Hematological Malignancies (Leukemias, Lymphomas, Myeloma) MCQs

Pathology · 191 free questions with answers & explanations.

1. A 35-year-old man presents with mediastinal mass, fever, and weight loss. Biopsy shows large binucleate cells with prominent 'owl-eye' nucleoli in a background of eosinophils, plasma cells, and lymphocytes. IHC shows CD15+, CD30+, CD45-. Which subtype of Hodgkin lymphoma is most likely?
2. A 65-year-old man has lytic bone lesions, serum M-spike of 4.2 g/dL, and plasma cells comprising 35% of bone marrow. Serum free light chain assay shows kappa:lambda ratio of 180. Which chromosome translocation most commonly seen in multiple myeloma confers the worst prognosis?
3. A 55-year-old presents with splenomegaly, peripheral blood showing small lymphocytes with 'hairy' cytoplasmic projections, and TRAP (tartrate-resistant acid phosphatase) positivity on cytochemistry. Which signaling pathway mutation is found in virtually all cases of this entity?
4. A 25-year-old African man presents with rapidly enlarging jaw mass. Biopsy shows a diffuse proliferation of intermediate-sized B-cells with a 'starry sky' pattern. FISH demonstrates translocation involving chromosome 8q24. Which oncogene is dysregulated by this translocation?
5. A 70-year-old patient with CLL undergoes repeat biopsy after clinical deterioration. Biopsy now shows large B-cell lymphoma. This transformation carries a median survival of less than 12 months and is termed:
6. A 35-year-old woman presents with cervical lymphadenopathy and constitutional symptoms. Biopsy shows large binucleated cells with prominent 'owl-eye' nucleoli, surrounded by a mixed inflammatory infiltrate. The Reed-Sternberg cells are most characteristically positive for which combination of markers?
7. The t(11;14)(q13;q32) translocation juxtaposing CCND1 (cyclin D1) next to the IGH locus is pathognomonic for which B-cell neoplasm?
8. In multiple myeloma, the characteristic 'M-spike' on serum protein electrophoresis represents a homogeneous immunoglobulin produced by the clonal plasma cells. The most common immunoglobulin type associated with this M-spike is:
9. Chronic myeloid leukemia (CML) in accelerated phase is defined by which of the following bone marrow findings?
10. A 60-year-old man is found to have lymphocytosis of 40,000/µL on routine CBC. Flow cytometry shows CD5+, CD19+, CD23+, CD10−, FMC7− B cells with weak surface immunoglobulin. Bone marrow shows diffuse lymphocytic infiltration. The smear shows numerous smudge cells. The diagnosis is:
11. A 68-year-old man presents with fatigue, splenomegaly, and peripheral blood showing 40% blasts with Auer rods. Cytogenetics reveal t(8;21)(q22;q22). Which fusion transcript does this translocation produce and what is its prognostic significance in AML?
12. A 55-year-old woman with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) after two prior lines achieves complete remission with axicabtagene ciloleucel (axi-cel). This CAR-T product targets which antigen and was evaluated in which landmark trial?
13. A 72-year-old man presents with progressive weakness, IgM monoclonal spike of 5.2 g/dL, bone marrow showing >10% lymphoplasmacytic cells, and MYD88 L265P mutation. He develops symptomatic hyperviscosity. What is the FIRST step in management?
14. In WHO 2022 classification, primary mediastinal large B-cell lymphoma (PMBL) is characterized by which immunophenotypic and molecular signature that distinguishes it from classic DLBCL?
15. A 48-year-old woman is diagnosed with follicular lymphoma grade 3B. Staging shows Ann Arbor stage IIIA. Which feature of grade 3B follicular lymphoma influences the treatment decision most significantly compared to grade 1–2 or 3A?
16. A 30-year-old presents with massive splenomegaly, leukocytosis (WBC 180,000/μL) with cells at all stages of granulocytic maturation, basophilia, and low LAP score. BCR-ABL1 is positive. Under the 2022 WHO classification, this disease in chronic phase is best categorized as:
17. A 55-year-old with diffuse large B-cell lymphoma (DLBCL) has biopsy demonstrating MYC rearrangement AND BCL-2 rearrangement by FISH. This entity is classified as:
18. In multiple myeloma, M-protein is detected in serum. The pathological basis for the renal lesion known as 'myeloma cast nephropathy' (myeloma kidney) involves:
19. Reed-Sternberg cells in classical Hodgkin lymphoma characteristically express CD30 and CD15 but are CD20-negative. The lineage ambiguity of RS cells is explained by the fact that they are derived from:
20. A 70-year-old with fatigue and back pain has serum protein electrophoresis showing an M-spike in the gamma region. Bone marrow biopsy shows 35% plasma cells. No lytic lesions, hypercalcemia, renal failure, or anemia. According to the IMWG 2014 criteria, this patient's diagnosis is:
21. A 45-year-old patient has a lymphoma with the following WHO 2022 classification features: CD10+, BCL6+, MUM1−, BCL2 rearrangement present, MYC rearrangement absent, Ki-67 80%. The GCB vs. ABC subtype assignment is best determined by:
22. A patient with plasma cell myeloma undergoes cytogenetics. FISH reveals t(4;14)(p16.3;q32). This translocation juxtaposes FGFR3 and MMSET (NSD2) to the IGH locus. The prognostic significance and therapeutic implication is:
23. A 70-year-old man has chronic lymphocytic leukemia. Genomic testing shows del(11q22.3) affecting ATM gene. Compared to del(13q14) as a sole abnormality, del(11q) confers:
24. A 35-year-old woman has follicular lymphoma. Biopsy shows BCL2 overexpression due to t(14;18)(q32;q21). The mechanism by which this translocation drives lymphomagenesis is:
25. A 58-year-old with a mediastinal mass on biopsy shows large cells with lacunar-type retraction artifact, CD15+, CD30+, CD20−, PAX5 dim+, CD45−, EBV EBER in situ hybridization negative. According to WHO 2022 classification, this is best classified as:
26. A 34-year-old woman presents with a rapidly enlarging neck mass. Biopsy shows large cells with voluminous pale cytoplasm in a 'starry sky' pattern, Ki-67 of nearly 100%, and positivity for CD10, BCL6, MYC, and BCL2 by IHC. FISH reveals concurrent translocations of MYC, BCL2, and BCL6. The WHO 2022 diagnosis is:
27. In multiple myeloma, the M-protein 'immunoparesis' (suppression of non-involved immunoglobulins) is caused primarily by which mechanism?
