Hematopathology MCQS

Question 1

A 62-year-old man has 3 months of dull back pain and develops a productive cough. CXR of the spine shows several 1–2 cm lytic vertebral lesions. Labs show BUN 49, creatinine 5, total protein 8.3, albumin 3.7. Sputum grows Streptococcus pneumoniae. Most likely bone marrow biopsy finding?

Accepted Answer

Numerous plasma cells — Lytic bone lesions + renal failure + high total protein + recurrent encapsulated bacterial infections = multiple myeloma. Bone marrow shows sheets of plasma cells producing the abnormal immunoglobulin.

Question 2

A 33-year-old woman has 2 months of low-grade fever, night sweats, and malaise. She has non-tender cervical and supraclavicular lymphadenopathy. Lymph node biopsy shows CD15+ and CD30+ Reed-Sternberg cells, large and small lymphocytes, and bands of fibrosis. Most likely diagnosis?

Accepted Answer

Hodgkin lymphoma — Reed-Sternberg cells (CD15+, CD30+) + fibrosis bands + cervical/supraclavicular nodes = Hodgkin lymphoma, nodular sclerosis type. Two lymph node groups on one side = stage II with good prognosis.

Question 3

A 17-year-old has 3 weeks of malaise, mild pharyngitis, tender axillary and inguinal lymphadenopathy, and a palpable spleen. CBC shows atypical lymphocytes on smear. Most likely acquisition mechanism?

Accepted Answer

From close contact on a date — Atypical lymphocytes + pharyngitis + generalized lymphadenopathy + splenomegaly in a teenager = infectious mononucleosis (EBV). Acquired through saliva via close personal contact — the 'kissing disease.'

Question 4

A 30-year-old woman has mild chronic fatigue. Exam shows a palpable spleen tip. CBC: Hgb 11.1, MCV 77, reticulocyte count 3.9%. Peripheral smear shows small RBCs lacking central pallor. Most likely pattern of inheritance?

Accepted Answer

Autosomal dominant, European ancestry — Small RBCs lacking central pallor (spherocytes) + mild chronic hemolytic anemia + splenomegaly = hereditary spherocytosis. Most common inherited hemolytic anemia in northern Europeans, autosomal dominant, from ankyrin or spectrin defects.

Question 5

A 3-year-old child has pinpoint hemorrhages on skin appearing over 3 days. CBC: Hgb 14.3, MCV 90, platelet count 19,300, WBC 9370. It resolves over a month without treatment. Most likely antecedent event?

Accepted Answer

Respiratory syncytial virus infection — Acute isolated thrombocytopenia in a child that resolves spontaneously = immune thrombocytopenic purpura (ITP). Usually preceded by a viral infection that triggers an immune response targeting platelets.

Question 6

A 30-year-old man has 5 days of sore throat and fever. Exam shows mildly tender cervical lymphadenopathy and enlarged erythematous tonsils with exudate. WBC 12,670 with 75 segs, 10 bands, 15 lymphs. Most likely diagnosis?

Accepted Answer

Group A Streptococcus infection — Exudative pharyngitis + tender cervical lymphadenopathy + leukocytosis with left shift = bacterial infection. Group A Streptococcus is the most common bacterial cause of exudative pharyngitis with reactive lymphadenopathy.

Question 7

A 30-year-old man has a month of worsening productive cough. Exam shows a palpable spleen tip and small axillary lymph nodes. CBC: WBC 67,000, Hgb 10.2, platelets 36,000. Peripheral smear shows many blasts with Auer rods. Most likely diagnosis?

Accepted Answer

Acute myelogenous leukemia — High WBC + blasts with Auer rods in a young adult = acute myelogenous leukemia (AML). Auer rods are formed from cytoplasmic granules of myeloid blasts and are pathognomonic for AML.

Question 8

A 68-year-old man has a year of malaise. CBC: Hgb 10.5, MCV 88, platelet count 211,000, WBC 6980. Total iron 130, TIBC 230, soluble serum transferrin receptor normal. Bone marrow shows normal maturation in all cell lines with increased stainable iron. Most likely underlying disease?

Accepted Answer

Hepatitis C infection — Normocytic anemia + high/normal iron saturation + increased iron stores + normal soluble transferrin receptor = anemia of chronic disease. Hepatitis C is a chronic disease that drives elevated hepcidin, blocking iron release from stores.

Question 9

A 69-year-old man has had firm, non-tender, movable right posterior cervical lymph nodes for 5 months. No hepatosplenomegaly. CBC is near normal. Lymph node biopsy shows numerous crowded nodules of small, monomorphic lymphocytes. Most likely diagnosis?

