Hematopathology Practice Questions

Q: A 50-year-old man presents with fever and diffuse lymphadenopathy. A lymph node biopsy reveals non-Hodgkin follicular lymphoma. Immunohistochemical staining of neoplastic lymphoid cells within the nodular areas of the lymph node would be expected to stain positively for which of the following protein markers?

Bcl-2. Explanation: Follicular Lymphoma (FL) is a B-cell neoplasm characterized by the translocation t(14;18)(q32;q21) [1, 2]. This translocation moves the BCL-2 gene from chromosome 18 to the immunoglobulin heavy chain (IgH) locus on chromosome 14 [1]. 1. Why Bcl-2 is correct: Under normal physiological conditions, germinal center B-cells are Bcl-2 negative to allow for apoptosis of cells that fail selection. In FL, the t(14;18) translocation leads to the overexpression of Bcl-2, an anti-apoptotic protein [1, 2]. This prevents programmed cell death, leading to the accumulation of neoplastic B-cells [2]. Immunohistochemistry (IHC) showing Bcl-2 positivity within the follicles is diagnostic, as it distinguishes FL from reactive follicular hyperplasia (where follicles are Bcl-2 negative) [1]. 2. Why other options are incorrect: * Abl: Associated with the t(9;22) Philadelphia chromosome, seen in Chronic Myeloid Leukemia (CML) and some cases of ALL. * Bax: A pro-apoptotic member of the Bcl-2 family. Overexpression of Bax would promote cell death, the opposite of what occurs in lymphoma. * Myc: Associated with the t(8;14) translocation, which is the hallmark of Burkitt Lymphoma, leading to rapid cellular proliferation. High-Yield Pearls for NEET-PG: * Morphology: Characterized by centrocytes (cleaved cells) and centroblasts [2]. * IHC Profile: CD19+, CD20+, CD10+, Bcl-2+, and Bcl-6+. Notably, it is CD5 negative (distinguishing it from CLL/SLL and Mantle Cell Lymphoma). * Clinical Course: Indolent (painless lymphadenopathy) but can transform into Diffuse Large B-cell Lymphoma (Richter-like transformation). **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. 602-604. [2] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Problems From Diseases Of The Urinary And Male Genital Tracts, pp. 561-562.

Q: HbE is common in which region of India?

Bengal. **Explanation:** **Hemoglobin E (HbE)** is a structural hemoglobin variant caused by a point mutation in the $\beta$-globin chain (substitution of glutamic acid by lysine at position 26). It is the most common hemoglobin variant in Southeast Asia and is highly prevalent in the **Eastern and North-Eastern regions of India**, particularly in **Bengal**, Assam, and Odisha. * **Bengal (Correct):** The gene frequency of HbE in West Bengal ranges from 3% to 10%. It is often found in the form of **E-$\beta$ Thalassemia**, which clinically presents as a condition similar to Thalassemia Intermedia or Major. * **Punjab (Incorrect):** This region is more commonly associated with a high prevalence of **$\beta$-Thalassemia trait** and **HbS (Sickle cell)** in specific tribal pockets, but not HbE. * **Kerala (Incorrect):** While hemoglobinopathies exist in South India, the prevalence of HbE is negligible compared to the Eastern belt. * **Maharashtra (Incorrect):** This region (specifically the Vidarbha belt) is a high-prevalence zone for **Sickle Cell Disease (HbS)** and $\beta$-Thalassemia, but HbE is not the dominant variant here. **High-Yield NEET-PG Pearls:** 1. **Electrophoresis:** On alkaline electrophoresis (pH 8.6), HbE migrates with **HbA2 and HbC** (Mnemonic: **A2CE** stay together). 2. **Morphology:** Peripheral smear typically shows **Target cells** and microcytic hypochromic indices. 3. **Protection:** Like HbS and Thalassemia, HbE is thought to provide a selective survival advantage against *Plasmodium falciparum* malaria. 4. **HbE-Thalassemia:** This is the most common cause of transfusion-dependent thalassemia in many parts of Eastern India.