28. A 67-year-old man with CLL develops sudden worsening of constitutional symptoms, rapid lymph node enlargement, and markedly elevated LDH. Biopsy reveals transformation to large B-cell lymphoma. This transformation is known as:
29. Flow cytometry in a patient with T-cell prolymphocytic leukemia (T-PLL) is most likely to show which immunophenotype?
30. Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) is distinguished from classical Hodgkin lymphoma primarily by which feature?
31. A 30-year-old man presents with painless cervical lymphadenopathy. Biopsy shows large binucleated Reed-Sternberg cells with prominent 'owl-eye' nucleoli in a background of eosinophils, plasma cells, and lymphocytes. Flow cytometry shows CD15+, CD30+, CD45−, CD20− phenotype. According to WHO 2022 classification, which specific variant of classical Hodgkin lymphoma shows the WORST prognosis?
32. A 65-year-old woman with multiple myeloma undergoes bone marrow biopsy. Cytogenetics reveals t(4;14)(p16;q32). This translocation juxtaposes the IGH gene with FGFR3/MMSET, and is significant because it predicts:
33. A 50-year-old patient with a history of H. pylori gastritis develops a gastric low-grade B-cell lymphoma. Histology shows centrocyte-like cells infiltrating the mucosa. The pathogenesis involves antigen-driven proliferation where H. pylori-specific T-cells stimulate neoplastic B-cells. Which molecular event, when acquired, makes this lymphoma H. pylori-eradication therapy RESISTANT?
34. Hairy cell leukemia (HCL) is characterized by tartrate-resistant acid phosphatase (TRAP) positivity and strong expression of which surface marker that also serves as a target for the monoclonal antibody rituximab?
35. A 28-year-old man presents with rapidly enlarging jaw mass. Biopsy shows a 'starry sky' pattern with medium-sized lymphocytes having basophilic cytoplasm and multiple nucleoli. FISH shows MYC/IGH rearrangement. The Ki-67 proliferation index is nearly 100%. According to WHO 2022 classification, this lymphoma is now called:
36. WHO 2022 classification now requires a blast count threshold for diagnosing AML with myelodysplasia-related changes (AML-MRC). What is the minimum blast percentage required?
37. A 35-year-old man presents with rapidly enlarging cervical nodes, fever, and a mediastinal mass. Biopsy shows large cells with pale cytoplasm, prominent nucleoli, and a background of inflammatory cells. CD30+ and CD15+ on IHC; CD20-, EBV-EBER negative. Which translocation is characteristically associated with this entity?
38. A 70-year-old man with multiple myeloma has del(17p13.1) detected by FISH. This deletion involves the TP53 locus and carries which prognostic significance?
39. In diffuse large B-cell lymphoma (DLBCL), the Hans algorithm uses IHC markers to classify COO (cell of origin). Which panel correctly identifies germinal center B-cell (GCB) subtype?
40. Chronic lymphocytic leukemia (CLL) prognosis is significantly stratified by IGHV (immunoglobulin heavy chain variable gene) mutation status. Which statement is correct?
41. A 55-year-old man has a mediastinal mass with biopsy showing large cells with lobulated nuclei, abundant clear cytoplasm, positive for CD30, CD15, CD20 (weak), and EBV-LMP1. He is HIV-negative. The WHO 2022 classification best characterizes this as:
42. A 70-year-old presents with bone marrow showing 15% plasma cells, serum M-protein of 2.8 g/dL IgG kappa, but no lytic lesions, anemia, hypercalcemia, or renal insufficiency. Fluorescence in situ hybridization (FISH) reveals t(4;14) translocation. The WHO 2022 classification would categorize this as:
43. A peripheral blood smear from a 35-year-old shows lymphocytes with condensed chromatin, round nuclei, and scanty cytoplasm. Flow cytometry reveals CD19+, CD5+, CD23−, FMC7+, CD10−, cyclin D1+. FISH shows t(11;14)(q13;q32). This translocation juxtaposes CCND1 with which genetic element?
44. A patient with CML on imatinib develops resistance. BCR-ABL kinase domain sequencing reveals a T315I 'gatekeeper' mutation. Which second-generation TKI retains activity against T315I?
45. Bone marrow biopsy in a 72-year-old shows hypercellularity with trilineage dysplasia, 8% blasts, and del(5q) as the sole cytogenetic abnormality with concurrent SF3B1 mutation. According to the WHO 2022 classification of myeloid neoplasms, what is the most appropriate classification?
46. A 65-year-old man has splenomegaly, leukocytosis (WBC 90,000), and peripheral blood shows numerous mature lymphocytes with smudge cells. Flow cytometry reveals CD5+, CD19+, CD23+, CD20 dim, surface Ig dim, FMC7-. The CLL International Prognostic Index (CLL-IPI) incorporates which molecular marker as the STRONGEST adverse independent prognostic factor?
