12 clinical MCQs in Uncategorized. A 7-year-old boy presents with fatigue, bone pain, and recurrent fever. His WBC is 85,000/. Kenya, Africa and global...
Q1. A 7-year-old boy presents with fatigue, bone pain, and recurrent fever. His WBC is 85,000/µL with blasts composing 40% of marrow cellularity. Blasts stain TdT+ and CD19+ but negative for CD3 and peroxidase. Which chromosomal abnormality would confer the BEST prognosis?
Answer: t(12;21) TEL1/AML1 fusion
Explanation: t(12;21) and hyperdiploidy are the "good prognosis" aberrations most common in children aged 2–10. t(9;22) BCR-ABL is the worst prognostic marker in B-ALL and is most common in adults. MLL rearrangements carry poor prognosis and predominate in children under 2. Hypodiploidy also carries poor prognosis. ---
Q2. A 17-year-old male presents with a large anterior mediastinal mass and lymphoblasts in peripheral blood. Blasts are TdT+, CD2+, CD7+, and CD19−. Which mutation is most commonly associated with this entity?
Answer: NOTCH1 mutation
Explanation: The clinical picture — adolescent male, anterior mediastinal mass, TdT+, T cell markers positive, CD19 negative — is classic pre-T cell ALL/lymphoblastic lymphoma. NOTCH1 mutations are the most commonly associated mutation in T-ALL. BCR-ABL and MLL are B-ALL associations. t(14;18) is the hallmark of follicular lymphoma. MYC translocations define Burkitt lymphoma. ---
Q3. A 65-year-old man is incidentally found to have a lymphocyte count of 18,000/µL. He has mild cervical lymphadenopathy. Biopsy shows proliferation centres and smudge cells on the blood smear. Immunophenotyping shows CD19+, CD5+, CD23+. Which molecular mechanism BEST explains tumour cell survival in this condition?
Answer: Loss of microRNAs on chromosome 13 upregulating BCL2
Explanation: This is CLL/SLL — CD5+ B cells with proliferation centres and smudge cells are pathognomonic. Unlike follicular lymphoma where BCL2 is overexpressed via t(14;18), in CLL/SLL BCL2 is upregulated through loss of regulatory microRNAs encoded on chromosome 13. Cyclin D1 overexpression from t(11;14) is the hallmark of mantle cell lymphoma. MYC overexpression defines Burkitt lymphoma. ---
Q4. A 60-year-old woman presents with painless generalised lymphadenopathy. Biopsy shows a nodular proliferation of centrocytes mixed with centroblasts. Immunophenotyping shows CD19+, CD20+, CD10+, BCL2+. Which statement about this condition is MOST accurate?
Answer: It is associated with t(14;18), BCL2 overexpression, and is not curable
Explanation: This is follicular lymphoma — nodular growth, centrocytes and centroblasts, CD10+, BCL2+. The t(14;18) translocation fuses BCL2 to the IgH locus causing inappropriate BCL2 overexpression and tumour cell survival. Despite a prolonged natural history (median survival 7–9 years), it is not curable with standard therapy. Transformation occurs to diffuse large B cell lymphoma (not AML) in about 40% of patients. ---
Q5. A 55-year-old man presents with fatigue, generalised lymphadenopathy, and GI tract involvement appearing as submucosal polyp-like nodules on colonoscopy. Immunophenotyping shows CD19+, CD5+, cyclin D1+, CD23−. Which translocation is characteristically associated with this condition?
Answer: t(11;14) involving cyclin D1 and IgH
Explanation: This is mantle cell lymphoma — CD5+ B cells that are CD23 negative (distinguishing it from CLL/SLL which is CD23+), with cyclin D1 expression. The t(11;14) translocation fuses cyclin D1 to the IgH locus dysregulating cell cycle progression. GI involvement presenting as lymphomatoid polyposis is a characteristic feature. The tumour is moderately aggressive and incurable with median survival 3–5 years. ---
Q6. A 12-year-old African boy presents with a rapidly enlarging jaw mass. Biopsy shows intermediate-sized cells with a "starry sky" pattern and extremely high mitotic rate. Tumour cells are CD10+, BCL6+, surface IgM+. EBV genomes are detected in tumour cells. What is the PRIMARY molecular driver of this tumour?
Answer: MYC dysregulation from t(8;14) driving uncontrolled proliferation
Explanation: This is endemic Burkitt lymphoma. The hallmark is MYC translocation, most commonly t(8;14), causing MYC overexpression and uncontrolled proliferation. EBV is present in most endemic cases but is not the primary driver — the question specifically asks for the primary molecular driver. BCL2 overexpression defines follicular lymphoma. TP53 mutations are the hallmark of high-grade serous carcinoma. ---
Q7. A 72-year-old man presents with back pain and confusion. X-ray shows punched-out lytic skull lesions. Serum electrophoresis shows an IgG M protein spike. Urine shows Bence Jones proteins. Bone marrow has 30% plasma cells. Creatinine is markedly elevated. Which mechanism BEST explains his renal dysfunction?
