Hematopathology Practice Questions

Q: Ring sideroblasts in myelodysplastic syndrome are associated with mutations in which gene?

SF3B1. **Explanation:** **Correct Answer: D. SF3B1** The presence of **ring sideroblasts** (erythroblasts with iron-laden mitochondria encircling the nucleus) is a hallmark of specific subtypes of Myelodysplastic Syndrome (MDS). The **SF3B1** (*Splicing Factor 3b Subunit 1*) gene mutation is highly specific for MDS with ring sideroblasts (MDS-RS). This gene encodes a core component of the RNA splicing machinery (spliceosome) [1]. Mutations lead to aberrant splicing of iron transporters (like *ABCB7*), causing mitochondrial iron accumulation. In the revised WHO/ICC classifications, the presence of an SF3B1 mutation allows for the diagnosis of MDS-RS even if the ring sideroblast count is as low as 5% (compared to the usual 15% threshold). **Incorrect Options:** * **A. ASXL1:** An epigenetic regulator. Mutations are common in MDS and AML but are associated with a **poor prognosis** and do not specifically correlate with ring sideroblasts [1]. * **B. EZH2:** Part of the Polycomb Repressive Complex 2 (PRC2). Mutations are linked to myelofibrosis and MDS but signify an adverse prognosis rather than a specific morphological feature [1]. * **C. TET2:** One of the most common mutations in MDS and Clonal Hematopoiesis of Indeterminate Potential (CHIP). It involves DNA demethylation; while common, it is not specific to the sideroblastic phenotype [1]. **High-Yield Clinical Pearls for NEET-PG:** * **Stain for Ring Sideroblasts:** Perls’ Prussian Blue stain. * **Definition:** ≥5 granules covering at least 1/3rd of the nuclear circumference. * **Prognostic Value:** SF3B1 mutations in MDS are generally associated with a **favorable prognosis** and lower risk of transformation to AML. * **Treatment:** Luspatercept is a newer agent used specifically for anemia in MDS-RS patients. **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, pp. 622-624.

Q: A 26-year-old African-American pilot develops anemia, hemoglobinemia, and hemoglobinuria several days after beginning primaquine chemoprophylaxis for Plasmodium vivax malaria. Special studies will likely reveal an abnormality in which of the following?

G6PD. **Explanation:** The clinical presentation of anemia, hemoglobinemia, and hemoglobinuria following the administration of **Primaquine** is a classic manifestation of **Glucose-6-Phosphate Dehydrogenase (G6PD) deficiency**. **1. Why G6PD is correct:** G6PD is the rate-limiting enzyme in the Pentose Phosphate Pathway, responsible for generating **NADPH**. NADPH is essential for maintaining a pool of reduced **glutathione**, which protects red blood cells (RBCs) from oxidative stress. Primaquine is an oxidizing agent. In G6PD-deficient individuals (common in African-American and Mediterranean populations), the RBCs cannot neutralize the oxidative stress caused by the drug, leading to the denaturation of hemoglobin (**Heinz bodies**), damage to the RBC membrane (**Bite cells**), and subsequent intravascular hemolysis. **2. Why other options are incorrect:** * **Duffy antigen:** Absence of this antigen on RBCs provides resistance to *Plasmodium vivax* infection, as the parasite uses it as a receptor for entry. It is not related to drug-induced hemolysis. * **Intrinsic factor:** Deficiency leads to Vitamin B12 malabsorption and Megaloblastic (Pernicious) anemia, not acute hemolytic anemia. * **PIG-A:** Mutations in the PIG-A gene lead to **Paroxysmal Nocturnal Hemoglobinuria (PNH)** due to a deficiency of GPI-anchored proteins (CD55/CD59). While it causes hemoglobinuria, it is not triggered by Primaquine. **High-Yield NEET-PG Pearls:** * **Inheritance:** G6PD deficiency is an **X-linked recessive** disorder. * **Morphology:** Look for **Heinz bodies** (denatured Hb) and **Bite cells** (degluticytes) on peripheral smear. * **Contraindication:** Always screen for G6PD deficiency before prescribing Primaquine or Dapsone. * **Primaquine's Role:** It is the drug of choice for the **radical cure** of *P. vivax* and *P. ovale* as it acts on **hypnozoites** (latent liver stages).

Q: Which of the following is NOT true about histiocytosis X?

