USMLE STEP 1 HIGH-YIELD EXAM |ACTUAL
QUESTIONS AND ANSWERS|GRADED A+
SECTION 1: PATHOLOGY
1. A 55-year-old man with a 40 pack-year smoking history presents with
hemoptysis and weight loss. CT scan shows a central lung mass with mediastinal
lymphadenopathy. Biopsy reveals small, round, blue cells with scant cytoplasm
and nuclear molding. What is the most likely diagnosis?
• A) Squamous cell carcinoma
• B) Adenocarcinoma
• C) Small cell carcinoma
• D) Large cell carcinoma
Correct Answer: C
Rationale: Small cell carcinoma (oat cell carcinoma) is characterized by small,
round, blue cells with scant cytoplasm, nuclear molding, and a high mitotic rate. It
is strongly associated with smoking and presents as a central mass with
mediastinal lymphadenopathy. It is the most aggressive type of lung cancer and
has paraneoplastic syndromes (SIADH, Cushing syndrome).
2. A 65-year-old woman with a history of hypertension presents with
progressive dyspnea and orthopnea. Echocardiogram shows left ventricular
hypertrophy with a thickened, hyperdynamic septum. What is the most likely
genetic mutation?
• A) MYH7 (β-myosin heavy chain)
• B) DMD (dystrophin)
, • C) CFTR (cystic fibrosis)
• D) FBN1 (fibrillin-1)
Correct Answer: A
*Rationale: Hypertrophic cardiomyopathy (HCM) is an autosomal dominant
condition caused by mutations in sarcomere proteins, most commonly β-myosin
heavy chain (MYH7). It presents with left ventricular hypertrophy (especially the
septum) and can cause syncope, sudden cardiac death, and heart failure. The
murmur of HCM is dynamic (increases with Valsalva).*
3. A 40-year-old woman presents with fatigue, joint pain, and a malar rash.
Laboratory studies show positive ANA, anti-dsDNA, and low complement levels.
Renal biopsy shows diffuse proliferative glomerulonephritis. What is the most
likely diagnosis?
• A) Systemic lupus erythematosus (SLE)
• B) Rheumatoid arthritis
• C) Sjögren syndrome
• D) Scleroderma
Correct Answer: A
Rationale: SLE is an autoimmune disease characterized by malar rash,
photosensitivity, oral ulcers, arthritis, serositis, renal disease, and hematologic
abnormalities. Anti-dsDNA and low complement levels are associated with lupus
nephritis (diffuse proliferative, Class IV). Treatment includes hydroxychloroquine
and corticosteroids.
4. A 55-year-old man with a history of alcohol use disorder presents with
jaundice, ascites, and asterixis. Liver biopsy shows micronodular cirrhosis with
Mallory bodies. What is the most likely diagnosis?
• A) Alcoholic liver disease
, • B) Hepatitis B
• C) Hepatitis C
• D) Wilson disease
Correct Answer: A
Rationale: Alcoholic liver disease is characterized by steatosis, hepatitis, and
cirrhosis. Mallory bodies (hyaline inclusions in hepatocytes) are a hallmark of
alcoholic hepatitis. Alcoholic cirrhosis is micronodular. Treatment includes
abstinence, nutritional support, and management of complications (ascites,
encephalopathy).
5. A 30-year-old man presents with a painless, rubbery lymph node in the neck,
fever, night sweats, and weight loss. Biopsy shows Reed-Sternberg cells
(binucleated "owl's eye" cells). What is the most likely diagnosis?
• A) Hodgkin lymphoma
• B) Diffuse large B-cell lymphoma
• C) Follicular lymphoma
• D) Burkitt lymphoma
Correct Answer: A
*Rationale: Hodgkin lymphoma is characterized by Reed-Sternberg cells (CD15+,
CD30+, CD45-) and B symptoms (fever, night sweats, weight loss). The most
common subtype is nodular sclerosis. Treatment includes ABVD chemotherapy
(Adriamycin, Bleomycin, Vinblastine, Dacarbazine).*
6. A 60-year-old man presents with a history of GERD and a 40 pack-year
smoking history. Upper endoscopy reveals a distal esophageal mass. Biopsy
shows adenocarcinoma. What is the most likely precursor lesion?
• A) Barrett esophagus
, • B) Squamous metaplasia
• C) Gastric metaplasia
• D) Achalasia
Correct Answer: A
Rationale: Barrett esophagus is a metaplastic change from squamous to columnar
epithelium in the distal esophagus. It is caused by chronic GERD and is a precursor
to esophageal adenocarcinoma. Risk factors include GERD, obesity, and smoking.
Surveillance endoscopy is recommended.
7. A 45-year-old woman presents with a breast mass. Mammogram shows
spiculated mass with microcalcifications. Biopsy reveals invasive ductal
carcinoma. The tumor is ER/PR positive and HER2 negative. What is the most
appropriate first-line therapy?
• A) Tamoxifen
• B) Trastuzumab
• C) Aromatase inhibitor
• D) Chemotherapy
Correct Answer: A
*Rationale: Tamoxifen (SERM) is first-line therapy for ER/PR-positive breast cancer
in premenopausal women. Aromatase inhibitors (anastrozole, letrozole) are first-
line for postmenopausal women. Trastuzumab is for HER2-positive tumors.
Chemotherapy is used for triple-negative or high-risk tumors.*
8. A 70-year-old man presents with painless hematuria. CT shows a solid renal
mass. What is the most likely diagnosis?
