Hematopathology — MCQs

A 28-year-old female presents with prolonged bleeding time and a normal platelet count. She reports a history of easy bruising, frequent gum bleeding, epistaxis, cutaneous bleeding, and menorrhagia. Further testing revealed a deficiency of Von Willebrand factor. Which of the following thrombogenic processes involving platelets is most directly impaired?

Q1247

Which of the following is the investigation of choice for CML?

Q1248

Basophilic stippling of red blood cells is most characteristically seen in which of the following conditions?

Q1249

Bernard-Soulier syndrome is caused by a defect in which of the following platelet glycoproteins?

Q1250

2-year-old with fever, lymphadenopathy and H&E shows hallmark cells. The diagnosis of anaplastic large cell lymphoma was made. Most likely translocation?

Hematopathology Indian Medical PG Practice Questions and MCQs

Question 1241: What is the effective red cell diameter?

A. Different in males and females
B. Diameter of 500 microns
C. Thalassemia minor anemia may present with normal RBC diameter (Correct Answer)
D. Mixed iron and folic deficiency anemia produce microcytic red blood cells

Explanation: **Explanation:** The "effective red cell diameter" refers to the average size of circulating erythrocytes, typically measured as the Mean Corpuscular Volume (MCV) or via peripheral smear examination. **Why Option C is Correct:** In **Thalassemia minor**, the red blood cell count is often paradoxically high (polycythemia) while the cells are microcytic and hypochromic [1]. However, in mild cases or early presentations, the MCV may remain within the lower end of the normal range (low-normal), making the red cell diameter appear effectively normal. A key diagnostic clue here is the **Mentzer Index** (MCV/RBC count); a ratio <13 strongly suggests Thalassemia over Iron Deficiency Anemia. **Analysis of Incorrect Options:** * **Option A:** The average diameter of a red blood cell (approx. 7.2–7.5 μm) is **constant** across both males and females. While hemoglobin levels and hematocrit differ by gender, the size of individual cells does not. * **Option B:** A diameter of 500 microns is physiologically impossible for a human cell; the standard RBC diameter is **7.2–7.5 microns** [2]. * **Option C:** Mixed deficiency (Iron + B12/Folate) typically results in a **dimorphic blood picture** [1]. The microcytic cells (from iron deficiency) and macrocytic cells (from B12/Folate deficiency) may average out to a "normal" MCV, but the cells are not uniformly microcytic. **NEET-PG High-Yield Pearls:** 1. **Mentzer Index:** MCV/RBC < 13 = Thalassemia; > 13 = Iron Deficiency Anemia. 2. **RDW (Red Cell Distribution Width):** Usually normal in Thalassemia minor but elevated in Iron Deficiency Anemia. 3. **Gold Standard for Thalassemia:** Hb Electrophoresis (showing increased HbA2 > 3.5%). 4. **RBC Lifespan:** 120 days; diameter is roughly the same size as the nucleus of a small lymphocyte [2]. **References:** [1] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Problems From Blood And Bone Marrow Disease, pp. 590-591. [2] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Problems From Blood And Bone Marrow Disease, pp. 577-578.

Question 1242: Ring sideroblasts, characterized by iron-laden mitochondria, are found in which cellular organelle?

