliferation. *Defect in DNA repair* - While defects in DNA repair can lead to malignancy (e.g., in Lynch syndrome, xeroderma pigmentosum), it is not the primary mechanism of oncogenesis in Burkitt lymphoma. - The hallmark of Burkitt lymphoma is a specific chromosomal translocation, not a generalized DNA repair defect. *Impairment of receptor function* - Impaired receptor function is associated with certain diseases (e.g., some autoimmune conditions, diabetes insipidus) but is not a direct mechanism for malignant transformation in Burkitt lymphoma. - Malignancy typically arises from uncontrolled cell growth and division, not directly from receptor dysfunction. *Inhibition of cell cycle arrest* - While Burkitt lymphoma cells do evade cell cycle arrest, this is a **consequence** of the *MYC* oncogene overexpression, not the primary mechanism of malignant transformation itself. - The **integration of viral DNA** leading to the *MYC* translocation is the upstream event that *causes* the inhibition of cell cycle arrest. *Activation of transcription* - **Activation of transcription** (specifically of the *MYC* oncogene) is a crucial step in the pathogenesis of Burkitt lymphoma, leading to uncontrolled cell growth. - However, the direct cause of this dysregulated transcriptional activation is the **chromosomal translocation** resulting from viral DNA integration.
Question 185: A 39-year-old African American woman is admitted to the hospital following a seizure with a severe post-ictal headache. She was diagnosed with breast cancer 1 year ago when she presented with a hard, rock-like, immobile mass with irregular borders accompanied by changes in the breast skin, including erythema and dimpling. She had ipsilateral mobile axillary lymphadenopathy at that time. A biopsy confirmed the diagnosis of stage 2B invasive breast cancer. Her mother died at 42 years of age due to the same type of breast cancer. A CT scan done during this admission reveals multiple metastatic lesions in the brain and liver, along with the involvement of supra- and infra-clavicular lymph nodes. Which of the following molecular profile most likely characterizes this patient?
- A. PR, ER, HER2 positive
- B. HER2 positive
- C. Progesterone receptor (PR) positive
- D. ER, PR, HER2 negative (Correct Answer)
- E. Estrogen receptor (ER) positive
Explanation: ***ER, PR, HER2 negative*** - This patient's presentation with aggressive breast cancer at a relatively young age (39 years old), family history of early-onset breast cancer, rapid progression to metastatic disease in the brain and liver, and involvement of multiple lymph nodes (axillary, supra- and infra-clavicular) are all highly suggestive of a **triple-negative breast cancer (TNBC)**. - TNBC is characterized by the absence of **estrogen receptors (ER)**, **progesterone receptors (PR)**, and **human epidermal growth factor receptor 2 (HER2)** overexpression, making it an aggressive subtype with limited targeted treatment options and a poor prognosis, consistent with the patient's rapidly worsening condition. *PR, ER, HER2 positive* - This molecular profile (also known as triple-positive breast cancer) generally indicates a more favorable prognosis due to the availability of **hormonal therapy** (for ER/PR positivity) and **anti-HER2 targeted therapy**. - The aggressive course and rapid metastatic spread described in the patient are less typical for triple-positive disease, which often responds well to various targeted treatments. *HER2 positive* - HER2-positive breast cancer can be aggressive, but the presence of HER2 positivity allows for **HER2-targeted therapies** (e.g., trastuzumab, pertuzumab), which significantly improve outcomes. - While HER2-positive cancers can metastasize to the brain, the overall clinical picture, especially the aggressive growth and lack of other receptor expression, aligns more with triple-negative disease. *Progesterone receptor (PR) positive* - PR positivity, often alongside ER positivity, indicates a **hormone-sensitive breast cancer**, which typically has a better prognosis and is amenable to **endocrine therapy**. - The aggressive and rapid metastatic progression to multiple sites, including brain and liver, is not characteristic of a purely PR-positive tumor without other aggressive features. *Estrogen receptor (ER) positive* - ER-positive breast cancer is the most common subtype and is generally associated with a **better prognosis** and responsiveness to **endocrine therapy**. - The patient's aggressive disease course, including early metastasis and family history of early-onset, aggressive breast cancer, does not align with the typical presentation of an exclusively ER-positive tumor.
Question 186: A 53-year-old farmer presents to the clinic for evaluation of a pigmented lesion on his arm. He states that he first noticed the lesion last year, but he believes that it has been slowly growing in size. He otherwise does not have any complaints and is generally healthy. Which of the following findings on physical exam would suggest a malignant diagnosis?
- A. Symmetrical ovoid lesion
- B. Flat lesion with symmetric hyperpigmentation
- C. Tenderness to palpation
- D. Hyperpigmented lesion with smooth borders
- E. Different pigmentation throughout the lesion (Correct Answer)
Explanation: ***Different pigmentation throughout the lesion*** - **Malignant melanoma** often presents with **multicolor variegation** or areas of differing pigmentation within the same lesion, which is a key indicator for malignancy (the "C" in ABCDE). - This **uneven coloration** reflects the uncontrolled proliferation of melanocytes producing melanin in varying amounts and patterns, a hallmark of dysplastic changes. *Symmetrical ovoid lesion* - **Benign nevi** (moles) typically maintain **symmetry** in their shape and border, meaning that if you were to draw a line through the middle of the lesion, both halves would largely match. - While some melanomas can be ovoid, **asymmetry** is a more concerning feature for malignancy, unlike the description provided here. *Flat lesion with symmetric hyperpigmentation* - A **benign lesion** often has **symmetric pigmentation** and a uniform color distribution, with a flat appearance. - **Irregular pigmentation** (color variegation) within the lesion is a more concerning sign for **melanoma**, falling under the "C" (color) criteria of the ABCDEs. *Tenderness to palpation* - **Tenderness** is not a typical characteristic of early or even advanced **melanoma**; pain or tenderness is often associated with inflammation, infection, or trauma rather than primary skin cancer. - While ulcerated or infected tumors can be painful, tenderness alone without other suspicious features is **not a primary diagnostic criterion** for melanoma. *Hyperpigmented lesion with smooth borders* - **Benign moles** typically have **smooth, regular, and well-defined borders**, making them appear round or oval. - In contrast, **malignant melanoma** often presents with **irregular, notched, or poorly defined borders (the "B" in ABCDE),** which would be more indicative of malignancy.
Question 187: A 40-year-old man presents with an episode of rectal bleeding. He is concerned because his mother died of colorectal cancer at 50 years of age. He has no further information about his family history. Physical examination and digital rectal examination are normal. He undergoes a colonoscopy and is found to have innumerable adenomas in the left side of the colon ranging in size from 4–15 mm. Which of the following is the most likely underlying mechanism of this patient illness?
- A. Mutation in DNA mismatch repair genes
- B. Inactivation of RB1 gene
- C. Alterations in STK11 gene
- D. Inactivation of BRCA1 and BRCA2 genes
- E. Mutations of the APC gene (Correct Answer)
Explanation: ***Mutations of the APC gene*** - The description of **innumerable adenomas** in the colon, particularly at a relatively young age and with a family history of early-onset colorectal cancer, is highly suggestive of **familial adenomatous polyposis (FAP)**. - FAP is an autosomal dominant condition caused by germline mutations in the **adenomatous polyposis coli (APC) gene**, a tumor suppressor gene, leading to the development of hundreds to thousands of adenomatous polyps and an almost 100% lifetime risk of colorectal cancer. *Mutation in DNA mismatch repair genes* - Mutations in **DNA mismatch repair genes** (e.g., MLH1, MSH2, MSH6, PMS2) are associated with **Lynch syndrome (hereditary nonpolyposis colorectal cancer)**. - Lynch syndrome typically presents with fewer polyps (though an increased risk of colorectal cancer, especially right-sided) and other extracolonic cancers, which is less consistent with "innumerable adenomas." *Inactivation of RB1 gene* - The **RB1 gene** is a tumor suppressor gene primarily associated with **retinoblastoma** and has a role in other cancers like osteosarcoma. - It is not the primary genetic mechanism for the development of multiple colonic adenomas described in this patient. *Alterations in STK11 gene* - Alterations in the **STK11 gene** are associated with **Peutz-Jeghers syndrome**, an autosomal dominant disorder characterized by the development of multiple **hamartomatous polyps** mainly in the gastrointestinal tract, especially the small intestine, and characteristic **mucocutaneous pigmentation**. - These polyps are hamartomatous, not adenomatous, and while they carry a cancer risk, the presentation of innumerable adenomas points away from Peutz-Jeghers syndrome. *Inactivation of BRCA1 and BRCA2 genes* - **BRCA1 and BRCA2 genes** are critical tumor suppressor genes primarily associated with an increased risk of **breast cancer** and **ovarian cancer**, as well as some other cancers like prostate and pancreatic cancer. - While these genes are important in cancer development, they are not directly implicated in the pathogenesis of familial adenomatous polyposis or the significant number of colonic adenomas described.
Question 188: A 55-year-old woman comes to the physician because of a 4-month history of a painless lump on her neck. Examination shows a hard nodule on the left side of her neck. A fine-needle aspiration biopsy shows well-differentiated cuboidal cells arranged spherically around colloid. She undergoes thyroidectomy. Histopathological examination of the surgical specimen shows invasion of the thyroid capsule and blood vessels. Which of the following cellular events is most likely involved in the pathogenesis of this patient's condition?
- A. TSH receptor gene mutation
- B. Activation mutation in the BRAF gene
- C. Mutation in the RET proto-oncogene
- D. p53 tumor suppressor gene inactivation
- E. PAX8-PPAR gamma gene rearrangement (Correct Answer)
Explanation: ***PAX8-PPAR gamma gene rearrangement*** - The description of a **painless neck lump**, **well-differentiated cuboidal cells arranged spherically around colloid**, and **invasion of the thyroid capsule and blood vessels** is highly classic for **follicular thyroid carcinoma**. - **PAX8-PPAR gamma rearrangement** is a characteristic genetic alteration found in a significant subset of **follicular thyroid carcinomas** and sometimes in follicular adenomas, playing a crucial role in tumorigenesis. *TSH receptor gene mutation* - This mutation is associated with **toxic thyroid adenomas** (Plummer's disease) and **diffuse toxic goiter** (Graves' disease), leading to hyperthyroidism. - While it can cause nodular growth, it typically results in a **hyperfunctioning nodule** and is not primarily linked to the invasive features of follicular carcinoma described. *Activation mutation in the BRAF gene* - **BRAF V600E mutation** is the most common genetic alteration found in **papillary thyroid carcinoma**, which typically presents with **papillary architecture**, nuclear features like **Orphan Annie eye nuclei**, and **psammoma bodies**. - The histological description of "well-differentiated cuboidal cells arranged spherically around colloid" does not fit papillary carcinoma. *Mutation in the RET proto-oncogene* - **RET proto-oncogene mutations** are characteristic of **medullary thyroid carcinoma**, a neuroendocrine tumor arising from parafollicular C cells. - Medullary thyroid carcinoma has distinct histological features (e.g., amyloid deposition) and clinical presentations (e.g., calcitonin secretion) that are not described in this case. *p53 tumor suppressor gene inactivation* - **p53 inactivation** is primarily associated with **anaplastic thyroid carcinoma** and **poorly differentiated thyroid carcinoma**. - These are highly aggressive tumors that would present with rapid growth, significant invasion, and poorly differentiated or anaplastic histology, which contradicts the "well-differentiated" description in the patient's biopsy.
Question 189: A 67-year-old man comes to the physician because of a 2-month history of generalized fatigue. On examination, he appears pale. He also has multiple pinpoint, red, nonblanching spots on his extremities. His spleen is significantly enlarged. Laboratory studies show a hemoglobin concentration of 8.3 g/dL, a leukocyte count of 81,000/mm3, and a platelet count of 35,600/mm3. A peripheral blood smear shows immature cells with large, prominent nucleoli and pink, elongated, needle-shaped cytoplasmic inclusions. Which of the following is the most likely diagnosis?
- A. Acute lymphoblastic leukemia
- B. Myelodysplastic syndrome
- C. Hairy cell leukemia
- D. Acute myelogenous leukemia (Correct Answer)
- E. Chronic myelogenous leukemia
Explanation: ***Acute myelogenous leukemia*** - The presence of immature cells with **large, prominent nucleoli** and **pink, elongated, needle-shaped cytoplasmic inclusions** (**Auer rods**) on peripheral blood smear is pathognomonic for **acute myeloid leukemia (AML)**. - The pancytopenia (anemia, thrombocytopenia) and extreme leukocytosis, along with generalized fatigue and pale appearance, are consistent with the presentation of AML. *Acute lymphoblastic leukemia* - Characterized by the proliferation of **lymphoblasts** (immature lymphocytes) in the bone marrow and peripheral blood, which typically lack Auer rods. - While it can present with fatigue, pallor, and cytopenias, the specific morphologic features of the blast cells are different. *Myelodysplastic syndrome* - Involves ineffective hematopoiesis leading to **cytopenias** and dysplastic features in mature blood cells, but typically features less aggressive proliferation of immature cells than acute leukemias and **lacks Auer rods**. - While it can progress to AML, the current description points to actively proliferating immature cells. *Hairy cell leukemia* - Characterized by **B lymphocytes with cytoplasmic projections** ("hairy cells") and is typically associated with **massive splenomegaly** and **pancytopenia**, but the characteristic Auer rods are absent. - The cell morphology described (large nucleoli, needle-shaped inclusions) is inconsistent with hairy cells. *Chronic myelogenous leukemia* - Characterized by the **Philadelphia chromosome (BCR-ABL1 fusion gene)** and a marked increase in mature and immature myeloid cells, including granulocytes at various stages of maturation, but typically **lacks Auer rods** and usually has a higher proportion of mature rather than acutely immature cells. - While it presents with leukocytosis and splenomegaly, the prominent immature cells with nucleoli and Auer rods are not features of CML.
Question 190: A 40-year-old woman residing at an iodine-deficient endemic area presents to the physician with a painless and gradually progressive anterior neck mass. She has occasional dysphagia, but has no history of prior head and neck irradiation. The examination shows a mass that moves with deglutition, suggesting a thyroid mass. An ultrasound of the neck reveals a 3 cm x 3 cm (1.2 in x 1.2 in) mass in the right thyroid lobe with punctate microcalcifications, hypoechogenicity, irregular margins, and enhanced vascularity. There is no cervical lymphadenopathy. Her serum TSH is 3.3 mU/L, serum T3 is 2.2 nmol/L, and serum T4 is 111 nmol/L. An FNAC of the nodule shows abundant follicular cells suspicious of follicular neoplasm. A right lobectomy with isthmectomy is performed. Which of the following histopathological finding is diagnostic?
- A. Well-differentiated follicular cells without vascular invasion
- B. Hyperplastic parafollicular C cells
- C. Follicular cells that lack nuclear atypia, with capsular and vascular invasion (Correct Answer)
- D. Highly undifferentiated malignant cells with areas of necrosis and inflammation
- E. Presence of Psammoma bodies
Explanation: ***Follicular cells that lack nuclear atypia, with capsular and vascular invasion*** - The presence of **capsular and vascular invasion** by follicular cells, even without nuclear atypia, is the diagnostic feature of **follicular thyroid carcinoma**. This invasion distinguishes it from follicular adenoma. - The ultrasound findings (microcalcifications, hypoechogenicity, irregular margins, enhanced vascularity) are highly suspicious for malignancy, and the FNAC suggested a follicular neoplasm, which requires surgical excision for definitive diagnosis. *Well-differentiated follicular cells without vascular invasion* - This description typically points to a **follicular adenoma**, a benign tumor. - Absence of **vascular or capsular invasion** is the key histological feature differentiating adenoma from carcinoma. *Hyperplastic parafollicular C cells* - An increase in **parafollicular C cells** (often with an amyloid stroma) is characteristic of **medullary thyroid carcinoma**. - This type of cancer is derived from neuroendocrine cells, not follicular cells, and has distinct histological features. *Highly undifferentiated malignant cells with areas of necrosis and inflammation* - This describes **anaplastic thyroid carcinoma**, a highly aggressive and poorly differentiated malignancy. - While malignant, the FNAC result of "follicular neoplasm" and the patient's presentation are more consistent with a differentiated follicular cancer rather than an anaplastic one. *Presence of Psammoma bodies* - **Psammoma bodies** are concentric calcified laminated structures characteristic of **papillary thyroid carcinoma**. - Papillary thyroid carcinoma also typically shows specific nuclear features (e.g., ground glass nuclei, nuclear grooves, intranuclear inclusions) that are not mentioned in the FNAC findings of "follicular neoplasm."
