Hematopathology Practice Questions

Q: A 4-year-old boy presents with chronic microcytic anemia and splenomegaly, but no other symptoms. His condition is due to decreased alpha-chain production, leading to the formation of four beta-chain tetramers (HbH). For this patient with a hemoglobin abnormality, what is the most likely diagnosis?

HbH disease. ### Explanation **Correct Answer: B. HbH disease** The clinical presentation and pathophysiology described are classic for **HbH disease**, a subtype of **Alpha-thalassemia**. 1. **Pathophysiology:** Alpha-thalassemia occurs due to the deletion of alpha-globin genes (normally four genes exist). HbH disease specifically results from the **deletion of 3 out of 4 alpha genes (--/-α)**. 2. **Mechanism:** When alpha-chain production is severely decreased, there is a relative excess of beta-chains. These excess beta-chains aggregate to form **tetramers ($\beta_4$)**, known as **Hemoglobin H (HbH)**. 3. **Clinical Features:** HbH has a very high affinity for oxygen, making it ineffective at delivering oxygen to tissues. It is also unstable and precipitates as **Heinz bodies**, leading to chronic hemolytic anemia and splenomegaly. --- ### Why the other options are incorrect: * **A. Beta-thalassemia major:** This is caused by a deficiency in beta-chain production, leading to an excess of alpha-chains (not beta-chains). It typically presents with severe anemia and "chipmunk facies" due to extramedullary hematopoiesis. * **C. Sickle cell disease:** This is a qualitative defect caused by a point mutation (glutamic acid to valine) in the beta-globin chain, forming HbS. It does not involve beta-tetramers. * **D. HbC disease:** This is caused by a mutation where glutamic acid is replaced by lysine. It is characterized by "HbC crystals" on peripheral smear, not HbH tetramers. --- ### NEET-PG High-Yield Pearls: * **Hb Bart’s:** A tetramer of four gamma chains ($\gamma_4$) seen in **Hydrops Fetalis** (deletion of all 4 alpha genes). * **Peripheral Smear:** HbH disease shows a "golf ball appearance" of RBCs when stained with **Supravital stains** (like Brilliant Cresyl Blue) due to precipitated HbH. * **Genetics:** Alpha-thalassemia is usually due to **gene deletions**, whereas Beta-thalassemia is usually due to **point mutations**.

Q: A 72-year-old female presents with complaints of generalized lymphadenopathy and a total WBC count of 80,000. Flow cytometry revealed CD19+, CD20+, CD5+, CD23-. Cyclin D1 is positive. Which of the following genetic abnormalities is expected in this condition?

t(11;14). ### Explanation The clinical presentation and immunophenotype point toward a diagnosis of **Mantle Cell Lymphoma (MCL)**. **1. Why t(11;14) is correct:** The key diagnostic markers in this case are **CD5+**, **CD23-**, and **Cyclin D1 positivity** [1]. While both Chronic Lymphocytic Leukemia (CLL) and MCL are CD5+ B-cell neoplasms, MCL is characteristically CD23 negative and expresses Cyclin D1 [1]. The genetic hallmark of MCL is **t(11;14)(q13;q32)**. This translocation involves the *CCND1* gene (Cyclin D1) on chromosome 11 and the *IGH* gene (Immunoglobulin Heavy chain) on chromosome 14. This leads to the overexpression of Cyclin D1, which promotes cell cycle progression from G1 to S phase. **2. Why the other options are incorrect:** * **t(8;21):** Associated with **Acute Myeloid Leukemia (AML-M2)**; it involves the *RUNX1-RUNX1T1* fusion. * **13q deletion:** The most common cytogenetic abnormality in **CLL/SLL**. CLL is typically CD5+ but, unlike this case, it is **CD23+** and Cyclin D1 negative [1]. * **t(11;18):** Associated with **MALT lymphoma** (Marginal Zone Lymphoma); it involves the *BIRC3-MALT1* fusion. **3. High-Yield Clinical Pearls for NEET-PG:** * **Mantle Cell Lymphoma:** Typically presents in elderly males with lymphadenopathy and often involves the GI tract (Lymphomatous polyposis). * **Immunophenotype Triad:** CD5+, CD23 negative, and FMC7+. * **Cyclin D1:** Overexpression is the "gold standard" for diagnosis; if Cyclin D1 is negative, **SOX11** is used as a highly specific alternative marker [1]. * **CLL vs. MCL:** Always check CD23. **CLL = CD23+**; **MCL = CD23-** [1]. **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. 610-612.

Q: A couple, with a family history of beta thalassemia major in a distant relative, has come for counseling. The husband has HbA2 of 4.8% and the wife has HbA2 of 2.3%. What is the risk of them having a child with beta thalassemia major?