Accepted Answer

Follicular lymphoma — Non-tender lymphadenopathy in an adult + crowded nodules of small monomorphic lymphocytes = follicular lymphoma. Indolent but difficult to eradicate; a small percentage transform into diffuse large B-cell lymphoma.

Question 10

A 45-year-old man has 2 years of increasing abdominal discomfort. Exam shows massive splenomegaly (estimated 3000g on CT). CBC: Hgb 9, WBC 5000, platelets 50,000. Most likely underlying condition?

Accepted Answer

Myelofibrosis — Massive splenomegaly + pancytopenia = myelofibrosis. As marrow hematopoiesis is replaced by fibrosis, extramedullary hematopoiesis develops in the spleen, causing massive enlargement.

Question 11

A 72-year-old man has increasing fatigue for a year. CBC: Hgb 9.1, MCV 96, WBC 3700, platelets 125,000. WBC differential shows 2 metamyelocytes, 1 myelocyte, and 5 nucleated RBCs/100 WBCs. Direct and indirect Coombs tests are negative. Most likely disease?

Accepted Answer

Metastatic carcinoma — Immature WBCs (metamyelocytes, myelocytes) + nucleated RBCs in peripheral blood = leukoerythroblastic picture from myelophthisic process. Metastatic carcinoma invading marrow displaces normal hematopoiesis, releasing immature cells into blood.

Question 12

A 40-year-old woman has a week of fever and mental confusion. Exam: T 38.2, BP 100/60. Widespread petechiae. Labs: BUN 52, creatinine 5.3, Hgb 12.2, platelets 19,000, WBC 8180. Schistocytes on smear. PT, PTT, and D-dimer are not elevated. Most likely diagnosis?

Accepted Answer

Thrombotic thrombocytopenic purpura — Fever + mental changes + renal failure + thrombocytopenia + microangiopathic hemolytic anemia (schistocytes) + normal coagulation = classic pentad of TTP. Platelet activation forms hyaline thrombi in small arteries causing organ ischemia.

Question 13

A 62-year-old man has 4 months of fatigue, abdominal discomfort, non-tender cervical lymphadenopathy, hepatomegaly, and splenomegaly. CBC: WBC 23,100 with 78% lymphs, Hgb 11.9, platelets 277,300. Direct Coombs test is positive. Most likely diagnosis?

Accepted Answer

Chronic lymphocytic leukemia — Marked lymphocytosis (78%) + hepatosplenomegaly + lymphadenopathy + positive Coombs (autoimmune hemolysis) in an older adult = chronic lymphocytic leukemia (CLL). Most circulating cells are small mature lymphocytes.

Question 14

A 16-year-old boy has had low energy his entire life. Exam shows a palpable spleen tip. CBC: Hgb 8.8, MCV 65, platelets 187,000, WBC 7400. Serum ferritin is 3740 ng/mL. Bone marrow shows myeloid:erythroid ratio of 1:4 and 4+ stainable iron. Most likely diagnosis?

Accepted Answer

Beta-thalassemia — Lifelong microcytic anemia + massively elevated ferritin + increased stainable bone marrow iron + erythroid hyperplasia (1:4 ratio) = beta-thalassemia. Reduced beta-globin leads to ineffective erythropoiesis and excessive iron absorption.

Question 15

An 83-year-old woman undergoes open reduction of a radial fracture and receives heparin prophylaxis. One week later platelets drop from 209,000 to 101,000. She suddenly cannot move her right arm. Most likely cause?

Accepted Answer

Drug-induced thrombocytopenia — Platelet drop 5–14 days after heparin + thrombotic stroke (not bleeding) = heparin-induced thrombocytopenia (HIT). Antibodies to platelet factor 4-heparin complex cause paradoxical thrombosis — the 'white clot' syndrome.

Question 16

A 48-year-old man has 6 months of malaise and difficulty concentrating. Exam shows splenomegaly, no lymphadenopathy. CBC: WBC 190,000 with metamyelocytes, myelocytes, myeloblasts, and basophils; Hgb 12, platelets 390,000. LAP score is very low. Most likely bone marrow finding?

Accepted Answer

Numerous mature and immature myeloid cells — Very high WBC with full myeloid spectrum + basophilia + low LAP score + splenomegaly = chronic myelogenous leukemia (CML). Driven by t(9;22) BCR-ABL fusion. Bone marrow shows hypercellularity with all stages of myeloid maturation.

