Hematopathology — MCQs

Hematopathology Indian Medical PG Practice Questions and MCQs

Question 591: Which of the following is true regarding Chediak-Higashi syndrome?

A. Defect in phagocytosis (Correct Answer)
B. Neutropenia
C. Agammaglobulinemia
D. IgA deficiency

Explanation: **Explanation:** **Chediak-Higashi Syndrome (CHS)** is a rare autosomal recessive disorder characterized by a defect in the **LYST gene** (Lysosomal Trafficking Regulator). This mutation leads to impaired microtubule formation and disordered intracellular trafficking of organelles. 1. **Why the correct answer is right:** The primary defect in CHS is the failure of **phagosome-lysosome fusion** [1]. While neutrophils can ingest bacteria, they cannot discharge lysosomal enzymes into the phagocytic vacuoles to kill them. This results in a profound **defect in phagocytosis** (specifically, intracellular killing). Morphologically, this is visualized as **giant peroxidase-positive granules** in neutrophils [1], which represent fused, dysfunctional lysosomes. 2. **Why the incorrect options are wrong:** * **Neutropenia:** While mild neutropenia can occur due to ineffective granulopoiesis in the bone marrow [1], the *hallmark* functional defect is the qualitative phagocytic failure, not a primary quantitative lack of cells. * **Agammaglobulinemia/IgA deficiency:** CHS is a defect of the innate immune system (phagocytes and NK cells). Humoral immunity (B-cells and antibody production) is generally intact, making these options incorrect. **High-Yield Clinical Pearls for NEET-PG:** * **Clinical Triad:** Partial oculocutaneous **albinism**, recurrent pyogenic infections (Staph/Strep), and progressive neurologic abnormalities [1]. * **Hematologic finding:** Giant lysosomal granules in leukocytes and platelets (causing mild bleeding tendencies) [1]. * **The "Accelerated Phase":** A dreaded complication involving a hemophagocytic lymphohistiocytosis (HLH)-like syndrome, often triggered by EBV. * **Diagnosis:** Peripheral blood smear showing giant granules [1]. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Diseases of the Immune System, pp. 245-246.

Question 592: Bone marrow findings in AL amyloidosis typically include:

A. Plasmacytosis (Correct Answer)
B. Granulomatous reaction
C. Fibrosis
D. Giant cell formation

Explanation: **Explanation:** **AL (Amyloid Light-chain) Amyloidosis** is a plasma cell dyscrasia characterized by the deposition of insoluble amyloid fibrils derived from monoclonal immunoglobulin light chains. 1. **Why Plasmacytosis is correct:** The underlying pathology in AL amyloidosis is a clonal proliferation of plasma cells in the bone marrow [1]. These abnormal plasma cells produce excess light chains (usually Lambda more than Kappa) that misfold and deposit in tissues [1]. While the plasma cell count is often low (typically <10%), it is the primary source of the amyloidogenic protein, making **plasmacytosis** the hallmark finding. In some cases, it may coexist with overt Multiple Myeloma. 2. **Why the other options are incorrect:** * **Granulomatous reaction:** This is characteristic of chronic inflammatory or infectious diseases (e.g., Tuberculosis, Sarcoidosis), not plasma cell disorders. * **Fibrosis:** While marrow fibrosis can be seen in Myelofibrosis or advanced Myeloma, it is not a defining or typical feature of AL amyloidosis. * **Giant cell formation:** This is associated with foreign body reactions or specific infections and is not a feature of the monoclonal protein production seen in amyloidosis. **High-Yield Clinical Pearls for NEET-PG:** * **Staining:** Amyloid shows **Apple-green birefringence** under polarized light when stained with **Congo Red**. * **Most Common Type:** AL amyloidosis is the most common form of systemic amyloidosis. * **Organ Involvement:** Macroglossia (enlarged tongue) and Periorbital ecchymosis ("Raccoon eyes") are highly suggestive clinical signs. * **Diagnosis:** While bone marrow shows plasmacytosis, the most sensitive site for biopsy to confirm amyloid deposition is **Abdominal Fat Pad aspiration** or rectal biopsy. **References:** [1] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Problems From Blood And Bone Marrow Disease, pp. 616-618.

Question 593: Bernad-Soulier syndrome is a defect in platelet?