Question 191: A 24-year-old woman complains of intermittent fever and joint pain. She says that these symptoms have been present for the past month. Before that, she had no signs or symptoms and was completely healthy. She has also lost her appetite and some weight. A complete blood count (CBC) showed severe pancytopenia. What is the next best step in evaluating this patient?
- A. Repeated CBCs for several weeks and reassess
- B. Treatment with corticosteroids
- C. Treatment with antibiotics
- D. Treatment for acute leukemia
- E. Bone marrow examination (Correct Answer)
Explanation: ***Bone marrow examination*** - The combination of **fever**, **joint pain**, **weight loss**, and **pancytopenia** in a previously healthy young woman raises suspicion for serious hematologic conditions like **aplastic anemia** or **acute leukemia**. - A **bone marrow examination** is crucial for definitive diagnosis by evaluating the cellularity, morphology, and presence of abnormal cells. *Repeated CBCs for several weeks and reassess* - This approach is inappropriate given the **severe pancytopenia** and progressive symptoms, which indicate an urgent underlying pathology. - Delaying diagnosis could worsen the patient's condition and compromise treatment outcomes due to the potential for severe infections or bleeding. *Treatment with corticosteroids* - While corticosteroids might be used in some autoimmune conditions causing pancytopenia, initiating treatment without a definitive diagnosis is premature and could mask the underlying cause, especially in cases of malignancy. - There is no specific indication for corticosteroid use in this scenario without further diagnostic information. *Treatment with antibiotics* - Although **fever** is present, there's no clear evidence of an infection (like localized symptoms or positive cultures), and **pancytopenia** is not primarily managed with antibiotics. - Administering antibiotics empirically without a confirmed infection addresses a symptom rather than the underlying progressive hematological disorder. *Treatment for acute leukemia* - While **acute leukemia** is a strong possibility, definitive treatment should only commence after a confirmed diagnosis through **bone marrow examination**, as misdiagnosis can lead to inappropriate and harmful therapy. - Other conditions like severe aplastic anemia also present with similar features but require different management strategies.
Question 192: A 75-year-old female comes to the physician’s office with complaints of right lower quadrant pain. She has been experiencing these symptoms for the last 6 months and they have progressively gotten worse. An ultrasound reveals a large ovarian mass and abdominal and pelvic CT reveals no metastases. Her serum levels of CA-125 are elevated and the biopsy reveals the primary neoplasm as ovarian in origin. Her cancer is characterized as invasive carcinoma without metastasis. Which of the following cellular changes is consistent with this diagnosis?
- A. Seeding via capillaries
- B. Increased proliferation of cells with preservation of size and shape
- C. Loss of E-cadherin (Correct Answer)
- D. Intact basement membrane
- E. Appropriate basal to apical differentiation
Explanation: ***Loss of E-cadherin*** - The diagnosis of **invasive carcinoma without metastasis** implies that tumor cells have gained the ability to invade surrounding tissues but have not yet spread to distant sites. - **Loss of E-cadherin** is a crucial step in the **epithelial-mesenchymal transition (EMT)**, allowing carcinoma cells to detach from the primary tumor and invade, consistent with an invasive but non-metastatic cancer. *Seeding via capillaries* - This describes **hematogenous spread**, a form of **metastasis** where tumor cells enter the bloodstream. - The clinical presentation states **no metastases**, making this an unlikely cellular characteristic for the current stage. *Increased proliferation of cells with preservation of size and shape* - **Increased proliferation** is a hallmark of cancer, but **preservation of size and shape** indicates a well-differentiated or benign tumor. - Invasive carcinoma typically involves **cellular pleomorphism** (variability in cell size and shape) and **loss of differentiation**. *Intact basement membrane* - An **intact basement membrane** is characteristic of **carcinoma in situ** or non-invasive tumors. - **Invasive carcinoma** is defined by the **breach of the basement membrane** by malignant cells. *Appropriate basal to apical differentiation* - **Appropriate differentiation** indicates normal tissue organization and function, which is inconsistent with cancer, especially invasive carcinoma. - Malignant tumors, including invasive carcinomas, are characterized by **dysplasia** and often a **loss of normal differentiation**.
Question 193: A 49-year-old woman presents to her physician with complaints of breast swelling and redness of the skin over her right breast for the past 1 month. She also mentions that the skin above her right breast appears to have thickened. She denies any pain or nipple discharge. The past medical history is significant for a total abdominal hysterectomy at 45 years of age. Her last mammogram 1 year ago was negative for any pathologic changes. On examination, the right breast was diffusely erythematous with gross edema and tenderness and appeared larger than the left breast. The right nipple was retracted and the right breast was warmer than the left breast. No localized mass was palpated. Which of the following statements best describes the patient’s most likely condition?
- A. It shows predominant lymphatic spread.
- B. The lesion expresses receptors for estrogen and progesterone.
- C. The lesion is due to Streptococcal infection.
- D. It is a benign lesion.
- E. The inflammation is due to obstruction of dermal lymphatic vessels. (Correct Answer)
Explanation: ***The inflammation is due to obstruction of dermal lymphatic vessels.*** - The presentation of **rapid-onset breast swelling, redness, thickening of the skin, warmth, and nipple retraction** without a palpable mass is highly suggestive of **inflammatory breast cancer (IBC)**. - IBC is characterized by the **obstruction of dermal lymphatic vessels by tumor cells**, leading to the classic inflammatory signs and **peau d'orange** appearance. *It shows predominant lymphatic spread.* - While IBC does involve **lymphatic spread**, this statement alone does not fully encompass the characteristic pathology of the condition causing the observed symptoms. - The obstruction of the **dermal lymphatic vessels** is a more precise description of the immediate cause of the clinical presentation. *The lesion expresses receptors for estrogen and progesterone.* - Although some breast cancers are **hormone receptor-positive (ER/PR positive)**, there is no direct information in the vignette to suggest this specificity for the patient's condition. - This statement refers to a **molecular characteristic** that is not a defining feature of the clinical presentation of IBC. *The lesion is due to Streptococcal infection.* - While a **bacterial infection** (like **streptococcal cellulitis**) can cause redness, swelling, and warmth, it typically presents with more acute symptoms, fever, and often a clearer response to antibiotics. - The **thickening of the skin** and **nipple retraction** point away from a simple infection and towards a malignant process. *It is a benign lesion.* - The rapid progression of symptoms, pronounced skin changes, and nipple retraction are all **red flags for malignancy**, specifically inflammatory breast cancer. - **Benign lesions** rarely cause such diffuse, severe, and rapidly progressing inflammatory signs.
Question 194: A 57-year-old woman comes to the physician because of a 1-month history of multiple swellings in both her axillae. She says they are generally painless, but are sometimes painful on the weekends. She also has increased fatigue, recurring low-grade fevers, and generalized pruritus. She does not smoke. She drinks five to six beers on the weekends. Her temperature is 37°C (98.6°F), pulse is 80/min, respirations are 12/min, and blood pressure is 130/70 mm Hg. Physical examination reveals multiple firm and nontender axillary lymph nodes. A lymph node biopsy shows multinucleate giant lymphocytes with prominent nucleoli that resemble eosinophilic inclusions. Which of the following additional findings would be associated with a poor prognosis in this patient?
- A. Axillary tumor 6 cm across
- B. Mediastinal tumor occupying 7% of the chest's width
- C. Leukocyte count of 9,000/mm3
- D. Erythocyte sedimentation rate of 65 mm/h (Correct Answer)
- E. Nodular lymphocyte predominant type tumor
Explanation: ***Erythocyte sedimentation rate of 65 mm/h*** - An **elevated ESR** (typically >50 mm/h or >70 mm/h, depending on the staging system used) is a recognized **adverse prognostic factor** in Hodgkin lymphoma per the International Prognostic Score (IPS). - It indicates significant systemic inflammation and disease activity, suggesting a more aggressive disease course or higher tumor burden. *Axillary tumor 6 cm across* - While a large tumor size can be a poor prognostic factor, it is often considered in relation to other factors like the number of involved nodal areas and extranodal extension. A single axillary tumor of this size alone is not as strong an indicator of poor prognosis as an elevated ESR per IPS. - The **IPS** typically defines a bulky disease as a single nodal mass >10 cm or >1/3 the chest width. Thus, 6 cm is significant but not above this IPS threshold for poor prognosis. *Mediastinal tumor occupying 7% of the chest's width* - This size of mediastinal tumor (7% of chest width) is typically not considered a poor prognostic indicator. Bulky mediastinal disease, defined as a mass >1/3 the chest width, is a poor prognostic factor. - **Bulky disease** (specifically mediastinal) of less than 1/3 the chest width is not considered a poor prognostic factor according to the International Prognostic Score (IPS) for Hodgkin lymphoma. *Leukocyte count of 9,000/mm3* - A leukocyte count of 9,000/mm3 is within the normal range (typically 4,000-11,000/mm3) and does not indicate an adverse prognosis. - **Leukocytosis** (WBC count >15,000/mm3) is considered a poor prognostic factor in Hodgkin lymphoma. *Nodular lymphocyte predominant type tumor* - **Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL)** typically has a more indolent course and an excellent prognosis compared to classical Hodgkin lymphoma (cHL), which is suggested by the Reed-Sternberg-like cells described. - While it can transform into an aggressive non-Hodgkin lymphoma in a minority of cases, its initial presentation is generally associated with a better prognosis and lower stage at diagnosis.
Question 195: A 6-year-old boy presents to your office with loss of his peripheral vision. His mother discovered this because he was almost struck by a vehicle that "he couldn't see at all". In addition, he has been complaining of a headache for the last several weeks and had an episode of vomiting 2 days ago. He has a family history of migraines in his mother and grandmother. He is currently in the 80th percentile for height and weight. On physical exam his temperature is 99°F (37.2°C), blood pressure is 110/75 mmHg, pulse is 100/min, respirations are 19/min, and pulse oximetry is 99% on room air. He is uncooperative for the rest of the physical exam. During workup, a lesion is found in this patient. Which of the following would most likely be seen during histopathologic analysis?
- A. Perivascular rosettes with rod-shaped blepharoplasts
- B. Round nuclei with clear cytoplasm
- C. Rosettes and small blue cells
- D. Eosinophilic, corkscrew fibers
- E. Cholesterol crystals and calcification (Correct Answer)
Explanation: ***Cholesterol crystals and calcification*** - The patient's symptoms (loss of peripheral vision, headache, vomiting) coupled with his age (6 years old) strongly suggest a **craniopharyngioma**. These tumors often contain **cholesterol crystals and calcifications**. - **Craniopharyngiomas** typically arise from Rathke's pouch remnants and are located in the sellar or suprasellar region, leading to **vision impairment** (e.g., **bitemporal hemianopsia** from optic chiasm compression), **headaches**, and symptoms of **increased intracranial pressure**. *Perivascular rosettes with rod-shaped blepharoplasts* - This description is characteristic of an **ependymoma**, which is a glial tumor that typically arises from the ependymal lining of the ventricles or spinal cord. - While ependymomas can cause increased intracranial pressure, they are less likely to present with isolated **peripheral vision loss** targeting the optic chiasm specifically. *Round nuclei with clear cytoplasm* - This describes **oligodendroglioma**, a type of glioma typically found in the cerebral hemispheres of adults. - Oligodendrogliomas are less common in children and usually present with seizures or focal neurological deficits, rather than primary vision loss and symptoms of increased ICP in this age group. *Rosettes and small blue cells* - This is characteristic of **medulloblastoma**, a highly malignant tumor originating in the cerebellum. - Medulloblastomas often cause hydrocephalus, ataxia, and symptoms of increased intracranial pressure, but **peripheral vision loss** as the primary presenting symptom is less typical compared to craniopharyngioma. *Eosinophilic, corkscrew fibers* - This describes **Rosenthal fibers**, which are characteristic of **pilocytic astrocytoma**, a common low-grade glioma in children, often found in the cerebellum or optic pathways. - While pilocytic astrocytomas of the optic pathway can cause visual deficits, the presence of **cholesterol crystals and calcifications** is more specific to craniopharyngioma, which fits the clinical picture of bitemporal hemianopsia from a suprasellar lesion.
Question 196: A 62-year-old man presents to his primary care physician because of abdominal pain that started after he went camping several months ago and drank from a mountain stream. This past year, he also went on a trip around the world, eating local foods at each stop. Furthermore, he has had a history of cholelithiasis and had his gallbladder removed 3 years ago. Otherwise, his medical history is significant for well-controlled hypertension and diabetes. Based on clinical suspicion, an endoscopy and biopsy was performed showing a mix of mononuclear cells and a motile, urease-positive, oxidase-positive, spiral shaped organism. The changes seen on biopsy in this patient most likely predispose him to which of the following pathologies?
- A. Gallbladder adenocarcinoma
- B. Esophageal adenocarcinoma
- C. Colon adenocarcinoma
- D. MALT lymphoma (Correct Answer)
- E. Pancreatic adenocarcinoma
Explanation: ***MALT lymphoma*** - The description of a **motile, urease-positive, oxidase-positive, spiral-shaped organism** from an endoscopic biopsy points to **Helicobacter pylori** infection. - **H. pylori** infection chronic gastritis is a significant risk factor for the development of **MALT (Mucosa-Associated Lymphoid Tissue) lymphoma** of the stomach. *Gallbladder adenocarcinoma* - This is primarily associated with chronic inflammation of the gallbladder, often due to **cholelithiasis**, but the patient's gallbladder was removed. - There is no direct link between **H. pylori infection** of the stomach and gallbladder adenocarcinoma. *Esophageal adenocarcinoma* - This is predominantly linked to **Barrett's esophagus**, which is caused by chronic **gastroesophageal reflux disease (GERD)**. - While H. pylori can sometimes be associated with GERD, it's not a primary direct cause of esophageal adenocarcinoma. *Colon adenocarcinoma* - This is primarily associated with genetic predispositions like **familial adenomatous polyposis** or **Lynch syndrome**, as well as environmental factors like diet and inflammatory bowel disease. - There is no direct causal link between **H. pylori** infection and colon adenocarcinoma. *Pancreatic adenocarcinoma* - Risk factors for pancreatic cancer include **smoking, obesity, chronic pancreatitis, and certain genetic syndromes**. - There is no established direct link between **H. pylori infection** and pancreatic adenocarcinoma.
Question 197: A 22-year-old woman comes to the physician because of hearing loss and unsteadiness while standing and walking for the past 2 months. She needs support from a wall to prevent herself from falling. She has not had any recent injuries and has no history of serious illness. Vital signs are within normal limits. Examination shows an unsteady gait. She sways when asked to stand upright with her feet together. She is unable to hear fingers rubbing next to her ears or repeat words whispered in her ears bilaterally. An MRI of the brain shows a 3-cm tumor in the right cerebellopontine angle and a 4.5-cm tumor in the left cerebellopontine angle. This patient is most likely to develop which of the following in the future?
- A. Renal cell carcinoma
- B. Telangiectasias
- C. Optic glioma
- D. Meningioma (Correct Answer)
- E. Astrocytoma
Explanation: ***Meningioma*** - This patient's bilateral **vestibular schwannomas** (tumors in the **cerebellopontine angle** causing hearing loss and unsteadiness) are highly suggestive of **Neurofibromatosis type 2 (NF2)**. - Patients with NF2 are predisposed to developing multiple central nervous system tumors, with **meningiomas** being a common manifestation, alongside schwannomas and ependymomas. *Renal cell carcinoma* - This is not typically associated with **Neurofibromatosis type 2**, which primarily involves tumors of the nervous system. - While various cancer syndromes exist, NF2 does not significantly increase the risk of **renal cell carcinoma**. *Telangiectasias* - **Telangiectasias** are dilated small blood vessels, often associated with conditions like **hereditary hemorrhagic telangiectasia** or **ataxia-telangiectasia**. - They are not a characteristic feature or complication of **Neurofibromatosis type 2**. *Optic glioma* - **Optic gliomas** are a hallmark feature of **Neurofibromatosis type 1 (NF1)**, not NF2. - NF1 is also associated with **café-au-lait spots** and **Lisch nodules**, which are distinct from the presentation of bilateral vestibular schwannomas. *Astrocytoma* - While NF2 patients can develop central nervous system tumors, **astrocytomas** are less common than **ependymomas** or **meningiomas** in this syndrome. - The most characteristic brain tumors in NF2 are **vestibular schwannomas** and **meningiomas**.
