HEMATOPATHOLOGY MCQS 2

Question 1

A 16-year-old boy has had recurrent nosebleeds and easy bruising since childhood. His older brother has the same problem. PT is normal. PTT is prolonged. Factor VIII activity is 2%. Most likely diagnosis?

Accepted Answer

Hemophilia A — Prolonged PTT + normal PT + severely reduced factor VIII + X-linked family history = hemophilia A. Factor VIII deficiency affects the intrinsic pathway, prolonging PTT but not PT.

Question 2

A 25-year-old woman has heavy menstrual bleeding since menarche and prolonged bleeding after a dental extraction. Her mother has similar problems. PT normal. PTT mildly prolonged. Ristocetin cofactor activity is reduced. Most likely diagnosis?

Accepted Answer

Von Willebrand disease — Mucosal bleeding + autosomal dominant family history + mildly prolonged PTT + reduced ristocetin cofactor = von Willebrand disease. VWF is required for platelet adhesion and carries factor VIII, explaining the mild PTT prolongation.

Question 3

A 9-year-old boy develops painful swelling of his right knee after minor trauma. His maternal uncle has a similar condition. PT normal. PTT prolonged. Factor IX activity is 3%. Most likely diagnosis?

Accepted Answer

Hemophilia B — Hemarthrosis after minor trauma + X-linked inheritance + prolonged PTT + severely reduced factor IX = hemophilia B (Christmas disease). Clinically identical to hemophilia A but caused by factor IX deficiency.

Question 4

A 35-year-old woman develops massive pulmonary emboli and DVT postpartum. Her mother died of a stroke at age 40. Protein C activity is 15%. Most likely diagnosis?

Accepted Answer

Protein C deficiency — Unprovoked thrombosis at young age + strong family history of early thrombotic death + severely reduced protein C = protein C deficiency. Protein C inactivates factors Va and VIIIa; deficiency leads to hypercoagulability.

Question 5

A 42-year-old man develops DVT during a long-haul flight. APC resistance ratio is very low. PCR confirms a point mutation in the factor V gene at position 506. Most likely diagnosis?

Accepted Answer

Factor V Leiden mutation — APC resistance + factor V gene mutation at position 506 = Factor V Leiden, the most common inherited thrombophilia. Mutant factor Va cannot be inactivated by activated protein C, maintaining a persistent procoagulant state.

Question 6

A 55-year-old man with metastatic prostate cancer develops oozing from IV sites, petechiae, and gum bleeding. PT prolonged, PTT prolonged, platelets 28,000, fibrinogen 80 mg/dL, D-dimer markedly elevated. Most likely diagnosis?

Accepted Answer

Disseminated intravascular coagulation — Metastatic cancer + prolonged PT and PTT + low platelets + low fibrinogen + elevated D-dimer = DIC. Unlike TTP, DIC involves the entire coagulation system with consumption of all clotting factors and platelets simultaneously.

Question 7

A 68-year-old man develops bleeding from multiple sites 3 days after a snake bite. PT 45 sec, PTT 80 sec, fibrinogen 60 mg/dL, platelets 40,000, schistocytes on smear, D-dimer markedly elevated. Most likely pathologic mechanism?

Accepted Answer

Consumption of clotting factors and platelets — Snake venom triggers systemic coagulation activation → consumption of all clotting factors and platelets → DIC. All coagulation tests are prolonged, fibrinogen is depleted, platelets are consumed, and schistocytes form from microangiopathy.

Question 8

A 30-year-old woman has recurrent DVTs and two unexplained miscarriages. DRVVT ratio is 1.8 and is not corrected by mixing with normal plasma. Anticardiolipin antibody titer is elevated on two occasions 12 weeks apart. Most likely diagnosis?

Accepted Answer

Antiphospholipid syndrome — Recurrent thrombosis + recurrent pregnancy loss + persistently elevated anticardiolipin antibody + positive lupus anticoagulant = antiphospholipid syndrome. Paradoxically causes thrombosis despite prolonging clotting tests in vitro.

Question 9

A 70-year-old man has fatigue, recurrent sinopulmonary infections, serum IgM of 42 g/L, and massive splenomegaly. Peripheral blood shows lymphoplasmacytoid cells. He develops blurred vision and headaches. Most likely diagnosis?

Accepted Answer

Waldenström macroglobulinemia — Markedly elevated IgM + lymphoplasmacytoid cells + massive splenomegaly + hyperviscosity symptoms (blurred vision, headaches) = Waldenström macroglobulinemia. Unlike myeloma it produces IgM and rarely causes lytic bone lesions.