A. Aggregation
B. Adhesion (Correct Answer)
C. Morphology
D. Release reaction

Explanation: **Explanation:** **Bernard-Soulier Syndrome (BSS)** is a rare autosomal recessive bleeding disorder characterized by a defect in **platelet adhesion** [1]. 1. **Why Adhesion is Correct:** Platelet adhesion is the first step of primary hemostasis, where platelets bind to the subendothelial collagen via **von Willebrand Factor (vWF)** [2]. BSS is caused by a deficiency or dysfunction of the **Glycoprotein Ib-IX-V (GpIb-IX-V) complex**, which serves as the primary receptor for vWF [1]. Without this receptor, platelets cannot adhere to the damaged vessel wall, leading to a prolonged bleeding time. 2. **Why Other Options are Incorrect:** * **Aggregation:** This refers to platelets sticking to each other via the **GpIIb/IIIa receptor** and fibrinogen [2]. Defects in aggregation are seen in **Glanzmann Thrombasthenia** [1]. * **Morphology:** While BSS does feature "Giant Platelets," the primary functional defect is physiological (adhesion), not just structural. * **Release Reaction:** This involves the secretion of alpha and delta granules (e.g., ADP, Serotonin). Defects here are seen in Storage Pool Diseases (e.g., Chediak-Higashi syndrome). **High-Yield Clinical Pearls for NEET-PG:** * **The Triad of BSS:** 1. Thrombocytopenia (low platelet count), 2. Giant Platelets (often as large as RBCs), 3. Prolonged Bleeding Time. * **Ristocetin Test:** In BSS, platelet agglutination **fails** with Ristocetin, and unlike von Willebrand Disease, it **cannot** be corrected by adding normal plasma. * **Peripheral Smear:** Look for "Giant Platelets" (Macrothrombocytopenia). * **Mnemonic:** **B**ernard-**S**oulier = **B**ig **S**urface (Giant platelets/Adhesion defect). **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Red Blood Cell and Bleeding Disorders, pp. 668-670. [2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Hemodynamic Disorders, Thromboembolic Disease, and Shock, p. 128.

Question 594: The Ham test is used for the detection of which of the following?

A. Ankyrin defect
B. GPI-linked protein defect (Correct Answer)
C. Spectrin defect
D. Mannose binding protein defect

Explanation: The Ham test (Acidified Serum Test) is a classic diagnostic tool for Paroxysmal Nocturnal Hemoglobinuria (PNH). PNH is an acquired clonal hematopoietic stem cell disorder caused by a mutation in the PIGA gene [1]. This mutation leads to a deficiency in Glycosylphosphatidylinositol (GPI) anchors, which are necessary to attach protective proteins like CD55 (Decay Accelerating Factor) and CD59 (MAC-inhibitory protein) to the red blood cell membrane [2]. Without these GPI-linked proteins, RBCs are hypersensitive to complement-mediated lysis [1]. In the Ham test, the patient's RBCs are placed in acidified serum; the acid activates the alternative complement pathway, leading to the lysis of the defective (GPI-deficient) cells. The tendency for red cells to lyse at night is explained by a slight decrease in blood pH during sleep, which increases the activity of complement [2]. Flow Cytometry is now the gold standard for PNH [2]. Triad of PNH: Hemolytic anemia, Pancytopenia, and Venous thrombosis [2]. **References:** [1] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Problems From Blood And Bone Marrow Disease, pp. 601-602. [2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Red Blood Cell and Bleeding Disorders, pp. 650-651.

Question 595: In Beta thalassemia, what is the typical alteration in globin chain production?

A. Increase in beta chain, decrease in alpha chain
B. Decrease in beta chain, increase in alpha chain (Correct Answer)
C. Decrease in beta chain, decrease in alpha chain
D. Increase in beta chain, increase in alpha chain