Question 198: A 42-year-old woman presents to her primary care physician with fatigue. She reports that over the past 2 months, she has felt increasingly tired despite no changes in her diet or exercise. Her past medical history is notable for obesity, seasonal allergies, and hypertension. She takes ranitidine as needed and hydrochlorothiazide daily. Her family history is notable for colorectal cancer in her mother and maternal uncle, endometrial cancer in her maternal aunt, and ovarian cancer in her maternal grandmother. Her temperature is 98.8°F (37.1°C), blood pressure is 132/71 mmHg, pulse is 89/min, and respirations are 17/min. On exam, she has conjunctival pallor. A stool sample is hemoccult positive. A colonoscopy reveals a fungating hemorrhagic mass in the ascending colon. Which of the following processes is likely impaired in this patient?
- A. Mismatch repair (Correct Answer)
- B. Non-homologous end joining
- C. Homologous recombination
- D. Base excision repair
- E. Nucleotide excision repair
Explanation: ***Mismatch repair*** - The patient's presentation with **colorectal cancer** at a relatively young age (42), combined with a strong family history of various cancers (colorectal, endometrial, ovarian) suggesting a **hereditary cancer syndrome**, points towards a defect in **mismatch repair (MMR)**. - Defective MMR leads to an accumulation of **mutations** during DNA replication, particularly in microsatellites, and is characteristic of **Lynch syndrome** (Hereditary Nonpolyposis Colorectal Cancer, HNPCC). *Non-homologous end joining* - This pathway is crucial for repairing **double-strand breaks** in DNA but is often error-prone. - Defects in non-homologous end joining are associated with conditions like **severe combined immunodeficiency** due to impaired V(D)J recombination, not typically Lynch syndrome. *Homologous recombination* - Involved in high-fidelity repair of **double-strand breaks** using a homologous DNA template. - Impairments are linked to increased risk of certain cancers, such as **BRCA1/2 mutations** causing breast and ovarian cancer, but are not the primary defect in Lynch syndrome. *Base excision repair* - This pathway is responsible for repairing **small, non-helix-distorting base lesions** caused by oxidation, alkylation, or deamination. - Defects can lead to increased mutagenicity but are not the primary mechanism underlying the cancer spectrum seen in Lynch syndrome. *Nucleotide excision repair* - This system repairs **bulky DNA adducts** and helix-distorting lesions, such as those caused by UV radiation (e.g., **pyrimidine dimers**). - Defects are associated with conditions like **xeroderma pigmentosum**, characterized by extreme sun sensitivity and skin cancers, which is not consistent with this patient's presentation.
Question 199: A 65-year-old man with a 40-pack-year smoking history presents with hemoptysis and a persistent cough. Chest CT shows a 3.5 cm centrally located mass in the right main bronchus. Positron emission tomography confirms a malignant nodule. Bronchoscopy with transbronchial biopsy is performed and a specimen sample of the nodule is sent for frozen section analysis. The tissue sample is most likely to show which of the following tumor types?
- A. Carcinoid tumor
- B. Metastasis of colorectal cancer
- C. Small cell lung carcinoma
- D. Large cell carcinoma
- E. Squamous cell carcinoma (Correct Answer)
Explanation: ***Squamous cell carcinoma*** - This is the most likely diagnosis given the **central location** in the main bronchus, **heavy smoking history**, and presentation with **hemoptysis**. - **Squamous cell carcinoma** accounts for 25-30% of lung cancers and characteristically arises in **central/proximal airways**, making it readily accessible by **bronchoscopy**. - Histologically, it shows **keratin pearls** and **intercellular bridges** on biopsy. - The **central endobronchial location** and ability to obtain tissue via transbronchial biopsy strongly favor squamous cell over peripheral tumors. *Carcinoid tumor* - **Carcinoid tumors** are **neuroendocrine tumors** that can present as central endobronchial masses and cause hemoptysis. - However, they are typically **slow-growing** with more indolent presentation, and PET scans show **variable uptake** (often less intense than aggressive carcinomas). - They represent only **1-2% of lung tumors** and occur more commonly in **younger, non-smoking patients**. *Metastasis of colorectal cancer* - While lung is a common site for **colorectal metastases**, these typically present as **multiple peripheral nodules** rather than a solitary central endobronchial mass. - The clinical presentation strongly suggests **primary lung cancer** rather than metastatic disease. - Without history of colorectal cancer, this is unlikely. *Small cell lung carcinoma* - **Small cell lung carcinoma** (SCLC) represents 15% of lung cancers and typically presents as a **large central mass** with early mediastinal involvement. - However, SCLC is usually **too extensive at presentation** for transbronchial biopsy alone and often requires mediastinoscopy or CT-guided biopsy. - Histology shows **small cells with scant cytoplasm**, **salt-and-pepper chromatin**, and **oat-cell morphology**. - While possible, the single accessible endobronchial mass is more characteristic of squamous cell. *Large cell carcinoma* - **Large cell carcinoma** is a **diagnosis of exclusion** made when tumors lack features of adenocarcinoma, squamous cell, or small cell differentiation. - It typically presents as **large peripheral masses** rather than central endobronchial lesions. - It represents only **10% of lung cancers** and is less common than squamous cell carcinoma in this clinical scenario.
Question 200: A 70-year-old man is brought to the emergency department by his wife because of progressive confusion for the past 2 weeks. He has also had a 4.5-kg (10-lb) weight loss and fatigue during the last 6 months. Physical examination shows enlarged lymph nodes in the right axilla and faint expiratory wheezing in the right middle lung field. He is only oriented to person. Serum studies show a sodium concentration of 125 mEq/L and increased antidiuretic hormone concentration. An x-ray of the chest shows a right-sided hilar mass with mediastinal fullness. A biopsy of the hilar mass is most likely to show cells that stain positive for which of the following?
- A. Neurofilament
- B. S-100
- C. Desmin
- D. Napsin A
- E. Neuron-specific enolase (Correct Answer)
Explanation: ***Neuron-specific enolase*** - The patient's presentation with a **right-sided hilar mass**, **mediastinal fullness**, **hyponatremia**, **increased antidiuretic hormone (ADH) concentration**, and **progressive confusion** is highly suggestive of **small cell lung carcinoma (SCLC)**. SCLC commonly produces ADH, leading to **syndrome of inappropriate antidiuretic hormone secretion (SIADH)**. - SCLC cells are of neuroendocrine origin and therefore typically stain positive for **neuroendocrine markers** such as chromogranin A, synaptophysin, and **neuron-specific enolase (NSE)**. *Neurofilament* - **Neurofilament** proteins are intermediate filaments found within the cytoplasm of neurons, forming the neuronal cytoskeleton. They are used as markers for neuronal differentiation and neuronal damage. - While SCLC cells have neuroendocrine features, **neurofilament** staining is more specific for mature neuronal structures and is less consistently positive in SCLC compared to other neuroendocrine markers like NSE. *S-100* - **S-100 protein** is a marker for cells of **neural crest origin**, including melanocytes, Schwann cells, and Langerhans cells, and is commonly used to diagnose melanoma and schwannomas. - It is not a primary marker for small cell lung carcinoma, which is thought to arise from neuroendocrine cells in the bronchial epithelium. *Desmin* - **Desmin** is an intermediate filament protein typically found in **muscle cells** (smooth, skeletal, and cardiac). It is a key marker for the diagnosis of **rhabdomyosarcoma** and other muscle-derived tumors. - Lung tumors, including small cell carcinoma, are not typically of muscle origin and would not stain positive for desmin. *Napsin A* - **Napsin A** is an aspartic proteinase that is a highly sensitive and specific immunohistochemical marker for **adenocarcinoma of the lung**. - The clinical presentation with a central hilar mass, SIADH, and rapid progression is much more characteristic of **small cell carcinoma** than adenocarcinoma.
Question 201: A 61-year-old male presents to the ER with abdominal discomfort and malaise over the past 2 weeks. He states he is married and monogamous. He has a temperature of 39.4°C (102.9°F) and complains of night sweats as well. On physical exam, he has an enlarged spleen with mild tenderness and pale nail beds. There is mild tonsillar erythema and the pulmonary exam demonstrates scattered crackles. A complete blood count demonstrates anemia, thrombocytopenia, and leukocytosis with lymphocytic predominance. A bone marrow aspiration is scheduled the next morning based on the peripheral blood smear findings but was inconclusive due to a low yield. The patient was admitted to the hospital due to the anemia and given a transfusion of packed red blood cells and wide spectrum antibiotics. He is released home the next day with instructions for primary care follow-up. Which of the following laboratory findings is most reliably positive for the primary cause of this illness?
- A. CD 25
- B. Quantiferon Gold
- C. Monospot
- D. Rapid streptococcal antigen
- E. Tartrate-resistant acid phosphatase (TRAP) (Correct Answer)
Explanation: ***Tartrate-resistant acid phosphatase (TRAP)*** - The patient's presentation with **splenomegaly**, **pancytopenia** (anemia, thrombocytopenia, leukocytosis with lymphocytic predominance), and an **inconclusive bone marrow aspiration due to low yield** (known as a "dry tap") is highly suggestive of **hairy cell leukemia**. - **TRAP staining** is a classic and highly reliable diagnostic marker for hairy cell leukemia, where the neoplastic B cells exhibit strong TRAP activity. *CD 25* - While **CD25** (the alpha chain of the IL-2 receptor) can be expressed on some leukemic cells, its presence is not uniquely diagnostic for hairy cell leukemia, as it can be found on other activated lymphocytes and some other leukemias/lymphomas. - The most characteristic immunophenotypic markers for hairy cell leukemia include **CD11c, CD20, CD22, CD103, and CD123**, in addition to CD25, but TRAP is a more specific enzymatic marker. *Quantiferon Gold* - **Quantiferon Gold** is an interferon-gamma release assay used to detect latent or active **tuberculosis infection**. - The patient's symptoms are not classic for tuberculosis, and while crackles are noted, there is no mention of cough or typical pulmonary involvement beyond general symptoms that could be attributed to infection or malignancy. *Monospot* - The **Monospot test** is used to detect heterophile antibodies associated with **infectious mononucleosis**, typically caused by the Epstein-Barr virus (EBV). - While leukocytosis with lymphocytic predominance and splenomegaly can occur in mononucleosis, the patient's age (61 years old) makes it a less likely primary diagnosis, and the overall clinical picture, particularly the "dry tap" bone marrow aspiration, points more strongly to a hematologic malignancy. *Rapid streptococcal antigen* - A **rapid streptococcal antigen test** is used to diagnose **Streptococcus pyogenes (Group A Strep)** pharyngitis. - While the patient has mild tonsillar erythema, his systemic symptoms (splenomegaly, pancytopenia, constitutional symptoms) are far broader and more severe than typical pharyngitis, making Strep throat an insufficient explanation for his overall condition.
Question 202: A 4-year-old girl is brought to the physician because of a 3-week history of generalized fatigue and easy bruising. During the past week, she has also had fever and severe leg pain that wakes her up at night. Her temperature is 38.3°C (100.9°F), pulse is 120/min, and respirations are 30/min. Examination shows cervical and axillary lymphadenopathy. The abdomen is soft and nontender; the liver is palpated 3 cm below the right costal margin, and the spleen is palpated 2 cm below the left costal margin. Laboratory studies show: Hemoglobin 10.1 g/dL Leukocyte count 63,000/mm3 Platelet count 27,000/mm3 A bone marrow aspirate predominantly shows immature cells that stain positive for CD10, CD19, and TdT. Which of the following is the most likely diagnosis?
- A. Aplastic anemia
- B. Hodgkin lymphoma
- C. Acute lymphoblastic leukemia (Correct Answer)
- D. Acute myeloid leukemia
- E. Hairy cell leukemia
Explanation: ***Acute lymphoblastic leukemia*** - The constellation of **generalized fatigue**, **easy bruising** (due to **thrombocytopenia**), fever, **severe leg pain** (bone marrow infiltration), **hepatosplenomegaly**, and **lymphadenopathy** in a child is highly suggestive of **acute leukemia**. - The laboratory findings of **anemia** (Hb 10.1 g/dL), **thrombocytopenia** (platelet count 27,000/mm³), and a **markedly elevated leukocyte count** (63,000/mm³) with **immature cells** (blasts) in the bone marrow, staining positive for **CD10, CD19, and TdT**, are pathognomonic for **B-cell acute lymphoblastic leukemia (ALL)**. *Aplastic anemia* - This condition is characterized by **pancytopenia** (low levels of all blood cell types) due to bone marrow failure, but it would not typically present with **lymphadenopathy**, **hepatosplenomegaly**, or an extremely high leukocyte count with immature cells. - The bone marrow would be **hypocellular** rather than hypercellular with blasts, as seen in this patient. *Hodgkin lymphoma* - While Hodgkin lymphoma can cause **lymphadenopathy** and systemic symptoms like fever and fatigue (B symptoms), it is less common in this age group and does not present with **pancytopenia** or an overwhelming presence of immature cells in the bone marrow. - Diagnosis relies on the identification of **Reed-Sternberg cells** in lymph node biopsy. *Acute myeloid leukemia* - **AML** can also present with similar symptoms and pancytopenia with elevated blasts, but the immunophenotype would differ, typically showing markers like **CD13, CD33, and myeloid-specific markers**, not **CD10, CD19, and TdT**. - **TdT** positivity is characteristic of lymphoid progenitors. *Hairy cell leukemia* - This is a rare, **chronic B-cell leukemia** primarily affecting older adults, not children, and is characterized by cells with **"hairy" projections**, **massive splenomegaly**, and typically **pancytopenia** without a high blast count. - The immunophenotype involves **CD11c, CD25, CD103, and CD123**.
Question 203: A 71-year-old African American man with a history of prostatic adenocarcinoma presents to his oncologist with low back pain. He was diagnosed with non-resectable prostatic adenocarcinoma 4 years ago. He has undergone radiation therapy and chemotherapy. Over the past 3 months, he has developed constant mild non-radiating low back pain that occasionally wakes him up from sleep. He denies any recent falls or trauma. His past medical history is notable for hypertension, diabetes mellitus, coronary artery disease, and gout. He also has a history of thyroid cancer and underwent thyroidectomy 5 years ago. He takes lisinopril, metoprolol, aspirin, metformin, and allopurinol. He has a 40-pack-year smoking history and drinks alcohol socially. His temperature is 99.2°F (37.3°C), blood pressure is 150/85 mmHg, pulse is 84/min, and respirations are 18/min. On exam, he is well-appearing and in no acute distress. He is mildly tender to palpation along the lumbar vertebral spinous processes. A computerized tomography (CT) scan of the lumbar spine demonstrates a blastic and sclerotic lesion in the L5 vertebral body. Which of the following findings would most likely be seen on a serum study of this patient?
- A. Increased calcium, decreased phosphate, increased alkaline phosphatase, and increased parathyroid hormone
- B. Decreased calcium, decreased phosphate, increased alkaline phosphatase, and increased parathyroid hormone
- C. Normal calcium, normal phosphate, increased alkaline phosphatase, and normal parathyroid hormone (Correct Answer)
- D. Decreased calcium, increased phosphate, increased alkaline phosphatase, and increased parathyroid hormone
- E. Normal calcium, normal phosphate, normal alkaline phosphatase, and normal parathyroid hormone
Explanation: ***Normal calcium, normal phosphate, increased alkaline phosphatase, and normal parathyroid hormone*** - This pattern is characteristic of **osteoblastic metastases** from prostate cancer, where bone formation is increased due to cancerous deposits. The body attempts to compensate by increasing *ALP* (marker of bone turnover) while maintaining normal calcium and phosphate levels through homeostatic mechanisms. - The **blastic and sclerotic lesion** on CT confirms increased bone formation, which elevates **alkaline phosphatase** (ALP), a marker of osteoblastic activity, while the general calcium and phosphate regulation remains within normal limits. *Increased calcium, decreased phosphate, increased alkaline phosphatase, and increased parathyroid hormone* - This profile suggests **primary hyperparathyroidism**, which is typically associated with bone resorption and hypercalcemia, not the blastic lesions seen here. - While *ALP* can be increased in severe hyperparathyroidism due to increased bone turnover, the combination of **hypercalcemia** and **hypophosphatemia** points away from metastatic prostate cancer. *Decreased calcium, decreased phosphate, increased alkaline phosphatase, and increased parathyroid hormone* - This pattern is indicative of **osteomalacia** or **rickets**, where poor mineralization leads to low calcium and phosphate, triggering secondary hyperparathyroidism. - This is inconsistent with the **sclerotic (blastic)** bone lesions observed in the patient. *Decreased calcium, increased phosphate, increased alkaline phosphatase, and increased parathyroid hormone* - This combination points towards **chronic kidney disease** with secondary hyperparathyroidism, where impaired phosphate excretion leads to hyperphosphatemia, causing hypocalcemia and a rise in PTH. - While *ALP* can be elevated in renal osteodystrophy, the primary bone lesion is typically osteitis fibrosa cystica rather than blastic metastases. *Normal calcium, normal phosphate, normal alkaline phosphatase, and normal parathyroid hormone* - This would suggest a **normal bone metabolism** with no significant bone disease or metastatic involvement. - This contradicts the presence of a **blastic lesion** on CT and the patient's symptoms of low back pain due to metastatic prostate cancer.