47. Anaplastic large cell lymphoma (ALCL) with ALK gene rearrangement most commonly involves which chromosomal translocation, and what fusion protein does it produce?
48. In multiple myeloma, the high-risk cytogenetic abnormality associated with the worst prognosis by ISS-R (Revised International Staging System) is:
49. A 35-year-old woman presents with mediastinal mass, fever, and night sweats. Biopsy shows large lacunar cells and rare Reed-Sternberg cells in a fibrous background. Immunohistochemistry: CD15+, CD30+, CD45-, PAX5 dim+, EBV-. The translocation most commonly seen in this specific Hodgkin lymphoma subtype is:
50. Hairy cell leukemia (HCL) characteristically shows which specific molecular mutation in virtually 100% of cases, now included in its WHO diagnostic criteria?
51. A 35-year-old woman presents with fever, lymphadenopathy and splenomegaly. Biopsy shows large CD30+ cells with bilobed nuclei and prominent 'owl-eye' eosinophilic nucleoli, accompanied by a background of eosinophils, plasma cells, and reactive T-cells. Immunophenotyping shows CD15+ CD30+ CD45– EBV-LMP1+. Which of the following chromosomal or molecular findings is most characteristically associated with this entity?
52. Flow cytometry of a bone marrow sample from a 70-year-old man with fatigue shows a clonal B-cell population expressing CD19+, CD5+, CD23+, CD20 (dim), CD38 (negative), with surface IgM (dim) and CD10 (negative). ZAP-70 is positive and IGHV genes are unmutated. What is the prognostic implication of unmutated IGHV status in this disease?
53. A 62-year-old man with newly diagnosed multiple myeloma has cytogenetics showing t(4;14)(p16.3;q32). Which of the following correctly identifies the oncogenic mechanism and risk category of this translocation?
54. A lymph node biopsy from a 25-year-old shows a diffuse pattern of large blastoid cells with a 'starry sky' appearance, extremely high mitotic rate (Ki-67 ~100%), and immunophenotype: CD20+, CD10+, BCL6+, BCL2 negative, TdT negative, surface IgM+. FISH confirms t(8;14)(q24;q32). Which epigenetic and transcriptional mechanism downstream of c-MYC overexpression is most directly responsible for the near-100% proliferation index?
55. A 52-year-old man with a prior follicular lymphoma now presents with rapidly growing lymphadenopathy, LDH of 1,800 U/L and B symptoms. New biopsy shows diffuse large B-cell lymphoma morphology. FISH reveals concurrent rearrangements of MYC and BCL2. What is the WHO 5th edition (2022) classification of this entity, and how does it alter clinical management compared to conventional DLBCL?
56. A 65-year-old man with chronic lymphocytic leukaemia (CLL) is found to have del(17p13) on FISH. This deletion targets TP53 and predicts all of the following EXCEPT:
57. On bone marrow biopsy, a patient with multiple myeloma shows plasma cells that are CD38+/CD138+/CD56+/CD19-/CD45-. CD56 expression in myeloma plasma cells (absent on normal plasma cells) is clinically significant because it:
58. The 2022 WHO classification of haematolymphoid tumours introduced 'large B-cell lymphoma with IRF4 rearrangement' as a distinct entity. Which of the following best characterises this entity?
59. Anaplastic large cell lymphoma (ALCL) ALK-positive shows the t(2;5)(p23;q35) translocation creating NPM1-ALK fusion. The ALK fusion protein drives lymphomagenesis primarily through constitutive activation of which signalling pathway?
60. A 32-year-old man presents with rapidly enlarging cervical lymphadenopathy, B symptoms and serum LDH 3x upper limit of normal. Biopsy shows large B-cells with prominent nucleoli and a 'starry-sky' pattern. FISH confirms MYC rearrangement at 8q24, BCL2 rearrangement at 18q21, and BCL6 rearrangement at 3q27. What is the WHO 2022 classification of this lymphoma?
61. Bone marrow biopsy of a patient with chronic myeloid leukemia shows 22% blasts and dysplastic features in two lineages. The BCR-ABL1 ratio (IS) is 35%. According to the WHO 2022 classification, how is this phase best classified?
62. A 68-year-old man with plasma cell myeloma undergoes cytogenetic workup. FISH shows del(17p13.1) with loss of TP53 and translocation t(4;14)(p16;q32). Which prognostic risk group does this combination confer per the Revised International Staging System (R-ISS)?
63. A lymph node biopsy shows effacement of architecture by large cells with prominent nucleoli, brisk mitoses and a high Ki-67 (~90%). IHC: CD10+, BCL6+, BCL2 strong, MUM1 negative, CD5 negative. Which cell-of-origin subtype (Hans classifier) does this immunophenotype represent and what is its prognostic significance?
64. A 55-year-old woman is found to have clonal plasma cells comprising 8% of bone marrow cellularity, serum M-protein of 2.8 g/dL (IgG kappa), and free light chain (FLC) ratio of 120 (kappa/lambda). There is no anemia, hypercalcemia, renal failure, or lytic bone lesions. Which is the most accurate diagnosis and next management step?
65. A 45-year-old woman presents with splenomegaly, eosinophilia, and WBC 80,000/μL with 15% myeloblasts. FISH reveals FIP1L1-PDGFRA fusion. Which statement about this condition and its management is MOST accurate?
66. In WHO 2022 classification, Large B-cell lymphoma with IRF4 rearrangement was introduced as a distinct provisional entity. Which clinical and histological features distinguish it from diffuse large B-cell lymphoma (DLBCL), NOS?
