Hematopathology Practice Questions

Q: All are seen in Thalassemia major EXCEPT:

Macrocytic anemia. **Explanation:** **Why Macrocytic Anemia is the Correct Answer:** Thalassemia major is characterized by **microcytic hypochromic anemia**, not macrocytic anemia. The underlying pathology involves a genetic defect in the synthesis of globin chains (specifically $\beta$-chains in $\beta$-Thalassemia). This leads to a decrease in hemoglobin production within the red blood cells, resulting in smaller (microcytic) and paler (hypochromic) cells. Macrocytic anemia (MCV >100 fL) is typically seen in Vitamin B12 or Folate deficiency. **Analysis of Incorrect Options:** * **Transfusion dependency:** In Thalassemia major, the severe imbalance of globin chains leads to profound anemia. Patients typically present in the first year of life and require lifelong regular blood transfusions to maintain hemoglobin levels and suppress ineffective erythropoiesis. * **Splenohepatomegaly:** This occurs due to two mechanisms: **extramedullary hematopoiesis** (the body attempting to produce RBCs outside the bone marrow) and **hemosiderosis** (iron overload from chronic transfusions). * **Ineffective erythropoiesis:** The precipitation of unpaired $\alpha$-globin chains causes oxidative damage to the RBC precursors in the bone marrow, leading to their premature destruction before they reach circulation. **High-Yield Clinical Pearls for NEET-PG:** * **Peripheral Smear:** Look for target cells, nucleated RBCs, and Howell-Jolly bodies. * **Skeletal Changes:** "Chipmunk facies" and "Hair-on-end" appearance on X-ray due to compensatory bone marrow expansion. * **Diagnosis:** **Hb Electrophoresis** or HPLC is the gold standard (shows increased HbF and absent/low HbA). * **Mentzer Index:** (MCV/RBC count) 13 suggests Iron Deficiency Anemia.

Q: Which of the following immunophenotypic markers is characteristic of mantle cell lymphoma?

CD5+, CD23-. **Explanation:** Mantle Cell Lymphoma (MCL) is a B-cell neoplasm characterized by the proliferation of small to medium-sized lymphocytes originating from the follicular mantle zone [1]. The hallmark of MCL is the chromosomal translocation **t(11;14)**, leading to the overexpression of **Cyclin D1** [1]. **Why Option D is Correct:** Mantle cell lymphoma typically expresses pan-B-cell markers (CD19, CD20) and is characteristically **CD5 positive** but **CD23 negative** [1]. This "CD5+, CD23-" profile is the most critical diagnostic feature used to distinguish it from Chronic Lymphocytic Leukemia (CLL/SLL). **Analysis of Incorrect Options:** * **Option A (CD5+, CD25-):** While MCL is CD25 negative, CD25 positivity is a classic marker for Hairy Cell Leukemia and Adult T-cell Leukemia/Lymphoma (ATLL). * **Option B (CD5+, CD10+):** CD10 is a germinal center marker. Follicular Lymphoma and Burkitt Lymphoma are CD10+, but they are typically CD5 negative. * **Option C (CD5+, CD23+):** This is the classic immunophenotype for **CLL/SLL**. The presence of CD23 is the primary flow cytometry finding that differentiates CLL from MCL [1]. **High-Yield Clinical Pearls for NEET-PG:** 1. **Genetics:** t(11;14) involving the *CCND1* gene and *IGH* locus [1]. 2. **Morphology:** Look for "pink" histiocytes and a lack of transformed centroblasts (unlike Follicular Lymphoma) [1]. 3. **Variant:** The **Blastoid variant** is highly aggressive with a high mitotic index [1]. 4. **Gastrointestinal Involvement:** MCL can present as **Lymphomatous Polyposis** (multiple polyps in the GI tract). 5. **Marker:** **SOX11** is a highly specific nuclear marker for MCL, especially useful in Cyclin D1-negative cases. **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: Leucocyte alkaline phosphatase (LAP) is raised in all conditions except?