Question 204: A 32-year-old woman visits her primary care provider with the results of a recent colonoscopy, which was ordered after 3 episodes of rectal bleeding in the last month. Her grandmother, mother, and sister all have been diagnosed with nonpolyposis colorectal cancer, at ages 65, 50, and 40 years, respectively. Colonoscopy for this patient revealed a large, flat, right-sided adenoma. Histopathological examination of the lesion showed villous histology and high-grade dysplasia. Which of the following helps explain the condition of this patient?
- A. Chromosomal instability
- B. Chemical carcinogenicity
- C. DNA hypermethylation
- D. Environmental carcinogenicity
- E. Microsatellite instability (Correct Answer)
Explanation: ***Microsatellite instability*** - The patient's **family history** of early-onset, **nonpolyposis colorectal cancer** in three first-degree relatives across three generations strongly suggests a **hereditary syndrome**, specifically **Lynch syndrome (HNPCC)**, which is characterized by **microsatellite instability**. - **Lynch syndrome** results from germline mutations in **DNA mismatch repair genes** (e.g., MLH1, MSH2, MSH6, PMS2), leading to accumulation of mutations in microsatellite regions and increased cancer risk. The patient's large, flat, right-sided adenoma with villous histology and high-grade dysplasia is also typical of Lynch syndrome-associated lesions. *Chromosomal instability* - **Chromosomal instability** (CIN) is characteristic of the **adenoma-carcinoma sequence** seen in sporadic colorectal cancer, involving large-scale chromosomal alterations (aneuploidy, translocations, deletions). - While CIN is common in sporadic colorectal cancers, the strong family history and early onset in this patient point away from the typical CIN pathway as the primary cause. *Chemical carcinogenicity* - **Chemical carcinogenicity** refers to cancer development due to exposure to specific chemicals, which is generally associated with sporadic cancers and lacks the clear hereditary pattern seen here. - While environmental factors can influence cancer risk, the striking familial presentation in this case makes a solely chemical cause unlikely. *DNA hypermethylation* - **DNA hypermethylation** of promoter regions leading to gene silencing, particularly the **CpG island methylator phenotype (CIMP)**, is found in both sporadic colorectal cancers and some Lynch syndrome cases (especially those with MLH1 promoter methylation). - However, **microsatellite instability** is the direct consequence of germline mutations in mismatch repair genes, which is the fundamental defect in Lynch syndrome suggested by the patient's family history. *Environmental carcinogenicity* - **Environmental carcinogenicity** broadly refers to cancer caused by external factors such as diet, smoking, or radiation. - While environmental factors can play a role in all cancers, the strong autosomal dominant inheritance pattern and early onset of nonpolyposis colorectal cancer in this patient's family point towards a specific genetic predisposition rather than solely environmental causes.
Question 205: A 58-year-old male undergoes a surveillance colonoscopy in which a 2 cm adenoma is identified and removed. Had this adenoma not been excised, the patient would have been at risk of progression to carcinoma. Which of the following is the final mutational step in the progression from adenoma to carcinoma?
- A. p53 inactivation (Correct Answer)
- B. APC mutation
- C. COX-2 overexpression
- D. SMAD 2/4 loss
- E. K-ras mutation
Explanation: ***p53 inactivation*** - **p53 loss of function** is typically the final genetic event in the **adenoma-to-carcinoma sequence**, facilitating unrestricted cell growth and preventing apoptosis in dysplastic cells. - The **p53 tumor suppressor gene** normally checkpoints cell division and induces programmed cell death, making its inactivation critical for malignant transformation. *APC mutation* - **APC (adenomatous polyposis coli) mutation** is often the **initiating event** in colorectal adenoma formation, leading to aberrant crypt foci and polyp formation. - While critical for early tumor genesis, it does not represent the final step in progression to invasive carcinoma. *COX-2 overexpression* - **Cyclooxygenase-2 (COX-2) overexpression** leads to increased prostaglandin production, which can promote cell proliferation, angiogenesis, and inhibit apoptosis. - It is an important factor in tumor growth and progression but occurs earlier in the sequence and is not the terminal mutational step for carcinoma. *SMAD 2/4 loss* - **SMAD 2/4 loss of function** disrupts the **TGF-β signaling pathway**, which normally inhibits cell growth and promotes differentiation. - This event typically occurs in the late adenoma stage, contributing to dysplasia, but **p53 inactivation** is considered the final critical step for full malignant transformation. *K-ras mutation* - **K-ras mutation** is a well-known event in the **adenoma-to-carcinoma sequence**, occurring earlier than p53 inactivation, usually in intermediate-sized adenomas. - It leads to constitutive activation of the RAS/MAPK pathway, promoting cell growth and survival, but generally before full malignant transformation.
Question 206: A 16-year-old male presents to the emergency department complaining of episodes of pounding headache, chest fluttering, and excessive sweating. He has a past history of kidney stones that are composed of calcium oxalate. He does not smoke or drink alcohol. Family history reveals that his mother died of thyroid cancer. Vital signs reveal a temperature of 37.1°C (98.7°F), blood pressure of 200/110 mm Hg and pulse of 120/min. His 24-hour urine calcium, serum metanephrines, and serum normetanephrines levels are all elevated. Mutation of which of the following genes is responsible for this patient's condition?
- A. RET proto-oncogene (Correct Answer)
- B. BCL2
- C. BRAF
- D. BCR-ABL
- E. HER-2/neu (C-erbB2)
Explanation: ***RET proto-oncogene*** - The patient's symptoms (pounding headache, chest fluttering, sweating, hypertension, tachycardia), elevated metanephrines, and a history of kidney stones (suggesting **hyperparathyroidism**) combined with a family history of **thyroid cancer** are classic for **Multiple Endocrine Neoplasia type 2A (MEN2A)**. - **MEN2A** is caused by a germline mutation in the **RET proto-oncogene** and typically involves **medullary thyroid carcinoma**, **pheochromocytoma** (explaining the adrenal symptoms), and **primary hyperparathyroidism**. *BCL2* - The **BCL2 gene** is an **anti-apoptotic gene** primarily associated with lymphomas, particularly **follicular lymphoma**, where its overexpression promotes cell survival. - Mutations or translocations involving BCL2 are not linked to endocrine disorders like MEN2A or the specific combination of symptoms seen in this patient. *BRAF* - The **BRAF gene** encodes a protein involved in cell growth signaling and is commonly mutated in various cancers, most notably **melanoma** and **papillary thyroid carcinoma**. - While associated with thyroid cancer, a BRAF mutation does not explain the pheochromocytoma, hyperparathyroidism, or the specific family history indicative of MEN2A. *BCR-ABL* - The **BCR-ABL fusion gene** results from the **Philadelphia chromosome translocation (t(9;22))** and is the hallmark of **chronic myeloid leukemia (CML)** and some cases of acute lymphoblastic leukemia. - This gene is a potent oncogene in hematopoietic malignancies and has no association with the endocrine tumors or symptoms described in the patient. *HER-2/neu (C-erbB2)* - **HER-2/neu (C-erbB2)** is an oncogene that encodes a receptor tyrosine kinase and is primarily associated with **breast cancer** and some **gastric cancers**, where its overexpression indicates a more aggressive tumor and guides targeted therapy. - This gene is not implicated in the pathogenesis of MEN2A or the constellation of symptoms observed in this patient.
Question 207: A 38-year-old man presents to his primary care practitioner for 2 months of rectal bleeding. He also reports occasional diarrhea and abdominal pain. His family history is relevant for his father and uncle, who died from complications of colorectal cancer. Colonoscopy shows more than 10 colorectal adenomas. Which of the following genes is most likely affected in this patient?
- A. RAS
- B. TP53
- C. hMLH1
- D. PPAR
- E. APC (Correct Answer)
Explanation: ***APC*** - This patient's presentation with **numerous colorectal adenomas** (over 10), early-onset symptoms (38 years old), and a strong **family history of colorectal cancer** (father and uncle) is highly characteristic of **Familial Adenomatous Polyposis (FAP)**. - FAP is an **autosomal dominant** condition caused by a germline mutation in the **APC tumor suppressor gene**, leading to the development of hundreds to thousands of adenomatous polyps in the colon, which inevitably progress to colorectal cancer if untreated. *RAS* - **RAS mutations** are commonly found in sporadic colorectal cancers and play a role in tumor growth and progression, but they are not typically associated with the **hereditary syndrome of multiple adenomas** seen in this patient. - RAS activation leads to an increase in **cell proliferation** and can contribute to the development of many cancers, but not as the primary genetic defect in a polyposis syndrome. *TP53* - **TP53** is a well-known tumor suppressor gene, and mutations are involved in various cancers, including colorectal cancer (often in its later stages). However, germline mutations in TP53 are associated with **Li-Fraumeni syndrome**, which involves a broad spectrum of early-onset cancers and is not primarily characterized by numerous colonic adenomas. - TP53 mutations are generally hallmarks of **genomic instability** and are more often seen in the progression of sporadic cancers rather than initiating a polyposis syndrome. *hMLH1* - **hMLH1** is a gene involved in **DNA mismatch repair**. Germline mutations in this gene, along with other mismatch repair genes (e.g., MSH2, MSH6, PMS2), are responsible for **Lynch syndrome (hereditary non-polyposis colorectal cancer - HNPCC)**. - While Lynch syndrome is an important cause of hereditary colorectal cancer, it is characterized by fewer polyps (typically <10) that progress rapidly to cancer, and an increased risk of other cancers (e.g., endometrial), which differs from the presentation of **hundreds of adenomas** seen in FAP. *PPAR* - **PPARs (Peroxisome Proliferator-Activated Receptors)** are a group of nuclear receptor proteins that play roles in metabolism, cell differentiation, and inflammation. - While PPAR pathways have been investigated for their potential role in cancer development and as therapeutic targets, **mutations in PPAR genes are not directly linked** to a common hereditary colorectal cancer syndrome characterized by numerous adenomas like FAP.
Question 208: A 72-year-old man presents to the emergency department with a complaint of rectal bleeding. He describes blood mixed in with the stool, which is associated with a change in his normal bowel habit such that he is going more frequently than normal. He also has some crampy left-sided abdominal pain and weight loss. His symptoms started 2 months ago, but he thought they are due to lack of dietary fiber intake and excess consumption of red meat. He has had type 2 diabetes mellitus for 35 years for which he takes metformin. He also uses daily low-dose aspirin for cardioprotection and occasional naproxen for knee pain. His family history is irrelevant. On examination, his abdomen and digital rectal examination are normal. Colonoscopy shows an ulcerating mucosal lesion with a narrow bowel lumen and biopsy shows a moderately differentiated adenocarcinoma. Which of the following is the greatest risk factor for colorectal cancer in this patient?
- A. Lack of dietary fiber intake
- B. Low-dose aspirin use
- C. Naproxen use
- D. Increasing age (Correct Answer)
- E. Metformin use
Explanation: ***Increasing age*** - **Age** is the most significant **non-modifiable risk factor** for colorectal cancer, with incidence rising sharply after age 50. - The patient's age of **72 years** places him in a high-risk category for developing colorectal cancer. *Lack of dietary fiber intake* - While a **low-fiber diet** is considered a risk factor for colorectal cancer, its impact is generally less significant compared to age. - This is a **modifiable risk factor**, and its absence doesn't outweigh the inherent risk associated with advanced age. *Low-dose aspirin use* - **Low-dose aspirin** is known to have a **protective effect** against colorectal cancer, particularly with long-term use. - Therefore, it would *decrease*, rather than increase, the risk in this patient. *Naproxen use* - **Naproxen**, an NSAID, is also associated with a **reduced risk** of colorectal cancer. - Similar to aspirin, its use would generally be considered protective, not a risk factor. *Metformin use* - Studies suggest that **metformin**, used for type 2 diabetes, may have a **protective effect** against colorectal cancer. - This medication is unlikely to be a risk factor and might even contribute to a lower risk.
Question 209: A 35-year-old woman, gravida 2, para 2, comes to the physician with intermenstrual bleeding and heavy menses for the past 4 months. She does not take any medications. Her father died of colon cancer at the age of 42 years. A curettage sample shows dysplastic tall, columnar, cells in the endometrium without intervening stroma. Germline sequencing shows a mutation in the MLH1 gene. Which of the following is the most likely underlying cause of neoplasia in this patient?
- A. Inability to excise bulky DNA adducts
- B. Defective checkpoint control transitions
- C. Impaired repair of deaminated DNA bases
- D. Accumulation of double-stranded DNA breaks
- E. Instability of short tandem DNA repeats (Correct Answer)
Explanation: ***Instability of short tandem DNA repeats*** - The presence of a **germline mutation in the MLH1 gene**, combined with a family history of early-onset colon cancer (father died at 42), is highly indicative of **Lynch syndrome (hereditary nonpolyposis colorectal cancer or HNPCC)**. - Lynch syndrome is caused by defects in **DNA mismatch repair (MMR) genes**, such as MLH1, which leads to microsatellite instability (MSI) where **short tandem DNA repeats** accumulate mutations due to inefficient repair. *Inability to excise bulky DNA adducts* - This mechanism is characteristic of defects in **nucleotide excision repair (NER)**, often seen in conditions like **xeroderma pigmentosum**, which is typically associated with skin cancers due to UV-induced DNA damage. - The patient's presentation and MLH1 mutation point specifically to microsatellite instability, not bulky adduct repair. *Defective checkpoint control transitions* - Defects in cell cycle checkpoint control lead to uncontrolled cell proliferation and genomic instability, but this is a general mechanism in many cancers and not directly linked to MLH1 or microsatellite instability in the specific way that mismatch repair defects are. - Mutations in genes like **p53** or **Rb** are classic examples of defective checkpoint controls, which is not the primary defect described by an MLH1 mutation. *Impaired repair of deaminated DNA bases* - This refers to defects in **base excision repair (BER)**, which is responsible for correcting small lesions like deaminated bases. - While critical for DNA integrity, BER defects are not the primary mechanism behind Lynch syndrome and MLH1 mutations, which are specifically involved in correcting errors during DNA replication. *Accumulation of double-stranded DNA breaks* - This is typically associated with defects in **homologous recombination** or **non-homologous end-joining pathways**, often seen in conditions like **BRCA1/2 mutations** leading to breast and ovarian cancers. - MLH1 mutations primarily affect mismatch repair and do not directly lead to an accumulation of double-stranded breaks.
Question 210: A 45-year-old woman presents with heavy menstrual bleeding between her periods. The patient also complains of experiencing an irregular menstrual cycle, weight loss, bloating, and constipation. She has had 3 uncomplicated pregnancies, all of which ended with normal vaginal deliveries at term. She has never taken oral contraception, and she does not take any medication at the time of presentation. She has no family history of any gynecological malignancy; however, her grandfather and mother had colon cancer that was diagnosed before they turned 50. On physical examination, the patient appears pale. Gynecological examination reveals a bloody cervical discharge and slight uterine enlargement. Endometrial biopsy reveals endometrial adenocarcinoma. Colonoscopy reveals several polyps located in the ascending colon, which are shown to be adenocarcinomas on histological evaluation. Which of the following mechanisms of DNA repair is likely to be disrupted in this patient?