Question 17

A 29-year-old woman has sudden fever, abdominal pain, tachycardia, and icteric conjunctivae. CBC: Hgb 9.0, MCV 99, platelets 209,500, WBC 6840. Reticulocyte count is 0.1%. Peripheral smear shows small RBCs lacking central pallor. Most likely initiating event?

Accepted Answer

Parvovirus infection — Hereditary spherocytosis (small RBCs lacking central pallor) + sudden drop in reticulocytes to near zero = aplastic crisis. Parvovirus B19 infects and destroys erythroid precursors, halting RBC production in patients with hemolytic anemias.

Question 18

A 55-year-old man has 3 months of fatigue, fever, and epistaxis. CBC: WBC 52,000, Hgb 12.5, platelets 170,000. Peripheral smear shows large blasts with Auer rods. Most likely preceding risk factor?

Accepted Answer

Myelodysplasia — Blasts with Auer rods = AML. Myelodysplastic syndromes are a well-established precursor to AML development, as are myeloproliferative disorders, PNH, and prior chemotherapy. Myelodysplasia is the most classic preceding risk factor.

Question 19

A 42-year-old woman has a month of easy bruising from minor bumps. Exam shows purpura on arms and legs. Labs: PT 12.9 sec, PTT 26.2 sec (both normal). CBC: Hgb 11.1, MCV 84, platelets 790,000, WBC 45,400. Bone marrow shows hypercellularity with myeloid and megakaryocytic hyperplasia. Most likely diagnosis?

Accepted Answer

Myeloproliferative disorder — Markedly elevated platelets + elevated WBC + hypercellular marrow with myeloid and megakaryocytic hyperplasia + bleeding despite high platelet count = myeloproliferative disorder. Platelets are functionally abnormal despite being numerous.

Question 20

A 20-year-old woman has worsening fatigue for a year. Mucous membranes are pale. No hepatosplenomegaly. CBC: Hgb 7.1, MCV 67, platelets 190,000, WBC 5400. No drug history. Most likely etiology?

Accepted Answer

Iron deficiency — Isolated microcytic anemia (low MCV) in a young woman of reproductive age with no other findings = iron deficiency anemia. The most common cause of anemia worldwide, and women of reproductive age are at highest risk from menstrual losses.

Question 21

A 25-year-old man takes anti-malarial prophylaxis for a trip to West Africa. Over the next week he develops fatigue. Hematocrit is 30%. Peripheral smear shows RBCs with numerous Heinz bodies. Males in his family are similarly affected. Most likely diagnosis?

Accepted Answer

G6PD deficiency — Hemolytic anemia triggered by anti-malarials + Heinz bodies (denatured hemoglobin) + X-linked family history (males affected) = G6PD deficiency. Loss of NADPH protection against oxidative stress leads to hemoglobin denaturation and hemolysis.

Question 22

A study estimates spleen sizes from CT scans in patients with hematologic disease complications. For which disease is the spleen most likely to remain normal in size?

Accepted Answer

Immune thrombocytopenic purpura — In ITP, circulating antibodies destroy platelets but the spleen itself is usually not enlarged. Contrast with autoimmune hemolytic anemia (splenomegaly from RBC sequestration) and myeloproliferative disorders (extramedullary hematopoiesis).

Question 23

A 51-year-old man has 10 months of increasing fatigue. No abnormal findings on exam. CBC: Hgb 9.2, MCV 132, platelets 242,000, WBC 7590. Most likely morphologic finding on peripheral smear?

Accepted Answer

Hypersegmented neutrophils — MCV 132 (markedly elevated) = macrocytic megaloblastic anemia from B12 or folate deficiency. Impaired DNA synthesis delays nuclear maturation, resulting in hypersegmented neutrophils (5+ lobes) and macro-ovalocytes.

Question 24

A 72-year-old man has 8 months of fatigue. No abnormal findings. CBC: Hgb 10.4, MCV 72, platelets 239,000, WBC 7500. Total bilirubin 1.0. Most likely morphologic finding on peripheral smear?

Accepted Answer

Hypochromasia — Low MCV + low hemoglobin in an older man = most likely iron deficiency anemia. Peripheral smear shows hypochromic, microcytic RBCs with increased central pallor — the hallmark of reduced hemoglobin content per cell.

Question 25

A 19-year-old primigravida of Southeast Asian ancestry delivers at 35 weeks. The infant is markedly hydropic with hematocrit 17%. Peripheral smear shows numerous nucleated RBCs and marked anisocytosis and poikilocytosis. Most likely disease?

