Hematopathology Practice Questions

Q: The peripheral blood smear is characteristic of which of the following hematological conditions?

Hereditary spherocytosis. ***Hereditary spherocytosis*** - Peripheral blood smear shows **spherocytes** - small, round, hyperchromatic RBCs with **absent central pallor** due to membrane loss. - **Osmotic fragility test** is positive, and patients often present with **hemolytic anemia**, **jaundice**, and **splenomegaly**. *Thalassemia* - Characteristic findings include **target cells**, **hypochromic microcytic RBCs**, and **basophilic stippling** on peripheral smear. - **Hemoglobin electrophoresis** shows elevated HbA2 and HbF levels, not spherocytes. *Sickle cell anemia* - Peripheral blood smear demonstrates **sickle-shaped** or **crescent-shaped** RBCs during sickling crises. - **Hemoglobin electrophoresis** reveals HbS, and patients experience **vaso-occlusive crises**. *G6PD deficiency* - Characteristic findings include **bite cells**, **blister cells**, and **Heinz bodies** on **supravital staining**. - Hemolysis typically occurs after exposure to **oxidative stress** from drugs or infections, not spontaneously.

Q: What is the concentration of Hb A2 in thalassemia trait?

Slightly increased. **Explanation:** In **$\beta$-thalassemia trait** (minor), there is a partial deficiency in the production of $\beta$-globin chains. To compensate for this deficit, the body increases the production of alternative hemoglobin types that do not require $\beta$-chains. 1. **Why "Slightly Increased" is correct:** In $\beta$-thalassemia trait, the excess $\alpha$-chains pair with $\delta$-chains to form **Hb A2 ($\alpha_2\delta_2$)**. In a healthy adult, Hb A2 is typically <3%. In $\beta$-thalassemia trait, it characteristically rises to **3.5% – 7%**. While this is a diagnostic increase, it is medically classified as "slight" compared to the massive shifts seen in other hemoglobinopathies. 2. **Analysis of Incorrect Options:** * **Normal:** A normal Hb A2 level (2-3%) usually rules out $\beta$-thalassemia trait (except in rare cases of co-existing iron deficiency). * **Increased/Markedly Increased:** These terms are imprecise or misleading. "Markedly increased" would describe HbF levels in $\beta$-thalassemia major (often >90%). In the context of standardized exams like NEET-PG, the specific elevation of Hb A2 in trait is classically described as "slight." **High-Yield Clinical Pearls for NEET-PG:** * **Gold Standard Diagnosis:** Hb electrophoresis showing Hb A2 >3.5% is the diagnostic hallmark of $\beta$-thalassemia trait. * **Mentzer Index:** (MCV/RBC count) 13 suggests Iron Deficiency Anemia (IDA). * **The IDA Trap:** Concomitant iron deficiency can mask $\beta$-thalassemia trait by lowering Hb A2 levels into the normal range. Always correct iron stores before testing. * **Peripheral Smear:** Shows microcytic hypochromic anemia with **target cells** and basophilic stippling [1]. **References:** [1] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Problems From Blood And Bone Marrow Disease, pp. 590-591.

Q: CAR-T cells are used in the treatment of which of the following cancers?

Acute lymphoblastic leukemia. **Explanation:** **Chimeric Antigen Receptor (CAR) T-cell therapy** is a revolutionary form of adoptive immunotherapy where a patient’s T-cells are genetically engineered to express a synthetic receptor that recognizes specific tumor antigens without the need for MHC presentation. **Why Option A is Correct:** The most successful application of CAR-T therapy to date is in B-cell malignancies. The engineered T-cells typically target **CD19**, a surface marker found on almost all B-cells. **Acute Lymphoblastic Leukemia (ALL)**, specifically B-ALL, shows high expression of CD19, making it highly susceptible to this therapy. It is currently FDA-approved for relapsed or refractory B-cell ALL in children and young adults [1]. **Why Other Options are Incorrect:** * **Options B, C, and D (Soft tissue sarcoma, Medulloblastoma, Small cell lung carcinoma):** These are all **solid tumors**. CAR-T therapy faces significant challenges in solid tumors due to the lack of unique tumor-specific antigens, poor penetration into the dense tumor microenvironment, and local immunosuppressive factors. While research is ongoing, they are not currently standard indications for CAR-T therapy. **High-Yield Clinical Pearls for NEET-PG:** * **Target Antigen:** Most common target is **CD19** (used in Tisagenlecleucel and Axicabtagene ciloleucel). * **Major Side Effect:** **Cytokine Release Syndrome (CRS)**, characterized by high fever and hypotension due to massive release of IL-6. * **Management of CRS:** The IL-6 receptor antagonist **Tocilizumab** is the drug of choice. * **Neurotoxicity:** Also known as ICANS (Immune Effector Cell-Associated Neurotoxicity Syndrome), it is the second most common serious side effect. **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. 635-636.