67. A 68-year-old man with IgG kappa myeloma undergoes bone marrow biopsy after initial treatment. Cytogenetics reveal del(17p13). Which downstream molecular pathway is primarily disrupted by this deletion, and how does this influence prognosis?
68. Hairy cell leukemia (HCL) has a near-universal somatic mutation in BRAF V600E. Which statement about the role of this mutation in HCL biology and therapy is MOST accurate?
69. A bone marrow trephine biopsy from a patient with suspected myeloproliferative neoplasm shows hypercellularity with prominent megakaryocytic proliferation, clustering of pleomorphic megakaryocytes with cloud-like nuclei, and no increase in reticulin fibrosis. JAK2 V617F is detected. Which diagnosis does WHO 5th edition 2022 support?
70. A 35-year-old woman presents with mediastinal mass, B-symptoms, and peripheral blood lymphocytosis. Biopsy shows large lacunar cells within a fibrous background with a Reed-Sternberg cell variant expressing CD15+, CD30+, CD20+ (weak), and PAX5+ (weak), with negative CD45. The WHO 5th edition (2022) classification most accurately designates this as:
71. In chronic myeloid leukemia (CML), the BCR-ABL1 p210 fusion protein drives leukemogenesis primarily by constitutive activation of which downstream pathway that confers growth factor independence?
72. A 70-year-old man with multiple myeloma undergoes bone marrow biopsy. FISH shows t(4;14)(p16;q32) involving FGFR3 and MMSET (NSD2). This translocation is associated with which prognostic and treatment-relevant feature?
73. A 50-year-old man with CLL on ibrutinib develops progressive lymphocytosis with rapid lymphadenopathy. Biopsy of the lymph node shows sheets of large centroblast-like cells with high Ki-67 (>80%), strong CD20, and MYC rearrangement. This complication is known as:
74. In acute promyelocytic leukemia (APL), the PML-RARA fusion protein causes leukemic block at the promyelocyte stage. The molecular mechanism by which ATRA (all-trans retinoic acid) restores differentiation is:
75. A 70-year-old man has progressive cytopenias, splenomegaly, and peripheral blood showing 'hairy' lymphocytes with flow cytometry positive for CD11c, CD25, CD103, and CD123. The BRAF V600E mutation is detected. What is the treatment of choice for this condition?
76. The 2022 WHO classification of lymphoid tumors now recognizes a new entity — 'large B-cell lymphoma with IRF4 rearrangement.' This lymphoma characteristically presents in which clinical setting?
77. A patient with multiple myeloma undergoes bone marrow biopsy. FISH shows t(4;14)(p16;q32) translocation involving MMSET/FGFR3. Compared to standard-risk myeloma, this translocation confers what prognostic significance and therapeutic implication?
78. A lymph node biopsy from a 35-year-old shows Reed-Sternberg cells in a background of lymphocytes, plasma cells, eosinophils, and fibrosis in a nodular pattern. Immunohistochemistry: RS cells are CD15+, CD30+, CD45-, PAX5 weakly positive. Which subtype of classical Hodgkin lymphoma is this, and what is the relevant EBV association?
79. A pediatric patient has mediastinal mass, lymphadenopathy, and peripheral blood shows lymphoblasts. Flow cytometry: TdT+, CD19+, CD10+, CD34+. Cytogenetics reveals a hyperdiploid karyotype (>50 chromosomes). What is the prognostic significance of this karyotype in B-ALL?
80. A 65-year-old man presents with lytic bone lesions, serum M-spike of 4.2 g/dL (IgG kappa), and plasma cells comprising 30% of the bone marrow. Cytogenetics reveals t(4;14) translocation. Which molecular target is activated by this translocation, and what is its therapeutic relevance?
81. A 38-year-old woman presents with fever, night sweats, and a mediastinal mass. Biopsy shows large cells with bilobed nuclei, prominent 'owl eye' nucleoli, and a background of T-lymphocytes, plasma cells, and eosinophils. Flow cytometry shows CD30+, CD15+, CD20-, PAX5 dim positive. Which translocation/molecular alteration is most characteristically found in the neoplastic cells?
82. A 70-year-old male with CLL develops rapid lymph node enlargement, B symptoms, and elevated LDH. Biopsy reveals transformation to diffuse large B-cell lymphoma. This transformation carries a particularly poor prognosis. The risk of this complication is highest in CLL cases with which molecular feature?
83. In the WHO 2022 classification of myeloid neoplasms, which entity has been newly recognized as a distinct AML subtype defined by mutations in NPM1, and what is its biological significance?
84. A 25-year-old presents with lymphadenopathy and a biopsy showing a centroblastic tumor with a germinal-center immunophenotype (CD10+, BCL-6+, MUM1-). The Ki-67 is 95%, and fluorescence in situ hybridization (FISH) shows rearrangements of MYC and BCL-2. Which diagnosis is correct and what is the clinical implication?
85. A 35-year-old man presents with fever, lymphadenopathy, and a mediastinal mass. Biopsy shows cells with immunophenotype CD2+, CD3+, CD4+, CD8−, CD1a+, TdT+. The diagnosis is:
86. In multiple myeloma, the presence of t(4;14) translocation is associated with upregulation of which oncogene, conferring a poor prognosis?
87. Hairy cell leukemia is characterized by a somatic point mutation in which gene, found in virtually 100% of cases?
88. Primary mediastinal (thymic) large B-cell lymphoma shares molecular features with which Hodgkin lymphoma subtype, including constitutive JAK-STAT activation?