Accepted Answer

Alpha-thalassemia — Hydrops fetalis + severe anemia + Southeast Asian ancestry = alpha-thalassemia (Hb Bart's disease). All 4 alpha globin genes are deleted; fetal hemoglobin cannot be made. The Southeast Asian type has both bad genes on the same chromosome, allowing homozygous inheritance.

Question 26

A 46-year-old man has a year of worsening arthritis and foot swelling. Exam shows rales in all lung fields. CXR shows cardiomegaly and pulmonary edema. Labs: serum iron 406, iron binding capacity 440, ferritin 830. CBC is near normal. Most likely diagnosis?

Accepted Answer

Beta-thalassemia — Massively elevated iron studies + arthritis + cardiomyopathy with pulmonary edema = hereditary hemochromatosis. Iron accumulates in heart, joints, liver, pancreas, skin, and gonads from increased intestinal absorption.

Question 27

A 52-year-old man has a month of fever and cough. Upper lobe cavitary lesions on CXR. Sputum positive for acid fast bacilli. CBC: WBC 44,500 with 59 segs, 20 bands, 8 metas, 4 myelos, 2 promyelos. Most likely additional lab finding?

Accepted Answer

High leukocyte alkaline phosphatase — Very high WBC with left shift in response to TB infection = leukemoid reaction. Unlike CML (which has low LAP), a leukemoid reaction has a HIGH leukocyte alkaline phosphatase score — a key distinguishing feature.

Question 28

A 5-year-old boy has 2 months of increasing lethargy and ecchymoses on his lower legs. CBC: Hgb 9.2, MCV 91, platelets 101,000, WBC 12,128. Bone marrow shows nearly 100% cellularity with primitive cells having large nuclei, delicate chromatin, and scanty cytoplasm. Which additional finding is most likely?

Accepted Answer

Elevated free erythrocyte protoporphyrin — Microcytic anemia + basophilic stippling + low haptoglobin (mild hemolysis) + cognitive decline in a child = lead poisoning. Lead inhibits heme synthesis, elevating zinc protoporphyrin and free erythrocyte protoporphyrin. Basophilic stippling indicates toxic RBC injury.

Question 29

A 2-year-old boy has a month of seborrheic eruption over the scalp and trunk, then develops right ear pain. Exam shows hepatosplenomegaly and generalized lymphadenopathy. CBC: Hgb 9.5, platelets 58,000, WBC 3540. Bone marrow shows 100% cellularity with CD1a+ macrophage-like cells with Birbeck granules on electron microscopy. Most likely condition?

Accepted Answer

Langerhans cell histiocytosis — Disseminated disease in a young child + CD1a+ cells + Birbeck granules (HX bodies) on electron microscopy = Langerhans cell histiocytosis (Letterer-Siwe disease). The disseminated form in young children is the most aggressive variant.

Question 30

A 73-year-old woman has 7 months of fatigue, 3 kg weight loss, and hands that turn purple and painful in the cold. Exam shows a palpable spleen tip. CBC: Hgb 10.5, MCV 99, platelets 193,600, WBC 5390. Direct Coombs test is positive at 4°C and negative at 37°C. Most likely underlying disease?

Accepted Answer

Non-Hodgkin lymphoma — Cold-induced color change + positive Coombs at 4°C (cold agglutinins) + splenomegaly = cold autoimmune hemolytic anemia. In an elderly patient with weight loss, underlying non-Hodgkin lymphoma must be excluded as the driving cause.

Question 31

A 12-year-old girl has sudden severe abdominal and back pain. No masses on exam. CBC: Hgb 6.5, MCV 99, platelets 149,000, WBC 11,200. Peripheral smear shows nucleated RBCs and sickled RBCs. Most likely type of gene mutation?

Accepted Answer

Missense — Sickle cell anemia is caused by a single missense mutation — a change in one base pair resulting in valine substituting for glutamic acid in the beta-globin chain. The beta-globin chain is still produced but structurally abnormal.

Question 32

A 32-year-old man has 2 months of worsening headaches. No lymphadenopathy or organomegaly. CBC: Hgb 12, platelets 250,000, WBC 6000 with 80% granulocytes and 10% lymphocytes. Head CT shows a 3 cm mass next to the right lateral ventricle. Biopsy shows diffuse large B-cell lymphoma. Most likely lab finding?

Accepted Answer

HIV-1 RNA of 80,000 copies/mL — Primary CNS diffuse large B-cell lymphoma in a 32-year-old with relative lymphopenia = AIDS-related lymphoma. HIV infection is the most important risk factor. HIV-1 RNA viral load would be detectable, reflecting underlying HIV infection driving the lymphoma.

