Hematopathology Practice Questions

Q: An 18-year-old woman presents with a low hemoglobin value of 10.5 g/dL on routine CBC testing. The red cells are microcytic, but WBC and platelet counts are normal. Her iron intake is adequate, menstrual flow is normal, and there is no other history of blood loss. Physical examination is normal, and iron studies reveal a normal ferritin level. She reports that other family members have also been diagnosed with anemia and alpha-thalassemia. Which of the following hemoglobins is increased in alpha-thalassemia?

Hemoglobin H. The clinical presentation of microcytic anemia with normal ferritin levels and a positive family history strongly suggests a thalassemia syndrome. In **Alpha-Thalassemia**, there is a deficiency in the production of alpha-globin chains. Since alpha chains are essential components of all normal adult hemoglobins (HbA, HbA2, and HbF), a deficiency leads to an excess of the remaining non-alpha chains. 1. **Why Hemoglobin H is correct:** In alpha-thalassemia (specifically the 3-gene deletion or HbH disease), the relative excess of beta-globin chains leads them to aggregate into tetramers ($\beta_4$). These tetramers are known as **Hemoglobin H**. In neonates with alpha-thalassemia, excess gamma chains form tetramers ($\gamma_4$) known as **Hb Barts**. 2. **Why other options are incorrect:** * **HbA ($\alpha_2\beta_2$):** This is the major adult hemoglobin. In alpha-thalassemia, its production is decreased, not increased. * **HbF ($\alpha_2\gamma_2$) and HbA2 ($\alpha_2\delta_2$):** Both require alpha chains. Unlike Beta-thalassemia (where HbA2 and HbF increase to compensate for the lack of beta chains), in Alpha-thalassemia, these levels are typically **normal or decreased** because the alpha-chain substrate is the limiting factor. **High-Yield Clinical Pearls for NEET-PG:** * **HbH Disease:** Characterized by a "3-gene deletion" (- - / - $\alpha$). * **Golf Ball Appearance:** On supra-vital staining (Brilliant Cresyl Blue), HbH precipitates as multiple small inclusions, giving RBCs a "golf ball" appearance. * **Mentzer Index:** (MCV/RBC count) 13 suggests Iron Deficiency Anemia. * **Diagnosis:** Hb Electrophoresis is the gold standard, but in alpha-thalassemia trait (1 or 2 gene deletion), electrophoresis may be normal; definitive diagnosis requires genetic testing.

Q: What type of red blood cells (RBCs) are typically seen in chronic renal failure?

Normocytic. ### Explanation **Correct Option: C. Normocytic** The anemia associated with **Chronic Renal Failure (CRF)** is typically **Normocytic Normochromic Anemia**. **Why it is correct:** The primary pathophysiology in CRF is the **deficiency of Erythropoietin (EPO)** [1]. EPO is a glycoprotein hormone produced by the peritubular interstitial cells of the kidney in response to hypoxia [1], [2]. In chronic kidney disease, the functional renal mass decreases, leading to inadequate EPO production [1]. Since the bone marrow is healthy but lacks the hormonal signal to produce more cells, the RBCs produced are normal in size (normocytic) and color (normochromic), but their absolute number is decreased. Other contributing factors include the accumulation of uremic toxins (which shorten RBC lifespan) and chronic inflammation (Anemia of Chronic Disease). **Why other options are incorrect:** * **A. Microcytic:** This is characteristic of Iron Deficiency Anemia (IDA) or Thalassemia. While CRF patients can develop IDA due to hemodialysis blood loss or poor absorption, the *primary* anemia of renal failure itself is normocytic. * **B. Macrocytic:** This is seen in Vitamin B12 or Folic acid deficiency. While some drugs used in renal patients might interfere with folate metabolism, it is not the classic presentation of renal anemia. **High-Yield Clinical Pearls for NEET-PG:** * **Target Hemoglobin:** In patients on Erythropoiesis-Stimulating Agents (ESAs), the target Hb is usually **10–11.5 g/dL**. Aiming for normal levels (>13 g/dL) increases the risk of stroke and cardiovascular events (CHOIR and CREATE trials). * **Burr Cells (Echinocytes):** These are small, spiked RBCs often seen on the peripheral smear of patients with uremia/CRF. * **First step in management:** Before starting EPO therapy, always ensure **iron stores are adequate** (Transferrin saturation >20% and Ferritin >100 ng/mL).

Q: The MYD88 L265P mutation is characteristically seen in which of the following hematological malignancies?

