Family Medicine Board Review · Case-Based · Difficult Level

Leukemia — Clinical Vignette MCQs

Board-style cases pulled from the leukemia summary — subtype recognition, diagnostic criteria, risk factors, and the two treatment emergencies. Tap "Reveal Answer" on each to check yourself, then read the pearl.

10 Questions ●●●● Difficult Single Best Answer
Q1ALL Risk Stratification●●●● Very Hard

An 11-year-old boy is diagnosed with acute lymphoblastic leukemia. Bone marrow biopsy shows 45% lymphoblasts. Initial WBC count is 22,000/mm³. Cytogenetics reveal t(12;21), and cells show hyperploidy. Post-induction testing shows no minimal residual disease. Which single factor in his case is most concerning for a worse prognosis?

Reveal Answer

Correct answer: A

The favorable age range for ALL is 1–9 years; age ≥10 (or <1 year) is the unfavorable category. At age 11, he falls into the unfavorable age group, despite every other factor in his case (WBC <50,000, t(12;21), hyperploidy, MRD-negative) being favorable.

Why the others are wrong B — WBC <50,000/mm³ is the favorable cutoff; his 22,000 fits. C — t(12;21) is the favorable cytogenetic marker (vs. unfavorable t(4;11) or t(9;22)). D — hyperploidy is favorable (vs. unfavorable hypoploidy). E — MRD-negative is the favorable finding (vs. unfavorable MRD-positive).
Exam Pearl Favorable ALL prognosis = age 1–9, WBC <50,000, hyperploidy, t(12;21), female sex, MRD-negative. Flip each for the unfavorable column. Boards love embedding one lone unfavorable factor inside an otherwise favorable-looking case — age ≥10 is an easy one to miss when everything else looks reassuring.
Q2AML vs. ALL Distinction●●●● Very Hard

A 71-year-old man presents with fatigue, easy bruising, and gum swelling with bleeding on brushing his teeth. Exam shows pallor and gingival hypertrophy but no palpable spleen or liver. Peripheral smear shows rod-shaped cytoplasmic inclusions in blast cells. What is the most likely diagnosis?

Reveal Answer

Correct answer: B

Auer rods (rod-shaped cytoplasmic inclusions) on peripheral smear are pathognomonic for AML. The clinical picture — older adult, gum infiltration, and notably absent hepatosplenomegaly — is classic for AML rather than ALL.

Why the others are wrong A — ALL mainly affects children and typically shows hepatosplenomegaly, which is absent here; also lacks Auer rods. C — CLL is typically indolent/asymptomatic with smudge cells, not Auer rods or acute bleeding symptoms. D — CML is defined by the Philadelphia chromosome, not Auer rods, and has a more indolent course. E — mono doesn't produce Auer rods or gum infiltration.
Exam Pearl Auer rods = AML, full stop. Gum/gingival infiltration and the relative absence of hepatosplenomegaly (compared to ALL) are the classic distinguishing clinical clues on boards.
Q3CLL Diagnostic Workup●●●● Very Hard

A 68-year-old asymptomatic man is found to have a persistently elevated lymphocyte count on routine labs. Peripheral smear shows small mature lymphocytes with fragile cells that appear disrupted ("smudged") during slide preparation. Absolute lymphocyte count is 7,200/µL. What is the most appropriate next step?

Reveal Answer

Correct answer: B

CLL diagnosis requires ≥5,000/µL monoclonal B lymphocytes on peripheral smear, confirmed with flow cytometry. His count of 7,200/µL with smudge cells is consistent with CLL, but flow cytometry is required to confirm clonality before finalizing the diagnosis. Bone marrow biopsy is notably not required.

Why the others are wrong A — this is the classic distractor; CLL is one of the few leukemias diagnosed without bone marrow biopsy. C — asymptomatic early-stage CLL is monitored without treatment ("watch and wait"), not treated immediately. D — PET/CT isn't the standard confirmatory test for CLL. E — simply repeating the CBC without confirmatory testing delays an actionable diagnosis.
Exam Pearl CLL diagnostic pathway: peripheral smear (smudge cells) → flow cytometry to confirm monoclonality → no bone marrow needed. And remember: asymptomatic early-stage CLL = observation, not treatment.
Q4CML + Pregnancy Safety●●●●● Extreme

A 29-year-old woman with CML on imatinib presents for preconception counseling; she and her partner would like to conceive within the next year. Cytogenetic testing confirms the Philadelphia chromosome remains detectable at low levels. What is the most appropriate guidance regarding her CML treatment during a future pregnancy?