Question 10

A 65-year-old man is found incidentally to have a small monoclonal IgG spike of 1.8 g/dL on serum electrophoresis. Bone marrow shows 4% plasma cells. No bone lesions, no renal failure, no anemia, no hypercalcemia. Most likely diagnosis?

Accepted Answer

Monoclonal gammopathy of undetermined significance — Small monoclonal spike + less than 10% marrow plasma cells + no CRAB features = MGUS. Progresses to myeloma at about 1% per year. Most common plasma cell dyscrasia, usually found incidentally.

Question 11

A 58-year-old man has fatigue and normocytic anemia. Bone marrow shows erythroblasts with iron-laden mitochondria forming a ring around the nucleus on Prussian blue stain. Serum iron and ferritin are elevated. Most likely diagnosis?

Accepted Answer

Sideroblastic anemia — Ringed sideroblasts on Prussian blue stain + elevated iron stores = sideroblastic anemia. Iron is acquired normally but cannot be incorporated into heme due to mitochondrial dysfunction. Can be hereditary or acquired from alcohol, lead, drugs, or myelodysplasia.

Question 12

A 65-year-old man has fatigue, macrocytic anemia, and 18% myeloblasts on bone marrow biopsy with dysplastic changes in all cell lines but no Auer rods. CBC shows pancytopenia. Most likely diagnosis?

Accepted Answer

Myelodysplastic syndrome — Dysplasia in all cell lines + increased but less than 20% blasts + pancytopenia = myelodysplastic syndrome. MDS is a clonal stem cell disorder that frequently progresses to AML. Blasts above 20% would qualify as AML.

Question 13

A 72-year-old man has progressive fatigue over 2 years. Bone marrow biopsy shows hypercellularity with dysplastic megakaryocytes, erythroid hyperplasia, and 6% blasts. Cytogenetics shows deletion of chromosome 5q. Most likely prognosis?

Accepted Answer

Good — 5q deletion is associated with favorable prognosis in MDS — Isolated 5q deletion in MDS (5q- syndrome) is associated with a favorable prognosis, macrocytic anemia, low blast count, and good response to lenalidomide. It is one of the best prognostic cytogenetic findings in MDS.

Question 14

A 45-year-old woman has fatigue and easy bruising. CBC shows hemoglobin 9 g/dL, WBC 2800, neutrophils 800, platelets 42,000. Bone marrow biopsy shows hypercellularity with dysplastic neutrophils having hyposegmented nuclei (pseudo-Pelger-Huët cells) and cytoplasmic hypogranularity. Most likely diagnosis?

Accepted Answer

Myelodysplastic syndrome — Pancytopenia + pseudo-Pelger-Huët cells + hypogranular neutrophils + dysplastic hypercellular marrow = myelodysplastic syndrome. Dysplasia affects maturation quality while the marrow remains cellular, distinguishing it from aplastic anemia.

Question 15

A 55-year-old man has had absolute neutrophil count of 900 for the past 6 months. He has had three episodes of bacterial pneumonia. He is otherwise healthy with no medications, no autoimmune disease, and no family history. Bone marrow is normocellular. Most likely explanation?

Accepted Answer

Chronic idiopathic neutropenia — Persistent mild to moderate neutropenia in an otherwise healthy adult + normal bone marrow + no identifiable cause = chronic idiopathic neutropenia. Unlike cyclic neutropenia (periodic drops) or drug-induced agranulocytosis (acute, severe), this is a stable benign condition.

Question 16

A 28-year-old woman develops sudden severe neutropenia (ANC 100) and fever 2 weeks after starting carbimazole for hyperthyroidism. She has no lymphadenopathy or organomegaly. Bone marrow shows absence of mature myeloid cells with preserved erythroid and megakaryocytic lineages. Most likely diagnosis?

Accepted Answer

Drug-induced agranulocytosis — Sudden severe neutropenia after starting a drug (carbimazole) + selective absence of mature myeloid cells in marrow + preserved other lineages = drug-induced agranulocytosis. Carbimazole, clozapine, and methimazole are classic culprits.

Question 17

A 6-year-old girl develops neutropenia every 21 days lasting 3–5 days, accompanied by fever, mouth ulcers, and lymphadenopathy. Between episodes she is completely well with a normal ANC. Most likely diagnosis?

Accepted Answer

Cyclic neutropenia — Predictable periodic neutropenia every 21 days + recurrent mouth ulcers and infections during nadirs + complete recovery between episodes = cyclic neutropenia. Caused by mutations in the ELANE gene encoding neutrophil elastase, with autosomal dominant inheritance.