Q: Which syndrome is not associated with leukemia?

Turner syndrome. **Explanation:** The correct answer is **Turner Syndrome (45, XO)**. Unlike the other options, Turner syndrome is a sex chromosome aneuploidy characterized by the absence of one X chromosome. It is primarily associated with congenital heart defects (coarctation of the aorta), short stature, and gonadal dysgenesis, but it does **not** carry an increased risk for leukemia. **Why the other options are incorrect:** * **Bloom Syndrome:** This is an autosomal recessive disorder caused by a mutation in the *BLM* gene (DNA helicase). It leads to chromosomal instability and "sister chromatid exchanges," significantly increasing the risk of various malignancies, particularly **Acute Myeloid Leukemia (AML)**. * **Down Syndrome (Trisomy 21):** This is the most high-yield association. Children with Down syndrome have a 10–20 fold increased risk of leukemia [1]. Specifically, they are prone to **Acute Megakaryoblastic Leukemia (AML-M7)** before age 3 and **Acute Lymphoblastic Leukemia (ALL)** after age 3. * **Ataxia Telangiectasia:** This is a DNA repair defect (ATM gene mutation). Patients have increased sensitivity to ionizing radiation and chromosomal instability, leading to a high predisposition for **T-cell ALL** and lymphomas. **NEET-PG High-Yield Pearls:** * **DNA Repair Defects:** Bloom syndrome, Fanconi anemia, and Ataxia telangiectasia are all "Chromosomal Breakage Syndromes" that predispose to leukemia. * **Down Syndrome Mnemonic:** Remember **"7 before 3, ALL after 3"** (M7 subtype of AML is common in those under 3 years old). * **Neurofibromatosis Type 1:** Also associated with an increased risk of Juvenile Myelomonocytic Leukemia (JMML). **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Genetic Disorders, pp. 170-172.

Q: A 32-year-old man has mild anemia diagnosed on routine testing. His clinical examination is normal, and a blood film reveals some target cells with some red cells having intraerythrocytic crystals. For this patient with a hemoglobin abnormality, what is the most likely diagnosis?

HbC disease. The correct answer is **HbC disease**. This diagnosis is classically associated with the presence of **intraerythrocytic crystals** (often described as "bar-of-gold" or rhomboid-shaped crystals) and **target cells** (codocytes) on a peripheral blood smear. **Why HbC disease is correct:** HbC results from a point mutation in the $\beta$-globin gene where **glutamic acid is replaced by lysine** at the 6th position. This substitution reduces the solubility of the hemoglobin, causing it to precipitate and form characteristic hexagonal or rod-shaped crystals within the red blood cells, especially in dehydrated cells or after splenectomy. Patients typically present with mild hemolytic anemia and splenomegaly, though many are asymptomatic. **Why other options are incorrect:** * **$\beta$-thalassemia major:** Presents with severe microcytic hypochromic anemia, nucleated RBCs, and significant target cells, but does not feature intraerythrocytic crystals. * **HbH disease:** A form of $\alpha$-thalassemia characterized by "golf ball" inclusions (precipitated $\beta$-globin tetramers) visible with supravital stains like Brilliant Cresyl Blue, not rhomboid crystals. * **Sickle cell disease (HbS):** Characterized by sickle-shaped cells (drepanocytes) due to the polymerization of hemoglobin under deoxygenated conditions [1]. While target cells can be seen, the pathognomonic finding is the sickle cell, not the HbC crystal [1]. **NEET-PG High-Yield Pearls:** * **Mnemonic for Mutations:** **S**ickle = **V**aline (Glutamic acid to Valine); Hb**C** = **L**ysine (Glutamic acid to **L**ysine). Remember: *"Ly-C-ne"* for HbC. * **Electrophoresis:** HbC migrates the slowest toward the anode (it is the most positively charged) among common variants (A, S, F, C) [1]. * **Target Cells:** Seen in "HALT" (HbC, Asplenia, Liver disease, Thalassemia).

Q: What is seen in lead poisoning?