Waldenstrom Macroglobulinemia. ### Explanation **Correct Answer: B. Waldenstrom Macroglobulinemia** **Mechanism:** The **MYD88 L265P** mutation is a gain-of-function mutation found in over **90-95%** of patients with Waldenstrom Macroglobulinemia (WM). MYD88 is an adapter protein in the Toll-like receptor (TLR) and Interleukin-1 receptor signaling pathways. The L265P mutation (substitution of proline for leucine at position 265) leads to constitutive activation of the **NF-̀B pathway**, promoting the survival and proliferation of malignant lymphoplasmacytic cells. **Analysis of Incorrect Options:** * **A. Hairy Cell Leukemia:** The hallmark genetic driver here is the **BRAF V600E** mutation (seen in >95% of cases). * **C. Multiple Myeloma:** Characterized by complex cytogenetics, most commonly involving **IGH translocations** [e.g., t(11;14), t(4;14)] or 13q deletions, rather than MYD88 mutations. * **D. Acute Myeloid Leukemia (AML):** Associated with mutations in **FLT3, NPM1, or DNMT3A**, and various chromosomal translocations [e.g., t(8;21), t(15;17)]. **High-Yield Clinical Pearls for NEET-PG:** * **Waldenstrom Macroglobulinemia (WM):** Defined as Lymphoplasmacytic Lymphoma (LPL) with bone marrow involvement and an **IgM monoclonal gammopathy** [1]. * **Clinical Triad:** Hyperviscosity syndrome (visual disturbances, neurological symptoms), hepatosplenomegaly, and lymphadenopathy [1]. * **Diagnostic Clue:** Absence of lytic bone lesions (unlike Multiple Myeloma) and presence of **Dutcher bodies** (intranuclear inclusions of immunoglobulins). * **Therapeutic Target:** The presence of MYD88 mutation makes these patients highly responsive to **Ibrutinib** (a BTK inhibitor). **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. 609-610.

Question 1

An 18-year-old woman presents with a low hemoglobin value of 10.5 g/dL on routine CBC testing. The red cells are microcytic, but WBC and platelet counts are normal. Her iron intake is adequate, menstrual flow is normal, and there is no other history of blood loss. Physical examination is normal, and iron studies reveal a normal ferritin level. She reports that other family members have also been diagnosed with anemia and alpha-thalassemia. Which of the following hemoglobins is increased in alpha-thalassemia?

Accepted Answer

Hemoglobin H

Answer

Hemoglobin A

Answer

Hemoglobin F

Answer

Hemoglobin A2

Question 2

Patients with lymphoproliferative disorders undergo cytogenetic analysis. A subset of these cases shows the BCR-ABL fusion gene from the reciprocal translocation t(9;22)(q34;11), resulting in increased tyrosine kinase activity. Which of the following conditions is most likely to present with this gene?

Accepted Answer

Chronic myelogenous leukemia

Answer

Acute promyelocytic leukemia

Answer

Follicular lymphoma

Answer

Hodgkin lymphoma, lymphocyte depletion type

Question 3

What is the major source of Von Willebrand factor (vWF)?

Accepted Answer

Endothelial cells

Answer

Erythrocytes

Answer

Neutrophils

Answer

Monocytes

Question 4

Hemophilia clinically manifests as a rise in which laboratory parameter?

Accepted Answer

Activated Partial Thromboplastin Time (APTT)

Answer

Prothrombin Time (PT)

Answer

Clotting Time (CT)

Answer

Fibrin Degradation Products (FDP)

Question 5

A young female patient presented with symptoms related to anemia. Peripheral blood smear showed neutrophil hypersegmentation and bone marrow aspirate smear showed giant myelocytes. Which of the following is the likely etiology?

Accepted Answer

Folic acid deficiency

Answer

Sideroblastic anemia

Answer

Iron deficiency anemia

Answer

Thalassemia

Question 6

What type of red blood cells (RBCs) are typically seen in chronic renal failure?

Accepted Answer

Normocytic

Answer

Microcytic

Answer

Macrocytic

Answer

None of the above

Question 7

What is the most common carcinoma that causes splenic metastasis?

Accepted Answer

Carcinoma of the ovary

Answer

Carcinoma of the pancreas

Answer

Carcinoma of the stomach

Answer

Carcinoma of the cervix

Question 8

Which of the following causes of anemia is associated with a hypoplastic marrow?

Accepted Answer

Fanconi's Anemia

Answer

Paroxysmal Nocturnal Hemoglobinuria (PNH)

Answer

Hypersplenism

Answer

Myelofibrosis

Question 9

Lacunar cells are characteristic of which of the following conditions?

Accepted Answer

Nodular sclerosing type of Hodgkin’s disease

Answer

Pleomorphic adenoma

Answer

Hurler’s syndrome

Answer

None of the above

Question 10

The MYD88 L265P mutation is characteristically seen in which of the following hematological malignancies?

Accepted Answer

Waldenstrom Macroglobulinemia

Answer

Hairy cell leukemia

Answer

Multiple Myeloma

Answer

Acute Myeloid Leukemia (AML)

Hematopathology — MCQs

Hematopathology — MCQs

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