Question 18

A 40-year-old man has a peripheral blood eosinophil count of 4500/microliter persisting for 6 months. He has no parasitic infection, no allergic disease, and no drug exposure. Bone marrow shows eosinophilic hyperplasia. FISH reveals FIP1L1-PDGFRA fusion gene. Most likely diagnosis?

Accepted Answer

Eosinophilic leukemia with PDGFRA rearrangement — Persistent marked eosinophilia + FIP1L1-PDGFRA fusion gene = eosinophilic leukemia. This is a clonal myeloid neoplasm driven by a tyrosine kinase fusion. Unlike reactive eosinophilia, it has a primary clonal driver and responds to imatinib.

Question 19

A 35-year-old man with no prior history develops peripheral blood basophilia with basophils of 1800/microliter. He has splenomegaly. CBC shows WBC 95,000 with the full myeloid spectrum present. LAP score is very low. Most likely underlying condition causing the basophilia?

Accepted Answer

Chronic myelogenous leukemia — Basophilia + very high WBC with full myeloid spectrum + low LAP score + splenomegaly = chronic myelogenous leukemia. Basophilia is a characteristic feature of CML driven by the BCR-ABL oncogene. It is not seen in leukemoid reactions.

Question 20

A 52-year-old woman has fatigue, pruritus after hot showers, headaches, and facial plethora. Hgb is 18.5 g/dL, Hct 58%, WBC 14,000, platelets 520,000. Serum erythropoietin is very low. JAK2 V617F mutation is detected. Most likely diagnosis?

Accepted Answer

Polycythemia vera — Elevated RBC mass + elevated WBC and platelets (panmyelosis) + very low EPO + JAK2 V617F mutation + aquagenic pruritus = polycythemia vera. Low EPO distinguishes it from secondary polycythemia where EPO is elevated.

Question 21

A 60-year-old woman has had headaches and visual disturbances for 3 months. Platelet count is 1,200,000/microliter. WBC and hemoglobin are normal. Bone marrow shows megakaryocytic hyperplasia with large clustered megakaryocytes. JAK2 mutation is present. Most likely diagnosis?

Accepted Answer

Essential thrombocythemia — Markedly elevated platelets + normal WBC and Hgb + megakaryocytic hyperplasia + JAK2 mutation + thrombotic symptoms = essential thrombocythemia. Reactive thrombocytosis does not cause symptoms and JAK2 is negative.

Question 22

A 50-year-old man has a fever of 38.5°C and a painful right anterior cervical lymph node for 5 days. The node is 2 cm, tender, and soft. He had a sore throat 2 weeks ago. WBC is 14,000 with 85% neutrophils and 10% bands. Most likely diagnosis?

Accepted Answer

Reactive lymphadenopathy — Tender soft lymph node + recent pharyngitis + fever + neutrophilia with left shift = reactive lymphadenopathy from bacterial infection. Malignant lymphadenopathy is typically firm, non-tender, and not associated with leukocytosis.

Question 23

A 35-year-old woman has a 3 cm firm non-tender left axillary lymph node. Biopsy shows follicular hyperplasia with prominent germinal centers, polyclonal B and T cells, plasma cells, and macrophages. No Reed-Sternberg cells. No monoclonal population on flow cytometry. Most likely diagnosis?

Accepted Answer

Reactive follicular hyperplasia — Prominent germinal centers + polyclonal mixed population + no monoclonal cells = reactive follicular hyperplasia. Unlike follicular lymphoma (monoclonal, crowded nodules, BCL2+), reactive hyperplasia has a mixed polyclonal population with preserved architecture.

Question 24

A 60-year-old man has had abdominal pain and early satiety for 8 months. He has a history of Helicobacter pylori gastritis. Endoscopy shows a gastric mucosal mass. Biopsy shows a low-grade B-cell lymphoma composed of small lymphocytes infiltrating the mucosa. Most likely diagnosis?

Accepted Answer

Marginal zone lymphoma (MALT lymphoma) — H. pylori gastritis + low-grade B-cell mucosal lymphoma = gastric MALT lymphoma (marginal zone lymphoma). H. pylori antigen chronically stimulates mucosal B cells leading to clonal proliferation. Early cases may regress with H. pylori eradication.

Question 25

A 50-year-old man has generalized lymphadenopathy and splenomegaly. Lymph node biopsy shows a diffuse proliferation of medium-sized lymphocytes co-expressing CD5, CD20, and cyclin D1. Cytogenetics shows t(11;14). Most likely diagnosis?