A. Endoplasmic reticulum
B. Nucleus
C. Mitochondria (Correct Answer)
D. Nuclear membrane

Explanation: **Explanation:** **1. Why Mitochondria is Correct:** Ring sideroblasts are hallmark cells found in **Sideroblastic Anemia**. The underlying pathology involves a defect in heme synthesis, specifically the inability to incorporate iron into protoporphyrin IX. When this process fails, iron continues to enter the erythroid precursor but cannot be utilized. This excess iron accumulates within the **mitochondria**, which are arranged in a "necklace-like" or perinuclear distribution around at least one-third of the nucleus [1]. On a **Prussian Blue (Perls') stain**, these iron-laden mitochondria appear as distinct blue granules, forming the characteristic "ring." **2. Why Other Options are Incorrect:** * **Endoplasmic Reticulum:** While involved in protein synthesis and calcium storage, the ER does not play a direct role in the terminal steps of heme synthesis or pathological iron sequestration. * **Nucleus:** Iron does not accumulate within the nucleus in sideroblastic anemia. The "ring" appearance is perinuclear (around the nucleus), not intranuclear. * **Nuclear Membrane:** Although the iron-laden mitochondria cluster closely around the nucleus, they are distinct organelles located in the cytoplasm and are not part of the nuclear membrane structure itself. **3. NEET-PG High-Yield Pearls:** * **Stain of Choice:** Prussian Blue (Perls') stain is essential to visualize ring sideroblasts. * **Definition:** A "ring sideroblast" must have $\geq$ 5 iron granules covering at least one-third of the nuclear circumference. * **Common Causes:** Hereditary (ALAS2 mutation), Lead poisoning, Alcoholism, Isoniazid (Vitamin B6 deficiency), and Myelodysplastic Syndrome (MDS-RS). * **Key Enzyme:** The most common hereditary defect is in **5-aminolevulinate synthase (ALAS2)**. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. With Illustrations By, pp. 18-19.

Question 1243: Which of the following is not a B cell marker?

A. CD 19
B. CD 20
C. CD 134 (Correct Answer)
D. CD 10

Explanation: ### Explanation **Correct Option: C (CD 134)** **Medical Concept:** B-cell markers are specific cluster of differentiation (CD) antigens expressed on the surface of B-lymphocytes at various stages of maturation. **CD 134**, also known as **OX40**, is a member of the tumor necrosis factor receptor superfamily. It is primarily expressed on **activated T-cells** (especially CD4+ T-cells) and acts as a potent co-stimulatory molecule [3]. It is not expressed on B-cells, making it the correct answer. **Analysis of Other Options:** * **CD 19:** This is the most specific and earliest marker for the B-cell lineage [2]. It is expressed from the pro-B cell stage until it is lost during terminal differentiation into plasma cells [2]. * **CD 20:** A widely used pan-B cell marker expressed on mature B-cells [2]. It is the target for the monoclonal antibody **Rituximab**. Like CD 19, it is lost during plasma cell differentiation [2]. * **CD 10:** Also known as **CALLA** (Common Acute Lymphoblastic Leukemia Antigen). It is a marker for pre-B cells and germinal center B-cells [2]. It is highly significant in diagnosing B-ALL and Follicular Lymphoma. **High-Yield Clinical Pearls for NEET-PG:** * **Pan-B cell markers:** CD19, CD20, CD22, CD79a [1] [2]. * **Plasma cell markers:** CD138 (Syndecan-1), CD38, and CD56 (in myeloma). * **T-cell markers:** CD3 (most specific), CD4, CD5, CD7, CD8 [2]. * **Germinal Center markers:** CD10, BCL-6. * **Mantle Zone marker:** CD5 (also a T-cell marker, but expressed in Mantle Cell Lymphoma and CLL) [2]. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Diseases of the Immune System, pp. 199-200. [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. 598. [3] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Diseases of the Immune System, pp. 198-199.

Question 1244: Factor V Leiden is caused by a mutation resulting in a substitution at position 506, changing glutamine to which of the following amino acids?

A. Alanine
B. Arginine (Correct Answer)
C. Glycine
D. Glutamine

Explanation: **Explanation:** **Factor V Leiden** is the most common inherited cause of hypercoagulability (thrombophilia) [1]. The underlying molecular defect is a specific point mutation in the Factor V gene, where **Guanine is replaced by Adenine (G1691A)**. This results in a single amino acid substitution at **position 506**, where **Arginine (Arg) is replaced by Glutamine (Gln)**. **Why Arginine is the Correct Answer:** Normally, Activated Protein C (APC) inactivates Factor Va by cleaving it at the Arg506 site. In Factor V Leiden, the substitution of Arginine with Glutamine renders the Factor V molecule resistant to cleavage by APC. This phenomenon is known as **Activated Protein C Resistance (APCR)**. Because Factor Va cannot be deactivated, it remains in the circulation longer, leading to a prothrombotic state and an increased risk of Deep Vein Thrombosis (DVT). **Analysis of Incorrect Options:** * **Option A (Alanine) & Option C (Glycine):** These amino acids are not involved in the specific point mutation that defines Factor V Leiden. * **Option D (Glutamine):** This is the amino acid that *replaces* Arginine. The question asks for the original amino acid at position 506 that is substituted. **High-Yield Clinical Pearls for NEET-PG:** * **Inheritance:** Autosomal Dominant. * **Clinical Presentation:** Recurrent DVT and pulmonary embolism; it is also associated with pregnancy complications like recurrent miscarriages. * **Diagnosis:** Screening is done via the **APC Resistance Test** (clotting assay); definitive diagnosis is made via **PCR** for the G1691A mutation. * **Risk:** Heterozygotes have a 5–10 fold increased risk of thrombosis, while homozygotes have an 80-fold increased risk. **References:** [1] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Problems From Cardiovascular Disease, pp. 281-282.