Explanation: **Explanation:** **1. Why Option B is Correct:** Beta-thalassemia is a quantitative hemoglobinopathy caused by mutations (usually point mutations) in the HBB gene on chromosome 11 [1]. This leads to **reduced ($eta^+$) or absent ($eta^0$) synthesis of beta-globin chains** [1]. The fundamental pathophysiology involves a **globin chain imbalance**. While beta-chain production is decreased, alpha-chain synthesis remains normal [1]. This results in a **relative excess of free alpha-chains**. These unpaired alpha-chains are highly unstable; they precipitate within erythroid precursors in the bone marrow, forming toxic inclusion bodies [1]. This leads to ineffective erythropoiesis and extravascular hemolysis [1]. **2. Why Other Options are Incorrect:** * **Option A:** This describes Alpha-thalassemia, where alpha chains are deficient and beta chains (in adults) or gamma chains (in neonates) are in relative excess, forming HbH ($eta_4$) or Hb Barts ($eta_4$) [1]. * **Option C:** A decrease in both chains is not characteristic of thalassemia. Thalassemia is defined by the *imbalance* between the two types of chains [1]. * **Option D:** Increased production of both chains does not occur in thalassemia; this would theoretically increase total hemoglobin, which contradicts the microcytic hypochromic anemia seen in this condition. **3. NEET-PG High-Yield Pearls:** * **Hallmark Peripheral Smear:** Target cells (leptocytes) and basophilic stippling. * **Diagnosis:** Gold standard is **Hb Electrophoresis**, showing increased **HbA2 (>3.5%)** and increased **HbF** [1]. * **Skeletal Changes:** "Crew-cut" appearance on skull X-ray and "chipmunk facies" due to compensatory extramedullary hematopoiesis. * **Mentzer Index:** (MCV/RBC count) < 13 suggests Thalassemia; > 13 suggests Iron Deficiency 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. 646-650.

Question 596: Schilling test is done for which condition?

A. Vitamin B12 deficiency (Correct Answer)
B. Folic acid deficiency
C. Vitamin B6 deficiency
D. Vitamin D deficiency

Explanation: The **Schilling test** is a classic diagnostic investigation used to determine the cause of **Vitamin B12 (Cobalamin) deficiency**. It specifically helps differentiate between dietary deficiency, Pernicious Anemia (lack of Intrinsic Factor), and intestinal malabsorption [1], [2]. **Why Option A is correct:** Vitamin B12 absorption is a complex process requiring gastric acid, Intrinsic Factor (IF) from parietal cells, and an intact terminal ileum [2]. The Schilling test involves administering oral radiolabeled B12 followed by an intramuscular "flushing dose" of unlabeled B12. By measuring the radioactivity in a 24-hour urine sample, clinicians can pinpoint where the absorption pathway is failing. **Why other options are incorrect:** * **B. Folic acid deficiency:** Folate is absorbed in the jejunum via a simpler mechanism that does not require Intrinsic Factor [2]; it is usually diagnosed via serum folate levels. * **C. Vitamin B6 deficiency:** Associated with sideroblastic anemia and peripheral neuropathy (often due to Isoniazid therapy); diagnosed via clinical history and blood levels. * **D. Vitamin D deficiency:** Related to calcium metabolism and bone health (Rickets/Osteomalacia); diagnosed via serum 25-hydroxyvitamin D levels. **High-Yield Clinical Pearls for NEET-PG:** * **Phases:** Phase I (B12 alone), Phase II (B12 + Intrinsic Factor), Phase III (B12 + Antibiotics), Phase IV (B12 + Pancreatic enzymes). * **Pernicious Anemia:** If Phase I is abnormal but Phase II is normal (correction with IF), the diagnosis is Pernicious Anemia [1]. * **Current Status:** Though high-yield for exams, the Schilling test is rarely used in modern clinical practice due to the use of radioactive isotopes and the availability of anti-intrinsic factor antibody assays [1]. * **Key Site:** Remember that Vitamin B12 is absorbed in the **terminal ileum** [2]. **References:** [1] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Problems From Blood And Bone Marrow Disease, pp. 588-593. [2] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. (Basic Pathology) introduces the student to key general principles of pathology, both as a medical science and as a clinical activity with a vital role in patient care. Part 2 (Disease Mechanisms) provides fundamental knowledge about the cellular and molecular processes involved in diseases, providing the rationale for their treatment. Part 3 (Systematic Pathology) deals in detail with specific diseases, with emphasis on the clinically important aspects., pp. 130-131.

Question 597: A child died soon after birth. On examination, there was hepatosplenomegaly and edema all over the body. What is the most probable diagnosis?