Accepted Answer

Mantle cell lymphoma — CD5+ CD20+ cyclin D1+ + t(11;14) (overexpression of cyclin D1 from juxtaposition with IgH gene) = mantle cell lymphoma. More aggressive than CLL despite similar immunophenotype; cyclin D1 and t(11;14) are the distinguishing features.

Question 26

A 45-year-old man has had weight loss, night sweats, and generalized lymphadenopathy for 4 months. Lymph node biopsy shows a diffuse proliferation of large B cells with prominent nucleoli and abundant cytoplasm. Ki-67 proliferation index is 85%. Most likely diagnosis?

Accepted Answer

Diffuse large B-cell lymphoma — Large B cells with prominent nucleoli + high Ki-67 (85%) + aggressive clinical course = diffuse large B-cell lymphoma. The most common aggressive non-Hodgkin lymphoma in adults. High proliferation index reflects its aggressive behavior.

Question 27

A 14-year-old boy has a rapidly enlarging jaw mass over 3 weeks. Biopsy shows a starry sky pattern with monotonous medium-sized B cells and a Ki-67 of nearly 100%. Cytogenetics shows t(8;14). EBV is detected. Most likely diagnosis?

Accepted Answer

Burkitt lymphoma — Jaw mass + starry sky pattern + Ki-67 nearly 100% + t(8;14) (c-myc/IgH) + EBV + African child = endemic Burkitt lymphoma. One of the fastest growing human tumors. The starry sky pattern results from macrophages engulfing apoptotic tumor cells.

Question 28

A 45-year-old woman has had a 6-month history of recurrent fever, night sweats, and weight loss. She has cervical and mediastinal lymphadenopathy. Lymph node biopsy shows a nodular pattern with broad bands of collagen and scattered lacunar cells that are CD15+ and CD30+. Most likely subtype of Hodgkin lymphoma?

Accepted Answer

Nodular sclerosis — Collagen bands + lacunar cells (RS cell variant) + mediastinal involvement in a young woman = nodular sclerosis Hodgkin lymphoma. The most common subtype, most often presenting in young women with mediastinal disease.

Question 29

A 35-year-old man has posterior cervical lymphadenopathy. Biopsy shows numerous lymphocytes and histiocytes (popcorn cells) with a nodular background. Reed-Sternberg cells are rare. Popcorn cells are CD20+ and CD45+ but CD15- and CD30-. Most likely subtype?

Accepted Answer

Lymphocyte predominance Hodgkin lymphoma — Popcorn cells (lymphocytic and histiocytic cells) + CD20+ CD45+ CD15- CD30- = lymphocyte predominance Hodgkin lymphoma. Distinct from classical Hodgkin lymphoma in immunophenotype. Generally has the best prognosis of all subtypes.

Question 30

A 60-year-old man has generalized lymphadenopathy and hepatosplenomegaly. Biopsy shows numerous Reed-Sternberg cells and variants in a background of eosinophils, plasma cells, and lymphocytes with no fibrosis. EBV is detected in most RS cells. Most likely subtype?

Accepted Answer

Mixed cellularity Hodgkin lymphoma — Numerous RS cells + eosinophils + plasma cells + no fibrosis + EBV association + older male = mixed cellularity Hodgkin lymphoma. Second most common subtype, more common in older males and strongly associated with EBV.

Question 31

A 55-year-old woman develops increasing fatigue and pallor. CBC shows hemoglobin 8 g/dL, MCV 78, WBC 6500, platelets 180,000. Serum iron is low, TIBC is high, ferritin is low. She has no dietary history suggesting deficiency. Colonoscopy reveals a 3 cm adenocarcinoma of the ascending colon. Most likely mechanism of her anemia?

Accepted Answer

Chronic blood loss causing iron deficiency — Microcytic hypochromic anemia + low iron + high TIBC + low ferritin in a middle-aged woman with a right-sided colon cancer = iron deficiency from chronic occult blood loss. Right colon cancers classically present this way with iron deficiency anemia rather than change in bowel habits.

Question 32

A 68-year-old man receives a blood transfusion. Within minutes he develops fever, rigors, back pain, hypotension, and hemoglobinuria. Direct Coombs test on post-transfusion sample is positive. Most likely type of transfusion reaction?

Accepted Answer

Acute hemolytic transfusion reaction — Immediate fever + back pain + hypotension + hemoglobinuria + positive Coombs = acute hemolytic transfusion reaction. Most often caused by ABO incompatibility from clerical error. Complement-mediated intravascular hemolysis is rapidly life-threatening.

Question 33

A 45-year-old woman receives a blood transfusion and develops sudden onset severe dyspnea and hypoxia within 2 hours. CXR shows bilateral pulmonary infiltrates. She is afebrile and not fluid overloaded. Her CVP is low. Most likely transfusion reaction?