89. In CLL, deletion of 17p13 (TP53 loss) is clinically important because it predicts:
90. A 30-year-old man presents with painless cervical lymphadenopathy and mediastinal widening. Biopsy shows large lacunar cells with multilobated nuclei in a background of eosinophils, plasma cells, and fibrosis dividing the lymph node into nodules. Which subtype of Hodgkin lymphoma does this represent?
91. A 68-year-old man presents with bone pain, anemia, renal failure, and a serum protein spike. Bone marrow biopsy shows 40% plasma cells. Serum immunofixation reveals IgG kappa paraprotein. Which feature, if present, would MOST reliably distinguish symptomatic multiple myeloma requiring treatment from smoldering myeloma?
92. A 55-year-old woman presents with splenomegaly and a white cell count of 120,000/µL with predominance of mature lymphocytes. Flow cytometry shows CD5+, CD19+, CD23+, CD20 (dim), surface IgM (dim), FMC7 negative. What is the MOST likely diagnosis?
93. A child presents with ALL. Cytogenetics show hyperdiploidy (>50 chromosomes). What is the prognostic implication and mechanism of improved drug response in hyperdiploid ALL?
94. A 70-year-old man with AML shows t(15;17) on cytogenetics and responds dramatically to all-trans retinoic acid (ATRA). Why does ATRA work specifically in this subtype?
95. A 35-year-old woman presents with mediastinal mass, fever, night sweats, and cervical lymphadenopathy. Biopsy shows large cells with bilobed nuclei, prominent owl-eye nucleoli, and a mixed inflammatory background. Immunohistochemistry shows CD15+, CD30+, CD45−, PAX5 dim+. The Reed-Sternberg cell in this disorder is thought to be derived from which cell lineage?
96. In Burkitt lymphoma, the characteristic t(8;14) translocation places the MYC oncogene under the control of which enhancer element?
97. A 72-year-old man is found to have serum M-protein 3.8 g/dL (IgG kappa), bone marrow plasma cells 22%, lytic skull lesions, and calcium 11.6 mg/dL. The hypercalcemia in multiple myeloma is primarily driven by osteoclast activation mediated by which paracrine factor secreted by myeloma cells and their microenvironment?
98. Which of the following lymphomas is MOST characteristically associated with angioimmunoblastic T-cell lymphoma (AITL)?
99. Hairy cell leukaemia is characterised by which highly specific molecular marker used in targeted therapy?
100. A bone marrow biopsy from a 65-year-old man with unexplained anemia shows increased plasma cells (>60%) with a monotypic kappa light chain. His serum protein electrophoresis reveals an M-spike in the gamma region. Serum free light chain ratio is markedly abnormal. According to IMWG 2014 criteria, which single finding alone qualifies as a 'myeloma-defining event' without end-organ damage?
101. Burkitt lymphoma is characterised by translocation t(8;14). The oncogene translocated to the IGH locus on chromosome 14 is:
102. A 35-year-old man presents with mediastinal mass, B-symptoms, and biopsy showing large lacunar cells in a collagen-rich stroma. Immunohistochemistry shows CD15+, CD30+, CD45−, CD20−. Which subtype of Hodgkin lymphoma does this represent?
103. Hairy cell leukemia is characterised by which specific molecular mutation that is also the target of vemurafenib?
104. On peripheral blood smear of a patient with CML, which finding would indicate blast crisis rather than chronic phase?
105. A 55-year-old man presents with fever, cervical lymphadenopathy, and night sweats. Biopsy shows large binucleate cells with prominent eosinophilic 'owl-eye' nucleoli on a background of plasma cells, eosinophils, and lymphocytes. The neoplastic cells are CD15+, CD30+, CD45−, and EBV-LMP1+. This morphological subtype of Hodgkin lymphoma most likely carries which WHO classification?
106. A 30-year-old HIV-positive man develops a rapidly enlarging jaw mass. Biopsy shows a 'starry sky' pattern with intermediate-sized lymphocytes showing high mitotic rate and Ki-67 near 100%. Cytogenetics reveals t(8;14). The oncogene dysregulated by this translocation is:
107. A 70-year-old woman with multiple myeloma develops bony pain and lytic lesions. The primary cytokine responsible for osteoclast activation in myeloma bone disease is:
108. A 60-year-old man is found to have an IgM paraprotein of 2 g/dL with 15% lymphoplasmacytic cells in bone marrow but no lytic lesions, anaemia, or hyperviscosity symptoms. Serum viscosity is normal. This condition is best classified as:
109. Hairy cell leukaemia is characterised by which of the following pathological features on bone marrow biopsy?
110. A 35-year-old woman presents with cervical lymphadenopathy. Biopsy shows nodular sclerosis Hodgkin lymphoma. The Reed-Sternberg (RS) cell variant most characteristic of this subtype is:
111. A 70-year-old man has smouldering multiple myeloma. His serum free light chain ratio (involved/uninvolved) is 110. According to IMWG 2014 criteria, this alone defines progression to:
112. Mantle cell lymphoma characteristically overexpresses cyclin D1 due to a translocation involving chromosomes 11 and 14. The breakpoints involve which specific genes?
113. A 25-year-old man with ALL has a Philadelphia chromosome. Compared with CML, the BCR-ABL1 fusion in Ph+ ALL most commonly produces a protein of:
114. On peripheral smear of a patient with hairy cell leukemia, which cytochemical stain is positive and not inhibited by tartrate?