Sideroblasts. **Explanation:** Lead poisoning (Plumbism) interferes with the heme biosynthetic pathway, specifically inhibiting the enzymes **delta-aminolevulinic acid dehydratase (ALAD)** and **ferrochelatase** [2]. Ferrochelatase is responsible for incorporating iron into the protoporphyrin ring to form heme. When this enzyme is inhibited, iron accumulates within the mitochondria of developing red blood cells in the bone marrow. These iron-laden mitochondria form a ring around the nucleus, creating **Ringed Sideroblasts**, which are characteristic of sideroblastic anemia. **Analysis of Options:** * **D. Sideroblasts (Correct):** As explained, the blockade of iron utilization leads to the formation of ringed sideroblasts in the bone marrow. * **A. Lymphoblasts:** These are immature precursors of lymphocytes seen in Acute Lymphoblastic Leukemia (ALL), not heavy metal poisoning. * **B. Normoblasts:** These are normal nucleated RBC precursors. While they may be present in the marrow, they are not the specific diagnostic hallmark of lead-induced pathology. * **C. Myeloblasts:** These are precursors of the myeloid lineage (granulocytes) and are the hallmark of Acute Myeloid Leukemia (AML). **High-Yield Clinical Pearls for NEET-PG:** * **Peripheral Smear:** Shows microcytic hypochromic anemia with **Basophilic Stippling** (due to inhibition of pyrimidine 5'-nucleotidase leading to RNA degradation products) [1], [4]. * **Burton’s Line:** A bluish-purple line on the gingival margins [4]. * **Radiology:** "Lead lines" (increased metaphyseal density) seen in children [1], [3]. * **Treatment:** Chelation therapy with **Succimer** (oral, first-line in children) or **Calcium EDTA/Dimercaprol** (for encephalopathy) [3].

Q: Which of the following statements is true regarding the cytochemistry of ALL?

PAS positive (Block positivity). In Hematopathology, cytochemistry is a vital tool for differentiating Acute Lymphoblastic Leukemia (ALL) from Acute Myeloid Leukemia (AML). **1. Why Option A is Correct:** **Periodic Acid-Schiff (PAS)** stains glycogen. In ALL, the lymphoblasts often show a characteristic **"block positivity"** or "coarse granular" pattern. This occurs because the glycogen is clustered in large chunks within the cytoplasm against a clear background. This is a classic diagnostic hallmark for the L1 and L2 subtypes of ALL (FAB classification). **2. Why the Other Options are Incorrect:** * **Myeloperoxidase (MPO):** This is the most sensitive and specific marker for the **myeloid lineage**. It is found in the primary granules of myeloid cells. ALL is characteristically **MPO negative**. * **Sudan Black B (SBB):** This stain detects phospholipids and sterols in the membranes of primary and secondary granules. Like MPO, it is positive in AML and **negative in ALL**. * **Non-specific Esterase (NSE):** This stain (e.g., alpha-naphthyl acetate esterase) is used to identify cells of the **monocytic lineage**. It is strongly positive in Acute Monocytic Leukemia (AML-M4 and M5) but negative in ALL. **3. High-Yield Clinical Pearls for NEET-PG:** * **Gold Standard:** While cytochemistry is high-yield for exams, **Immunophenotyping (Flow Cytometry)** is the current gold standard for diagnosing ALL (look for TdT, CD10, CD19, and CD3) [1]. * **TdT (Terminal Deoxynucleotidyl Transferase):** A specialized DNA polymerase that is positive in >95% of ALL cases but negative in AML. * **Acid Phosphatase:** Shows **focal polar (paranuclear) positivity** specifically in **T-cell ALL** [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. 596-600.

Q: Which syndrome is associated with Acute Myeloid Leukemia (AML) and Acute Lymphoblastic Leukemia (ALL)?