Associated with angiomyolipoma of the kidney. **Explanation:** **Histiocytosis X**, now more commonly known as **Langerhans Cell Histiocytosis (LCH)**, is a clonal proliferation of Langerhans cells [1]. **Why Option D is the correct answer:** Langerhans Cell Histiocytosis is **not** associated with renal angiomyolipoma. Angiomyolipoma of the kidney is a classic feature of **Tuberous Sclerosis**, a neurocutaneous syndrome [2]. LCH, while multisystemic, primarily involves the bone, skin, and lungs, but does not typically manifest with renal hamartomas [2]. **Analysis of Incorrect Options:** * **Option A:** Seborrheic-like dermatitis (scaly, erythematous rash) is a classic cutaneous presentation of LCH, particularly in the Letterer-Siwe disease variant seen in infants. * **Option B:** **Birbeck granules** are the pathognomonic ultrastructural hallmark of LCH [1]. Seen on electron microscopy, they are "tennis-racket" shaped pentalaminar structures containing the protein **Langerin (CD207)** [1]. * **Option C:** Lytic "punched-out" bony lesions (especially in the skull) are the most common clinical presentation, particularly in the Eosinophilic Granuloma variant. **High-Yield Clinical Pearls for NEET-PG:** * **Immunophenotype:** LCH cells are positive for **S100, CD1a, and Langerin (CD207)** [1]. * **Hand-Schüller-Christian Disease:** A clinical triad of LCH consisting of: 1. Lytic skull lesions, 2. Exophthalmos, and 3. Diabetes Insipidus. * **Morphology:** Cells have characteristic "coffee-bean" nuclei (grooved nuclei) [1]. * **Prognosis:** Letterer-Siwe (Multisystem) has the worst prognosis; Eosinophilic Granuloma (Unifocal) has the best. **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, pp. 629-630. [2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. The Central Nervous System, pp. 1318-1319.

Question 1

A 33-year-old alcoholic patient on anti-tuberculosis treatment (ATT) presents with increased serum iron and increased transferrin saturation. What is the most likely diagnosis?

Accepted Answer

Sideroblastic anemia

Answer

Iron deficiency anemia

Answer

Megaloblastic anemia

Answer

Anemia of chronic disease

Question 2

Ring sideroblasts in myelodysplastic syndrome are associated with mutations in which gene?

Accepted Answer

SF3B1

Answer

ASXL1

Answer

EZH2

Answer

TET2

Question 3

A 16-year-old girl presents with bowel obstruction. Laparotomy reveals markedly enlarged para-aortic lymph nodes. Biopsy of the lymph nodes exhibits a diffuse neoplastic infiltrate of small, round lymphocytes with a 'starry sky' appearance on low power. The cytoplasm of some lymphocytes is vacuolated and fat stains are positive. What would you expect the neoplastic cells to demonstrate?

Accepted Answer

t(8;14) translocation

Answer

Positive non-specific esterase stain of the cells

Answer

Positive specific esterase stain of the cells

Answer

Low leukocyte alkaline phosphatase score

Question 4

A 26-year-old African-American pilot develops anemia, hemoglobinemia, and hemoglobinuria several days after beginning primaquine chemoprophylaxis for Plasmodium vivax malaria. Special studies will likely reveal an abnormality in which of the following?

Accepted Answer

G6PD

Answer

Duffy antigen

Answer

Intrinsic factor

Answer

PIG-A

Question 5

In Von Willebrand disease, what is the primary defect?

Accepted Answer

Defects in von Willebrand factor

Answer

Factor VII deficiency

Answer

Factor VIII C deficiency

Answer

Factor X deficiency

Question 6

In the Philadelphia chromosome, what genetic defect is present?

Accepted Answer

Long arm of chromosome 22

Answer

Short arm of chromosome 22

Answer

Short arm of chromosome 9

Answer

Chromosome 21

Question 7

Classical 'Rain drop' lesions are seen in which of the following conditions?

Accepted Answer

Multiple myeloma

Answer

Burkitt's lymphoma

Answer

Hodgkin's lymphoma

Answer

Haemophilia

Question 8

Which of the following is NOT true about histiocytosis X?

Accepted Answer

Associated with angiomyolipoma of the kidney

Answer

Seborrheic dermatitis is a known feature

Answer

Birbeck's granules are a characteristic feature

Answer

Lytic bony lesions are known

Question 9

A patient develops an ovarian mass that is picked up on pelvic examination. Resection of the mass demonstrates a lymphoma composed of small lymphocytes with interspersed macrophages surrounded by clear spaces. This lesion would be most likely to be associated with which of the following?

Accepted Answer

c-MYC activation

Answer

ABL-BCR hybrid

Answer

BCL-2 activation

Answer

t(9;22)

Question 10

Which of the following haemoglobin estimations will be diagnostically helpful in a case of beta thalassemia trait?

Accepted Answer

Hb-A2

Answer

Hb-F

Answer

Hb-C

Answer

Hb-H

Hematopathology — MCQs

Hematopathology — MCQs

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