115. A 65-year-old man presents with fatigue, bone pain, serum calcium 11.8 mg/dL, creatinine 2.4 mg/dL, and a monoclonal IgG spike on serum protein electrophoresis. Bone marrow biopsy shows 35% plasma cells. The M-protein is most likely produced as a result of:
116. The Philadelphia chromosome t(9;22)(q34;q11) in CML generates the BCR-ABL1 fusion oncogene. The mechanism by which BCR-ABL1 drives leukemogenesis is:
117. On peripheral smear of a patient with CLL, the characteristic finding that results from mechanical fragility of leukemic lymphocytes during smear preparation is:
118. Burkitt lymphoma characteristically shows a translocation involving MYC oncogene. The most common translocation is t(8;14), which juxtaposes MYC with:
119. A 35-year-old woman has enlarged cervical lymph nodes. Biopsy shows nodular sclerosis with lacunar cells and a background of eosinophils, plasma cells, and lymphocytes. The tumor cells stain CD15+, CD30+, CD45−. What is the diagnosis?
120. A 65-year-old man has fatigue, bone pain, serum calcium 11.8 mg/dL, creatinine 2.4 mg/dL, and a monoclonal IgG spike on SPEP. Bone marrow biopsy shows 35% plasma cells. Osteolytic lesions are mediated primarily by which mechanism?
121. The Philadelphia chromosome t(9;22)(q34;q11) in CML generates BCR-ABL1. The mechanism by which BCR-ABL1 drives leukemogenesis is:
122. On peripheral smear of a patient with CLL, smudge (basket) cells are seen. These result from:
123. Burkitt lymphoma t(8;14) juxtaposes MYC with the immunoglobulin heavy chain locus, causing constitutive MYC overexpression. Which feature on biopsy is most characteristic of Burkitt lymphoma?
124. A 35-year-old woman has enlarged cervical lymph nodes. Biopsy shows nodular sclerosis with lacunar cells, eosinophils, plasma cells, and lymphocytes. Tumor cells are CD15+, CD30+, CD45−. Which additional marker confirms the B-cell lineage of the Reed-Sternberg cell?
125. A 35-year-old presents with fatigue, splenomegaly, and a WBC of 120,000/µL with predominantly mature granulocytes. Philadelphia chromosome is detected. The BCR-ABL fusion protein in CML constitutively activates which kinase?
126. A lymph node biopsy from a 28-year-old with mediastinal mass shows large cells with bilobed nuclei, prominent eosinophilic 'owl-eye' nucleoli, and a background of lymphocytes, eosinophils, and plasma cells. CD15 and CD30 are positive; CD45 is negative. Which subtype of Hodgkin lymphoma is most likely?
127. A 70-year-old presents with bone pain, serum calcium 11.8 mg/dL, creatinine 2.4 mg/dL, and a monoclonal protein of 4.2 g/dL on SPEP. Bone marrow shows 35% plasma cells. The lytic bone lesions in multiple myeloma are primarily caused by:
128. A 55-year-old presents with painless cervical lymphadenopathy and night sweats. Biopsy shows a follicular architecture with small cleaved lymphocytes; BCL2 protein is overexpressed. The chromosomal translocation responsible places BCL2 under control of which promoter?
129. In T-cell acute lymphoblastic leukemia/lymphoma (T-ALL), the most commonly mutated signalling pathway drives transcription of target genes via intracellular domain cleavage. This pathway involves which protein?
130. A 65-year-old presents with splenomegaly, anemia, tear-drop-shaped RBCs, and a dry tap on bone marrow aspiration. Core biopsy shows extensive reticulin fibrosis. The JAK2 V617F mutation is positive. The diagnosis is:
131. Burkitt lymphoma has a characteristic chromosomal translocation that results in MYC oncogene overexpression. The translocation juxtaposes MYC with:
132. A 70-year-old man presents with absolute lymphocytosis of 60,000/µL of small mature-appearing lymphocytes. He is asymptomatic. Flow cytometry shows CD19+, CD5+, CD23+, CD10- with weak surface IgM. This phenotype is diagnostic of:
133. A 55-year-old woman presents with fatigue and lymphadenopathy. Bone marrow biopsy shows 70% lymphocytes with a proliferation center pattern. Flow cytometry: CD19+, CD5+, CD23+, ZAP-70+. Cytogenetics show del(17p). This cytogenetic finding in CLL is associated with:
134. A 65-year-old man with CLL develops sudden worsening of lymphadenopathy, high fever, elevated LDH, and markedly elevated Ki-67 index on biopsy showing large transformed B cells. This transformation is called:
135. Which chromosomal translocation is characteristically associated with mantle cell lymphoma, and what genes are involved?
136. A 55-year-old woman with multiple myeloma is found to have deletion of chromosome 17p on FISH. This deletion most likely involves which gene and confers what prognostic significance?
137. Classic Reed-Sternberg cells in nodular sclerosis Hodgkin lymphoma are derived from which lineage as confirmed by immunophenotyping?
138. In acute promyelocytic leukemia (APL), the fusion protein PML-RARα causes leukemogenesis primarily by:
139. A 35-year-old patient is found to have Philadelphia chromosome t(9;22). The resulting BCR-ABL1 fusion protein has constitutively active kinase activity. In chronic phase CML, which cell lineage is predominantly expanded?
140. A 70-year-old man has monoclonal IgG kappa in serum, 8% plasma cells in bone marrow, serum M-protein 2.8 g/dL, no end-organ damage (CRAB criteria absent). This is best classified as:
141. Reed-Sternberg cells in classical Hodgkin lymphoma typically express which combination of markers, distinguishing them from non-Hodgkin lymphoma cells?
