Hematopathology — MCQs
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Which of the following causes aplastic crisis in hereditary spherocytosis?
A 45-year-old woman comes to the physician because of a 1-week history of fatigue and bruises on her elbows. Examination shows a soft, nontender abdomen with no organomegaly. Laboratory studies show a hemoglobin concentration of 7 g/dL, a leukocyte count of 2,000/mm3, a platelet count of 40,000/mm3, and a reticulocyte count of 0.2%. Serum electrolyte concentrations are within normal limits. A bone marrow biopsy is most likely to show which of the following findings?
A 3-year-old boy is brought to the physician because of a 4-week history of generalized fatigue and malaise. He was born at term and has been healthy since. His mother has a history of recurrent anemia. He appears pale. His temperature is 37°C (98.6°F) and pulse is 97/min. Examination shows pale conjunctivae and jaundice. The abdomen is soft and nontender; the spleen is palpated 3–4 cm below the left costal margin. Laboratory studies show: Hemoglobin 9.3 g/dL Mean corpuscular volume 81.3 μm3 Mean corpuscular hemoglobin concentration 39% Hb/cell Leukocyte count 7300/mm3 Platelet count 200,000/mm3 Red cell distribution width 19% (N = 13–15) Which of the following is most likely to confirm the diagnosis?
A lymph node biopsy shows 'tennis racket' appearance of follicles. Which immunohistochemical finding would confirm progressive transformation of germinal centers?
A peripheral blood smear shows erythrocytes with 'cross-hatched' membrane appearance. Which additional finding would confirm hereditary xerocytosis?
A bone marrow biopsy in a patient with suspected myelofibrosis shows atypical megakaryocyte proliferation. Which additional finding would confirm the diagnosis?
A blood smear shows RBCs with fragmented, bizarre shapes and microspherocytes. Which additional finding would confirm hereditary pyropoikilocytosis?
A lymph node biopsy shows 'onion skin' pattern of lymphoid cells. Which immunophenotype would confirm Castleman disease?
A peripheral blood smear shows 'figure-8' shaped RBCs. Which additional finding would confirm Southeast Asian ovalocytosis?
A cervical lymph node biopsy shows 'starry sky' pattern. Which immunophenotype would best support Burkitt lymphoma?
Hematopathology Indian Medical PG Practice Questions and MCQs
Question 1281: Which of the following causes aplastic crisis in hereditary spherocytosis?
- A. Poxvirus
- B. Parvovirus (Correct Answer)
- C. Adenovirus
- D. Epstein-Barr virus
Explanation: ***Parvovirus*** - **Parvovirus B19** specifically targets and destroys **erythroid precursors** in the bone marrow, leading to a temporary cessation of red blood cell production [1]. - In patients with conditions like **hereditary spherocytosis** who already have chronic hemolysis and increased erythropoiesis, this interruption can cause a sudden and severe drop in hemoglobin, known as an **aplastic crisis** [1]. *Poxvirus* - Poxviruses primarily cause **skin lesions** and systemic symptoms like fever and malaise, with diseases such as smallpox or molluscum contagiosum. - They are not known to directly cause **aplastic crisis** by targeting erythroid progenitors. *Adenovirus* - Adenoviruses commonly cause **respiratory tract infections**, gastroenteritis, and conjunctivitis. - While they can cause various symptoms, they are not typically associated with **aplastic crisis** in the context of hereditary spherocytosis. *Epstein-Barr virus* - **Epstein-Barr virus (EBV)** is known to cause **infectious mononucleosis** and is associated with certain lymphomas and nasopharyngeal carcinoma. - Although it can rarely cause **hemophagocytic lymphohistiocytosis** leading to pancytopenia, it does not typically induce **aplastic crisis** in hereditary spherocytosis by directly targeting erythroid precursors. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Red Blood Cell and Bleeding Disorders, pp. 641-642.