• A) Renal cell carcinoma (clear cell carcinoma)
• B) Transitional cell carcinoma
QUESTIONS AND ANSWERS|GRADED A+
SECTION 1: PATHOLOGY
1. A 55-year-old man with a 40 pack-year smoking history presents with
hemoptysis and weight loss. CT scan shows a central lung mass with mediastinal
lymphadenopathy. Biopsy reveals small, round, blue cells with scant cytoplasm
and nuclear molding. What is the most likely diagnosis?
• A) Squamous cell carcinoma
• B) Adenocarcinoma
• C) Small cell carcinoma
• D) Large cell carcinoma
Correct Answer: C
Rationale: Small cell carcinoma (oat cell carcinoma) is characterized by small,
round, blue cells with scant cytoplasm, nuclear molding, and a high mitotic rate. It
is strongly associated with smoking and presents as a central mass with
mediastinal lymphadenopathy. It is the most aggressive type of lung cancer and
has paraneoplastic syndromes (SIADH, Cushing syndrome).
2. A 65-year-old woman with a history of hypertension presents with
progressive dyspnea and orthopnea. Echocardiogram shows left ventricular
hypertrophy with a thickened, hyperdynamic septum. What is the most likely
genetic mutation?
• A) MYH7 (β-myosin heavy chain)
• B) DMD (dystrophin)
, • C) CFTR (cystic fibrosis)
• D) FBN1 (fibrillin-1)
Correct Answer: A
*Rationale: Hypertrophic cardiomyopathy (HCM) is an autosomal dominant
condition caused by mutations in sarcomere proteins, most commonly β-myosin
heavy chain (MYH7). It presents with left ventricular hypertrophy (especially the
septum) and can cause syncope, sudden cardiac death, and heart failure. The
murmur of HCM is dynamic (increases with Valsalva).*
3. A 40-year-old woman presents with fatigue, joint pain, and a malar rash.
Laboratory studies show positive ANA, anti-dsDNA, and low complement levels.
Renal biopsy shows diffuse proliferative glomerulonephritis. What is the most
likely diagnosis?
• A) Systemic lupus erythematosus (SLE)
• B) Rheumatoid arthritis
• C) Sjögren syndrome
• D) Scleroderma
Correct Answer: A
Rationale: SLE is an autoimmune disease characterized by malar rash,
photosensitivity, oral ulcers, arthritis, serositis, renal disease, and hematologic
abnormalities. Anti-dsDNA and low complement levels are associated with lupus
nephritis (diffuse proliferative, Class IV). Treatment includes hydroxychloroquine
and corticosteroids.
4. A 55-year-old man with a history of alcohol use disorder presents with
jaundice, ascites, and asterixis. Liver biopsy shows micronodular cirrhosis with
Mallory bodies. What is the most likely diagnosis?
• A) Alcoholic liver disease
, • B) Hepatitis B
• C) Hepatitis C
• D) Wilson disease
Correct Answer: A
Rationale: Alcoholic liver disease is characterized by steatosis, hepatitis, and
cirrhosis. Mallory bodies (hyaline inclusions in hepatocytes) are a hallmark of
alcoholic hepatitis. Alcoholic cirrhosis is micronodular. Treatment includes
abstinence, nutritional support, and management of complications (ascites,
encephalopathy).
5. A 30-year-old man presents with a painless, rubbery lymph node in the neck,
fever, night sweats, and weight loss. Biopsy shows Reed-Sternberg cells
(binucleated "owl's eye" cells). What is the most likely diagnosis?
• A) Hodgkin lymphoma
• B) Diffuse large B-cell lymphoma
• C) Follicular lymphoma
• D) Burkitt lymphoma
Correct Answer: A
*Rationale: Hodgkin lymphoma is characterized by Reed-Sternberg cells (CD15+,
CD30+, CD45-) and B symptoms (fever, night sweats, weight loss). The most
common subtype is nodular sclerosis. Treatment includes ABVD chemotherapy
(Adriamycin, Bleomycin, Vinblastine, Dacarbazine).*
6. A 60-year-old man presents with a history of GERD and a 40 pack-year
smoking history. Upper endoscopy reveals a distal esophageal mass. Biopsy
shows adenocarcinoma. What is the most likely precursor lesion?
• A) Barrett esophagus
, • B) Squamous metaplasia
• C) Gastric metaplasia
• D) Achalasia
Correct Answer: A
Rationale: Barrett esophagus is a metaplastic change from squamous to columnar
epithelium in the distal esophagus. It is caused by chronic GERD and is a precursor
to esophageal adenocarcinoma. Risk factors include GERD, obesity, and smoking.
Surveillance endoscopy is recommended.
7. A 45-year-old woman presents with a breast mass. Mammogram shows
spiculated mass with microcalcifications. Biopsy reveals invasive ductal
carcinoma. The tumor is ER/PR positive and HER2 negative. What is the most
appropriate first-line therapy?
• A) Tamoxifen
• B) Trastuzumab
• C) Aromatase inhibitor
• D) Chemotherapy
Correct Answer: A
*Rationale: Tamoxifen (SERM) is first-line therapy for ER/PR-positive breast cancer
in premenopausal women. Aromatase inhibitors (anastrozole, letrozole) are first-
line for postmenopausal women. Trastuzumab is for HER2-positive tumors.
Chemotherapy is used for triple-negative or high-risk tumors.*
8. A 70-year-old man presents with painless hematuria. CT shows a solid renal
mass. What is the most likely diagnosis?
• A) Renal cell carcinoma (clear cell carcinoma)
• B) Transitional cell carcinoma