Turner syndrome. **Explanation:** The correct answer is **Turner Syndrome (45, XO)**. While Turner syndrome is primarily known for physical findings like short stature and webbed neck, it is associated with an increased risk of both **Acute Lymphoblastic Leukemia (ALL)** and **Acute Myeloid Leukemia (AML)**. The underlying mechanism is thought to involve chromosomal instability and the loss of tumor suppressor genes on the X chromosome. **Analysis of Options:** * **Down Syndrome (Trisomy 21):** This is the most common chromosomal disorder associated with leukemia. However, it has a very specific pattern: a 10-20 fold increased risk of ALL and a unique association with **AML-M7 (Acute Megakaryoblastic Leukemia)**, often preceded by Transient Myeloproliferative Disorder (TMD). * **Noonan Syndrome:** This "male version of Turner" is caused by mutations in the RAS-MAPK pathway. It is specifically associated with **Juvenile Myelomonocytic Leukemia (JMML)**, not typically a balanced risk of ALL/AML. * **Klinefelter Syndrome (47, XXY):** This syndrome is primarily associated with an increased risk of **extragonadal germ cell tumors** (specifically mediastinal) and breast cancer, rather than a significant predisposition to childhood leukemias. **High-Yield Clinical Pearls for NEET-PG:** * **Down Syndrome:** Under age 3, AML (M7) is more common; over age 3, ALL is more common. * **Fanconi Anemia:** Highest risk for **AML** and squamous cell carcinomas. * **Bloom Syndrome & Ataxia-Telangiectasia:** High risk for both ALL and AML due to DNA repair defects. * **Li-Fraumeni Syndrome (p53 mutation):** Associated with ALL, soft tissue sarcomas, and adrenocortical carcinoma.

Question 1

A patient presents with Hb level 6 g/dL, TLC 3500/mm
3, and platelet count 50,000/mm
3. What is the most probable diagnosis?

Accepted Answer

Aplastic anemia

Answer

Leukemia

Answer

Multiple myeloma

Answer

Megaloblastic anemia

Question 2

A 50-year-old man presents with fever and diffuse lymphadenopathy. A lymph node biopsy reveals non-Hodgkin follicular lymphoma. Immunohistochemical staining of neoplastic lymphoid cells within the nodular areas of the lymph node would be expected to stain positively for which of the following protein markers?

Accepted Answer

Bcl-2

Answer

Abl

Answer

Bax

Answer

Myc

Question 3

HbE is common in which region of India?

Accepted Answer

Bengal

Answer

Punjab

Answer

Kerala

Answer

Maharashtra

Question 4

Which syndrome is not associated with leukemia?

Accepted Answer

Turner syndrome

Answer

Bloom syndrome

Answer

Down syndrome

Answer

Ataxia telangiectasia

Question 5

A 32-year-old man has mild anemia diagnosed on routine testing. His clinical examination is normal, and a blood film reveals some target cells with some red cells having intraerythrocytic crystals. For this patient with a hemoglobin abnormality, what is the most likely diagnosis?

Accepted Answer

HbC disease

Answer

beta-thalassemia major

Answer

HbH disease

Answer

sickle cell disease

Question 6

What is seen in lead poisoning?

Accepted Answer

Sideroblasts

Answer

Lymphoblasts

Answer

Normoblasts

Answer

Myeloblasts

Question 7

Which of the following statements is true regarding the cytochemistry of ALL?

Accepted Answer

PAS positive (Block positivity)

Answer

Myeloperoxidase positive

Answer

Sudan Black B positive

Answer

Non-specific esterase positive

Question 8

Which syndrome is associated with Acute Myeloid Leukemia (AML) and Acute Lymphoblastic Leukemia (ALL)?

Accepted Answer

Turner syndrome

Answer

Down syndrome

Answer

Noonan syndrome

Answer

Klinefelter syndrome

Question 9

Proliferation and survival of myeloma cells are dependent on which of the following cytokines?

Accepted Answer

IL-6

Answer

IL-1

Answer

IL-2

Answer

IL-5

Question 10

Diagnosis of Hodgkin's disease is based on all of the following, except:

Accepted Answer

Atypical cells in background

Answer

Reed-Sternberg cells

Answer

Reactive cellular background

Answer

CD30 positivity

Hematopathology — MCQs

Hematopathology — MCQs

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