NBME Pathology 3 — Questions and Answers
Question 1: A 60-year-old smoker develops Cushing syndrome without an adrenal or pituitary cause. Chest CT reveals a central hilar mass. What is the tumor type?
- Small cell (oat cell) carcinoma (Correct answer)
- Squamous cell carcinoma
- Adenocarcinoma
- Large cell carcinoma
Correct answer: Small cell (oat cell) carcinoma
Small cell carcinoma of the lung is a neuroendocrine tumor that frequently secretes ACTH ectopically, causing paraneoplastic Cushing syndrome.
Question 2: A biopsy of a lymph node shows Reed-Sternberg cells with an 'owl-eye' appearance. Flow cytometry shows CD15+/CD30+/CD45- cells. What is the diagnosis?
- Classic Hodgkin lymphoma (Correct answer)
- Burkitt lymphoma
- Diffuse large B-cell lymphoma
- Anaplastic large cell lymphoma
Correct answer: Classic Hodgkin lymphoma
Classic Hodgkin lymphoma Reed-Sternberg cells are CD15+, CD30+, and characteristically CD45- (leukocyte common antigen negative).
Question 3: A 45-year-old woman presents with symmetric joint pain, morning stiffness >1 hour, and subcutaneous nodules. Serology shows anti-CCP antibodies. Which pathological process drives joint destruction?
- Pannus formation with enzymatic erosion of cartilage and bone (Correct answer)
- Urate crystal deposition in synovium
- Chondrocyte hypertrophy and endochondral ossification
- Fibrocartilage degeneration from mechanical wear
Correct answer: Pannus formation with enzymatic erosion of cartilage and bone
In rheumatoid arthritis, synovial hyperplasia forms pannus tissue containing proteases and osteoclast-activating cytokines that erode cartilage and bone.
Question 4: A 35-year-old man with hemoptysis has a chest X-ray showing bilateral pulmonary infiltrates. Urine shows hematuria. Immunofluorescence of kidney biopsy reveals linear IgG deposits along the GBM. What is the antigen?
- Type IV collagen alpha-3 chain (Goodpasture antigen) (Correct answer)
- Phospholipase A2 receptor
- ANCA (MPO or PR3)
- Complement factor H
Correct answer: Type IV collagen alpha-3 chain (Goodpasture antigen)
Goodpasture syndrome results from autoantibodies targeting the alpha-3 chain of type IV collagen in both glomerular and alveolar basement membranes.
Question 5: A 70-year-old woman has a lytic skull lesion, hypercalcemia, anemia, and rouleaux formation on peripheral smear. Urine protein electrophoresis shows a Bence Jones protein. Which cells are malignant?
- Plasma cells (Correct answer)
- B lymphocytes
- NK cells
- Myeloid precursors
Correct answer: Plasma cells
Multiple myeloma is a malignancy of terminally differentiated plasma cells that produce monoclonal immunoglobulin (M protein) and free light chains (Bence Jones proteins).
Question 6: A 25-year-old woman has a thyroid mass. Histology shows papillae with fibrovascular cores, ground-glass 'Orphan Annie eye' nuclei, and intranuclear inclusions. What is the most common mutation?
- BRAF V600E point mutation (Correct answer)
- RAS mutation
- RET/PTC rearrangement
- PAX8-PPAR gamma fusion
Correct answer: BRAF V600E point mutation
BRAF V600E mutation is found in ~60% of papillary thyroid carcinomas and is associated with the characteristic nuclear features of this tumor.
Question 7: A 55-year-old man with longstanding GERD develops Barrett esophagus. Which metaplastic change defines this condition?
- Intestinal-type columnar epithelium replaces stratified squamous epithelium (Correct answer)
- Squamous epithelium replaces gastric mucosa
- Pseudostratified ciliated columnar epithelium replaces squamous mucosa
- Transitional epithelium replaces squamous epithelium
Correct answer: Intestinal-type columnar epithelium replaces stratified squamous epithelium
Barrett esophagus is defined by replacement of normal esophageal squamous epithelium by specialized intestinal-type columnar epithelium with goblet cells.
NBME Pathology 3
A 60-year-old smoker develops Cushing syndrome without an adrenal or pituitary cause.
Chest CT reveals a central hilar mass.
What is the tumor type?