Q: Poorest prognosis in Acute Myeloid Leukemia (AML) is seen in which cytogenetic abnormality?

Monosomy 7. **Explanation:** In Acute Myeloid Leukemia (AML), cytogenetics is the single most important predictor of treatment response and overall survival [1]. **Why Monosomy 7 is the Correct Answer:** Monosomy 7 (-7) or a deletion of the long arm of chromosome 7 (7q-) is categorized under the **Adverse/Poor Risk group** [1]. It is frequently associated with complex karyotypes, prior exposure to chemotherapy (therapy-related AML), or evolution from Myelodysplastic Syndrome (MDS). These cases are notorious for multi-drug resistance and a very high rate of relapse, often requiring Allogeneic Stem Cell Transplant as the only curative option [1]. **Analysis of Incorrect Options:** * **B. No cytogenetic abnormality:** This represents the **Intermediate Risk group** [1]. While not as favorable as specific translocations, it has a significantly better prognosis than Monosomy 7. * **C. t(15;17):** This is the hallmark of Acute Promyelocytic Leukemia (APL). It carries a **Favorable prognosis** due to its high sensitivity to All-trans Retinoic Acid (ATRA) and Arsenic Trioxide [1]. * **D. inv(16):** Along with t(8;21), this belongs to the Core Binding Factor (CBF) leukemias. It is categorized as a **Favorable prognosis** with high rates of complete remission following high-dose Cytarabine [1]. **High-Yield NEET-PG Pearls:** * **Best Prognosis:** t(15;17) followed by t(8;21) and inv(16) [1]. * **Worst Prognosis:** Monosomy 7, Monosomy 5, 11q23 abnormalities, and complex karyotypes (≥3 abnormalities) [1]. * **FLT3-ITD Mutation:** The most common molecular abnormality associated with a poor prognosis in otherwise normal cytogenetics. * **NPM1 and CEBPA Mutations:** Generally associated with a favorable prognosis in cytogenetically normal AML.

Q: Histopathological examination reveals the diagnosis as:

Hodgkin lymphoma. ***Hodgkin lymphoma*** - Characterized by the presence of **Reed-Sternberg cells** with **owl-eye nucleoli** and **binucleated giant cells**. - The classic histopathological appearance includes a **mixed inflammatory infiltrate** surrounding the characteristic malignant cells. *Ewing sarcoma* - Shows **small round blue cells** with **uniform nuclear morphology** and **high nuclear-to-cytoplasmic ratio**. - Typically positive for **CD99** immunostain and lacks the characteristic giant cells seen in lymphomas. *Kaposi Sarcoma* - Demonstrates **spindle cells** arranged in **fascicles** with **slit-like vascular spaces**. - Associated with **HHV-8 infection** and shows **extravasated red blood cells** with **hemosiderin deposits**. *Burkitt lymphoma* - Exhibits a **starry-sky pattern** due to **scattered tingible body macrophages** among uniform lymphoid cells. - Composed of **monomorphic medium-sized B cells** with **multiple nucleoli** and high mitotic activity.

Q: A 65-year-old patient presented with weakness, fatigue for 6 months, and mild abdominal discomfort. Examination revealed moderate splenomegaly. Lab findings showed severe normocytic normochromic anemia, neutropenia with monocytopenia, and thrombocytopenia. Bone marrow aspiration resulted in a 'dry' tap. A bone marrow biopsy was performed. Which of the following CD markers can be positive in this condition EXCEPT?

CD117. The clinical presentation of an elderly patient with pancytopenia (including characteristic **monocytopenia**), splenomegaly, and a **"dry tap"** on bone marrow aspiration strongly suggests **Hairy Cell Leukemia (HCL)**. HCL is a rare B-cell lymphoproliferative disorder where the bone marrow becomes fibrotic, necessitating a biopsy which typically shows "fried-egg" appearance cells. **Why CD117 is the Correct Answer:** * **CD117 (c-kit)** is a marker for hematopoietic stem cells and myeloid precursors. It is typically positive in **Acute Myeloid Leukemia (AML)** and Mastocytosis. It is **not** expressed in Hairy Cell Leukemia, making it the correct "except" choice. **Analysis of Incorrect Options (Markers positive in HCL):** * **CD11c:** An adhesion molecule (integrin) highly expressed in HCL. * **CD103:** Considered the most specific marker for HCL among the B-cell disorders. * **CD25:** The IL-2 receptor alpha chain, characteristically positive in HCL (unlike most other B-cell lymphomas). * *Note: Other positive markers include CD19, CD20, CD22, and Annexin A1 (most specific).* **Clinical Pearls for NEET-PG:** 1. **TRAP Positive:** Hairy cells show Tartrate-Resistant Acid Phosphatase (TRAP) activity. 2. **BRAF V600E Mutation:** Present in nearly 100% of classic HCL cases. 3. **Monocytopenia:** A high-yield diagnostic clue; HCL is one of the few conditions where pancytopenia specifically includes a lack of monocytes. 4. **Treatment:** Cladribine (2-CdA) is the drug of choice.

