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?
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.