Question 1245: Hereditary spherocytosis is characterized by:

A. Anemia
B. Splenomegaly
C. Jaundice
D. All of the above (Correct Answer)

Explanation: **Explanation:** Hereditary Spherocytosis (HS) is an autosomal dominant disorder caused by mutations in red blood cell (RBC) membrane proteins, most commonly **Ankyrin**, followed by Band 3, Spectrin, and Protein 4.2. These defects lead to a loss of membrane surface area, forcing the RBCs to assume a spherical shape (spherocytes) [1]. The correct answer is **"All of the above"** because of the classic clinical triad of HS: 1. **Anemia:** Spherocytes are non-deformable. As they pass through the narrow splenic cords, they are trapped and destroyed by splenic macrophages (**extravascular hemolysis**), leading to anemia [1]. 2. **Splenomegaly:** Constant sequestration and destruction of abnormal RBCs lead to work hypertrophy of the spleen, making splenomegaly a hallmark finding [1]. 3. **Jaundice:** Chronic extravascular hemolysis results in increased production of unconjugated bilirubin, leading to acholuric jaundice and a high risk of **pigmented (calcium bilirubinate) gallstones** [1], [2]. **Why individual options are insufficient:** While Anemia, Splenomegaly, and Jaundice are all present, selecting only one would be incomplete as they collectively form the diagnostic clinical presentation of the disease. **High-Yield Clinical Pearls for NEET-PG:** * **Best Initial Test:** Peripheral smear (shows spherocytes with loss of central pallor) [1]. * **Confirmatory Test (Gold Standard):** Eosin-5-maleimide (EMA) binding test via flow cytometry. * **Classic Lab Finding:** Increased **MCHC** (>36 g/dL) due to relative dehydration of the cell. * **Osmotic Fragility Test:** Shows increased fragility (cells lyse in less hypotonic solutions) [1]. * **Complication:** Aplastic crisis triggered by **Parvovirus B19** infection [1]. * **Treatment of Choice:** Splenectomy (usually deferred until after age 6 to reduce sepsis risk) [1]. **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. 640.

Question 1246: A 28-year-old female presents with prolonged bleeding time and a normal platelet count. She reports a history of easy bruising, frequent gum bleeding, epistaxis, cutaneous bleeding, and menorrhagia. Further testing revealed a deficiency of Von Willebrand factor. Which of the following thrombogenic processes involving platelets is most directly impaired?

A. Adhesion (Correct Answer)
B. Aggregation
C. Formation of fibrinogen bridges
D. Conformational change with activation of phospholipid surface