Answer: Obstructive casts of Bence Jones proteins in distal tubules causing tubular necrosis
Explanation: This is multiple myeloma. Renal dysfunction results primarily from obstructive proteinaceous casts — composed mostly of Bence Jones proteins (free light chains) along with Tamm-Horsfall protein and albumin — forming in the distal convoluted tubules and collecting ducts. Adjacent epithelial cells become necrotic from the toxic effects of Bence Jones proteins. It is hypercalcaemia (not hypocalcaemia) that also contributes to renal dysfunction. Lymphomatous infiltration is not a feature of myeloma. ---
Q8. A 68-year-old woman is found to have 2.1 g/dL of monoclonal IgG in her serum on a routine check. She has no bone pain, no anaemia, no Bence Jones proteinuria, and bone marrow shows 8% plasma cells. She is asymptomatic. What is the risk of this condition progressing to symptomatic myeloma?
Answer: It progresses at approximately 1% per year and contains the same chromosomal translocations as myeloma
Explanation: This is MGUS — the most common plasma cell proliferation, found in 1–3% of healthy persons over 50. Despite its name, MGUS is a precursor lesion that progresses to symptomatic plasma cell tumour at approximately 1% per year. The clonal plasma cells in MGUS already contain the same chromosomal translocations as full-blown myeloma. Diagnosis of MGUS requires less than 3 g/dL monoclonal protein and no Bence Jones proteinuria — both criteria are met here. ---
Q9. A 25-year-old woman presents with fever, sore throat, and marked cervical lymphadenopathy. Blood smear shows large atypical lymphocytes with abundant cytoplasm. Monospot test is positive. Which of the following statements about the atypical lymphocytes seen in this condition is CORRECT?
Answer: They are virus-specific CD8+ T cells responding to EBV-infected B cells
Explanation: This is infectious mononucleosis. The atypical lymphocytes are virus-specific CD8+ cytotoxic T cells appearing in the circulation in response to EBV-infected B cells — not the infected B cells themselves. The latently infected B cells undergo polyclonal activation and secrete heterophil antibodies, but they are not the atypical lymphocytes seen on the blood smear. NK cells play a role in control but are not the characteristic atypical cells. ---
Q10. A 16-year-old boy is known to have X-linked lymphoproliferative syndrome. He presents acutely unwell with massive hepatosplenomegaly and liver failure following EBV infection. Which gene is mutated in this condition and what is its normal function?
Answer: SH2D1A — normally participates in activation of T cells, NK cells, and antibody production
Explanation: X-linked lymphoproliferative syndrome is caused by mutations in SH2D1A, which encodes a signalling protein that participates in the activation of T cells and NK cells and in antibody production. Without this, the immune response to EBV is ineffective — leading to overwhelming fatal infection in 50% of cases, or lymphoma or hypogammaglobulinaemia in survivors. BRCA1, ATM, and RAG1 have entirely different functions. ---
Q11. A patient with Hodgkin lymphoma has disease on both sides of the diaphragm involving multiple lymph node groups and the spleen, with no systemic symptoms. What is his Ann Arbor stage and what does the absence of systemic symptoms signify?
Answer: Stage III-A — disease on both sides of diaphragm including spleen, no systemic symptoms
Explanation: Stage III involves lymph node regions on both sides of the diaphragm; the S suffix denotes splenic involvement giving Stage IIIS. The suffix A indicates absence of systemic symptoms (fever, night sweats, unexplained 10% weight loss). Stage B would indicate presence of these symptoms. Stage IV requires disseminated extralymphatic organ involvement which is not described here. ---
Q12. A 65-year-old man presents with massive splenomegaly and anaemia. Peripheral blood smear shows teardrop cells, nucleated red cells, and immature myeloid cells. Bone marrow trephine is hypocellular and fibrotic. Which of the following BEST explains the origin of the marrow fibrosis?
Answer: TGF-β and PDGF released from neoplastic megakaryocytes stimulating non-neoplastic fibroblasts
Explanation: This is primary myelofibrosis — teardrop cells, leukoerythroblastosis, and fibrotic marrow. A critical concept is that the fibroblasts are NOT part of the neoplastic clone. The fibrosis is secondary — stimulated by PDGF and TGF-β released from neoplastic megakaryocytes. BCR-ABL is the driver in CML, not primary myelofibrosis. IL-6 drives myeloma cell proliferation and bone resorption, not marrow fibrosis. ---