- A. Mismatch repair (Correct Answer)
- B. Homologous recombination
- C. Nucleotide-excision repair
- D. Non-homologous end joining
- E. Base-excision repair
Explanation: ***Mismatch repair*** - The patient's presentation with **endometrial adenocarcinoma** and **synchronous colon adenocarcinomas** (diagnosed before age 50 in multiple family members) is highly suggestive of **Lynch syndrome (hereditary nonpolyposis colorectal cancer or HNPCC)**. - Lynch syndrome is caused by a germline mutation in one of the **DNA mismatch repair (MMR) genes** (e.g., MLH1, MSH2, MSH6, PMS2), leading to an inability to correct replication errors and resulting in microsatellite instability and cancer development. *Homologous recombination* - This pathway is crucial for repairing **double-strand DNA breaks** and is often deficient in cancers associated with **BRCA1/2 mutations**, leading to syndromes like hereditary breast and ovarian cancer. - While homologous recombination defects can cause cancer, they are not typically linked to the specific constellation of endometrial and colon cancers seen in Lynch syndrome. *Nucleotide-excision repair* - This pathway is primarily responsible for repairing bulky DNA lesions, such as those caused by **UV radiation** or certain **chemotherapeutic agents**. - Defects in nucleotide-excision repair are associated with conditions like **xeroderma pigmentosum**, characterized by extreme sensitivity to sunlight and skin cancers, which is not relevant to this patient's presentation. *Non-homologous end joining* - This is another major pathway for repairing **double-strand DNA breaks**, but it is generally considered more error-prone than homologous recombination. - While defects in this pathway can lead to genomic instability and cancer, it is not the primary mechanism disrupted in Lynch syndrome. *Base-excision repair* - This pathway is responsible for removing damaged or modified bases from DNA, often initiated by **oxidative damage or alkylation**. - While essential for maintaining genomic integrity, defects in base-excision repair are not the characteristic mechanism underlying the cancer predisposition seen in Lynch syndrome.
Question 211: A 41-year-old man with HIV comes to the physician because of rectal bleeding and itching for 2 weeks. During this period, he has also had pain with defecation. Four months ago, he was diagnosed with anogenital warts that were treated with cryotherapy. Over the past year, he has been sexually active with 3 male partners. He uses condoms inconsistently. Current medications are zidovudine, emtricitabine, and efavirenz. Digital rectal examination and anoscopy show an exophytic mass on the anal margin that is protruding into the anal canal. The mass is tender to palpation and bleeds easily on contact. Laboratory studies show a leukocyte count of 7,600/mm3 and a CD4+ T-lymphocyte count of 410/mm3 (N ≥ 500). A biopsy specimen of the lesion shows a well-differentiated squamous cell carcinoma. Which of the following cellular processes was most likely involved in the pathogenesis of this patient's malignancy?
- A. Activation of c-myc gene
- B. Inactivation of TP53 gene (Correct Answer)
- C. Activation of TAX gene
- D. Inactivation of VHL gene
- E. Inactivation of WT1 gene
Explanation: ***Inactivation of TP53 gene*** - This patient's **squamous cell carcinoma** (SCC) of the anus is strongly associated with **human papillomavirus (HPV) infection**, which is common in HIV-positive sexually active men. HPV oncoproteins, particularly E6, promote the degradation of the **TP53 tumor suppressor protein**. - Inactivating mutations or degradation of **TP53** remove a critical checkpoint in the cell cycle, allowing cells with DNA damage to proliferate uncontrollably and contributing to carcinogenesis. *Activation of c-myc gene* - The **c-myc proto-oncogene** is involved in cell proliferation, differentiation, and apoptosis, and its activation is commonly seen in lymphomas (e.g., Burkitt lymphoma) and other cancers. - While *c-myc* activation can contribute to various malignancies, it is not the **primary molecular mechanism** linked to HPV-associated anal squamous cell carcinoma. *Activation of TAX gene* - The **TAX gene** is a transforming gene of **human T-cell lymphotropic virus type 1 (HTLV-1)**, responsible for T-cell leukemia/lymphoma. - This patient's presentation with anal squamous cell carcinoma, rather than a hematologic malignancy, makes HTLV-1 and TAX gene activation an unlikely cause. *Inactivation of VHL gene* - The **VHL (Von Hippel-Lindau) gene** is a tumor suppressor gene whose inactivation is strongly associated with **renal cell carcinoma** (clear cell type) and other tumors like pheochromocytoma and hemangioblastoma. - Inactivation of **VHL** is not a primary mechanism in the development of anal squamous cell carcinoma. *Inactivation of WT1 gene* - The **WT1 (Wilms tumor 1) gene** is a tumor suppressor gene primarily associated with **Wilms tumor**, a kidney cancer that typically affects children. - Inactivation of **WT1** is not a known pathogenic mechanism for anal squamous cell carcinoma in adults.
Question 212: A 5-year-old male is brought to his pediatrician after recurrent, prolonged upper respiratory infections over a period of several months. Physical exam reveals petechiae on the patient's legs and arms. Laboratory studies show hemoglobin: 10 g/dL, platelet count: 35,000/mm^3, leukocyte count: 6,600/mm^3. A bone marrow aspiration shows an abundance of lymphoblasts indicative of acute lymphoblastic leukemia (ALL). Positive immunostaining for which of the following would support a diagnosis of precursor B-cell leukemia?
- A. CD2, CD8
- B. TdT, HER-2
- C. CD4, CD5
- D. CD19, CD10 (Correct Answer)
- E. CD30, CD15
Explanation: ***CD19, CD10*** - **CD19** is a pan B-cell marker, expressed on almost all B-lymphocytes from early pre-B-cells through mature B-cells. Its presence, along with **CD10**, is highly characteristic of **precursor B-cell ALL (B-ALL)**. - **CD10**, also known as common acute lymphoblastic leukemia antigen (CALLA), is typically expressed on **early B-cell progenitors** and is a reliable marker for differentiating B-ALL from other leukemias. *CD2, CD8* - **CD2** and **CD8** are markers primarily associated with **T-lymphocytes**. While CD2 is a pan T-cell marker, CD8 identifies cytotoxic T cells. - Their positivity would suggest a **T-cell ALL (T-ALL)**, not the precursor B-cell type indicated by the clinical scenario. *TdT, HER-2* - **Terminal deoxynucleotidyl transferase (TdT)** is an enzyme found in immature lymphocytes (both B and T cells) and is positive in most ALL cases, but it is not specific for B-cell lineage. - **HER-2** is an oncogene and a growth factor receptor overexpressed in certain solid tumors (especially breast cancer) but is not a marker used for leukemia classification. *CD4, CD5* - **CD4** is a marker for helper T cells, while **CD5** is expressed on a subset of T cells and some B-cell malignancies (e.g., chronic lymphocytic leukemia/small lymphocytic lymphoma). - These markers are primarily associated with **T-cell lineages** and would not support a diagnosis of precursor B-cell leukemia in this context. *CD30, CD15* - **CD30** and **CD15** are classical markers for **Hodgkin lymphoma** (specifically the classical type). - Their presence would point towards a lymphoproliferative disorder different from acute lymphoblastic leukemia.
Question 213: A 65-year-old man comes to the physician for evaluation of a neck mass and weight loss. He first noticed the growing mass 2 months ago. The mass is not painful. He also has decreased appetite and intermittent abdominal pain. He has lost 10 kg (22 lb) of weight over the past 3 months. Sometimes, he wakes up in the morning drenched in sweat. He takes daily over-the-counter multivitamins. He appears pale. His pulse is 65/min, blood pressure is 110/70 mm Hg, and temperature is 38.1°C (100.6°F). Physical exam shows a painless, golf ball-sized mass in the anterior triangle of the neck. A biopsy shows large cells with a bilobed nucleus that are CD15-positive and CD30-positive. Laboratory analysis of serum shows a calcium level of 14.5 mg/dL and a parathyroid hormone level of 40 pg/mL. Which of the following is the most likely explanation of this patient's laboratory findings?
- A. Ectopic vitamin D production
- B. Osteolytic metastasis
- C. Ectopic PTH-related protein production (Correct Answer)
- D. Multivitamin overdose
- E. Osteoblastic metastasis
Explanation: ***Ectopic PTH-related protein production*** - The patient's symptoms (neck mass, weight loss, night sweats, fever) and biopsy findings (CD15+ and CD30+ large cells with bilobed nucleus) are highly suggestive of **Hodgkin lymphoma** with classic Reed-Sternberg cells. - **Hypercalcemia (14.5 mg/dL)** with **inappropriately normal PTH (40 pg/mL)** in the context of malignancy points to **humoral hypercalcemia of malignancy (HHM)**, mediated by **PTH-related protein (PTHrP)** produced ectopically by tumor cells. - PTH should be suppressed (<20 pg/mL) in the setting of hypercalcemia, so a level of 40 pg/mL indicates autonomous calcium elevation from a non-PTH source. *Ectopic vitamin D production* - While some lymphomas can produce **1,25-dihydroxyvitamin D** (through activated macrophages), leading to hypercalcemia, this would also cause **suppressed PTH**. - This mechanism occurs in Hodgkin lymphoma but is less common than PTHrP-mediated hypercalcemia in most cases of malignancy-associated hypercalcemia. *Osteolytic metastasis* - **Osteolytic metastases** (e.g., from multiple myeloma or breast cancer) can cause hypercalcemia by directly destroying bone and releasing calcium. - The biopsy is consistent with Hodgkin lymphoma, not a solid tumor that typically produces purely lytic bone metastases. - While Hodgkin lymphoma can involve bone, systemic hypercalcemia due to direct bone destruction is less common than HHM through PTHrP. *Multivitamin overdose* - Overdosing on multivitamins could potentially lead to **vitamin D toxicity** and hypercalcemia if the supplements contained extremely high doses of vitamin D. - However, the patient's symptoms, neck mass, fever, and biopsy findings clearly indicate a malignancy (Hodgkin lymphoma), making multivitamin overdose an unlikely cause of his profound hypercalcemia. *Osteoblastic metastasis* - **Osteoblastic metastases** (e.g., from prostate cancer) stimulate new bone formation and typically cause **elevated alkaline phosphatase** with normal or slightly elevated calcium, not profound hypercalcemia. - Furthermore, the biopsy findings (Reed-Sternberg cells) are not consistent with a tumor type that causes osteoblastic metastases.
Question 214: A 55-year-old male presents with complaints of intermittent facial flushing. He also reports feeling itchy after showering. On review of systems, the patient says he has been having new onset headaches recently. On physical exam, his vital signs, including O2 saturation, are normal. He has an abnormal abdominal mass palpable in the left upper quadrant. A complete blood count reveals: WBCs 6500/microliter; Hgb 18.2 g/dL; Platelets 385,000/microliter. Which of the following is most likely responsible for his presentation?
- A. BCR-ABL fusion
- B. Chronic hypoxemia
- C. Tyrosine kinase mutation (Correct Answer)
- D. Fibrosis of bone marrow
- E. Elevated serum erythropoietin levels
Explanation: ***Tyrosine kinase mutation*** - The patient's symptoms (facial flushing, post-showering pruritus, headaches) along with **elevated hemoglobin** (18.2 g/dL) and **splenomegaly** (abdominal mass in LUQ) strongly suggest **Polycythemia Vera (PV)**. - PV is a **myeloproliferative neoplasm** typically caused by a **JAK2 V617F mutation**, which is a type of **tyrosine kinase mutation**, leading to constitutive activation of the JAK-STAT pathway and uncontrolled erythropoiesis. *BCR-ABL fusion* - A **BCR-ABL fusion gene** is characteristic of **Chronic Myeloid Leukemia (CML)**, which typically presents with markedly elevated WBCs and splenomegaly. - While splenomegaly is present here, the patient's symptoms and hematologic findings (elevated Hgb, normal WBCs) are not consistent with CML. *Chronic hypoxemia* - **Chronic hypoxemia** can cause **secondary erythrocytosis** due to increased erythropoietin production in response to low oxygen levels. - However, the patient's **O2 saturation is normal**, ruling out chronic hypoxemia as the cause of his elevated hemoglobin. *Fibrosis of bone marrow* - **Bone marrow fibrosis** is a hallmark of **Primary Myelofibrosis**, another myeloproliferative neoplasm, which typically presents with anemia, marked splenomegaly, and teardrop cells on peripheral smear. - While it can manifest with constitutional symptoms, the patient's **high hemoglobin** and absent anemia make primary myelofibrosis less likely. *Elevated serum erythropoietin levels* - **Elevated serum erythropoietin (EPO) levels** are characteristic of **secondary erythrocytosis**, where EPO production increases due to conditions like hypoxemia, renal tumors, or exogenous EPO use. - In **Polycythemia Vera**, EPO levels are typically **low or undetectable** due to feedback inhibition from the high red blood cell mass.
Question 215: A 53-year-old man is being evaluated for a 3-week history of fatigue, difficulty to concentrate, dyspnea with exertion, dizziness, and digital pain that improves with cold. He has smoked half a pack of cigarettes a day since he was 20. His current medical history involves hypertension. He takes enalapril daily. The vital signs include a blood pressure of 131/82 mm Hg, a heart rate of 95/min, and a temperature of 36.9°C (98.4°F). On physical examination, splenomegaly is found. A complete blood count reveals thrombocytosis of 700,000 cells/μL. Lab work further shows decreased serum iron, iron saturation, and serum ferritin and increased total iron binding capacity. A blood smear reveals an increased number of abnormal platelets, and a bone marrow aspirate confirmed the presence of dysplastic megakaryocytes. A mutation on his chromosome 9 confirms the physician's suspicion of a certain clonal myeloproliferative disease. The patient is started on hydroxyurea. What is the most likely diagnosis?
- A. Aplastic anemia
- B. Chronic myelogenous leukemia
- C. Polycythemia vera
- D. Essential thrombocythemia (Correct Answer)
- E. Myelofibrosis with myeloid metaplasia
Explanation: ***Essential thrombocythemia*** - The patient presents with **thrombocytosis** (>450,000 cells/uL), **splenomegaly**, and **dysplastic megakaryocytes** in the bone marrow, which are characteristic findings. - The presence of a **mutation on chromosome 9** (specifically, a **JAK2 V617F mutation**, although not explicitly named, is typical for this description) further supports the diagnosis, leading to increased platelet production. *Aplastic anemia* - Characterized by **pancytopenia** (low levels of all blood cell types), not thrombocytosis or splenomegaly. - Bone marrow would show **hypocellularity** and fat replacement, not dysplastic megakaryocytes. *Chronic myelogenous leukemia* - While it can present with splenomegaly and high white blood cell counts, the hallmark is the **BCR-ABL1 fusion gene (Philadelphia chromosome)**, and typically presents with a very high white blood cell count, not primarily thrombocytosis of this magnitude as the presenting feature. - The mutation on chromosome 9 mentioned (likely JAK2) is associated with other myeloproliferative neoplasms, not CML. *Polycythemia vera* - Primarily defined by **elevated red blood cell mass** (high hematocrit) in addition to potential thrombocytosis and leukocytosis. - Although it shares the **JAK2 V617F mutation** and splenomegaly, the patient's symptoms (fatigue, dyspnea, dizziness) are attributed to the thrombocytosis, and there is no mention of erythrocytosis. *Myelofibrosis with myeloid metaplasia* - Characterized by **bone marrow fibrosis**, **extramedullary hematopoiesis** (leading to significant splenomegaly), and typically a **leukoerythroblastic blood smear** with teardrop cells. - While thrombocytosis can occur early, the dominant feature is marrow fibrosis and progressive cytopenias.
Question 216: A 43-year-old woman presents to your clinic for the evaluation of an abnormal skin lesion on her forearm. The patient is worried because her mother passed away from melanoma. You believe that the lesion warrants biopsy for further evaluation for possible melanoma. Your patient is concerned about her risk for malignant disease. What is the most important prognostic factor of melanoma?
- A. Depth of invasion of atypical cells (Correct Answer)
- B. S-100 tumor marker present
- C. Evolution of lesion over time
- D. Age at presentation
- E. Level of irregularity of the borders
Explanation: ***Depth of invasion of atypical cells*** - The **Breslow depth**, which measures the vertical thickness of the melanoma from the granular layer of the epidermis to the deepest part of the tumor, is the **single most important prognostic factor** for localized melanoma. - A greater depth of invasion correlates directly with a higher risk of **metastasis** and a poorer prognosis due to increased likelihood of reaching dermal lymphatics or blood vessels. *S-100 tumor marker present* - While **S-100 protein** is a marker expressed in melanoma cells and can be used to detect metastatic disease (e.g., in lymph nodes), its mere presence does not serve as the primary prognostic indicator for the primary lesion itself. - S-100 reflects the presence of melanoma cells but does not provide information about the **depth or biological aggressiveness** of the initial tumor. *Evolution of lesion over time* - The **evolution or change** in a lesion (e.g., in size, shape, color, new symptoms) is a crucial diagnostic criterion for identifying suspicious lesions for biopsy. - While important for diagnosis, it is not a direct prognostic factor once melanoma is confirmed; the **pathological features** after biopsy, particularly depth, determine prognosis. *Age at presentation* - **Age** can influence treatment decisions and overall health status, but it is not the most important independent prognostic factor for melanoma. - Prognosis is primarily driven by tumor-specific characteristics rather than the patient's age. *Level of irregularity of the borders* - **Border irregularity** is one of the ABCDE criteria (Asymmetry, Border irregularity, Color variation, Diameter >6mm, Evolving) used to identify suspicious pigmented lesions. - It is a diagnostic indicator that warrants further investigation but does not independently determine **prognosis** as definitively as the Breslow depth after biopsy.