142. A 25-year-old presents with jaw swelling, and biopsy shows a 'starry sky' pattern with monotonous intermediate-sized lymphoid cells, frequent mitoses, and a Ki-67 of nearly 100%. The translocation most likely involves:
143. In multiple myeloma, hypercalcemia is primarily mediated through which mechanism?
144. A 65-year-old man has lymphocytosis of 80 × 10⁹/L with mature-appearing lymphocytes. Flow cytometry shows CD5+, CD23+, CD19+, dim surface IgM, and CD20 dim. Which genetic abnormality is most commonly associated with a favorable prognosis in this condition?
145. Reed-Sternberg cells in classical Hodgkin lymphoma characteristically express which combination of markers?
146. A 70-year-old man has lytic bone lesions, serum M-protein of 4 g/dL, and bone marrow showing 30% plasma cells. He develops acute kidney injury. The most important mechanism of renal injury in multiple myeloma is:
147. Which translocation in follicular lymphoma leads to overexpression of BCL2, preventing apoptosis of germinal center B cells?
148. A patient with AML shows t(15;17) on karyotyping. The PML-RARα fusion protein in APL causes disease primarily by:
149. A 35-year-old man presents with painless cervical lymphadenopathy. Biopsy shows a nodular pattern with centrocytes and centroblasts, CD10+, CD20+, BCL2+, BCL6+. The cytogenetic finding most expected is:
150. A 70-year-old man with multiple myeloma has urinary Bence-Jones protein. The principal mechanism of 'myeloma kidney' (cast nephropathy) is:
151. Flow cytometry shows CD5+, CD20+(dim), CD23+, CD10−, cyclin D1−, surface IgM dim. This immunophenotype is most consistent with:
152. A 28-year-old HIV-negative man has a rapidly enlarging jaw mass. Biopsy shows a 'starry sky' pattern with uniform medium-sized lymphocytes, ~100% Ki-67, and t(8;14). What is the molecular consequence of this translocation?
153. A 65-year-old man has fatigue, splenomegaly, WBC 130,000/µL with the full myeloid series, basophilia, and BCR-ABL1 fusion without JAK2 mutation. The pathophysiological consequence of BCR-ABL tyrosine kinase is:
154. Reed-Sternberg cells are CD15+, CD30+, CD45−, and B-cell marker-negative despite having clonal Ig gene rearrangements. Their loss of B-cell markers is best explained by:
155. A 65-year-old woman is found to have an IgM paraprotein of 3.2 g/dL, bone marrow showing >10% lymphoplasmacytic cells, and splenomegaly. She does NOT have lytic bone lesions. What is the most likely diagnosis?
156. A 4-year-old boy presents with pallor, bone pain, and lymphadenopathy. CBC shows WBC 80,000/μL with lymphoblasts. Immunophenotyping reveals TdT+, CD10+, CD19+, CD34+. Cytogenetics shows t(12;21) translocation. Which statement about this translocation is MOST accurate?
157. Histology of a lymph node biopsy shows a bimodal pattern with scattered large lacunar cells (RS variants) in a background of nodular sclerosis with collagen bands and mixed cellularity. CD15+, CD30+, CD45−. What distinguishes this Hodgkin lymphoma subtype histologically?
158. A 55-year-old man presents with anemia, bone pain, and a monoclonal IgG kappa spike of 5 g/dL. Bone marrow shows 35% plasma cells. Serum calcium is 11.8 mg/dL. The mechanism of osteolytic lesions in multiple myeloma primarily involves:
159. A 25-year-old woman has mediastinal lymphadenopathy, eosinophilia, and a lymph node biopsy showing large binucleated cells with prominent 'owl-eye' nucleoli in a background of lymphocytes, eosinophils, and plasma cells. The cell of origin of these large cells is:
160. In chronic myeloid leukemia (CML), the BCR-ABL1 fusion protein on the Philadelphia chromosome results from which translocation, and its primary oncogenic mechanism is:
161. A 70-year-old man has renal failure, hypercalcemia, and lytic bone lesions. Serum protein electrophoresis shows an M-spike in the gamma region. Which mechanism accounts for bone destruction in multiple myeloma?
162. Hairy cell leukemia is characterised by which specific mutation that also serves as a therapeutic target?
163. A bone marrow biopsy in a patient with ALL shows positive staining for TdT (terminal deoxynucleotidyl transferase). What does TdT positivity indicate?
164. A 35-year-old woman has cervical lymphadenopathy. Biopsy shows Reed-Sternberg cells in a background of numerous eosinophils, plasma cells, and lymphocytes, with bands of collagenous fibrosis dividing the lymph node into nodules. Which subtype of Hodgkin lymphoma does this represent?
165. A 70-year-old man presents with fatigue, recurrent infections, and lymphocytosis of 80 × 10⁹/L. Peripheral blood shows small, mature-appearing lymphocytes with frequent smudge (basket) cells. Flow cytometry shows CD5+, CD19+, CD20(dim)+, CD23+. The cytogenetic finding that confers the BEST prognosis in this disease is:
166. In multiple myeloma, the characteristic monoclonal immunoglobulin spike on serum protein electrophoresis (SPEP) is called the M-spike. Which immunoglobulin class is most commonly overproduced?
