USMLE Step 2 Quiz: Hematologic Malignancies
8 questions · exam conditions
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Hematologic MalignanciesQuestion 1 of 8

A 70-year-old woman presents with headaches, blurred vision, and recurrent nosebleeds. Physical examination reveals mild hepatosplenomegaly. Laboratory evaluation shows a normocytic anemia and a large M-spike on serum protein electrophoresis. Immunofixation identifies the monoclonal protein as IgM. The serum viscosity is found to be significantly elevated.

This patient's constellation of findings is most characteristic of which of the following disorders?

Multiple myeloma
Waldenström macroglobulinemia
Monoclonal gammopathy of undetermined significance
Heavy chain disease
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USMLE Step 2 Quiz

USMLE Step 2 Quiz: Hematologic Malignancies

Practice Hematologic Malignancies in USMLE Step 2 with focused quiz questions that help you check what you know, review explanations, and build confidence with test-style prompts.

What this quiz covers

This quiz focuses on Hematologic Malignancies, giving you a quick way to practice the rules, question types, and explanations that matter most for USMLE Step 2.

How to use this quiz

Try each quiz question before looking at the correct answer. Use the explanations to review missed ideas, then come back to similar questions until the pattern feels familiar.

All questions

Question 1

A 70-year-old woman presents with headaches, blurred vision, and recurrent nosebleeds. Physical examination reveals mild hepatosplenomegaly. Laboratory evaluation shows a normocytic anemia and a large M-spike on serum protein electrophoresis. Immunofixation identifies the monoclonal protein as IgM. The serum viscosity is found to be significantly elevated.

This patient's constellation of findings is most characteristic of which of the following disorders?

  1. Multiple myeloma
  2. Waldenström macroglobulinemia (correct answer)
  3. Monoclonal gammopathy of undetermined significance
  4. Heavy chain disease
Explanation: Waldenström macroglobulinemia is a lymphoplasmacytic lymphoma characterized by the production of monoclonal IgM. The large pentameric structure of IgM molecules leads to a significant increase in serum viscosity, causing hyperviscosity syndrome. The classic symptoms of hyperviscosity syndrome include blurry vision, headaches, confusion, and mucosal bleeding (e.g., epistaxis), as seen in this patient. Multiple myeloma typically involves IgG or IgA and rarely causes hyperviscosity.

Question 2

A 50-year-old woman presents for a follow-up visit. She was treated for Stage IIB Hodgkin lymphoma 25 years ago with chemotherapy and mantle field radiation therapy. She is currently asymptomatic. Her blood pressure is 130/80 mm Hg and her BMI is 24 kg/m². She does not smoke.

This patient is at a significantly increased risk for which of the following long-term complications?

  1. Coronary artery disease (correct answer)
  2. Osteoporosis
  3. Chronic liver disease
  4. Autoimmune thyroiditis
Explanation: A major long-term complication of mantle field radiation (radiation to the mediastinum, neck, and axillae) for Hodgkin lymphoma is radiation-induced cardiovascular disease. This includes premature coronary artery disease, valvular abnormalities, pericardial disease, and cardiomyopathy. These complications can manifest decades after treatment. Therefore, survivors require diligent screening and aggressive management of cardiovascular risk factors.

Question 3

A 48-year-old woman is diagnosed with chronic phase chronic myeloid leukemia after a workup for leukocytosis. Cytogenetic analysis confirms the presence of the t(9;22) translocation.

Which of the following medications is the most appropriate first-line treatment for this patient?

  1. Imatinib (correct answer)
  2. Hydroxyurea
  3. Ruxolitinib
  4. Rituximab
Explanation: The t(9;22) translocation results in the BCR-ABL fusion gene, which produces a constitutively active tyrosine kinase that drives the proliferation of granulocytes in Chronic Myeloid Leukemia (CML). Imatinib is a tyrosine kinase inhibitor (TKI) that specifically targets the BCR-ABL protein. TKIs are the standard first-line therapy for chronic phase CML and have dramatically improved prognosis, inducing long-term remissions in the vast majority of patients.

Question 4

A 58-year-old man presents with a 1-year history of fatigue and recurrent infections. Physical examination reveals massive splenomegaly. Laboratory studies show pancytopenia: hemoglobin 8.9 g/dL, WBC 2,500/µL, and platelets 70,000/µL. The peripheral smear shows lymphocytes with irregular, fine, hair-like cytoplasmic projections. A bone marrow aspiration attempt results in a 'dry tap'.

Which of the following is the most appropriate next step in establishing the diagnosis?