Question 1282: A 45-year-old woman comes to the physician because of a 1-week history of fatigue and bruises on her elbows. Examination shows a soft, nontender abdomen with no organomegaly. Laboratory studies show a hemoglobin concentration of 7 g/dL, a leukocyte count of 2,000/mm3, a platelet count of 40,000/mm3, and a reticulocyte count of 0.2%. Serum electrolyte concentrations are within normal limits. A bone marrow biopsy is most likely to show which of the following findings?
- A. Increased myeloblast count
- B. Sheets of abnormal plasma cells
- C. Wrinkled cells with a fibrillary cytoplasm
- D. Hypocellular bone marrow (Correct Answer)
- E. Dysplastic bone with ringed sideroblasts
Explanation: ***Hypocellular bone marrow*** - The patient presents with **pancytopenia** (low hemoglobin, leukocytes, and platelets) and a very low **reticulocyte count**, indicating severely impaired hematopoiesis [1]. - This constellation of findings, in the absence of organomegaly or other specific features, strongly suggests **aplastic anemia**, which is characterized by a **hypocellular bone marrow** with significant reduction in hematopoietic cells and replacement by fat [1][3]. *Increased myeloblast count* - An increased **myeloblast count** in the bone marrow is characteristic of **acute myeloid leukemia (AML)**. - While pancytopenia can occur in AML, the distinguishing feature would be a high percentage of blasts (typically >20%) in the bone marrow, which is not implied by the general presentation [1]. *Sheets of abnormal plasma cells* - **Sheets of abnormal plasma cells** are the hallmark of **multiple myeloma** [2]. - This condition primarily presents with bone pain, hypercalemia, renal failure, and anemia, but not typically with severe pancytopenia and bruising as the primary presenting symptoms without other myeloma-defining events [2]. *Wrinkled cells with a fibrillary cytoplasm* - **Wrinkled cells with a fibrillary cytoplasm** (Gaucher cells) are pathognomonic for **Gaucher disease**, a lysosomal storage disorder. - Gaucher disease typically presents with hepatosplenomegaly, bone crises, and neurological symptoms, not primarily with aplastic anemia. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Red Blood Cell and Bleeding Disorders, pp. 662-663. [2] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Problems From Blood And Bone Marrow Disease, pp. 617-618. [3] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Problems From Blood And Bone Marrow Disease, pp. 595-596.
Question 1283: A 3-year-old boy is brought to the physician because of a 4-week history of generalized fatigue and malaise. He was born at term and has been healthy since. His mother has a history of recurrent anemia. He appears pale. His temperature is 37°C (98.6°F) and pulse is 97/min. Examination shows pale conjunctivae and jaundice. The abdomen is soft and nontender; the spleen is palpated 3–4 cm below the left costal margin. Laboratory studies show: Hemoglobin 9.3 g/dL Mean corpuscular volume 81.3 μm3 Mean corpuscular hemoglobin concentration 39% Hb/cell Leukocyte count 7300/mm3 Platelet count 200,000/mm3 Red cell distribution width 19% (N = 13–15) Which of the following is most likely to confirm the diagnosis?