Explanation: **Explanation:** The clinical presentation of mucosal bleeding (epistaxis, menorrhagia) and easy bruising with a prolonged bleeding time but normal platelet count is classic for **Von Willebrand Disease (vWD)**. **1. Why Adhesion is the Correct Answer:** Platelet plug formation occurs in three stages: Adhesion, Activation, and Aggregation [1]. **Von Willebrand Factor (vWF)** acts as a molecular bridge between the exposed subendothelial collagen and the platelet surface receptor **GpIb-IX-V** [1], [2]. In the absence or deficiency of vWF, platelets cannot "stick" to the site of vascular injury, directly impairing the **Adhesion** phase [2]. This is the primary defect in vWD. **2. Why the Other Options are Incorrect:** * **Aggregation (Option B):** This refers to platelets sticking to *each other*. While vWF can play a minor role in aggregation under high shear stress, the primary mediator of aggregation is Fibrinogen [1]. * **Formation of fibrinogen bridges (Option C):** This is the mechanism of platelet aggregation, mediated by the **GpIIb/IIIa** receptor [2]. This process is impaired in Glanzmann Thrombasthenia, not vWD [3]. * **Conformational change (Option D):** This occurs during platelet **Activation** [1]. Once platelets adhere, they change shape and flip their membrane phospholipids (procoagulant surface) to facilitate the coagulation cascade. This is a downstream effect of successful adhesion. **NEET-PG High-Yield Pearls:** * **vWD** is the most common inherited bleeding disorder. * **Dual Role of vWF:** It mediates platelet adhesion AND acts as a carrier protein to stabilize **Factor VIII** [2]. Therefore, vWD can sometimes present with a prolonged aPTT. * **Ristocetin Cofactor Assay:** This is the gold standard test for vWF function. Ristocetin induces vWF-mediated platelet agglutination; in vWD, this agglutination is absent or decreased. * **Treatment:** Desmopressin (DDAVP) is used to release stored vWF from Weibel-Palade bodies in endothelial cells. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Hemodynamic Disorders, Thromboembolic Disease, and Shock, p. 128. [2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Red Blood Cell and Bleeding Disorders, pp. 668-670. [3] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Red Blood Cell and Bleeding Disorders, pp. 668-669.

Question 1247: Which of the following is the investigation of choice for CML?

A. LAP score
B. FISH
C. Molecular testing (BCR-ABL PCR)
D. Karyotyping (Correct Answer)

Explanation: ***Karyotyping (Conventional Cytogenetics)*** - **Gold standard** and investigation of choice for CML diagnosis - Detects the **Philadelphia chromosome t(9;22)** present in 95% of CML cases [2] - WHO diagnostic criterion for CML - Can identify additional chromosomal abnormalities with prognostic significance - Provides complete chromosomal analysis *FISH (Fluorescence In Situ Hybridization)* - Used as **complementary technique** when karyotyping fails or metaphases are inadequate - More sensitive than karyotyping but NOT the first-line investigation [2] - Useful for monitoring minimal residual disease - Cannot detect additional chromosomal abnormalities *Molecular testing (BCR-ABL PCR)* - Used for **monitoring treatment response** and detecting minimal residual disease [1] - Highly sensitive and quantitative [1] - Not the initial investigation of choice for diagnosis *LAP score (Leukocyte Alkaline Phosphatase)* - Used to differentiate CML from leukemoid reaction - Low in CML, high in leukemoid reaction - Older diagnostic tool, now largely replaced by molecular methods - Not the investigation of choice **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Genetic Disorders, pp. 185-187. [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. 225-226.

Question 1248: Basophilic stippling of red blood cells is most characteristically seen in which of the following conditions?

A. Lead poisoning (Correct Answer)
B. Megaloblastic anemia
C. Hereditary spherocytosis
D. Iron deficiency anaemia

Explanation: ***Lead poisoning*** - Lead inhibits several enzymes in the heme synthesis pathway and also inhibits **ribonuclease**, which is responsible for degrading residual ribosomal RNA (rRNA) in reticulocytes [1]. This leads to aggregation of ribosomes, appearing as coarse blue granules known as **basophilic stippling**. - While also seen in conditions like thalassemias and sideroblastic anemia, coarse basophilic stippling is a classic and highly characteristic finding in lead poisoning. *Iron deficiency anaemia* - The characteristic peripheral smear findings are **microcytic** and **hypochromic** red blood cells, which appear smaller and paler than normal [2]. - **Pencil cells** (elliptocytes) and **thrombocytosis** (an increased platelet count) are also commonly observed, but basophilic stippling is not a typical feature [2]. *Megaloblastic anemia* - This anemia, due to **vitamin B12** or **folate** deficiency, is characterized by **macro-ovalocytes** (large, oval red blood cells) and **hypersegmented neutrophils** on the peripheral smear [3]. - Other inclusions like **Howell-Jolly bodies** may be present, but basophilic stippling is not the defining feature. *Hereditary spherocytosis* - This is a genetic disorder affecting red blood cell membrane proteins, leading to the formation of **spherocytes** – small, round RBCs lacking central pallor. - The key findings are spherocytes on the smear and an increased **mean corpuscular hemoglobin concentration (MCHC)**, not basophilic stippling. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Infectious Diseases, pp. 418-419. [2] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Problems From Blood And Bone Marrow Disease, pp. 590-591. [3] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Problems From Blood And Bone Marrow Disease, pp. 594-595.