167. A 25-year-old presents with mediastinal mass, fever, night sweats, and weight loss. LDH is elevated. Biopsy shows large cells with vesicular nuclei and prominent nucleoli in a 'starry sky' pattern with numerous tingible-body macrophages. Cells are BCL-2-negative and show near-100% Ki-67 proliferation index. The translocation most likely responsible is:
168. A 68-year-old man has bone pain, serum calcium 12.5 mg/dL, creatinine 2.8 mg/dL, Hb 9 g/dL, and rouleaux formation on peripheral smear. Bone marrow biopsy shows 45% plasma cells. Skeletal survey shows multiple 'punched-out' lytic lesions. The mechanism responsible for hypercalcemia in this condition is primarily:
169. A 55-year-old man has leukocytosis of 120 × 10⁹/L with the full myeloid spectrum (blasts 3%, myelocytes, metamyelocytes, bands, neutrophils), basophilia, eosinophilia, and splenomegaly. BCR-ABL1 fusion gene is confirmed. The mechanism by which the BCR-ABL1 oncoprotein causes CML is:
170. A 75-year-old man has anemia, fatigue, and recurrent infections. Bone marrow shows hypercellular marrow with dysplastic changes in all three cell lines: hypogranular neutrophils with pseudo-Pelger-Huet anomaly, ringed sideroblasts (>15%), and megakaryocytes with hypolobated nuclei. Blasts are 4%. Cytogenetics shows deletion 5q. The diagnosis is:
171. A 35-year-old woman with B-cell lymphoma has tumor cells demonstrating t(14;18) translocation. This translocation juxtaposes the BCL2 gene next to immunoglobulin heavy chain locus, resulting in overexpression of BCL2. What is the primary anti-apoptotic mechanism of BCL2 protein?
172. A 70-year-old man with multiple myeloma has bone pain, serum M-protein of 4.2 g/dL, and lytic lesions on X-ray. The pathological fractures result from osteoclast activation; which cytokine produced by myeloma cells is most responsible for this osteoclast activation?
173. Reed-Sternberg (RS) cells in classic Hodgkin lymphoma are derived from germinal center B cells but have lost B-cell identity. Which transcription factor, normally critical for B-cell identity, is silenced in RS cells through epigenetic mechanisms, contributing to their aberrant phenotype?
174. A 55-year-old man with CML on imatinib therapy develops resistance. Bone marrow biopsy shows BCR-ABL kinase domain mutation T315I ('gatekeeper mutation'). Why does T315I confer resistance to both first and second generation TKIs but responds to ponatinib?
175. A 65-year-old man has an absolute lymphocyte count of 28,000/µL with small mature-appearing lymphocytes on smear. Flow cytometry shows CD5+, CD19+, CD23+, CD20 (dim), and surface immunoglobulin (dim). The most likely diagnosis is:
176. Reed-Sternberg cells in classical Hodgkin lymphoma characteristically express which immunohistochemical markers?
177. In multiple myeloma, the lytic bone lesions are caused primarily by:
178. A 30-year-old presents with a jaw mass, elevated LDH, and rapidly enlarging abdominal lymph nodes. Biopsy shows intermediate-sized lymphocytes with multiple small nucleoli, numerous mitoses, and a 'starry sky' pattern. The translocation most likely driving this lymphoma is:
179. The BCR-ABL1 fusion in chronic myeloid leukemia results from t(9;22). The constitutively active tyrosine kinase produced preferentially phosphorylates substrates that activate which downstream pathway responsible for leukemic proliferation?
180. A 35-year-old woman presents with fever, lymphadenopathy, and night sweats. Biopsy shows large lacunar cells in a collagen-banded background with inflammatory cells. Which cytogenetic finding is most characteristic of this condition?
181. A 68-year-old man with multiple myeloma on bortezomib therapy develops painful, burning paresthesias in his hands and feet. The pathophysiological mechanism of this drug-related complication involves:
182. In chronic myeloid leukemia (CML), the BCR-ABL1 fusion protein of the p210 isoform constitutively activates which downstream signaling pathway primarily responsible for anti-apoptotic survival?
183. Which of the following immunohistochemical profiles is most consistent with Burkitt lymphoma?
184. A 55-year-old man with plasma cell myeloma has a serum free light chain ratio of 110 (kappa/lambda). Which of the following CRAB criteria does he still need to establish before diagnosing symptomatic myeloma if no other features are present?
185. Burkitt lymphoma demonstrates t(8;14) translocation. The molecular consequence of juxtaposing MYC to the immunoglobulin heavy chain locus is:
186. A 70-year-old man has serum protein electrophoresis showing an M-spike at 4.2 g/dL (IgG kappa). Bone marrow biopsy reveals 35% plasma cells. He has lytic skull lesions and serum calcium of 11.8 mg/dL. Which cytokine produced by myeloma plasma cells most directly mediates osteoclast activation and lytic bone disease?
187. Anaplastic large cell lymphoma (ALCL) expressing nuclear ALK protein with a paranuclear dot pattern carries the translocation:
188. Hairy cell leukemia (HCL) is distinguished from other B-cell leukemias by expression of CD25 and annexin A1, as well as a pathognomonic mutation in:
189. A 65-year-old woman has recurrent infections, peripheral blood showing 40,000 mature-appearing small lymphocytes, and positive Coombs test with hemolytic anemia. Flow cytometry shows CD5+, CD19+, CD23+, CD10- surface immunoglobulin dim. The most likely diagnosis is chronic lymphocytic leukemia (CLL). Which genetic abnormality in CLL is associated with the worst prognosis?
190. A 68-year-old man with slowly progressive lymphocytosis, lymphadenopathy, and splenomegaly has a WBC of 85 × 10⁹/L with mature-looking small lymphocytes. Flow cytometry shows CD5+, CD19+, CD23+, CD20 dim+, and surface Ig dim+. The cytogenetic finding associated with the BEST prognosis in CLL is:
191. Plasma cell myeloma with t(4;14) translocation juxtaposes FGFR3 (and MMSET/NSD2) to the IgH locus. Which histological variant of myeloma is characterised by flame-red cytoplasmic inclusions representing IgA paraprotein?