These 12 board-style pathology questions cover findings that appear again and again on medical school exams and the USMLE: classic lab clues, autoantibodies, tumor markers and disease mechanisms. Pick an answer, then open Answer and Explanation to check yourself.
Questions written by Dr. Ray Makar, retired dermatologist and USMLE teacher.
Inflammation and Autoimmune Disease
Q1. A 24-year-old woman has had joint pain and chest pain for 2 years. Examination reveals a pericardial friction rub and dullness to percussion over the back. A chest x-ray shows bilateral pleural effusions. What is the next step in the workup?
A. Antinuclear antibody test
B. CD4 lymphocyte count
C. Erythrocyte sedimentation rate
D. Sputum culture
Answer and Explanation
A. Antinuclear antibody test. A young woman with arthralgias and serositis (pericarditis and pleural effusions) most likely has systemic lupus erythematosus. ANA is the best screening test because it is very sensitive. Anti-dsDNA and anti-Smith antibodies are more specific.
Q2. A 36-year-old man had abdominal surgery 3 months ago. He now has a small, painless nodule at the sutured incision site, with no fever or redness. What is the cause of this nodule?
A. Acute inflammation
B. Antigen–antibody reaction
C. Dermoid cyst
D. Foreign body reaction
Answer and Explanation
D. Foreign body reaction. Suture material can cause a foreign-body granuloma: macrophages and multinucleated giant cells surround material the body cannot digest. It is a form of chronic inflammation, which is why there is no fever, pain or redness.
Gastrointestinal and Liver Pathology
Q3. Which condition is characterized by flattening of the intestinal villi?
A. Celiac disease
B. Crohn’s disease
C. Duodenal ulcer
D. Ulcerative colitis
Answer and Explanation
A. Celiac disease. Gluten sensitivity causes villous atrophy, crypt hyperplasia and intraepithelial lymphocytes, mostly in the duodenum and jejunum. Anti-tissue transglutaminase IgA is the screening test.
Q4. Anti-mitochondrial antibodies are most likely found in which condition?
A. Gastric ulcer
B. Primary biliary cholangitis (primary biliary cirrhosis)
C. Rheumatic fever
D. Hepatitis B
Answer and Explanation
B. Primary biliary cholangitis. This autoimmune destruction of small bile ducts typically affects middle-aged women, causing fatigue, pruritus and a high alkaline phosphatase. Anti-mitochondrial antibodies are the hallmark.
Q5. A patient develops acute pancreatitis. Which enzyme is mainly responsible for autodigestion of the pancreas?
A. Amylase
B. Elastase
C. Lipase
D. Trypsin
Answer and Explanation
D. Trypsin. Inappropriate activation of trypsinogen to trypsin starts the process, because trypsin then activates the other digestive enzymes (elastase, phospholipase, lipase). Amylase and lipase are used for diagnosis, but trypsin drives the damage.
Q6. Which finding is most likely in a patient with colon adenocarcinoma?
A. Detection of HIV RNA
B. DNA topoisomerase I antibody
C. KRAS mutation in tumor cells
D. Tumor cells positive for vimentin
Answer and Explanation
C. KRAS mutation in tumor cells. In the adenoma–carcinoma sequence, APC loss is followed by KRAS mutation and then p53 loss. Topoisomerase I (Scl-70) antibodies point to systemic sclerosis, and vimentin is a marker of mesenchymal tumors (sarcomas), not carcinomas.
Kidney, Blood and Genetics
Q7. A patient develops acute renal failure caused by hyperplastic arteriolosclerosis. Which substance is most likely elevated in the blood?
A. Calcium
B. Cholesterol
C. Renin
D. Triglycerides
Answer and Explanation
C. Renin. Hyperplastic (“onion-skin”) arteriolosclerosis is seen in malignant hypertension. Narrowed renal arterioles reduce kidney perfusion, which stimulates renin release and worsens the hypertension.
Q8. A 67-year-old woman has fatigue and bone pain. Serum protein electrophoresis shows an M spike, and a bone marrow biopsy shows more than 10% plasma cells. Which other finding is most likely?
A. Auer rods
B. Bence Jones proteins in the urine
C. Hypersegmented neutrophils
D. Reed–Sternberg cells
Answer and Explanation
B. Bence Jones proteins in the urine. This is multiple myeloma. Free light chains (Bence Jones proteins) appear in the urine. Remember CRAB: hyperCalcemia, Renal failure, Anemia and Bone lesions. Auer rods suggest AML, and Reed–Sternberg cells suggest Hodgkin lymphoma.
Q9. A mutation decreases the function of CFTR channels. Which ion transport abnormality is expected in sweat glands?
A. Decreased chloride reabsorption
B. Increased chloride reabsorption
C. Increased sodium secretion
D. Increased potassium reabsorption
Answer and Explanation
A. Decreased chloride reabsorption. In cystic fibrosis, sweat duct cells cannot reabsorb chloride (and sodium follows), so sweat is salty. That is why the sweat chloride test is used for diagnosis.
Classic Pathology Clues
Q10. A lung biopsy from a patient with tuberculosis shows granulomas with a cheese-like, amorphous center. What type of necrosis is this?
A. Caseous necrosis
B. Coagulative necrosis
C. Fat necrosis
D. Liquefactive necrosis
Answer and Explanation
A. Caseous necrosis. Caseous necrosis is typical of tuberculosis and some fungal infections. Coagulative necrosis is seen in infarcts of solid organs, liquefactive necrosis in the brain and abscesses, and fat necrosis in acute pancreatitis.
Q11. A lymph node biopsy shows large binucleate cells with prominent “owl-eye” nucleoli that are CD15 and CD30 positive. What is the diagnosis?
A. Burkitt lymphoma
B. Chronic lymphocytic leukemia
C. Hodgkin lymphoma
D. Multiple myeloma
Answer and Explanation
C. Hodgkin lymphoma. Reed–Sternberg cells (CD15+, CD30+) are the hallmark of classical Hodgkin lymphoma. Burkitt lymphoma shows a “starry sky” pattern and t(8;14).
Q12. A thyroid nodule biopsy shows cells with “Orphan Annie eye” nuclei, nuclear grooves and psammoma bodies. What is the diagnosis?
A. Anaplastic carcinoma
B. Follicular carcinoma
C. Medullary carcinoma
D. Papillary carcinoma
Answer and Explanation
D. Papillary carcinoma. It is the most common thyroid cancer and has an excellent prognosis. Psammoma bodies are also seen in serous ovarian carcinoma, meningioma and mesothelioma. Medullary carcinoma comes from C cells and makes calcitonin.
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