0%. ### Explanation The risk of a child having Beta Thalassemia Major depends on the carrier status of **both** parents. Beta thalassemia is an autosomal recessive disorder. **1. Why the correct answer is 0%:** * **The Husband:** An **HbA2 level >3.5%** (specifically 4%–8%) is the diagnostic hallmark of **Beta Thalassemia Trait (BTT)**. With an HbA2 of 4.8%, the husband is a carrier. * **The Wife:** A normal HbA2 level is typically **between 2% and 3%**. Her level of 2.3% is well within the normal range, indicating she is **not a carrier** of the beta-thalassemia gene. * **The Inheritance:** For a child to have Thalassemia Major, they must inherit one mutated gene from *each* parent (Homozygous state). Since the wife is hematologically normal, she will always pass on a normal gene. Therefore, the couple can only have children who are either normal or carriers (Thalassemia Minor), but the risk of Thalassemia Major is **0%**. **2. Why the incorrect options are wrong:** * **25%:** This would be the risk if **both** parents were carriers (BTT x BTT). * **50%:** This would be the risk of having a child with **Thalassemia Minor** (carrier) in this specific scenario, or the risk of Major if one parent had Thalassemia Intermedia/Major and the other was a carrier. * **5%:** This value does not correspond to standard Mendelian inheritance patterns for this condition. **3. Clinical Pearls for NEET-PG:** * **Screening Gold Standard:** Hb-HPLC (High-Performance Liquid Chromatography) is used to quantify HbA2. * **Mentzer Index:** (MCV/RBC count) 13 suggests Iron Deficiency Anemia. * **Silent Carriers:** If a patient has microcytic anemia but normal HbA2, consider **Alpha Thalassemia** or co-existing Iron Deficiency (which can falsely lower HbA2). * **Rule of Thumb:** If one parent is normal, Thalassemia Major is impossible in the offspring.

Question 1

A 62-year-old man develops itchy, scaling, and non-scaling patches and plaques over his chest and back. The rest of the examination is normal, except for lymphadenopathy. Blood film and skin biopsy histology both reveal unusually large monocytoid cells. Which of the following is the most likely diagnosis?

Accepted Answer

Primary cutaneous T-cell lymphoma

Answer

Leukemia

Answer

Visceral B-cell lymphoma

Answer

Viral infection (usually Epstein-Barr)

Question 2

Which of the following conditions is LEAST likely to be accompanied by lymphocytosis in the peripheral blood?

Accepted Answer

Bacterial infection

Answer

Viral infection

Answer

Fungal infection

Answer

Protozoal infection

Question 3

What is the most common cause of congestive splenomegaly?

Accepted Answer

Cirrhosis

Answer

Chronic congestive cardiac failure

Answer

Hepatic vein occlusion

Answer

Stenosis of the splenic vein

Question 4

A 4-year-old boy presents with chronic microcytic anemia and splenomegaly, but no other symptoms. His condition is due to decreased alpha-chain production, leading to the formation of four beta-chain tetramers (HbH). For this patient with a hemoglobin abnormality, what is the most likely diagnosis?

Accepted Answer

HbH disease

Answer

Beta-thalassemia major

Answer

Sickle cell disease

Answer

HbC disease

Question 5

A 72-year-old female presents with complaints of generalized lymphadenopathy and a total WBC count of 80,000. Flow cytometry revealed CD19+, CD20+, CD5+, CD23-. Cyclin D1 is positive. Which of the following genetic abnormalities is expected in this condition?

Accepted Answer

t(11;14)

Answer

t(8;21)

Answer

13q deletion

Answer

t(11;18)

Question 6

Which of the following statements is true of hereditary spherocytosis (HS)?

Accepted Answer

Pigment-type gallstones are common.

Answer

Diagnosis can be made in the neonatal period easily by examination of a blood film.

Answer

Intravascular hemolysis is a common feature.

Answer

Autosomal recessive inheritance is seen in the majority of cases.

Question 7

Antibodies in Immune Thrombocytopenic Purpura (ITP) are typically:

Accepted Answer

IgG

Answer

IgM

Answer

IgE

Answer

IgD

Question 8

A couple, with a family history of beta thalassemia major in a distant relative, has come for counseling. The husband has HbA2 of 4.8% and the wife has HbA2 of 2.3%. What is the risk of them having a child with beta thalassemia major?

Accepted Answer

0%

Answer

50%

Answer

25%

Answer

5%

Question 9

Which of the following is NOT an intrinsic cause of hemolytic anemia?

Accepted Answer

Hypersplenism

Answer

G6PD deficiency

Answer

Hereditary spherocytosis

Answer

Pyruvate kinase deficiency

Question 10

All of the following are major complications of massive blood transfusion except?

Accepted Answer

Hyperthermia

Answer

Hyperkalemia

Answer

Coagulopathy

Answer

Hypocalcemia

Hematopathology — MCQs

Hematopathology — MCQs

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