MCQ: Here are the full MCQs with answers and explanations:

Question 1

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?

Accepted Answer

t(12;21) TEL1/AML1 fusion — 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.

Question 2

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?

Accepted Answer

NOTCH1 mutation — 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.

Question 3

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?

Accepted Answer

Loss of microRNAs on chromosome 13 upregulating BCL2 — 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.

Question 4

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?

Accepted Answer

It is associated with t(14;18), BCL2 overexpression, and is not curable — 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.

Question 5

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?

Accepted Answer

t(11;14) involving cyclin D1 and IgH — 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.

Question 6

A 70-year-old man presents with a rapidly enlarging cervical mass. Biopsy shows large cells in a diffuse pattern with prominent nucleoli. He achieves complete remission with R-CHOP. Molecular analysis shows a mutation in the BCL6 promoter. Three years later he relapses. His new biopsy is identical. Which feature would make his relapsed disease HARDER to cure than if he had presented with it de novo?

Accepted Answer

The relapsed tumour has acquired a t(14;18) from prior follicular lymphoma transformation — This tests a subtle concept — DLBCL arising from transformed follicular lymphoma (carrying t(14;18)) is much less curable than de novo DLBCL even when they appear histologically identical. BCL6 promoter mutations are the most common finding in de novo DLBCL. CD20 expression is not lost in relapse. Transformation to Burkitt lymphoma is a different entity entirely.

Question 7

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?

Accepted Answer

MYC dysregulation from t(8;14) driving uncontrolled proliferation — 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.

Question 8

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?

Accepted Answer

Obstructive casts of Bence Jones proteins in distal tubules causing tubular necrosis — 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.

Question 9

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?

Accepted Answer

It progresses at approximately 1% per year and contains the same chromosomal translocations as myeloma — 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.

Question 10

A 70-year-old man presents with visual disturbances and neurological symptoms. Blood tests show markedly elevated IgM. Serum viscosity is very high. Bone marrow biopsy shows a mixture of small lymphocytes, plasmacytic lymphocytes, and plasma cells. Which finding would MOST help distinguish this condition from multiple myeloma?

Accepted Answer

Absence of lytic bone lesions and no Bence Jones proteinuria — This is lymphoplasmacytic lymphoma causing Waldenström macroglobulinaemia. The key distinguishing features from multiple myeloma are the absence of lytic bone lesions and the absence of Bence Jones proteinuria (because heavy and light chain synthesis is balanced, producing no free light chains). Both conditions involve bone marrow, both produce elevated immunoglobulins, and both occur in the elderly — making these poor discriminators.

Question 11

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?

Accepted Answer

They are virus-specific CD8+ T cells responding to EBV-infected B cells — 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.

Question 12

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?

Accepted Answer

SH2D1A — normally participates in activation of T cells, NK cells, and antibody production — 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.

Question 13

A lymph node biopsy from a patient with rheumatoid arthritis shows enlarged reactive follicles containing activated B cells, tingible body macrophages, and follicular dendritic cells. The architecture is preserved and germinal centres vary in size and shape. Which feature would MOST suggest follicular lymphoma rather than follicular hyperplasia?

Accepted Answer

Uniform follicles with BCL2-positive germinal centre B cells — BCL2 positivity in germinal centre B cells is the key distinguishing feature — normal germinal centre B cells do NOT express BCL2, so BCL2 positivity in follicular cells strongly suggests follicular lymphoma. Prominent mitotic activity, tingible body macrophages, and variation in follicle size and shape all favour reactive follicular hyperplasia rather than lymphoma.

Question 14

A 45-year-old man presents with fever, night sweats, and mediastinal lymphadenopathy. Biopsy shows collagen bands dividing the lymph node into nodules, with large pale cells sitting in clear spaces surrounded by eosinophils and lymphocytes. These cells express CD15 and CD30 but are negative for CD45 and CD20. What is the cell of origin of the malignant cells in this condition?