Reveal Answer

Correct answer: B

Imatinib, despite its otherwise favorable long-term safety profile, should not be used during pregnancy. This requires proactive preconception counseling and coordination with hematology to plan an alternative approach for disease control during conception and pregnancy.

Why the others are wrong A — directly contradicts the specific pregnancy contraindication. C — abruptly stopping without any monitoring or alternative plan risks disease progression; the answer is proactive planning, not simply stopping with no plan. D — allopurinol treats hyperuricemia/tumor lysis risk, not CML itself; it isn't a substitute therapy. E — CML is not an absolute contraindication to pregnancy; it requires careful management, not automatic avoidance.
Exam Pearl Imatinib + pregnancy is a classic isolated safety fact tested on boards: contraindicated in pregnancy despite being otherwise well-tolerated long-term. Preconception counseling in reproductive-age CML patients is a high-yield family medicine touchpoint.
Q5Tumor Lysis Syndrome●●●●● Extreme

A 9-year-old boy with newly diagnosed acute lymphoblastic leukemia begins induction chemotherapy. Eighteen hours later, labs show potassium 6.2 mEq/L, uric acid 11 mg/dL, phosphorus 7.8 mg/dL, and calcium 6.9 mg/dL, with rising creatinine. What is the most appropriate immediate management?

Reveal Answer

Correct answer: B

This is classic tumor lysis syndrome: hyperkalemia, hyperuricemia, hyperphosphatemia, hypocalcemia, and rising creatinine occurring after initiation of cytotoxic therapy — more common in acute leukemias. Core management is aggressive IV hydration plus allopurinol (or rasburicase in high-risk/established cases) to manage uric acid burden and protect renal function.

Why the others are wrong A — fluid restriction is the opposite of correct management; aggressive hydration is protective against renal failure here. C — calcium is given only for symptomatic hypocalcemia (e.g., arrhythmia, tetany), not as the sole or primary intervention for the syndrome. D — TLS is managed medically alongside continued oncologic care, not by permanently stopping treatment. E — these values reflect a true metabolic emergency requiring active intervention, not passive observation.
Exam Pearl TLS metabolic pattern: ↑K⁺, ↑uric acid, ↑phosphate, ↓Ca²⁺ (calcium is bound by the rising phosphate). It can occur spontaneously or after treatment initiation and is most common in acute leukemias. First-line management is hydration + allopurinol.
Q6Neutropenic Fever●●●● Very Hard

A 55-year-old woman receiving chemotherapy for AML presents to the emergency department with a temperature of 38.9°C (102°F). Labs show an absolute neutrophil count of 0.3 × 10⁹/L. She appears uncomfortable but is hemodynamically stable. Blood cultures are drawn. What is the most appropriate next step?

Reveal Answer

Correct answer: B

Neutropenic fever (ANC <0.5 with fever) is a true emergency requiring immediate evaluation and empirical broad-spectrum antibiotics — do not wait for culture results, which can take 24–48+ hours while an occult infection progresses rapidly in an immunocompromised host.

Why the others are wrong A — delaying antibiotics for culture results risks rapid deterioration/sepsis. C — antipyretics alone don't address the underlying infectious risk in a neutropenic patient. D — neutropenic fever requires immediate, typically inpatient, IV empirical therapy — not outpatient oral management. E — bone marrow biopsy is not part of the acute neutropenic fever workup and would dangerously delay treatment.
Exam Pearl ANC <0.5 + fever = start empirical antibiotics now, don't wait for cultures. This pairs with the initial workup: UA, CXR, and blood cultures should be sent, but treatment starts immediately regardless of pending results.
Q7Risk Factor Recognition●●●○ Hard

A 34-year-old man with chronic hepatitis C infection is found to have an absolute lymphocyte count of 6,500/µL on routine bloodwork, with smudge cells noted on peripheral smear. He is otherwise asymptomatic. Which leukemia subtype is he at increased risk for given his hepatitis C status?

Reveal Answer

Correct answer: C

Hepatitis C infection is specifically associated with an increased risk of CLL. His labs (elevated monoclonal-appearing lymphocytosis, smudge cells) fit this pattern.

