USMLE Step 2

Sample

1. A 68-year-old man reports 3 months of fatigue and early satiety. Examination shows massive splenomegaly. Laboratory studies show WBC 92,000/uL with a left-shifted myeloid series including basophils and eosinophils, platelets 550,000/uL, and low leukocyte alkaline phosphatase. Which of the following is the most appropriate next step to confirm the diagnosis?

The presentation of leukocytosis with a full myeloid spectrum, basophilia, splenomegaly, and low LAP is classic for chronic myeloid leukemia. Detection of the BCR-ABL1 fusion (Philadelphia chromosome) confirms the diagnosis and guides tyrosine kinase inhibitor therapy. Flow cytometry for CD5/CD23 evaluates CLL, not CML.

Sample

2. A 24-year-old woman presents with fatigue and painless cervical lymphadenopathy for 2 months. She reports drenching night sweats and a 6 kg weight loss. Excisional lymph node biopsy shows Reed-Sternberg cells. Which of the following is the most appropriate next step in management?

Once Hodgkin lymphoma is confirmed by biopsy showing Reed-Sternberg cells, accurate staging with PET-CT is required before therapy because treatment intensity and radiation fields depend on stage. Beginning chemotherapy before staging would be premature. Splenectomy is not part of modern staging.

Sample

3. A 55-year-old man with newly diagnosed multiple myeloma develops confusion, constipation, and polyuria. Serum calcium is 14.2 mg/dL and creatinine is 2.1 mg/dL. Which of the following is the most appropriate initial step in management?

Symptomatic severe hypercalcemia is managed first with aggressive isotonic saline to restore volume and promote calciuresis. Bisphosphonates are added but take 2-4 days to work and require adequate hydration to avoid nephrotoxicity. Dialysis is reserved for refractory cases or renal failure.

Sample

4. A 40-year-old woman is found to have a hemoglobin of 8.2 g/dL, MCV 72 fL, and low ferritin. She reports heavy menstrual bleeding. After iron replacement is initiated, which of the following is the most appropriate next step to evaluate the cause?

Iron deficiency anemia in a menstruating woman with documented heavy menstrual bleeding warrants gynecologic evaluation to identify and treat the source. Bone marrow biopsy is unnecessary when the cause is apparent. Electrophoresis evaluates thalassemia or hemoglobinopathy, not the source of blood loss.

Sample

5. A 62-year-old man presents with fatigue and is found to have hemoglobin 9.0 g/dL, MCV 110 fL, and hypersegmented neutrophils. Serum B12 is low. Which of the following tests best identifies the underlying cause?

Macrocytic anemia with hypersegmented neutrophils and low B12 suggests deficiency, most commonly from pernicious anemia in older adults. Anti-intrinsic factor antibodies are highly specific and confirm autoimmune gastritis as the cause. Methylmalonic acid confirms B12 deficiency but does not identify pernicious anemia specifically.

Sample

6. A 30-year-old woman of Mediterranean descent has microcytic anemia with hemoglobin 10.5 g/dL and MCV 68 fL. Iron studies are normal and RBC count is elevated. Which of the following is the most appropriate next step?

Microcytosis disproportionate to the degree of anemia with a high RBC count and normal iron studies suggests thalassemia trait. Hemoglobin electrophoresis identifies elevated HbA2 in beta-thalassemia minor. Iron supplementation is inappropriate and potentially harmful without documented deficiency.

Sample

7. A 45-year-old man presents with abdominal fullness and pruritus after showers. Hemoglobin is 19 g/dL, hematocrit 58%, and he has splenomegaly. Oxygen saturation is normal. Which of the following studies is most likely to confirm the diagnosis?

Erythrocytosis with splenomegaly, aquagenic pruritus, and normal oxygen saturation suggests polycythemia vera. A low serum erythropoietin with a JAK2 V617F mutation strongly supports the diagnosis. Secondary causes such as hypoxia or renal tumors typically show elevated erythropoietin.

Sample

8. A 58-year-old woman with metastatic breast cancer develops sudden dyspnea and pleuritic chest pain. Heart rate is 118/min and oxygen saturation is 88%. Which of the following is the most appropriate next step in management?

A cancer patient with acute dyspnea, tachycardia, and hypoxemia has high pretest probability for pulmonary embolism. CT pulmonary angiography is the diagnostic test of choice in this setting. D-dimer is not useful when pretest probability is high because it lacks specificity in malignancy.

Sample

9. A 70-year-old man is found to have absolute lymphocytosis of 25,000/uL on routine testing. He is asymptomatic. Peripheral smear shows small mature lymphocytes and smudge cells. Which of the following confirms the diagnosis?

Asymptomatic mature lymphocytosis with smudge cells suggests chronic lymphocytic leukemia. Flow cytometry showing coexpression of CD5, CD19, CD20, and CD23 with light chain restriction confirms the diagnosis noninvasively. Bone marrow biopsy is not required for diagnosis.

Sample

10. A 26-year-old man presents with fatigue, gum bleeding, and easy bruising. WBC is 2,000/uL, hemoglobin 7 g/dL, and platelets 15,000/uL. Peripheral smear shows blasts with Auer rods. Coagulation studies show prolonged PT/PTT and low fibrinogen. Which of the following is the most appropriate immediate intervention?

Auer rods with disseminated intravascular coagulation strongly suggest acute promyelocytic leukemia. All-trans retinoic acid should be started immediately on clinical suspicion because it reverses the coagulopathy and reduces early hemorrhagic death. Awaiting confirmation delays lifesaving therapy.