Hematopathology Practice Questions

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

Mitochondria. **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.

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

Arginine. **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.

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

Karyotyping. ***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.

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

Lead poisoning. ***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.

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

GpIb/IX complex. ***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.

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

t(2;5). ***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.

Question 1

What is the effective red cell diameter?

Accepted Answer

Thalassemia minor anemia may present with normal RBC diameter

Answer

Different in males and females

Answer

Diameter of 500 microns

Answer

Mixed iron and folic deficiency anemia produce microcytic red blood cells

Question 2

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

Accepted Answer

Mitochondria

Answer

Endoplasmic reticulum

Answer

Nucleus

Answer

Nuclear membrane

Question 3

Which of the following is not a B cell marker?

Accepted Answer

CD 134

Answer

CD 19

Answer

CD 20

Answer

CD 10

Question 4

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

Accepted Answer

Arginine

Answer

Alanine

Answer

Glycine

Answer

Glutamine

Question 5

Hereditary spherocytosis is characterized by:

Accepted Answer

All of the above

Answer

Anemia

Answer

Splenomegaly

Answer

Jaundice

Question 6

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?

Accepted Answer

Adhesion

Answer

Aggregation

Answer

Formation of fibrinogen bridges

Answer

Conformational change with activation of phospholipid surface

Question 7

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

Accepted Answer

Karyotyping

Answer

LAP score

Answer

FISH

Answer

Molecular testing (BCR-ABL PCR)

Question 8

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

Accepted Answer

Lead poisoning

Answer

Megaloblastic anemia

Answer

Hereditary spherocytosis

Answer

Iron deficiency anaemia

Question 9

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

Accepted Answer

GpIb/IX complex

Answer

GpIV

Answer

GpIa/IIa

Answer

GpIIb/IIIa

Question 10

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

Accepted Answer

t(2;5)

Answer

t(14;18)

Answer

t(8;22)

Answer

t(8;14)

Hematopathology — MCQs

Hematopathology — MCQs

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