Question 217: An investigator studying targeted therapy in patients with gastrointestinal stromal tumors requires a reliable test to determine the spatial distribution of CD117-positive cells in biopsy specimens. Which of the following is the most appropriate test?
- A. Northern blot
- B. Immunohistochemistry (Correct Answer)
- C. Flow cytometry
- D. Fluorescence in-situ hybridization
- E. Western blot
Explanation: ***Immunohistochemistry*** - **Immunohistochemistry (IHC)** uses **antibodies** to target specific antigens (like **CD117**) within tissue sections, allowing for **visualization of their spatial distribution** under a microscope. - This technique is ideal for identifying the precise location and quantity of **CD117-positive cells** within a biopsy, which is crucial for assessing targeted therapy in gastrointestinal stromal tumors. *Northern blot* - **Northern blot** is used to detect and quantify specific **RNA** sequences in a sample. - It does not provide information about **protein expression** or the **spatial distribution of cells** within tissue. *Flow cytometry* - **Flow cytometry** is used for analyzing and sorting cells based on their **surface or intracellular markers** by passing them in a fluid stream through laser light. - While it can quantify **CD117-positive cells**, it requires cells to be in suspension and thus **destroys the tissue architecture**, preventing analysis of spatial distribution. *Fluorescence in-situ hybridization* - **Fluorescence in-situ hybridization (FISH)** uses **fluorescent probes** to detect and locate specific **DNA or RNA sequences** on chromosomes or in cells. - FISH is primarily used for genetic analysis and **does not directly assess protein expression** or cellular distribution in the context of targeted therapy. *Western blot* - **Western blot** is used to detect and quantify specific **proteins** from a sample by separating them by size, but it is performed on **tissue homogenates**. - This technique provides information on the **total protein content** but **does not preserve the spatial arrangement** of cells within the original tissue.
Question 218: A 70-year-old man presents to his physician for evaluation of fullness and swelling of the left side of the abdomen over the last month. During this time, he has had night sweats and lost 2 kg (4.4 lb) unintentionally. He has no history of severe illness and takes no medications. The vital signs include: blood pressure 115/75 mm Hg, pulse 75/min, and temperature 36.8℃ (98.2℉). The abdomen has asymmetric distention. Percussion and palpation of the left upper quadrant reveal splenomegaly. No lymphadenopathy is detected. Heart and lung examination shows no abnormalities. The laboratory studies show the following: Hemoglobin 9.5 g/dL Mean corpuscular volume 95 μm3 Leukocyte count 8,000/mm3 Platelet count 240,000/mm3 Ultrasound shows a spleen size of 15 cm, mild hepatomegaly, and mild ascites. The peripheral blood smear shows teardrop-shaped and nucleated red blood cells (RBCs) and immature myeloid cells. Marrow is very difficult to aspirate but reveals hyperplasia of all 3 lineages. The tartrate-resistant acid phosphatase (TRAP) test is negative. The cytogenetic analysis is negative for translocation between chromosomes 9 and 22. Which of the following laboratory findings is most likely to be present in this patient?
- A. Monoclonal elevation of IgG
- B. Hair-like cell-membrane projections
- C. JAK2 mutation (Correct Answer)
- D. Philadelphia chromosome
- E. Reed-Sternberg cells
Explanation: ***JAK2 mutation*** - The patient's presentation with **splenomegaly**, **night sweats**, **weight loss**, **teardrop cells**, **nucleated red blood cells**, and a "dry tap" (difficulty aspirating marrow) are highly suggestive of **primary myelofibrosis**. - A **JAK2 mutation** (specifically JAK2 V617F) is found in approximately 50-60% of patients with primary myelofibrosis and is a crucial diagnostic marker, distinguishing it from other myeloproliferative neoplasms. Other driver mutations include CALR (~25-30%) and MPL (~5-10%). *Monoclonal elevation of IgG* - **Monoclonal elevation of IgG** is characteristic of **plasma cell disorders** such as **multiple myeloma** or **monoclonal gammopathy of undetermined significance (MGUS)**. - This patient's symptoms and laboratory findings, particularly the peripheral blood smear with **teardrop cells** and a "dry tap," do not align with a plasma cell dyscrasia. *Hair-like cell-membrane projections* - **Hair-like cell-membrane projections** are the hallmark of **hairy cell leukemia**, a rare B-cell lymphoproliferative disorder. - While hairy cell leukemia can cause **splenomegaly** and **pancytopenia**, the presence of **teardrop cells** and **immature myeloid cells** in the peripheral smear, along with a "dry tap," makes this diagnosis unlikely. The **negative TRAP test** also argues against hairy cell leukemia since TRAP positivity is characteristic of this condition. *Philadelphia chromosome* - The **Philadelphia chromosome (t(9;22))** encoding the **BCR-ABL1 fusion gene** is the defining characteristic of **chronic myeloid leukemia (CML)**. - While CML can present with **splenomegaly** and **myeloid immature cells**, the absence of the Philadelphia chromosome on cytogenetic analysis (as stated in the stem) and the presence of **teardrop cells** and **dry tap** rule out CML in favor of myelofibrosis. *Reed-Sternberg cells* - **Reed-Sternberg cells** are large, multinucleated cells characteristic of **Hodgkin lymphoma**. - Hodgkin lymphoma typically presents with **lymphadenopathy** and systemic symptoms, but the hematological findings and evidence of myelofibrosis in this patient do not support a diagnosis of lymphoma.
Question 219: A 59-year-old woman comes to the physician because of a 2-month history of fatigue and abdominal discomfort. Over the past 6 months, she has had a 5.4-kg (12-lb) weight loss. She takes no medications. Her temperature is 37.8°C (100°F), pulse is 70/min, respirations are 13/min, and blood pressure is 125/80 mm Hg. Cardiopulmonary examination shows no abnormalities. The spleen is palpated 3 cm below the left costal margin. Laboratory studies show: Hemoglobin 9.4 g/dL Mean corpuscular volume 86 μm3 Leukocyte count 58,000/mm3 Segmented neutrophils 54% Bands 8% Lymphocytes 7% Myelocytes 5% Metamyelocytes 10% Promyelocytes 4% Blasts 5% Monocytes 1% Eosinophils 4% Basophils 2% Platelet count 850,000/mm3 Serum Creatinine 0.9 mg/dL LDH 501 U/L Bone marrow biopsy shows hyperplastic myelopoiesis with granulocytosis. Which of the following is the most appropriate next step in management?
- A. Serum protein electrophoresis
- B. Cytogenetic studies (Correct Answer)
- C. Observation and follow-up
- D. All-trans retinoic acid
- E. Cytarabine and daunorubicin
Explanation: ***Cytogenetic studies*** - The patient's presentation with **splenomegaly**, **leukocytosis with a left shift** (including myelocytes, metamyelocytes, and some blasts), **thrombocytosis**, and **fatigue, weight loss, and abdominal discomfort** are highly suggestive of a myeloproliferative neoplasm, specifically **chronic myeloid leukemia (CML)**. - **Cytogenetic studies** (e.g., FISH or conventional karyotyping) are crucial to confirm CML by detecting the **Philadelphia chromosome (t(9;22))**, which forms the **BCR-ABL1 fusion gene**, the hallmark of this disease. *Serum protein electrophoresis* - **Serum protein electrophoresis (SPEP)** is primarily used to diagnose and monitor **monoclonal gammopathies**, such as multiple myeloma or Waldenström macroglobulinemia. - It is not relevant for the diagnosis of myeloproliferative disorders like CML, which involve myeloid cell lines, not plasma cells. *Observation and follow-up* - Given the patient's symptomatic presentation (fatigue, weight loss, abdominal discomfort), significant leukocytosis, thrombocytosis, and splenomegaly, **active intervention and diagnosis are warranted**. - Observing a patient with suspected CML is not appropriate, as it can progress to an accelerated phase or blast crisis if left untreated. *All-trans retinoic acid* - **All-trans retinoic acid (ATRA)** is a specific treatment used for **acute promyelocytic leukemia (APL)**, a subtype of acute myeloid leukemia. - APL characteristically presents with mature promyelocytes and is associated with the **t(15;17) translocation**, which is distinct from the findings and suspected diagnosis in this patient. *Cytarabine and daunorubicin* - **Cytarabine and daunorubicin** constitute a common chemotherapy regimen used for **induction therapy in acute myeloid leukemia (AML)**. - The patient's blood counts, particularly the lower blast percentage (5%) and prominent left shift with mature myeloid forms, are more consistent with a chronic myeloproliferative disorder like CML, rather than an acute leukemia that would necessitate this aggressive treatment.
Question 220: An 11-year-old boy is brought to the pediatrician by his mother for vomiting. The patient has been vomiting for the past week, and his symptoms have not been improving. His symptoms are worse in the morning and tend to improve throughout the day. The patient also complains of occasional headaches and had diarrhea several days ago. The patient eats a balanced diet and does not drink soda or juice. The patient's brothers both had diarrhea recently that resolved spontaneously. His temperature is 99.5°F (37.5°C), blood pressure is 80/45 mmHg, pulse is 90/min, respirations are 16/min, and oxygen saturation is 98% on room air. On physical exam, the patient appears to be in no acute distress. Cardiopulmonary exam reveals a minor flow murmur. Neurological exam reveals cranial nerves II-XII as grossly intact with mild narrowing of the patient's visual fields. The patient's gait is stable, and he is able to jump up and down. Which of the following is the most likely direct cause of this patient's presentation?
- A. Remnant of Rathke's pouch (Correct Answer)
- B. Intracerebellar mass
- C. Gram-positive enterotoxin
- D. Gram-negative microaerophilic bacteria
- E. Non-enveloped, (+) ssRNA virus
Explanation: ***Remnant of Rathke's pouch*** - The patient's symptoms, including **morning vomiting**, **headaches**, and **visual field narrowing**, are highly suggestive of **increased intracranial pressure** from a **craniopharyngioma**. - **Craniopharyngiomas** are benign tumors derived from remnants of **Rathke's pouch** and are the most common supratentorial tumors in children. - These suprasellar masses compress the **optic chiasm**, causing **bitemporal hemianopsia** (visual field defects). *Intracerebellar mass* - While an intracerebellar mass could cause **increased intracranial pressure** and vomiting, the specific **visual field narrowing** points toward a suprasellar lesion affecting the optic chiasm, not a cerebellar location. - Cerebellar masses typically cause **ataxia**, **nystagmus**, and coordination problems, which are not present in this patient. *Gram-positive enterotoxin* - A **gram-positive enterotoxin** (e.g., *S. aureus*, *B. cereus*) would cause acute onset, severe gastrointestinal symptoms with vomiting and diarrhea, but would not explain the **neurological symptoms** like headaches and visual field deficits. - The patient's prolonged symptoms (one week of vomiting) and neurological findings do not align with acute food poisoning. *Gram-negative microaerophilic bacteria* - **Gram-negative microaerophilic bacteria** like *Helicobacter pylori* or *Campylobacter* can cause gastritis or gastroenteritis, but do not explain the **neurological signs** of increased intracranial pressure or visual field defects. - The patient's chronic vomiting with neurological signs indicates intracranial pathology rather than gastrointestinal infection. *Non-enveloped, (+) ssRNA virus* - A **non-enveloped, (+) ssRNA virus** (e.g., norovirus, enterovirus) would cause acute, self-limiting gastroenteritis with vomiting and diarrhea. - It would not explain the **progressive neurological symptoms** and the prolonged duration of vomiting, which suggests a structural intracranial lesion rather than viral gastroenteritis.
Question 221: A 55-year-old female presents to her primary care physician complaining of a mass in her mid-thigh. The mass has grown slowly over the past six months and is not painful. The patient’s past medical history is notable for hypertension and hyperlipidemia. She takes lisinopril and rosuvastatin. On examination, there is a firm, immobile mass on the medial aspect of the distal thigh. She has full range of motion and strength in her lower extremities and patellar reflexes are 2+ bilaterally. A biopsy of the mass reveals multiple pleomorphic smooth muscle cells with nuclear atypia. The patient subsequently initiates radiation therapy with plans to undergo surgical resection. This tumor will most strongly stain for which of the following?
- A. Cytokeratin
- B. Desmin (Correct Answer)
- C. Chromogranin
- D. Neurofilament
- E. Glial fibrillary acidic protein
Explanation: ***Desmin*** - The biopsy results describe **pleomorphic smooth muscle cells with nuclear atypia**, which is characteristic of a **leiomyosarcoma**, a malignant tumor derived from smooth muscle. - **Desmin** is a muscle-specific intermediate filament that is strongly positive in tumors of smooth muscle origin, including leiomyosarcomas, making it the most appropriate stain for diagnosis. *Cytokeratin* - **Cytokeratin** is an intermediate filament protein found in **epithelial cells** and is a marker for carcinomas. - Leiomyosarcomas are mesenchymal tumors, so they would typically be **negative for cytokeratin**. *Chromogranin* - **Chromogranin** is a marker for **neuroendocrine tumors**, such as carcinoids and pheochromocytomas. - This tumor's histological features and derivation from smooth muscle rule out a neuroendocrine origin. *Neurofilament* - **Neurofilament** proteins are found in **neurons** and are markers for tumors of neural origin, such as neuroblastomas or schwannomas. - The presented tumor is of mesenchymal origin, not neural. *Glial fibrillary acidic protein* - **Glial fibrillary acidic protein (GFAP)** is an intermediate filament found in **astrocytes** and is a marker for glial tumors, such as astrocytomas and glioblastomas, which originate in the central nervous system. - A thigh mass is not consistent with a glial tumor.
Question 222: A 71-year-old man presents to the primary care clinic with non-specific complaints of fatigue and malaise. His past medical history is significant for diabetes mellitus type II, hypertension, non-seminomatous testicular cancer, and hypercholesterolemia. He currently smokes 1 pack of cigarettes per day, drinks a glass of wine per day, and he currently denies any illicit drug use. His vital signs include: temperature, 36.7°C (98.0°F); blood pressure, 126/74 mm Hg; heart rate, 87/min; and respiratory rate, 17/min. On examination, his physician notices cervical and inguinal lymphadenopathy bilaterally, as well as splenomegaly. The patient comments that he has lost 18.1 kg (40 lb) over the past 6 months without a change in diet or exercise, which he was initially not concerned about. The physician orders a complete blood count and adds on flow cytometry. Based on his age and overall epidemiology, which of the following is the most likely diagnosis?
- A. Hairy cell leukemia
- B. Acute myelogenous leukemia
- C. Chronic myelogenous leukemia
- D. Acute lymphocytic leukemia
- E. Chronic lymphocytic leukemia (Correct Answer)
Explanation: ***Chronic lymphocytic leukemia*** - The patient's age (71 years), non-specific symptoms like **fatigue and malaise**, unexplained **weight loss**, and findings of **lymphadenopathy** and **splenomegaly** are highly suggestive of **chronic lymphocytic leukemia (CLL)**. - CLL is the most common leukemia in adults in Western countries, typically affecting older individuals, and is characterized by the accumulation of **monoclonal B lymphocytes** which can lead to lymphadenopathy and splenomegaly. *Hairy cell leukemia* - This condition is characterized by **pancytopenia**, **splenomegaly**, and the presence of **"hairy" cells** on peripheral smear and bone marrow. - Lymphadenopathy is typically **less prominent or absent** in hairy cell leukemia compared to CLL. *Acute myelogenous leukemia* - AML typically presents with a **rapid onset of symptoms** due to bone marrow failure, such as severe anemia, thrombocytopenia (bleeding), and granulocytopenia (infections). - While it can cause fatigue, the **lymphadenopathy and splenomegaly** are less characteristic as the primary presenting features compared to CLL, and the leukemia is defined by the proliferation of **myeloblasts**. *Chronic myelogenous leukemia* - CML is often associated with the **Philadelphia chromosome (BCR-ABL fusion gene)** while this patient's case is not specified. - It usually presents with marked **leukocytosis with a left shift** (including myelocytes, metamyelocytes, and band forms), prominent splenomegaly, but often **less pronounced lymphadenopathy** than seen in CLL. *Acute lymphocytic leukemia* - ALL is primarily a disease of **childhood**, though it can occur in adults, but it is much less common in this age group than CLL. - It usually presents with **abrupt onset** symptoms related to bone marrow failure, like fever, pallor, petechiae, and can have more prominent lymphadenopathy and hepatosplenomegaly but the age and chronic nature of symptoms point away from ALL.