- A. Fluorescent spot test
- B. Eosin-5-maleimide binding test (Correct Answer)
- C. Direct antiglobulin test
- D. Peripheral smear
- E. Indirect antiglobulin test
Explanation: ***Eosin-5-maleimide binding test*** - This patient's symptoms (anemia, jaundice, splenomegaly) and lab findings (normocytic anemia, elevated MCHC, increased RDW) are highly suggestive of **hereditary spherocytosis** [1]. - The **eosin-5-maleimide (EMA) binding test** is the most sensitive and specific flow cytometry-based test for hereditary spherocytosis, as it detects a deficiency of red cell membrane proteins (e.g., band 3, ankyrin) leading to reduced EMA binding [1]. *Fluorescent spot test* - The fluorescent spot test is used to screen for **G6PD deficiency**, which typically presents with episodic hemolytic anemia triggered by oxidative stress, not the chronic symptoms described [3]. - While G6PD deficiency is a cause of hemolytic anemia, the elevated MCHC and absence of triggers make it less likely in this context [3]. *Direct antiglobulin test* - The direct antiglobulin test (DAT), or **Coombs test**, checks for antibodies or complement components bound to the surface of red blood cells, indicating an **autoimmune hemolytic anemia** [4]. - Although the patient has hemolytic anemia, the family history of recurrent anemia and the specific lab findings (high MCHC) point away from an autoimmune cause and towards a hereditary membrane defect [4]. *Peripheral smear* - A peripheral smear would likely show **spherocytes**, which are small, dense red cells lacking central pallor, supporting a diagnosis of hereditary spherocytosis [2]. - However, while suggestive, spherocytes can also be seen in other conditions (e.g., autoimmune hemolytic anemia), so it is not definitively confirmative on its own, unlike the EMA binding test [2], [4]. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Red Blood Cell and Bleeding Disorders, pp. 640-641. [2] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Problems From Blood And Bone Marrow Disease, pp. 597-598. [3] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Red Blood Cell and Bleeding Disorders, pp. 642-643. [4] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Problems From Blood And Bone Marrow Disease, pp. 602-603.
Question 1284: A lymph node biopsy shows 'tennis racket' appearance of follicles. Which immunohistochemical finding would confirm progressive transformation of germinal centers?
- A. Expanded CD23+ FDC meshwork (Correct Answer)
- B. CD30+ large cells
- C. Cyclin D1+ mantle cells
- D. CD138+ plasma cells
Explanation: ***Expanded CD23+ FDC meshwork*** - Progressive transformation of germinal centers (PTGC) is characterized morphologically by abnormally large, irregular germinal centers with a "tennis racket" or serpiginous appearance. This histological feature is due to an **expanded and disorganized follicular dendritic cell (FDC) meshwork**, which can be highlighted by **CD23 immunohistochemistry**. - **CD23** is a marker for follicular dendritic cells (FDCs), and an expanded CD23+ FDC meshwork confirms the abnormal germinal center architecture seen in PTGC, distinguishing it from normal germinal centers or other lymphoid disorders. *CD30+ large cells* - **CD30+ large cells** are characteristic of **Classical Hodgkin Lymphoma**, particularly the nodular sclerosis and mixed cellularity subtypes [1]. - While Hodgkin lymphoma can present with lymphadenopathy, it does not typically show the "tennis racket" morphology of follicles or an expanded CD23+ FDC meshwork, and its clinical management differs significantly from PTGC [1]. *Cyclin D1+ mantle cells* - **Cyclin D1 expression** in mantle cells is the hallmark of **Mantle Cell Lymphoma**, arising from the t(11;14) translocation [2]. - Mantle cell lymphoma typically infiltrates the mantle zone around follicles in a "mantle zone pattern" or diffuse pattern, but it does not exhibit the "tennis racket" follicular morphology or expanded FDC meshwork seen in PTGC [3]. *CD138+ plasma cells* - **CD138 (Syndecan-1)** is a marker for **plasma cells** and is commonly used in the diagnosis of plasma cell dyscrasias like multiple myeloma or plasmacytoma. - An increase in plasma cells is not a characteristic feature of PTGC, nor is the "tennis racket" follicular appearance associated with plasma cell proliferation. **References:** [1] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Problems From Diseases Of The Urinary And Male Genital Tracts, pp. 558-559. [2] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Problems From Diseases Of The Urinary And Male Genital Tracts, pp. 562-563. [3] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Diseases of White Blood Cells, Lymph Nodes, Spleen, and Thymus, pp. 610-612.
Question 1285: A peripheral blood smear shows erythrocytes with 'cross-hatched' membrane appearance. Which additional finding would confirm hereditary xerocytosis?