Question 33

A 28-year-old woman has 2 months of worsening fatigue and an erythematous macular rash on her chest, forearms, and face. CBC: Hgb 9.2, MCV 101, platelets 179,000, reticulocyte count 4.2%. Serum haptoglobin 3 mg/dL. Total bilirubin 3.3, direct bilirubin 0.8. Hemoglobinuria on urinalysis. Most likely underlying condition?

Accepted Answer

Systemic lupus erythematosus — Malar-distribution rash + hemolytic anemia (low haptoglobin, elevated indirect bilirubin, hemoglobinuria, high reticulocyte count) + polychromasia = warm autoimmune hemolytic anemia complicating SLE. Intravascular hemolysis explains the hemoglobinuria.

Question 34

A 37-year-old HIV-positive man has 3 days of abdominal pain, distension, and absent bowel sounds. CT shows a mass in the small intestine. Surgery removes a 10 cm firm white near-encircling mass infiltrating through the bowel wall. Most likely neoplasm?

Accepted Answer

High-grade B-cell lymphoma — HIV infection + extranodal GI lymphoma infiltrating bowel = high-grade B-cell lymphoma. AIDS-related lymphomas are typically high grade, extranodal, and diagnostic of AIDS. Burkitt and diffuse large B-cell are the most common types.

Question 35

A 20-year-old healthy man undergoes splenectomy after blunt abdominal trauma causes a splenic hematoma. Following splenectomy, which peripheral blood morphologic finding is most likely to appear?

Accepted Answer

RBC inclusions — After splenectomy, the spleen can no longer remove RBC inclusions such as Howell-Jolly bodies (nuclear remnants) and Pappenheimer bodies (iron granules). These inclusions appear in circulating RBCs because the filtering function of the spleen is lost.

Question 36

A 10-year-old girl has 8 months of increasing facial distortion from a right mandibular mass. Biopsy shows a monotonous pattern of small non-cleaved lymphocytes. Cytogenetics shows t(8;14). Infection with which organism is most likely associated?

Accepted Answer

Epstein-Barr virus — Jaw mass + monotonous small non-cleaved lymphocytes + t(8;14) (c-myc translocation) in an African child = endemic Burkitt lymphoma. EBV infection after malaria exposure gives African children selective pressure driving this B-cell lymphoma. Starry sky appearance on histology.

Question 37

Two teenage sisters have frequent nosebleeds, easy bruising, and menorrhagia since menarche. No family history. CBC: Hgb 14, MCV 90, platelets 242,000, WBC 7720. PT 12 sec, PTT 25 sec (both normal). Platelet aggregation studies show decreased aggregation to ADP, collagen, epinephrine, and thrombin. Most likely disorder?

Accepted Answer

Glanzmann thrombasthenia — Normal platelet count + normal PT and PTT + severely impaired platelet aggregation to all agonists = Glanzmann thrombasthenia. Autosomal recessive deficiency of glycoprotein IIb/IIIa prevents platelet aggregation. No family history is typical of autosomal recessive disorders.

Question 38

A 44-year-old man has chronic fatigue for a year. No abnormal findings on exam. CBC: Hgb 10.8, MCV 105, platelets 239,000, WBC 7720. Peripheral smear shows mild poikilocytosis and a few target cells. Serum B12 and methylmalonic acid are normal. Haptoglobin is normal. Direct and indirect Coombs tests are negative. Most likely underlying condition?

Accepted Answer

Chronic alcohol abuse — Mild macrocytosis (MCV 105) + target cells + normal B12 + no hemolysis = chronic alcohol abuse. Alcohol causes direct RBC membrane abnormalities (target cells), macrocytosis, and can impair folate metabolism. MCV above 105 more likely indicates megaloblastic anemia.

Question 39

A 42-year-old man has multiple episodes of painful red skin nodules from dermal venous thrombosis and abdominal pain from mesenteric vein thrombosis over the past year. He passes darker urine. CBC: Hgb 9.4, MCV 100, platelets 215,000, WBC 8800. RBCs show increased sensitivity to complement lysis. Flow cytometry shows reduced CD55 on RBCs. Most likely condition?

Accepted Answer

Paroxysmal nocturnal hemoglobinuria — Venous thrombosis in unusual sites + dark urine (hemoglobinuria) + increased complement sensitivity + reduced CD55 (and CD59) on RBCs = paroxysmal nocturnal hemoglobinuria (PNH). PIGA gene mutation renders RBCs sensitive to complement lysis.

Hematopathology MCQS

Questions, Answers & Explanations