A. alpha-thalassemia (Correct Answer)
B. beta-thalassemia
C. hereditary spherocytosis
D. ABO incompatibility

Explanation: ### Explanation The clinical presentation of a neonate with generalized edema (hydrops fetalis) and hepatosplenomegaly immediately after birth is classic for **Hb Bart’s (Hydrops Fetalis)**, the most severe form of **̑-thalassemia** [3]. #### Why ̑-thalassemia is correct: In ̑-thalassemia major, all four ̑-globin genes are deleted (--/--). Since ̑-chains are essential for the formation of fetal hemoglobin (HbF, ̑2̳2) and adult hemoglobin (HbA, ̑2̢2), their absence leads to the formation of ̳-tetramers, known as **Hb Bart’s**. Hb Bart’s has an extremely high affinity for oxygen, resulting in severe tissue hypoxia, high-output heart failure, massive extramedullary hematopoiesis (causing hepatosplenomegaly) [2], and ultimately, **hydrops fetalis** and intrauterine or neonatal death [3]. #### Why other options are incorrect: * **̢-thalassemia:** This does not manifest at birth because ̢-globin chains are not required for HbF. Symptoms only appear after 6 months of age when the "gamma-to-beta" switch occurs. * **Hereditary Spherocytosis:** While it can cause neonatal jaundice and splenomegaly, it rarely causes hydrops fetalis or immediate neonatal death. * **ABO Incompatibility:** This is usually a mild condition causing neonatal jaundice. Unlike Rh incompatibility, it does not typically result in severe hydrops fetalis [1]. #### High-Yield Clinical Pearls for NEET-PG: * **Hb Bart’s:** ̳4 (Four gamma chains); seen in 4-gene deletion ̑-thalassemia [3]. * **HbH Disease:** ̢4 (Four beta chains); seen in 3-gene deletion ̑-thalassemia (presents as microcytic anemia with "golf ball" inclusions on brilliant cresyl blue stain) [3]. * **Hydrops Fetalis:** Defined as abnormal fluid accumulation in ≥2 fetal compartments (e.g., ascites, pleural effusion, skin edema) [2]. * **Inheritance:** ̑-thalassemia is most common in Southeast Asian populations (cis-deletion) and African populations (trans-deletion) [3]. **References:** [1] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Problems From Blood And Bone Marrow Disease, pp. 603-604. [2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Diseases of Infancy and Childhood, pp. 470-472. [3] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Red Blood Cell and Bleeding Disorders, pp. 649-650.

Question 598: Basophils are decreased in which of the following conditions?

A. Polycythemia
B. Basophilic leukemia
C. Cushing's syndrome (Correct Answer)
D. Chronic myeloid leukemia (CML)

Explanation: **Explanation:** The correct answer is **Cushing’s syndrome**. **1. Why Cushing’s Syndrome is Correct:** Basopenia (a decrease in basophil count) is a characteristic finding in states of **hypercortisolism**, such as Cushing’s syndrome or exogenous steroid administration [1]. Glucocorticoids cause a redistribution of basophils from the peripheral blood into other compartments and inhibit their release from the bone marrow. Additionally, basopenia can be seen in acute stress (due to endogenous cortisol release), hyperthyroidism, and acute hypersensitivity reactions (where basophils degranulate and are sequestered in tissues). **2. Why the Other Options are Incorrect:** * **Polycythemia Vera:** This is a myeloproliferative neoplasm (MPN) characterized by the overproduction of all three cell lines (panmyelosis). Basophilia (increased basophils) is a common diagnostic clue in MPNs. * **Basophilic Leukemia:** This is a rare form of acute myeloid leukemia where primary proliferation consists of basophilic precursors, leading to a massive increase in basophil counts. * **Chronic Myeloid Leukemia (CML):** Basophilia is a hallmark of CML. In fact, a rising basophil count in a known CML patient is a significant clinical sign indicating **disease progression** toward the Accelerated Phase or Blast Crisis. **Clinical Pearls for NEET-PG:** * **Basophilia** is most commonly associated with Myeloproliferative Neoplasms (CML, Polycythemia Vera). * **Cushing’s Mnemonic:** Steroids cause an increase in "Neutrophils" but a decrease in "B.E.L." (**B**asophils, **E**osinophils, and **L**ymphocytes). * **High-Yield Fact:** Basophils contain coarse granules rich in **Heparin and Histamine**. Their membranes express **IgE receptors (FcεRI)**, playing a crucial role in Type I Hypersensitivity reactions. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. The Endocrine System, p. 1127.

Question 599: A 32-year-old man has mild anemia diagnosed on routine testing. His clinical examination is normal, and a blood film reveals some target cells with some red cells having intraerythrocytic crystals. For the above patient with a hemoglobin abnormality, select the most likely diagnosis?