- A. Osmotic fragility
- B. G6PD deficiency
- C. PIEZO1 mutation (Correct Answer)
- D. Spectrin deficiency
Explanation: ***PIEZO1 mutation*** - **Hereditary xerocytosis** is characterized by dehydrated red blood cells, which can exhibit a 'cross-hatched' membrane appearance on peripheral blood smear. - Mutations in the **PIEZO1 gene** encoding a mechanosensitive ion channel are the most common genetic cause of hereditary xerocytosis, leading to increased permeability to cations and subsequent cellular dehydration. *Osmotic fragility* - **Osmotic fragility testing** assesses the red blood cell's ability to withstand hypotonic solutions, with **decreased osmotic fragility** indicating increased resistance to lysis in hypotonic solutions seen in hereditary xerocytosis due to cellular dehydration. - While decreased osmotic fragility is a characteristic feature of hereditary xerocytosis, it is a functional assay and does not directly confirm the genetic defect like a **PIEZO1 mutation**. *G6PD deficiency* - **G6PD deficiency** is an enzyme defect leading to oxidative stress and **hemolytic anemia**, often triggered by certain drugs, infections, or fava beans, and is not directly associated with the 'cross-hatched' membrane appearance or a primary membrane channel defect [2]. - The hallmark of G6PD deficiency is the presence of **Heinz bodies** and **bite cells**, which differ from the morphological changes seen in hereditary xerocytosis [3]. *Spectrin deficiency* - **Spectrin deficiency** is primarily associated with **hereditary spherocytosis** and **hereditary elliptocytosis**, conditions characterized by abnormal red blood cell shapes (spherocytes, elliptocytes) and increased osmotic fragility [1]. - While it affects red blood cell membrane integrity, it does not lead to the specific 'cross-hatched' appearance or the dehydration seen in hereditary xerocytosis. **References:** [1] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Problems From Blood And Bone Marrow Disease, pp. 597-598. [2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Red Blood Cell and Bleeding Disorders, p. 638. [3] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Red Blood Cell and Bleeding Disorders, pp. 642-643.
Question 1286: A bone marrow biopsy in a patient with suspected myelofibrosis shows atypical megakaryocyte proliferation. Which additional finding would confirm the diagnosis?
- A. Increased reticulin fibrosis (Correct Answer)
- B. Sea-blue histiocytes
- C. Pseudo-Gaucher cells
- D. Crystal-storing histiocytes
Explanation: Detailed Analysis: ***Increased reticulin fibrosis*** - **Increased reticulin fibrosis** (grade 2-3) detected by reticulin staining is the **hallmark diagnostic feature** of myelofibrosis [2]. - Myelofibrosis is characterized by proliferation of atypical **megakaryocytes** that release growth factors (PDGF, TGF-̠) leading to reactive **reticulin and collagen deposition** [1], [2]. - Diagnosis requires both **atypical megakaryocytes** and **increased bone marrow fibrosis** on biopsy. *Sea-blue histiocytes* - These are lipid-laden macrophages seen in **Niemann-Pick disease**, **chronic myeloid leukemia**, and some storage disorders. - Not a diagnostic criterion for myelofibrosis. - Their presence is incidental and non-specific. *Pseudo-Gaucher cells* - These resemble Gaucher cells but are found in **chronic myeloid leukemia** and other myeloproliferative neoplasms. - They are macrophages with wrinkled-paper cytoplasm due to lipid accumulation. - Not specific for myelofibrosis diagnosis. *Crystal-storing histiocytes* - Rare finding associated with **monoclonal gammopathies** and **plasma cell dyscrasias**. - Histiocytes contain immunoglobulin crystals. - Not related to myelofibrosis pathogenesis or diagnosis. **References:** [1] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Problems From Blood And Bone Marrow Disease, pp. 614-615. [2] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Problems From Blood And Bone Marrow Disease, pp. 615-616.