Question 223: A 64-year-old male presents to his primary care physician. Laboratory work-up and physical examination are suggestive of a diagnosis of prostatic adenocarcinoma. A tissue biopsy is obtained, which confirms the diagnosis. Which of the following is indicative of metastatic disease?
- A. Decreased serum alkaline phosphatase
- B. New-onset lower back pain (Correct Answer)
- C. Palpation of a hard nodule on digital rectal examination
- D. Involvement of the periurethral zone
- E. Elevated prostatic acid phosphatase (PAP)
Explanation: ***New-onset lower back pain*** - **Lower back pain** in a patient with prostatic adenocarcinoma is a classic symptom of **bone metastases**, as prostate cancer frequently spreads to the spine. - This symptom suggests the tumor has invaded the **vertebrae**, causing pain due to bone destruction or nerve compression. *Decreased serum alkaline phosphatase* - **Decreased serum alkaline phosphatase** is generally not indicative of metastatic prostate cancer; rather, **elevated alkaline phosphatase** typically suggests **bone metastases** due to increased osteoblastic activity. - Lowering of this enzyme might be seen if a patient is undergoing successful treatment, but not as an indicator of new metastatic disease. *Palpation of a hard nodule on digital rectal examination* - A **hard nodule** on digital rectal examination is a common finding in **localized prostate cancer** but does not specifically indicate metastatic disease. - This finding suggests a primary tumor within the prostate gland, not necessarily spread to distant sites. *Involvement of the periurethral zone* - **Prostate cancer** typically originates in the **peripheral zone** of the prostate, not the periurethral zone. - While involvement of any zone indicates presence of cancer, it does not, by itself, suggest **metastatic disease** unless there is further evidence of spread beyond the prostate capsule. *Elevated prostatic acid phosphatase (PAP)* - While **elevated prostatic acid phosphatase (PAP)** can be a marker for prostate cancer activity and, in some cases, advanced or metastatic disease, it is **less specific and sensitive** than **PSA** for general screening and monitoring. - In modern practice, it's not the primary indicator used to confirm metastatic spread on its own when more definitive markers and imaging are available.
Question 224: A 70-year-old man comes to the physician because of right-sided back pain, red urine, and weight loss for the last 4 months. He has smoked one pack of cigarettes daily for 40 years. A CT scan of the abdomen shows a large right-sided renal mass. Biopsy of the mass shows polygonal clear cells filled with lipids. Which of the following features is necessary to determine the tumor grade in this patient?
- A. Invasion of surrounding structures
- B. Response to chemotherapy
- C. Nuclear pleomorphism and nucleolar prominence (Correct Answer)
- D. Involvement of regional lymph nodes
- E. Size of malignant proliferation
Explanation: ***Nuclear pleomorphism and nucleolar prominence*** - The **Fuhrman nuclear grading system** (and newer WHO/ISUP grading system) for renal cell carcinoma is based on **nuclear morphologic features**: nuclear size, nuclear contour irregularity, and most importantly, **nucleolar prominence**. - **Grade 1**: Small uniform nuclei with inconspicuous nucleoli - **Grade 2**: Slightly irregular nuclei with small nucleoli visible at 400× magnification - **Grade 3**: Moderately irregular nuclei with prominent nucleoli visible at 100× magnification - **Grade 4**: Marked nuclear pleomorphism, multilobated nuclei, and prominent nucleoli - Higher nuclear grades correlate with more aggressive tumor behavior and worse prognosis. *Invasion of surrounding structures* - This feature is crucial for **tumor staging (T stage)**, specifically T3 disease when perinephric fat, renal vein, or IVC is invaded, and T4 when beyond Gerota's fascia. - **Invasion** determines surgical approach and prognosis related to local spread but does not define histological grade. *Response to chemotherapy* - **Response to chemotherapy** is evaluated after treatment and is not a feature used for grading at diagnosis. - Clear cell RCC is **chemoresistant**; treatment typically involves targeted therapy (VEGF inhibitors, mTOR inhibitors) or immunotherapy, not traditional chemotherapy. *Involvement of regional lymph nodes* - **Lymph node involvement** is a component of **tumor staging (N stage)**: N0 (no nodes), N1 (regional nodes positive). - It indicates metastatic spread and significantly worsens prognosis but does not contribute to **histological grade**, which assesses cellular differentiation. *Size of malignant proliferation* - **Tumor size** is the primary criterion for **T staging**: T1a (≤4 cm), T1b (>4-7 cm), T2a (>7-10 cm), T2b (>10 cm), all confined to kidney. - Size is a prognostic factor but does not determine **histological grade**, which is based exclusively on nuclear microscopic features.
Question 225: A newborn of a mother with poor antenatal care is found to have a larger than normal head circumference with bulging fontanelles. Physical examination reveals a predominant downward gaze with marked eyelid retraction and convergence-retraction nystagmus. Ultrasound examination showed dilated lateral ventricles and a dilated third ventricle. Further imaging studies reveal a solid mass in the pineal region. Which of the following is the most likely underlying pathophysiological mechanism responsible for the neurological signs in this patient?
- A. Stenotic intraventricular foramina
- B. Dilated cisterna magna
- C. Hypertrophic arachnoid granulations
- D. Normal lumbar puncture opening pressure
- E. Compression of periaqueductal grey matter (Correct Answer)
Explanation: ***Compression of periaqueductal grey matter*** - The constellation of a **large head circumference**, **bulging fontanelles**, **dilated lateral and third ventricles**, and a **pineal region mass** indicates **obstructive hydrocephalus**. - The **downward gaze** (sunsetting sign), **marked eyelid retraction**, and **convergence-retraction nystagmus** are classic signs of **Parinaud's syndrome**, which results from compression of the **dorsal midbrain** (periaqueductal gray matter and superior colliculi) due to **hydrocephalus** or a **pineal tumor**. *Stenotic intraventricular foramina* - While **stenotic intraventricular foramina** (of Monro) can lead to **hydrocephalus** by obstructing CSF flow from the lateral to the third ventricle, the imaging specifically mentions a **dilated third ventricle**. - This suggests the obstruction is *distal* to the third ventricle, likely at the aqueduct of Sylvius, rather than the foramina of Monro. *Dilated cisterna magna* - A **dilated cisterna magna** is a characteristic finding in conditions like the **Dandy-Walker malformation** or benign enlargement of the subarachnoid spaces. - This finding would not directly explain the obstructive hydrocephalus with dilated lateral and third ventricles, nor the specific signs of Parinaud's syndrome. *Hypertrophic arachnoid granulations* - **Arachnoid granulations** are responsible for **CSF reabsorption** into the venous system. Hypertrophic arachnoid granulations would theoretically increase CSF reabsorption, leading to **decreased intracranial pressure**, rather than hydrocephalus. - They do not cause compressive syndromes associated with a pineal mass and obstructive hydrocephalus. *Normal lumbar puncture opening pressure* - A **normal lumbar puncture opening pressure** in the presence of **bulging fontanelles** and **dilated ventricles** is diagnostically contradictory for hydrocephalus. - Obstructive hydrocephalus, as described, would typically lead to **elevated intracranial pressure** and thus an **elevated opening pressure**.
Question 226: A 65-year-old man presents with painless swelling of the neck over the past week. He also has noted severe night sweats, which require a change of clothes and bed linens the next day. His medical history is significant for long-standing hypertension. He received a kidney transplant 6 years ago. His current medications include amlodipine, metoprolol, furosemide, aspirin, tacrolimus, and mycophenolate. His family history is significant for his sister, who died last year from lymphoma. A review of systems is positive for a 6-kg (13.2-lb) unintentional weight loss over the past 2 months. His vital signs include: temperature 37.8°C (100.0°F) and blood pressure 120/75 mm Hg. On physical examination, there are multiple painless lymph nodes, averaging 2 cm in diameter, palpable in the anterior and posterior triangles of the neck bilaterally. Axillary and inguinal lymphadenopathy is palpated on the right side. Abdominal examination is significant for a spleen of 16 cm below the costal margin on percussion. Laboratory studies are significant for the following: Hemoglobin 9 g/dL Mean corpuscular volume 88 μm3 Leukocyte count 12,000/mm3 Platelet count 130,000/mm3 Creatinine 1.1 mg/dL Lactate dehydrogenase (LDH) 1,000 U/L A peripheral blood smear is unremarkable. Which of the following is the most likely diagnosis in this patient?
- A. Multiple myeloma
- B. Non-Hodgkin’s lymphoma (NHL) (Correct Answer)
- C. Drug-induced lymphadenopathy
- D. Chronic lymphocytic leukemia (CLL)
- E. Cytomegalovirus infection
Explanation: ***Non-Hodgkin’s lymphoma (NHL)*** - This patient presents with **B symptoms** (**unintentional weight loss**, **night sweats**, fever), diffuse **lymphadenopathy**, and **splenomegaly**, which are classic signs of lymphoma. Elevated **LDH** and a history of kidney transplant requiring immunosuppression (tacrolimus, mycophenolate) significantly increase the risk of **post-transplant lymphoproliferative disorder (PTLD)**, a type of NHL. - The **anemia**, **thrombocytopenia**, and **leukocytosis** (with an otherwise unremarkable peripheral smear) are consistent with bone marrow involvement or chronic disease in lymphoma. *Multiple myeloma* - Multiple myeloma is a plasma cell dyscrasia characterized by **bone pain**, **renal failure**, **hypercalcemia**, and **anemia**. While anemia and potential renal impairment are present, the widespread lymphadenopathy and splenomegaly are not typical features. - The elevated LDH and presence of B symptoms are more indicative of lymphoma than multiple myeloma. *Drug-induced lymphadenopathy* - While some medications can cause lymphadenopathy, it is typically less severe, often without systemic B symptoms, and usually resolves upon discontinuation of the causative drug. - The combination of severe B symptoms, impressive splenomegaly, and significantly elevated LDH points to a more aggressive underlying malignancy rather than a drug reaction. *Chronic lymphocytic leukemia (CLL)* - CLL is characterized by a persistent **lymphocytosis** (often >5,000 mature lymphocytes/µL) on peripheral smear, which is not described here ("unremarkable"). - While CLL can cause lymphadenopathy and splenomegaly, the rapid onset of severe B symptoms and the extremely high LDH are more suggestive of an aggressive lymphoma rather than indolent CLL. *Cytomegalovirus infection* - CMV infection can cause lymphadenopathy, fever, and fatigue, particularly in immunocompromised patients. However, the degree of **weight loss**, **splenomegaly**, and elevated **LDH** seen here are uncharacteristic of CMV infection and point towards a more serious underlying malignancy. - CMV typically presents with a more acute, mononucleosis-like illness and often lymphocytosis with atypical lymphocytes on peripheral smear.
Question 227: A 61-year-old woman presents to her primary care physician for a routine check-up. Physical examination demonstrates asymmetric peripheral neuropathy in her feet. The patient has no previous relevant history and denies any symptoms of diabetes. Routine blood work shows normal results, and she is referred to a hematologist. Subsequent serum protein electrophoresis demonstrates a slightly elevated gamma globulin level, and monoclonal gammopathy of undetermined significance is diagnosed. Which of the following diseases is most likely to develop over the course of this patient’s condition?
- A. Acute myelocytic leukemia
- B. Chronic myelocytic leukemia
- C. Multiple myeloma (Correct Answer)
- D. Waldenström macroglobulinemia
- E. Chronic lymphocytic leukemia
Explanation: ***Multiple myeloma*** - This patient has **monoclonal gammopathy of undetermined significance (MGUS)**, confirmed by the asymmetric peripheral neuropathy, elevated gamma globulin, and monoclonal gammopathy. MGUS has a 1% annual risk of progressing to **multiple myeloma**. - **Peripheral neuropathy** is a common initial presentation of MGUS, and its progression to multiple myeloma involves the proliferation of **plasma cells** in the bone marrow, leading to end-organ damage. *Acute myelocytic leukemia* - This is a **myeloid malignancy** characterized by rapid proliferation of abnormal myeloid blasts in the bone marrow, not typically preceded by MGUS or presenting with peripheral neuropathy. - It usually presents with symptoms like **fatigue**, **bleeding**, and **infections**, unrelated to the monoclonal gammopathy. *Chronic myelocytic leukemia* - This is a **myeloproliferative disorder** associated with the **Philadelphia chromosome (BCR-ABL1 fusion gene)**, which is distinct from conditions involving plasma cell dyscrasias like MGUS. - It classically presents with **splenomegaly** and a high white blood cell count with a myeloid shift. *Waldenström macroglobulinemia* - This is a **lymphoplasmacytic lymphoma** involving IgM monoclonal gammopathy, which can cause neuropathy similar to MGUS. However, MGUS with IgG or IgA is more common and has a higher progression risk to multiple myeloma than to Waldenström macroglobulinemia. - While it involves **monoclonal gammopathy**, the clinical picture of MGUS with its specific progression risk profile is more indicative of eventual multiple myeloma. *Chronic lymphocytic leukemia* - This is a **lymphoid malignancy** characterized by the accumulation of mature but functionally incompetent lymphocytes, particularly B-cells. - It is not typically preceded by MGUS and usually presents with **lymphadenopathy**, **splenomegaly**, and **lymphocytosis**.
Question 228: A 40-year-old female comes in with several months of unintentional weight loss, epigastric pain, and a sensation of abdominal pressure. She has diabetes well-controlled on metformin but no other prior medical history. She has not previously had any surgeries. On physical exam, her doctor notices brown velvety areas of pigmentation on her neck. Her doctor also notices an enlarged, left supraclavicular node. Endoscopic findings show a stomach wall that appears to be grossly thickened. Which of the following findings would most likely be seen on biopsy?
- A. Keratin pearls
- B. Noncaseating granulomas
- C. Peyer's patches
- D. Psammoma bodies
- E. Cells with central mucin pool (Correct Answer)
Explanation: ***Cells with central mucin pool*** - The patient's symptoms (unintentional weight loss, epigastric pain, abdominal pressure, **acanthosis nigricans**, and a **Virchow node**) are highly suggestive of **gastric adenocarcinoma**, particularly the **diffuse type**. - **Signet ring cells**, characterized by a **large central mucin vacuole** that displaces the nucleus to the periphery, are pathognomonic for **diffuse gastric adenocarcinoma**. *Keratin pearls* - **Keratin pearls** are a hallmark feature of **squamous cell carcinoma**, which is a type of cancer arising from squamous epithelial cells. - While squamous cell carcinoma can occur in the esophagus, it is an extremely rare finding in the stomach, which is lined by glandular epithelium. *Noncaseating granulomas* - **Noncaseating granulomas** are characteristic of conditions like **Crohn's disease** or **sarcoidosis**. - These conditions do not typically present with the described aggressive features of gastric malignancy or the presence of acanthosis nigricans and a Virchow node. *Peyer's patches* - **Peyer's patches** are normal lymphoid structures found in the **ileum** of the small intestine, playing a role in immune surveillance. - Their presence in a biopsy would indicate normal small intestinal tissue, not a malignant gastric lesion. *Psammoma bodies* - **Psammoma bodies** are concentric, laminated calcified structures typically seen in certain types of **cancers with serous or papillary differentiation**, such as **papillary thyroid carcinoma**, **meningioma**, and **serous ovarian carcinoma**. - They are not a characteristic finding in gastric adenocarcinoma.
Question 229: A 67-year-old woman presents to a surgeon with a painless, slowly growing ulcer in the periauricular region for the last 2 months. On physical examination, there is an irregular-shaped ulcer, 2 cm x 1 cm in its dimensions, with irregular margins and crusting over the surface. The woman is a fair-skinned individual who loves to go sunbathing. There is no family history of malignancy. After a complete physical examination, the surgeon performs a biopsy of the lesion under local anesthesia and sends the tissue for histopathological examination. The pathologist confirms the diagnosis of squamous cell carcinoma of the skin. When she asks about the cause, the surgeon explains that there are many possible causes, but it is likely that she has developed squamous cell carcinoma on her face due to repeated exposure to ultraviolet rays from the sun, especially ultraviolet B (UVB) rays. If the surgeon’s opinion is correct, which of the following mechanisms is most likely involved in the pathogenesis of the condition?