Q: What is the most common subtype of acute lymphoblastic leukemia (ALL) in children?

Pre-B cell ALL. **Explanation:** Acute Lymphoblastic Leukemia (ALL) is the most common pediatric malignancy. It is classified based on the lineage and maturity of the malignant lymphoblasts. **1. Why Pre-B cell ALL is Correct:** Approximately **80–85%** of all pediatric ALL cases are of **B-cell lineage**. Within this group, the **Early Pre-B (Pro-B)** and **Pre-B cell** subtypes are the most frequent. These cells are characterized by the expression of CD19, CD20, and CD10 (Common ALL Antigen or CALLA). The high prevalence of these immature B-cell precursors in the bone marrow during childhood development explains why this subtype is the most common. **2. Why Incorrect Options are Wrong:** * **Mature B cell ALL (Burkitt-type):** This accounts for only **2–3%** of cases. It is characterized by surface immunoglobulin expression and specific translocations like t(8;14). * **Pre-T cell ALL:** This accounts for about **12–15%** of cases. It typically presents in older adolescent males with a high white cell count and a mediastinal mass. * **Mature T cell ALL:** This is a rare subtype and significantly less common than the precursor (Pre-T) stage. **Clinical Pearls for NEET-PG:** * **Peak Age:** 2 to 5 years. * **Best Prognostic Marker:** Hyperdiploidy (>50 chromosomes) and t(12;21) [ETV6-RUNX1]. * **Poor Prognostic Marker:** Hypodiploidy and t(9;22) [Philadelphia Chromosome]. * **Common Site of Relapse:** Central Nervous System (CNS) and Testes (sanctuary sites). * **Immunophenotype:** CD10 (CALLA) positivity is a marker for a better prognosis compared to CD10 negative cases.

Question 1

All of the following are true regarding the findings of peripheral smear in vitamin B12 deficiency except?

Accepted Answer

Microcytic red cells

Answer

Hypercellular marrow

Answer

Poikilocytosis

Answer

Hypersegmented neutrophils

Question 2

Which of the following lymph nodes are commonly affected in non-Hodgkin's Lymphoma, except?

Accepted Answer

Mediastinal lymph nodes

Answer

Epitrochlear lymph nodes

Answer

Peripheral lymph nodes

Answer

Inner Waldeyer ring

Question 3

The peripheral blood smear is characteristic of which of the following hematological conditions?

Accepted Answer

Hereditary spherocytosis

Answer

Thalassemia

Answer

Sickle cell anemia

Answer

G6PD deficiency

Question 4

What is the concentration of Hb A2 in thalassemia trait?

Accepted Answer

Slightly increased

Answer

Normal

Answer

Increased

Answer

Markedly increased

Question 5

CAR-T cells are used in the treatment of which of the following cancers?

Accepted Answer

Acute lymphoblastic leukemia

Answer

Soft tissue sarcoma

Answer

Medulloblastoma

Answer

Small cell lung carcinoma

Question 6

Poorest prognosis in Acute Myeloid Leukemia (AML) is seen in which cytogenetic abnormality?

Accepted Answer

Monosomy 7

Answer

No cytogenetic abnormality

Answer

t(15;17)

Answer

inv(16)

Question 7

What is the characteristic CD marker for Langerhans cells?

Accepted Answer

CD1

Answer

CD2

Answer

CD4

Answer

CD56

Question 8

Histopathological examination reveals the diagnosis as:

Accepted Answer

Hodgkin lymphoma

Answer

Ewing sarcoma

Answer

Kaposi Sarcoma

Answer

Burkitt lymphoma

Question 9

A 65-year-old patient presented with weakness, fatigue for 6 months, and mild abdominal discomfort. Examination revealed moderate splenomegaly. Lab findings showed severe normocytic normochromic anemia, neutropenia with monocytopenia, and thrombocytopenia. Bone marrow aspiration resulted in a 'dry' tap. A bone marrow biopsy was performed. Which of the following CD markers can be positive in this condition EXCEPT?

Accepted Answer

CD117

Answer

CD11c

Answer

CD103

Answer

CD25

Question 10

What is the most common subtype of acute lymphoblastic leukemia (ALL) in children?

Accepted Answer

Pre-B cell ALL

Answer

Mature B cell ALL

Answer

Pre-T cell ALL

Answer

Mature T cell ALL

Hematopathology — MCQs

Hematopathology — MCQs

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