Question 1287: A blood smear shows RBCs with fragmented, bizarre shapes and microspherocytes. Which additional finding would confirm hereditary pyropoikilocytosis?
- A. Spectrin mutations (Correct Answer)
- B. Osmotic fragility
- C. G6PD deficiency
- D. Hemoglobin H inclusions
Explanation: ***Spectrin mutations*** - **Hereditary pyropoikilocytosis** is an autosomal recessive disorder caused by a **quantitative** or **qualitative defect in spectrin** (a key red cell membrane protein), often leading to **thermal instability** of RBCs. - The characteristic **fragmented**, **bizarre-shaped RBCs** (poikilocytes) and **microspherocytes** on the blood smear, along with suspicion of a hereditary red cell membrane defect, point to spectrin mutations as the specific confirmatory finding [1]. *Osmotic fragility* - While **increased osmotic fragility** is characteristic of **spherocytes** (and thus present in hereditary spherocytosis and often in HPP due to the presence of microspherocytes), it is a functional test that indicates membrane instability but does not specifically confirm the underlying genetic defect of hereditary pyropoikilocytosis [2]. - Osmotic fragility testing is more indicative of **hereditary spherocytosis** which primarily involves spectrin and ankyrin *deficiency*, rather than spectrin *mutation* with severe membrane instability seen in HPP [1]. *G6PD deficiency* - **G6PD deficiency** is an **enzymopathy** that causes **hemolytic anemia** due to **oxidative stress**, leading to **Heinz bodies** and **bite cells**, but not the characteristic **pyropoikilocytes** or the specific membrane protein defects seen in HPP. - A definitive diagnosis of G6PD deficiency requires specific **enzyme assays**, not primarily based on the blood smear morphology described here unless there is evidence of oxidative damage. *Hemoglobin H inclusions* - **Hemoglobin H inclusions** are found in **alpha-thalassemia intermedia** (HbH disease), where excess **beta-globin chains** precipitate. - These inclusions are visible with **supravital stains** and are not associated with the **red cell membrane protein defects** or the specific bizarre-shaped red cells seen in hereditary pyropoikilocytosis. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Red Blood Cell and Bleeding Disorders, pp. 640-641. [2] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Problems From Blood And Bone Marrow Disease, pp. 597-598.
Question 1288: A lymph node biopsy shows 'onion skin' pattern of lymphoid cells. Which immunophenotype would confirm Castleman disease?
- A. CD30+ Reed-Sternberg cells
- B. CD5+/cyclin D1+ small cells
- C. CD10+/BCL6+ large cells
- D. CD21+ follicular dendritic meshworks with polyclonal plasma cells (Correct Answer)
Explanation: ***CD21+ follicular dendritic meshworks with polyclonal plasma cells*** - Castleman disease, especially the hyaline-vascular type, is characterized by **atypical, regressed germinal centers** surrounded by concentric rings of lymphocytes, creating the classic **"onion skin" appearance**. - **CD21 expression** highlights the expanded and dysplastic **follicular dendritic cell (FDC) networks**, and a significant presence of **polyclonal plasma cells** is also typical. *CD30+ Reed-Sternberg cells* - This immunophenotype is characteristic of **classical Hodgkin lymphoma**, not Castleman disease [2]. - **Reed-Sternberg cells** are large, often binucleated cells, and the histology of Hodgkin lymphoma differs significantly from the "onion skin" appearance seen in Castleman disease [1]. *CD5+/cyclin D1+ small cells* - This immunophenotype is diagnostic of **mantle cell lymphoma** [3]. - Mantle cell lymphoma typically shows proliferation of small to medium-sized lymphocytes in the mantle zone, expressing **CD5** and **cyclin D1**, which is not consistent with the morphology or immunophenotype of Castleman disease [3]. *CD10+/BCL6+ large cells* - This immunophenotype is typical of **germinal center B-cell type diffuse large B-cell lymphoma (DLBCL)**. - While DLBCL involves large cells, its immunophenotype and architectural effacement of lymph node rather than characteristic "onion skin" findings are distinct from Castleman disease. **References:** [1] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Problems From Diseases Of The Urinary And Male Genital Tracts, pp. 558-559. [2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Diseases of White Blood Cells, Lymph Nodes, Spleen, and Thymus, p. 616. [3] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Diseases of White Blood Cells, Lymph Nodes, Spleen, and Thymus, pp. 610-612.