  1. Flow cytometry of peripheral blood (correct answer)
  2. JAK2 mutation testing
  3. Bone marrow biopsy
  4. Cytogenetic analysis
Explanation: This patient's clinical picture of pancytopenia, massive splenomegaly, a dry bone marrow tap, and characteristic hairy cells on peripheral smear is highly suggestive of hairy cell leukemia. Flow cytometry of peripheral blood to identify characteristic markers (CD11c, CD25, CD103) is the most appropriate next diagnostic step. The dry tap makes bone marrow aspiration difficult, and flow cytometry can establish the diagnosis without invasive procedures.

Question 5

A 78-year-old man with a 10-year history of stable, asymptomatic chronic lymphocytic leukemia presents with a 1-month history of drenching night sweats, fevers, and rapid growth of a lymph node in his neck. His lactate dehydrogenase (LDH) level is markedly elevated. A biopsy of the enlarged node is performed.

This patient's clinical change is most likely due to transformation to which of the following?

  1. Acute myeloid leukemia
  2. Hodgkin lymphoma
  3. Diffuse large B-cell lymphoma (correct answer)
  4. Prolymphocytic leukemia
Explanation: The development of aggressive symptoms (B symptoms, rapidly enlarging nodes) and a high LDH in a patient with previously indolent CLL is highly concerning for Richter's transformation. This is the transformation of CLL into a high-grade lymphoma, most commonly Diffuse Large B-cell Lymphoma (DLBCL). This transformation carries a very poor prognosis and requires aggressive chemoimmunotherapy.

Question 6

A 55-year-old woman with newly diagnosed acute myeloid leukemia presents to the emergency department with headache, shortness of breath, and confusion. Her initial white blood cell count is 180,000/µL, with 92% blasts. Her oxygen saturation is 92% on room air.

Which of the following interventions is most urgently indicated to prevent life-threatening complications?

  1. Leukapheresis (correct answer)
  2. Whole brain irradiation
  3. Intrathecal methotrexate
  4. Packed red blood cell transfusion
Explanation: This patient has symptomatic hyperleukocytosis, a condition known as leukostasis. It is an oncologic emergency caused by the sludging of leukemic blasts in the microvasculature, particularly in the lungs and central nervous system. This leads to hypoxemia and neurologic deficits. The most urgent intervention is to rapidly decrease the circulating blast count, which is most effectively achieved with leukapheresis. Induction chemotherapy is also initiated, but leukapheresis provides a more immediate reduction in cell burden.

Question 7

A 65-year-old man with multiple myeloma develops acute kidney injury with a creatinine of 3.5 mg/dL. He has no signs of volume depletion or obstruction. Urinalysis shows 1+ protein on dipstick, but a 24-hour urine protein collection reveals 4 grams of protein. Urine microscopy shows numerous eosinophilic, tubular casts.

The patient's renal failure is most likely due to which of the following mechanisms?

  1. Light chain cast nephropathy (correct answer)
  2. Glomerular amyloid deposition
  3. Hypercalcemia-induced vasoconstriction
  4. Direct infiltration of the kidneys by plasma cells
Explanation: The most common cause of acute kidney injury in multiple myeloma is light chain cast nephropathy, also known as myeloma kidney. Excess monoclonal light chains (Bence-Jones proteins) are filtered by the glomerulus and then precipitate within the distal tubules, combining with Tamm-Horsfall protein to form obstructive casts. This leads to tubular damage and renal failure. The discrepancy between the dipstick (which primarily detects albumin) and the 24-hour protein is a classic clue, as the dipstick does not detect light chains well.

Question 8

A 40-year-old man presents with severe fatigue, fever, and extensive bruising. Laboratory studies show pancytopenia and a peripheral smear reveals numerous promyelocytes containing multiple Auer rods ('faggot cells'). A coagulation panel shows a prolonged PT and PTT, low fibrinogen, and elevated D-dimer. Genetic testing is pending but is expected to show a t(15;17) translocation.

Which of the following agents should be started immediately, even before genetic confirmation?

  1. All-trans-retinoic acid (ATRA) (correct answer)
  2. Cytarabine
  3. Imatinib
  4. Fresh frozen plasma
Explanation: The clinical picture of promyelocytes with multiple Auer rods and disseminated intravascular coagulation (DIC) is classic for Acute Promyelocytic Leukemia (APL), which is associated with the t(15;17) translocation. APL is a medical emergency due to the high risk of life-threatening hemorrhage from DIC. The cornerstone of treatment is all-trans-retinoic acid (ATRA), which induces differentiation of the malignant promyelocytes, leading to rapid resolution of the coagulopathy. Treatment with ATRA should be initiated immediately upon suspicion of APL and not delayed for genetic confirmation.