Why the others are wrong A, B, D — none of these are the specific leukemia subtype linked to hepatitis C in this framework; the tested association is exclusively with CLL. E — hairy cell leukemia isn't the association being tested here.
Exam Pearl Memorize the isolated infection-leukemia link: hepatitis C → CLL. This is a favorite single-fact board question, often paired with a smudge-cell peripheral smear description to reinforce the CLL diagnosis simultaneously.
Q8Peripheral Smear Indications●●●○ Hard

A 6-year-old boy presents with two weeks of fatigue, low-grade fevers, and easy bruising. Exam reveals pallor, scattered petechiae, and palpable splenomegaly. CBC shows WBC 4,200/µL, hemoglobin 8.1 g/dL, and platelets 62,000/µL. Given these findings, what is the most appropriate next diagnostic step?

Reveal Answer

Correct answer: B

Thrombocytopenia, hepatosplenomegaly (via splenomegaly), and unexplained constitutional symptoms (fatigue, fever) are all listed indications for peripheral smear. In a child with these findings plus bruising/petechiae, malignancy (e.g., ALL) must be excluded before proceeding down other diagnostic pathways.

Why the others are wrong A — these findings (cytopenias, splenomegaly, constitutional symptoms) warrant prompt evaluation, not reassurance and delay. C — the anemia here isn't clearly iron-deficiency pattern, and empirical treatment without evaluation risks missing an underlying leukemia. D — imaging alone doesn't address the peripheral cytopenias or need for cellular evaluation. E — starting steroids before ruling out leukemia is dangerous, as steroids can partially treat leukemia and obscure the diagnosis (similar principle to not treating before diagnosis in lymphoma).
Exam Pearl Peripheral smear triggers: hyperleukocytosis with anemia, thrombocytopenia, thrombocytosis, hepatosplenomegaly, lymphadenopathy, or unexplained constitutional symptoms. A pediatric patient with cytopenias + splenomegaly + constitutional symptoms should raise leukemia on the differential before steroids are ever considered.
Q9CML Recognition●●●● Very Hard

A 46-year-old man presents with early satiety and a dragging sensation in his left upper abdomen. Exam reveals massive splenomegaly. He denies fevers, weight loss, or night sweats. CBC shows marked leukocytosis with a full spectrum of granulocyte maturation stages. Cytogenetic testing of peripheral blood confirms a reciprocal translocation. What is the most appropriate first-line treatment?

Reveal Answer

Correct answer: B

This presentation (massive splenomegaly, granulocytosis across all maturation stages, reciprocal translocation = Philadelphia chromosome t(9;22)) is classic CML. First-line treatment is imatinib, a BCR-ABL1 tyrosine kinase inhibitor, which provides consistent long-term disease control with minimal side effects.

Why the others are wrong A — intensive induction chemotherapy is the approach for acute leukemias, not the first-line for CML, which responds well to targeted TKI therapy. C — unlike early asymptomatic CLL, CML with this presentation is treated, not observed. D — splenectomy is not first-line management. E — allopurinol addresses hyperuricemia/tumor lysis risk, not the underlying disease process.
Exam Pearl CML = Philadelphia chromosome (BCR-ABL1) + imatinib as the pairing to memorize. Contrast with ALL/AML, which require intensive combination chemotherapy — CML is the leukemia "success story" of targeted oral therapy.
Q10Integrative — Genetic Risk●●●●● Extreme

A mother brings in her 3-year-old son with Down syndrome for a well-child visit. She has read that his condition increases his risk of leukemia and asks what workup, if any, is indicated given he is currently asymptomatic with a normal exam. What is the most appropriate response?

Reveal Answer

Correct answer: B

Down syndrome is a recognized genetic risk factor for leukemia, but this does not translate into routine invasive screening (e.g., bone marrow biopsy) in an asymptomatic child. The appropriate approach is increased clinical vigilance — a lower threshold to obtain a peripheral smear if he develops any of the recognized indications (cytopenias, hepatosplenomegaly, lymphadenopathy, unexplained constitutional symptoms).

Why the others are wrong A — invasive testing isn't indicated without clinical findings prompting concern. C — there is no role for prophylactic chemotherapy based on risk factor status alone. D — the Philadelphia chromosome is specific to CML, not a general leukemia screening test, and isn't indicated here. E — this is factually incorrect; Down syndrome is an established leukemia risk factor and should not be dismissed.
Exam Pearl Genetic risk factors (Down syndrome, Klinefelter syndrome, Fanconi anemia) raise your index of suspicion — they don't trigger automatic invasive screening. The peripheral smear indications list is your trigger point for actually initiating workup.
Leukemia Board Review · Case-Based MCQ Set · 10/10 Questions