Question 1289: A peripheral blood smear shows 'figure-8' shaped RBCs. Which additional finding would confirm Southeast Asian ovalocytosis?
- A. Heinz bodies
- B. Band 3 protein mutation (Correct Answer)
- C. Spectrin deficiency
- D. Increased osmotic fragility
Explanation: ***Band 3 protein mutation*** - **Southeast Asian ovalocytosis (SAO)** is caused by a specific mutation (deletion of 27 base pairs) in the gene encoding the **Band 3 protein**, leading to a truncated and rigid protein. - This rigidity of the **red blood cell (RBC) membrane**, due to the abnormal Band 3 protein, results in the characteristic **oval or 'figure-8' shape** seen on peripheral blood smears. *Heinz bodies* - **Heinz bodies** are precipitates of denatured hemoglobin, typically seen in conditions like **G6PD deficiency** or unstable hemoglobinopathies. - Their presence does not confirm SAO, which is a **membrane disorder**, not primarily a hemoglobinopathy. *Spectrin deficiency* - **Spectrin deficiency** is primarily associated with **hereditary spherocytosis** and **hereditary elliptocytosis**, causing spherocytes or elliptical RBCs, respectively [1]. - While it affects RBC shape, the specific **'figure-8' morphology** and the underlying genetic defect in SAO are distinct from spectrin abnormalities. *Increased osmotic fragility* - **Increased osmotic fragility** is a hallmark of conditions like **hereditary spherocytosis**, where RBCs are more susceptible to lysis in hypotonic solutions due to their spherical shape [1]. - In contrast, SAO RBCs often exhibit **decreased osmotic fragility** due to their increased membrane rigidity, providing protection against malaria. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Red Blood Cell and Bleeding Disorders, pp. 640-641.
Question 1290: A cervical lymph node biopsy shows 'starry sky' pattern. Which immunophenotype would best support Burkitt lymphoma?
- A. CD30+/ALK+
- B. CD15+/CD30+
- C. CD5+/cyclin D1+
- D. CD10+/c-myc+ (Correct Answer)
Explanation: ***CD10+/c-myc+*** - **Burkitt lymphoma** is characterized by the **t(8;14) translocation**, leading to **c-myc overexpression**, which is a key diagnostic marker. - **CD10** positivity is typical for **Burkitt lymphoma**, as it is a marker of germinal center B-cells from which this lymphoma originates [1]. *CD30+/ALK+* - This immunophenotype is characteristic of **anaplastic large cell lymphoma (ALCL)**, which presents with different histological features and clinical behavior. - ALK-positive ALCL is often seen in younger patients and has a distinct genetic alteration involving the **ALK gene**. *CD15+/CD30+* - This immunophenotype is classic for **classical Hodgkin lymphoma**, particularly the **nodular sclerosis** and **mixed cellularity** subtypes. - Hodgkin lymphoma involves large, atypical **Reed-Sternberg cells** surrounded by inflammatory cells, which is distinct from the "starry sky" pattern [1]. *CD5+/cyclin D1+* - This immunophenotype is highly suggestive of **mantle cell lymphoma**, which is associated with the **t(11;14) translocation** leading to **cyclin D1 overexpression**. - Mantle cell lymphoma typically has a diffuse or nodular growth pattern and does not exhibit the "starry sky" morphology. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Diseases of White Blood Cells, Lymph Nodes, Spleen, and Thymus, p. 606.
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