Question 1249: Bernard-Soulier syndrome is caused by a defect in which of the following platelet glycoproteins?

A. GpIb/IX complex (Correct Answer)
B. GpIV
C. GpIa/IIa
D. GpIIb/IIIa

Explanation: ***GpIb/IX complex***- Bernard-Soulier syndrome (BSS) is a rare, autosomal recessive bleeding disorder caused by a quantitative or qualitative defect in the **platelet GpIb/IX/V complex** [1].- This complex acts as the essential high-affinity receptor for **von Willebrand factor (vWF)**, mediating initial **platelet adhesion** to the injured vessel wall, which is impaired in BSS [1], [2].*GpIIb/IIIa*- A defect in **GpIIb/IIIa** (integrin $\alpha_{IIb}\beta_3$) causes **Glanzmann thrombasthenia**, which presents with impaired **platelet aggregation**, not adhesion [1].- GpIIb/IIIa is the receptor for **fibrinogen**, which is necessary to link aggregating platelets [1], [2].*GpIa/IIa*- **GpIa/IIa** (integrin $\alpha_2\beta_1$) is primarily a receptor for **collagen** on the platelet surface, mediating adhesion in parallel with GpIb/vWF.- While important for hemostasis, defects in this receptor generally cause only mild bleeding and not the characteristic **giant platelets** or severe adhesion defect seen in BSS.*GpIV*- **GpIV** (also known as CD36) is a scavenger receptor that binds to **thrombospondin** and sometimes collagen.- Platelet defects related to GpIV are rare and usually involve mild aggregation defects, distinct from the severe adhesion failure defined by BSS. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Red Blood Cell and Bleeding Disorders, pp. 668-669. [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 1250: 2-year-old with fever, lymphadenopathy and H&E shows hallmark cells. The diagnosis of anaplastic large cell lymphoma was made. Most likely translocation?

A. t(14;18)
B. t(8;22)
C. t(2;5) (Correct Answer)
D. t(8;14)

Explanation: ***Correct: t(2;5)*** - This is the **most common and classic translocation** found in systemic **Anaplastic Large Cell Lymphoma (ALCL)**, especially in children [1] - Occurs in approximately **60-85% of systemic ALCL cases** - Fuses the **NPM (Nucleophosmin)** gene on chromosome 5 with the **ALK** gene on chromosome 2 [1] - Results in constitutively active **ALK tyrosine kinase** that drives cell proliferation [1] - **ALK-positive ALCL** has a better prognosis, particularly in pediatric patients [1] *Incorrect: t(8;14)* - This is the hallmark translocation of **Burkitt Lymphoma (BL)**, not ALCL [2] - Juxtaposes the **MYC oncogene** on chromosome 8 to the **IgH promoter** on chromosome 14 [2] - Burkitt Lymphoma presents with rapidly growing masses and characteristic **"starry sky"** microscopic appearance [3] - Distinct from ALCL's hallmark cells (large cells with eccentric horseshoe/kidney-shaped nuclei) *Incorrect: t(8;22)* - A variant translocation associated with **Burkitt Lymphoma (BL)** [2] - Translocates **MYC gene** to the **kappa light chain locus** on chromosome 22 [2] - Results in MYC overexpression, which is pathognomonic for Burkitt Lymphoma - Not associated with Anaplastic Large Cell Lymphoma *Incorrect: t(14;18)* - Characteristic translocation of **Follicular Lymphoma (FL)** - Leads to overexpression of the **BCL2 anti-apoptotic protein** - Follicular Lymphoma is typically seen in adults and is a **B-cell lymphoma** - ALCL is a **T-cell/null-cell lymphoma**, making this translocation irrelevant **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. 565-566. [2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Neoplasia, pp. 324-325. [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, p. 606.

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Hemolytic Anemias

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Chronic Leukemias

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Plasma Cell Disorders

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Bleeding Disorders

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Thrombotic Disorders

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