Accepted Answer

Germinal centre B cells that have lost normal B cell gene expression programmes — This is nodular sclerosis Hodgkin lymphoma — collagen bands, lacunar cells in clear spaces, CD15+, CD30+, CD45−. Elegant molecular studies on single microdissected Reed-Sternberg cells showed identical immunoglobulin gene rearrangements with somatic hypermutation in every RS cell — proving origin from germinal centre B cells. However, these cells have lost normal B cell gene expression programmes, which is why they fail to express CD20 and other B cell markers.

Question 15

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?

Accepted Answer

Stage III-A — disease on both sides of diaphragm including spleen, no systemic symptoms — 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.

Question 16

A 55-year-old man presents with splenomegaly and a WBC of 120,000/µL showing predominantly neutrophils, metamyelocytes, myelocytes, basophils, and eosinophils with <5% blasts. BCR-ABL fusion gene is confirmed. He is started on imatinib and achieves complete remission. Two years later he relapses. The most likely explanation for resistance is:

Accepted Answer

Acquired mutations in the BCR-ABL kinase domain preventing imatinib binding — This is CML treated with a tyrosine kinase inhibitor. When patients on BCR-ABL inhibitors relapse, their tumours have frequently acquired mutations in the kinase domain of BCR-ABL that prevent the drugs from binding. These mutations are present in small numbers of cells at diagnosis and are selected out by the powerful antitumour effects of imatinib. The tumours are still "addicted" to BCR-ABL signalling — loss of BCR-ABL expression does not occur.

Question 17

A 60-year-old woman presents with pruritus, plethora, headache, and a haematocrit of 62%. Her WBC is 18,000/µL and platelets are 550,000/µL. Serum erythropoietin is very low. Which mutation is responsible for this condition and why is erythropoietin low?

Accepted Answer

JAK2 V617F mutation — causes growth factor independent proliferation making EPO signalling unnecessary — This is polycythaemia vera — panmyelosis, low EPO, JAK2 V617F mutation. The JAK2 V617F mutation causes constitutive activation of JAK2, a tyrosine kinase downstream of the erythropoietin receptor, making haematopoietic cells growth factor independent. Because the red cell mass is already expanded by EPO-independent growth, the feedback loop suppresses EPO production — hence the characteristically low EPO level that distinguishes it from reactive polycythaemia.

Question 18

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?

Accepted Answer

TGF-β and PDGF released from neoplastic megakaryocytes stimulating non-neoplastic fibroblasts — 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.

Question 19

A 2-year-old child presents with a seborrheic-like skin rash, hepatosplenomegaly, lymphadenopathy, and recurrent otitis media. Bone marrow biopsy shows infiltration by cells expressing CD1a and langerin with tennis-racket shaped Birbeck granules on electron microscopy. Which molecular finding is shared between this condition and hairy cell leukaemia?

Accepted Answer

BRAF V600E activating mutation — This is multisystem Langerhans cell histiocytosis (Letterer-Siwe disease) — CD1a+, langerin+, Birbeck granules. The BRAF V600E mutation is found in different clinical forms of Langerhans cell histiocytosis and is also found in virtually all cases of hairy cell leukaemia — an important shared molecular feature. JAK2 V617F defines BCR-ABL-negative myeloproliferative disorders. t(11;18) defines extranodal marginal zone lymphoma.

Question 20

A patient presents with sepsis following an elective bowel resection. He develops widespread bleeding from IV sites, petechiae, and signs of renal failure. Investigations show prolonged PT, prolonged PTT, thrombocytopenia, elevated fibrin degradation products, and microangiopathic haemolytic anaemia on blood smear. Which statement BEST explains why this patient is BOTH forming clots AND bleeding simultaneously?

Accepted Answer

Systemic coagulation activation consumes platelets and clotting factors while secondary fibrinolysis generates products that inhibit remaining haemostatic function — This is DIC — the consumptive coagulopathy paradox. Systemic activation of coagulation causes widespread microvascular thrombosis consuming platelets and clotting factors faster than they can be replaced. Secondary fibrinolysis is then activated — plasmin cleaves fibrin, factors V and VIII, and generates fibrin degradation products that further inhibit platelet aggregation, have antithrombin activity, and impair fibrin polymerisation. The result is simultaneous thrombosis and haemorrhage — the defining paradox of DIC.

MCQ: Here are the full MCQs with answers and explanations:

Questions, Answers & Explanations