A. beta-thalassemia major
B. HbH disease
C. sickle cell disease
D. HbC disease (Correct Answer)

Explanation: **Explanation:** The correct answer is **HbC disease**. This diagnosis is classically characterized by the presence of **target cells** and pathognomonic **intraerythrocytic crystals** (HbC crystals) on a peripheral blood smear. **1. Why HbC disease is correct:** HbC disease results from a point mutation in the $\beta$-globin chain where **glutamic acid is replaced by lysine** at the 6th position ($\beta^6 Glu \to Lys$) [1]. In the oxygenated state, HbC tends to crystallize, forming dark red, hexagonal, or rod-shaped "Washington Monument" crystals within the red cells. Clinically, patients are often asymptomatic or present with mild hemolytic anemia and splenomegaly [1]. **2. Why other options are incorrect:** * **Beta-thalassemia major:** Presents with severe microcytic hypochromic anemia, skeletal deformities (chipmunk facies), and significant hepatosplenomegaly [3], [5]. While target cells are present, intraerythrocytic crystals are not. * **HbH disease (Alpha-thalassemia):** Characterized by "golf ball" inclusions (precipitated $\beta$-globin tetramers) seen with supravital stains, not hexagonal crystals [3]. * **Sickle cell disease (HbSS):** Characterized by sickle-shaped cells (drepanocytes) and Howell-Jolly bodies [2], [4]. The mutation here is $\beta^6 Glu \to Val$ [2]. **Clinical Pearls for NEET-PG:** * **Mnemonic for Mutation:** Hb**C** = **L**ysine (C is close to L in the alphabet; or "Ly**C**ine"). * **Electrophoresis:** HbC moves the slowest toward the anode among common variants (Mnemonic: **A** fat **S**low **C**at — HbA is fastest, HbC is slowest). * **Target Cells (Codocytes):** Seen in **HALT** (HbC, Asplenia, Liver disease, Thalassemia). **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Red Blood Cell and Bleeding Disorders, pp. 643-644. [2] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Problems From Blood And Bone Marrow Disease, pp. 598-599. [3] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Problems From Blood And Bone Marrow Disease, pp. 600-601. [4] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Red Blood Cell and Bleeding Disorders, pp. 644-645. [5] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Red Blood Cell and Bleeding Disorders, p. 648.

Question 600: What is the minimum percentage of blasts in the peripheral blood or bone marrow required for the diagnosis of Acute Myeloid Leukemia?

A. 8%
B. 15%
C. 20% (Correct Answer)
D. 25%

Explanation: ### Explanation The diagnosis of **Acute Myeloid Leukemia (AML)** is primarily based on the quantification of myeloblasts in the bone marrow or peripheral blood. **1. Why 20% is the Correct Answer:** According to the **WHO Classification of Tumors of Haematopoietic and Lymphoid Tissues**, the threshold for diagnosing AML is a blast count of **≥20%**. This criterion distinguishes acute leukemia from Myelodysplastic Syndromes (MDS), where the blast count is typically lower [1]. * **Exception (High-Yield):** If specific genetic abnormalities are present—namely **t(8;21), inv(16), or t(15;17)**—the diagnosis of AML can be made even if the blast count is **less than 20%**. **2. Why Other Options are Incorrect:** * **A (8%) & B (15%):** These percentages fall within the range of **Myelodysplastic Syndromes (MDS)**. Specifically, MDS with excess blasts (MDS-EB-1) involves 5-9% blasts, and MDS-EB-2 involves 10-19% blasts [1]. * **D (25%):** Historically, the **FAB (French-American-British) classification** required a blast count of **≥30%** for a diagnosis of AML. The 25% mark is an arbitrary number that does not align with current or historical diagnostic thresholds. **3. Clinical Pearls for NEET-PG:** * **Auer Rods:** Their presence in blasts is pathognomonic for myeloid lineage (AML), even if the blast count is low. * **MPO (Myeloperoxidase):** The most specific histochemical stain for AML. * **Flow Cytometry:** Essential for lineage markers; **CD33 and CD13** are common pan-myeloid markers. * **Pure Erythroid Leukemia:** A rare subtype where blasts are ≥80% of the marrow cells. **References:** [1] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Problems From Blood And Bone Marrow Disease, pp. 613-614.

Practice by Chapter

Anemias: Classification and Approach

Practice Questions

Hemolytic Anemias

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Myeloproliferative Neoplasms

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Myelodysplastic Syndromes

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Acute Leukemias

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Chronic Leukemias

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Lymphomas and Lymphoid Neoplasms

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Plasma Cell Disorders

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Bleeding Disorders

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Thrombotic Disorders

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