Accepted Answer

Transfusion-related acute lung injury — Sudden dyspnea + bilateral infiltrates + within 6 hours of transfusion + not fluid overloaded + low CVP = TRALI (transfusion-related acute lung injury). Caused by donor antibodies against recipient neutrophils, activating them in pulmonary capillaries causing non-cardiogenic pulmonary edema.

Question 34

A 72-year-old man with heart failure receives two units of packed red cells. During the second unit he develops dyspnea, hypertension, and an elevated JVP. CXR shows pulmonary edema. Most likely transfusion complication?

Accepted Answer

Transfusion-associated circulatory overload — Dyspnea + hypertension + elevated JVP + pulmonary edema in a patient with heart failure after transfusion = TACO (transfusion-associated circulatory overload). Unlike TRALI, TACO is cardiogenic and patients have elevated filling pressures. Treated with diuretics.

Question 35

A 30-year-old woman with selective IgA deficiency receives a blood transfusion and immediately develops urticaria, angioedema, bronchospasm, and hypotension. Her temperature is normal. Most likely transfusion reaction?

Accepted Answer

Anaphylactic transfusion reaction — IgA deficiency + anti-IgA antibodies + immediate allergic reaction with urticaria, bronchospasm, hypotension = anaphylactic transfusion reaction. IgA-deficient patients form anti-IgA antibodies and react severely when exposed to IgA in transfused blood products.

Question 36

A 45-year-old man receives a blood transfusion and develops a low-grade fever and mild chills during the infusion. No hemoglobinuria, no hypotension, no dyspnea. Direct Coombs test is negative. Most likely transfusion reaction?

Accepted Answer

Febrile non-hemolytic transfusion reaction — Mild fever and chills during transfusion + no hemolysis + negative Coombs = febrile non-hemolytic transfusion reaction. Caused by recipient antibodies against donor leukocyte antigens or cytokines in stored blood. The most common transfusion reaction. Managed by slowing or stopping transfusion and giving antipyretics.

Question 37

A 25-year-old man receives a blood transfusion during surgery. Ten days later he develops jaundice, a falling hemoglobin, and a newly positive direct Coombs test. He had no immediate reaction during the transfusion. Most likely explanation?

Accepted Answer

Delayed hemolytic transfusion reaction — Jaundice + falling hemoglobin + positive Coombs appearing 5–10 days after transfusion = delayed hemolytic transfusion reaction. Caused by an anamnestic antibody response to donor RBC antigens (commonly Kidd, Duffy, or Kell) from prior sensitization.

Question 38

A 50-year-old immunocompromised man receives non-irradiated blood products after bone marrow transplantation. Two weeks later he develops an extensive skin rash, profuse diarrhea, rising liver enzymes, and severe pancytopenia. Most likely diagnosis?

Accepted Answer

Graft-versus-host disease from transfusion — Immunocompromised patient + non-irradiated blood + skin rash + diarrhea + liver dysfunction + pancytopenia = transfusion-associated graft-versus-host disease. Donor lymphocytes engraft and attack host tissues. Prevented by irradiating blood products for immunocompromised recipients.

Question 39

A 62-year-old man with CLL receives a blood transfusion. Two weeks later he has fever, a maculopapular rash over the trunk, watery diarrhea, and his CBC shows pancytopenia. Skin biopsy shows lymphocytic infiltration with epidermal apoptosis. Most likely complication?

Accepted Answer

Transfusion-associated graft-versus-host disease — CLL (immunocompromised) + non-irradiated transfusion + rash + diarrhea + pancytopenia + epidermal apoptosis on biopsy = transfusion-associated GVHD. Unlike bone marrow GVHD, this is almost universally fatal with no effective treatment. Prevention by irradiation is critical.

Question 40

A 55-year-old man is found to have absolute neutrophilia with WBC 22,000 and 88% neutrophils including bands, metamyelocytes, and myelocytes on peripheral smear. LAP score is markedly elevated. He has a fever of 39°C and a productive cough. Sputum grows Klebsiella pneumoniae. No splenomegaly. Most likely explanation for his WBC?

Accepted Answer

Leukemoid reaction — Marked neutrophilia with left shift + markedly elevated LAP score + no splenomegaly + active bacterial infection = leukemoid reaction. Unlike CML (low LAP, splenomegaly, basophilia, t(9;22)), a leukemoid reaction has a high LAP score and a clear infectious or inflammatory cause.

HEMATOPATHOLOGY MCQS 2

Questions, Answers & Explanations