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?
Q2
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?
Q3
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?
Q4
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?
Q5
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?
Q6
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?
Q7
A 62-year-old man comes to the physician because of a skin lesion on his nose. The patient has had the lesion for 11 months and it has increased in size over the past few months. He is a farmer and lives together with his wife. His mother died of metastatic melanoma at the age of 67 years. The patient has smoked a pack of cigarettes daily for the past 30 years and drinks 1–2 glasses of whiskey on weekends. His temperature is 36.8°C (98.2°F), pulse is 75/min, and blood pressure is 140/78 mm Hg. Examination of the skin shows a nontender lesion at the right root of the nose. An image of the lesion is shown. Which of the following is the most likely diagnosis in this patient?
Q8
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?
Q9
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?
Q10
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?
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 62-year-old man comes to the physician because of a skin lesion on his nose. The patient has had the lesion for 11 months and it has increased in size over the past few months. He is a farmer and lives together with his wife. His mother died of metastatic melanoma at the age of 67 years. The patient has smoked a pack of cigarettes daily for the past 30 years and drinks 1–2 glasses of whiskey on weekends. His temperature is 36.8°C (98.2°F), pulse is 75/min, and blood pressure is 140/78 mm Hg. Examination of the skin shows a nontender lesion at the right root of the nose. An image of the lesion is shown. Which of the following is the most likely diagnosis in this patient?
A. Molluscum contagiosum
B. Actinic keratosis
C. Squamous cell carcinoma
D. Basal cell carcinoma (Correct Answer)
E. Keratoacanthoma
Explanation: ***Basal cell carcinoma***
- The patient's lesion is a **pearly**, **translucent nodule** with raised borders and **telangiectatic vessels**, which are classic features of basal cell carcinoma (BCC).
- His history as a farmer suggests significant **sun exposure**, a primary risk factor for BCC, and the lesion's slow but steady growth over 11 months is typical.
*Molluscum contagiosum*
- Characterized by **small, dome-shaped papules** with a **central umbilication**, which is not present in the image.
- While it can occur in adults, it's more common in children or immunocompromised individuals and typically has a different appearance.
*Actinic keratosis*
- These are **premalignant lesions** that appear as **rough, scaly patches** on sun-exposed skin, not a nodular lesion with pearly borders.
- While common in patients with significant sun exposure, the morphology in the image is not consistent with actinic keratosis.
*Squamous cell carcinoma*
- Often presents as a **red, scaly patch** or **firm nodule** with a **crusted or ulcerated surface**, and may grow more rapidly than BCC, but it typically lacks the pearly appearance and prominent telangiectasia seen here.
- While sun exposure is a risk factor, the specific lesion morphology points away from typical SCC.
*Keratoacanthoma*
- Characterized by **rapid growth** followed by **spontaneous involution**, often forming a **dome-shaped nodule** with a central keratin plug, which is not clearly depicted.
- Although it can resemble SCC, the long duration of 11 months and the lack of a central plug make it less likely.
Question 8: 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 9: 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 10: 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.