- A. Upregulation of expression of cyclin D2
- B. Loss-of-function mutations of TP53
- C. Activation of transcription factor NF-κB
- D. Intrastrand cross-linking of thymidine residues in DNA (Correct Answer)
- E. DNA damage caused by the formation of reactive oxygen species
Explanation: ***Intrastrand cross-linking of thymidine residues in DNA*** - **UVB radiation** primarily causes direct DNA damage, leading to the formation of **pyrimidine dimers**, particularly cyclobutane pyrimidine dimers (CPDs) and pyrimidine-pyrimidone (6-4) photoproducts. - This **intrastrand cross-linking** between adjacent thymidine or cytosine bases on the same DNA strand disrupts the DNA structure and interferes with DNA replication and transcription, promoting mutations that can initiate carcinogenesis. *Upregulation of expression of cyclin D2* - While **cyclin D2** is involved in cell cycle progression, its upregulation is a downstream effect of various oncogenic pathways and not the *direct mechanism* of DNA damage by UVB. - **UVB's primary action** is DNA damage, which then secondarily drives cellular responses potentially including altered cell cycle protein expression. *Loss-of-function mutations of TP53* - **TP53 mutations** are very common in skin cancers, especially squamous cell carcinoma, and greatly contribute to carcinogenesis by abolishing tumor suppressor functions. - However, the *primary mechanism* by which **UVB** causes these mutations is through direct DNA damage, specifically the induction of pyrimidine dimers that are then misrepaired, leading to TP53 mutations as a *consequence* rather than the initial mechanism. *Activation of transcription factor NF-κB* - **NF-κB activation** is involved in inflammatory responses and cell survival pathways, which can contribute to tumor progression. - While UVB can activate NF-κB, this is a **downstream signaling event** in response to cellular stress and damage, not the primary mechanism of **UVB-induced DNA damage**. *DNA damage caused by the formation of reactive oxygen species* - **Reactive oxygen species (ROS)** are a major cause of DNA damage, often associated with **UVA radiation** and oxidative stress. - However, **UVB radiation** primarily causes *direct DNA damage* through the formation of pyrimidine dimers, rather than indirectly through ROS generation as its main carcinogenic effect.
Question 230: A 30-year-old man comes to the physician for his annual health maintenance examination. The patient has no particular health concerns. He has a history of bilateral cryptorchidism treated with orchidopexy at 8 months of age. This patient is at increased risk for which of the following?
- A. Yolk sac tumor
- B. Leydig cell tumor
- C. Testicular lymphoma
- D. Sertoli cell tumor
- E. Teratocarcinoma (Correct Answer)
Explanation: ***Teratocarcinoma*** - Cryptorchidism is a known risk factor for the development of **testicular germ cell tumors**, which includes **teratocarcinoma**. Orchidopexy may make screening easier but does not eliminate the increased risk. - Testicular germ cell tumors, such as teratocarcinoma, typically present in young men and can derive from **undifferentiated germ cells** that remain in the undescended testis. *Yolk sac tumor* - While a type of **germ cell tumor**, yolk sac tumors are more common in infants and young children, and less frequently the primary presentation in an adult with a history of treated cryptorchidism. - In adults, yolk sac components can be part of a mixed germ cell tumor but are rarely the sole diagnosis in this age group in the context of cryptorchidism risk. *Leydig cell tumor* - Leydig cell tumors are **sex cord-stromal tumors**, not germ cell tumors, and are not significantly associated with a history of cryptorchidism. - These tumors typically present with symptoms related to **hormone production**, such as gynecomastia or precocious puberty. *Testicular lymphoma* - Testicular lymphoma is the most common testicular tumor in men over **60 years old** and is not primarily linked to a history of cryptorchidism. - This is a **hematopoietic neoplasm** that can originate in the testis or metastasize there, rather than a primary testicular tumor associated with developmental abnormalities. *Sertoli cell tumor* - Sertoli cell tumors are also **sex cord-stromal tumors** and are not strongly associated with cryptorchidism. - They are generally rare and can sometimes produce hormones, leading to clinical manifestations like **gynecomastia**.
Question 231: A 35-year-old man presents with a mass on the central part of his neck. He reports it has been growing steadily for the past 2 weeks, and he has also been experiencing fatigue and recurrent fevers. No significant past medical history. The patient denies any smoking history, or alcohol or recreational drug use. He denies any recent travel in the previous 6 months. On physical examination, there are multiple enlarged submandibular and cervical lymph nodes that are firm, mobile, and non-tender. A biopsy of one of the lymph nodes is performed and shows predominantly lymphocytes and histiocytes present in a pattern ‘resembling popcorn’. A flow cytometry analysis demonstrates cells that are CD19 and CD20 positive and CD15 and CD30 negative. Which of the following is the most likely diagnosis in this patient?
- A. Nodular sclerosis classical Hodgkin lymphoma
- B. Nodular lymphocyte-predominant Hodgkin lymphoma (Correct Answer)
- C. Lymphocyte depleted Hodgkin lymphoma
- D. Mixed cellularity classical Hodgkin lymphoma
- E. Lymphocyte rich classical Hodgkin lymphoma
Explanation: ***Nodular lymphocyte-predominant Hodgkin lymphoma*** - The key features are **lymphohistiocytic (L&H) cells**, also known as **popcorn cells**, which are large, multilobed Hodgkin-Reed-Sternberg (HRS) cell variants. - Immunophenotypically, these cells are typically **CD19+, CD20+, CD45+, and CD30-, CD15-**, consistent with the flow cytometry findings. *Nodular sclerosis classical Hodgkin lymphoma* - Characterized by **lacunar cells** (a variant of HRS cells) and broad bands of **collagen fibrosis**, which are not described. - HRS cells in classical Hodgkin lymphoma (cHL) are typically **CD15+ and CD30+**, and usually **CD20-**, which contradicts the flow cytometry results. *Lymphocyte depleted Hodgkin lymphoma* - This is a rare form of cHL with **few lymphocytes** and abundant atypical HRS cells, often seen in older, immunosuppressed patients. - The flow cytometry profile (CD15+, CD30+) and the histological description of "popcorn cells" do not fit this subtype. *Mixed cellularity classical Hodgkin lymphoma* - This subtype of cHL features a heterogeneous cellular infiltrate and classic **HRS cells (CD15+, CD30+)**, which differ from the described immunophenotype. - It lacks the "popcorn cell" morphology and the nodal sclerosis seen in other cHL subtypes. *Lymphocyte rich classical Hodgkin lymphoma* - While it has abundant lymphocytes, the characteristic cells are still **classic HRS cells (CD15+, CD30+)**, not the popcorn cells described. - The immunophenotype **CD20+ and CD15-, CD30-** is inconsistent with any form of classical Hodgkin lymphoma.
Question 232: A 62-year-old woman presents to her physician with a painless breast mass on her left breast for the past 4 months. She mentions that she noticed the swelling suddenly one day and thought it would resolve by itself. Instead, it has been slowly increasing in size. On physical examination of the breasts, the physician notes a single non-tender, hard, and fixed nodule over left breast. An ultrasonogram of the breast shows a solid mass, and a fine-needle aspiration biopsy confirms the mass to be lobular carcinoma of the breast. When the patient asks about her prognosis, the physician says that the prognosis can be best determined after both grading and staging of the tumor. Based on the current diagnostic information, the physician says that they can only grade, but no stage, the neoplasm. Which of the following facts about the neoplasm is currently available to the physician?
- A. The tumor invades the pectoralis major.
- B. The tumor has spread via blood-borne metastasis.
- C. The tumor has not metastasized to the contralateral superior mediastinal lymph nodes.
- D. The tumor has metastasized to the axillary lymph nodes.
- E. The tumor cells exhibit marked nuclear atypia. (Correct Answer)
Explanation: ***The tumor cells exhibit marked nuclear atypia.*** - **Grading** assesses the **histological appearance** of cancer cells and tissues, including features like nuclear atypia, mitotic rate, and architectural features, which are directly observable from the **fine-needle aspiration biopsy**. - **Nuclear atypia** refers to abnormal changes in the size, shape, and chromatin pattern of cell nuclei, indicating a higher degree of anaplasia and aggressiveness. *The tumor invades the pectoralis major.* - **Invasion into surrounding tissues**, especially muscle, is a feature determined during **surgical staging** or comprehensive imaging, which is not described as being performed yet. - This information relates to the **"T" (tumor size/extension)** component of TNM staging, which cannot be fully assessed with only a biopsy. *The tumor has spread via blood-borne metastasis.* - **Distant metastasis** is part of the **"M" (metastasis)** component of TNM staging, requiring imaging studies (e.g., PET scan, CT scan) or biopsies of suspected metastatic sites. - The current diagnostic information (biopsy of the primary tumor) does not provide details about **blood-borne spread**. *The tumor has not metastasized to the contralateral superior mediastinal lymph nodes.* - Information about **lymph node involvement**, even in distant locations like the mediastinum, falls under the **"N" (nodes)** component of TNM staging, which requires thorough imaging or surgical dissection. - The current biopsy focuses on the primary breast mass and cannot rule out distant lymph node metastasis. *The tumor has metastasized to the axillary lymph nodes.* - **Axillary lymph node metastasis** is also part of the **"N" component** of staging and is typically determined by sentinel lymph node biopsy or axillary dissection performed during surgery, or through imaging. - A fine-needle aspiration of the primary breast mass does not provide information about regional lymph node involvement.
Question 233: A 57-year-old post-menopausal woman comes to the physician because of intermittent, bloody post-coital vaginal discharge for the past month. She does not have pain with intercourse. Eleven years ago, she had LSIL on a routine Pap smear and testing for high-risk HPV strains was positive. Colposcopy showed CIN 1. She has not returned for follow-up Pap smears since then. She is sexually active with her husband only, and they do not use condoms. She has smoked half a pack of cigarettes per day for the past 25 years and does not drink alcohol. On speculum exam, a 1.4 cm, erythematous exophytic mass with ulceration is noted on the posterior wall of the upper third of the vagina. Which of the following is the most probable histopathology of this mass?
- A. Basal cell carcinoma
- B. Melanoma
- C. Adenocarcinoma
- D. Sarcoma botryoides
- E. Squamous cell carcinoma (Correct Answer)
Explanation: ***Squamous cell carcinoma*** - The patient's history of **LSIL** with **high-risk HPV** and **non-adherence to follow-up Pap smears** strongly suggests a progression to squamous cell carcinoma. - **Smoking** is a significant risk factor for SCC, and the description of an **erythematous exophytic mass with ulceration** is consistent with this diagnosis. *Basal cell carcinoma* - This is a common skin cancer, but it is **extremely rare in the vagina**, typically occurring in sun-exposed areas. - While it can manifest as an ulcerated lesion, the risk factors and location do not align with this patient's presentation. *Melanoma* - Although **vaginal melanoma** can occur, it is rare and typically presents as a **pigmented lesion**, which is not described. - The patient's risk factors (HPV, smoking) are not primary drivers of melanoma development. *Adenocarcinoma* - **Vaginal adenocarcinoma** is rare and often associated with **diethylstilbestrol (DES) exposure** in utero, which is absent in this case. - While an exophytic mass can occur, the strong history of **HPV-related dysplasia** points away from adenocarcinoma. *Sarcoma botryoides* - This is a rare form of **rhabdomyosarcoma** and typically presents in **infants and young children** as a grapelike mass protruding from the vagina. - It is not seen in post-menopausal women and is histologically distinct from the likely HPV-related malignancy.
Question 234: A 55-year-old man comes to the physician because of fatigue and worsening abdominal pain for 4 weeks. He also reports excessive night sweats and a 5.4-kg (12-lb) weight loss during this time. He has a neck swelling for 4 days. Physical examination shows a nontender, enlarged, and fixed supraclavicular lymph node. There is splenomegaly. A CT scan of the thorax and abdomen shows massively enlarged axillary, mediastinal, and cervical lymph nodes. Analysis of an excised cervical lymph node shows lymphocytes with a high proliferative index that stain positive for CD20. Which of the following is the most likely diagnosis?
- A. Hodgkin lymphoma
- B. Burkitt lymphoma
- C. Follicular lymphoma
- D. Adult T-cell lymphoma
- E. Diffuse large B-cell lymphoma (Correct Answer)
Explanation: ***Diffuse large B-cell lymphoma*** - The patient presents with rapidly progressing **B symptoms** (night sweats, weight loss, fatigue), widespread **lymphadenopathy** (cervical, axillary, mediastinal, supraclavicular), and **splenomegaly**. - A lymph node biopsy showing **CD20 positivity** and a **high proliferative index** in lymphocytes is characteristic of Diffuse Large B-cell Lymphoma (DLBCL), a rapidly growing, aggressive non-Hodgkin lymphoma. *Hodgkin lymphoma* - While it can present with B symptoms and lymphadenopathy, Hodgkin lymphoma is characterized by the presence of **Reed-Sternberg cells** on biopsy. - The description of lymphocytes with a high proliferative index staining positive for CD20 points away from Hodgkin lymphoma. *Burkitt lymphoma* - Recognized by its characteristic **starry-sky appearance** on microscopy and a **translocation of the _MYC_ gene** on biopsy (often t(8;14)). - Though highly aggressive with a high proliferative index, it typically presents differently, often with extranodal involvement (e.g., jaw in endemic forms, ileocecal region in sporadic forms). *Follicular lymphoma* - This is an **indolent (slow-growing) non-Hodgkin lymphoma** that typically presents with waxing and waning lymphadenopathy and usually lacks prominent aggressive B symptoms. - The rapid progression of symptoms and high proliferative index are inconsistent with follicular lymphoma. *Adult T-cell lymphoma* - Caused by HTLV-1 infection and characterized by **CD4+ T-cell proliferation**. It primarily affects skin, lymph nodes, liver, and spleen, and can cause hypercalcemia. - The biopsy showing **CD20 positivity** (a B-cell marker) rules out this diagnosis, which would typically show T-cell markers.
Question 235: A 52-year-old woman comes to the physician because of a 6-month history of generalized fatigue, low-grade fever, and a 10-kg (22-lb) weight loss. Physical examination shows generalized pallor and splenomegaly. Her hemoglobin concentration is 7.5 g/dL and leukocyte count is 41,800/mm3. Leukocyte alkaline phosphatase activity is low. Peripheral blood smear shows basophilia with myelocytes and metamyelocytes. Bone marrow biopsy shows cellular hyperplasia with proliferation of immature granulocytic cells. Which of the following mechanisms is most likely responsible for this patient's condition?
- A. Cytokine-independent activation of the JAK-STAT pathway
- B. Unregulated expression of the ABL1 gene (Correct Answer)
- C. Loss of function of the APC gene
- D. Overexpression of the c-KIT gene
- E. Altered expression of the retinoic acid receptor gene
Explanation: ***Unregulated expression of the ABL1 gene*** - This patient's presentation with **fatigue, weight loss, splenomegaly, elevated white blood cell count (41,800/mm³)**, **basophilia, myelocytes, and metamyelocytes** on peripheral smear, and **low leukocyte alkaline phosphatase (LAP) activity** is highly characteristic of **chronic myeloid leukemia (CML)**. - CML is defined by the **Philadelphia chromosome (Ph chromosome)**, which results from a **t(9;22) translocation** and leads to the formation of the **BCR-ABL1 fusion gene**. This gene encodes a **constitutively active tyrosine kinase** that leads to unregulated cell proliferation. *Cytokine-independent activation of the JAK-STAT pathway* - This mechanism is characteristic of other **myeloproliferative neoplasms (MPNs)**, such as **polycythemia vera**, **essential thrombocythemia**, and **primary myelofibrosis**. - These conditions often involve mutations in genes like **JAK2** (e.g., V617F), leading to cytokine-independent signaling, but their clinical and hematologic features differ from CML. *Loss of function of the APC gene* - Loss of function of the **adenomatous polyposis coli (APC) gene** is primarily associated with **familial adenomatous polyposis (FAP)** and a significant proportion of **sporadic colorectal cancers**. - It plays a crucial role in the **Wnt signaling pathway** and cell adhesion, but it is not directly involved in the pathogenesis of CML. *Overexpression of the c-KIT gene* - **Overexpression or activating mutations of the c-KIT gene** (a receptor tyrosine kinase) are associated with conditions like **gastrointestinal stromal tumors (GISTs)** and some forms of **mastocytosis**. - While it involves a tyrosine kinase, the specific clinical and hematological picture of this patient does not align with disorders driven by c-KIT dysregulation. *Altered expression of the retinoic acid receptor gene* - **Altered expression or fusion genes involving the retinoic acid receptor alpha (RARα) gene** (e.g., PML-RARα fusion) are pathognomonic for **acute promyelocytic leukemia (APL)**. - APL presents as an **acute leukemia** with a predominance of abnormal promyelocytes and is associated with a high risk of **disseminated intravascular coagulation (DIC)**, which is distinct from the chronic myeloproliferative disorder described.
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