Chronic myeloid leukemia. **Explanation:** The **Leucocyte Alkaline Phosphatase (LAP) score** (also known as the Neutrophil Alkaline Phosphatase/NAP score) is a measure of the enzyme activity within mature neutrophils. It is a crucial diagnostic tool used to differentiate a **Leukemoid reaction** or **Myeloproliferative Neoplasms (MPNs)** from **Chronic Myeloid Leukemia (CML)**. **Why CML is the correct answer:** In **Chronic Myeloid Leukemia**, the neoplastic neutrophils are biochemically abnormal and lack the LAP enzyme [1]. Therefore, a **low or zero LAP score** is a hallmark of CML (specifically in the chronic phase). This helps distinguish it from a Leukemoid reaction, where the score is significantly elevated. **Analysis of other options:** * **Polycythemia Vera (PV), Essential Thrombocythemia (ET), and Myelofibrosis:** These are all BCR-ABL negative Myeloproliferative Neoplasms [1]. Unlike CML, the mature neutrophils produced in these conditions are functionally and biochemically capable of producing the LAP enzyme, leading to a **raised or normal LAP score**. * **Leukemoid Reaction:** Though not an option here, it is the most common cause of a highly raised LAP score. **High-Yield Clinical Pearls for NEET-PG:** * **LAP Score in CML:** It is **decreased** in the chronic phase but may **increase** during a Blast Crisis or if there is a concurrent infection. * **Other causes of Low LAP Score:** Paroxysmal Nocturnal Hemoglobinuria (PNH), Hypophosphatasia, and Acute Myeloid Leukemia (AML) [1]. * **Causes of High LAP Score:** Pregnancy, Oral Contraceptive Pills (OCPs), Leukemoid reaction, and MPNs (PV, ET, Myelofibrosis) [1]. * **Modern Diagnosis:** While the LAP score is high-yield for exams, modern diagnosis of CML relies on demonstrating the **Philadelphia chromosome t(9;22)** or the **BCR-ABL1** fusion gene via FISH or PCR [1].

Q: All of the following are poor prognostic markers of multiple myeloma, except?

t(1;14). **Explanation:** In Multiple Myeloma (MM), cytogenetic abnormalities are the strongest predictors of prognosis. These are broadly categorized into **High-Risk (Poor Prognosis)** and **Standard-Risk (Good/Intermediate Prognosis)**. **1. Why t(1;14) is the correct answer:** Translocation **t(1;14)** involves the *BCL9* gene and the immunoglobulin heavy chain (*IGH*) locus. Unlike other translocations involving chromosome 14, t(1;14) is considered a **standard-risk** cytogenetic marker. Patients with this translocation generally have outcomes similar to those with standard-risk disease, making it the "exception" among the poor prognostic markers listed. **2. Analysis of Incorrect Options (Poor Prognostic Markers):** * **t(14;16):** Involves the *MAF* gene. It is a classic high-risk translocation associated with aggressive disease and shorter survival. * **1q gain:** Gain of the long arm of chromosome 1 (1q21) is one of the most common high-risk features. It is associated with disease progression and resistance to standard therapies. * **t(14;20):** Involves the *MAFB* gene. Similar to t(14;16), it is categorized as a high-risk cytogenetic abnormality. **High-Yield Clinical Pearls for NEET-PG:** * **High-Risk Markers (Poor Prognosis):** del(17p) [TP53 mutation], t(4;14), t(14;16), t(14;20), and 1q gain. * **Standard-Risk Markers:** t(11;14), t(6;14), and hyperdiploidy. * **Revised ISS (R-ISS):** Prognosis is now determined by combining Serum Albumin, Beta-2 Microglobulin, LDH levels, and High-risk Cytogenetics (FISH) [1]. * **Most common translocation in MM:** t(11;14). (Note: While the provided literature discusses the clinical features and protein types in Multiple Myeloma [1], it confirms that renal failure is a significant poor prognostic indicator [1].) **References:** [1] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Problems From Blood And Bone Marrow Disease, pp. 618-619.

Q: Multiple punched-out lesions in the soft skull are characteristic of which condition?

Multiple myeloma. ### Explanation **Multiple Myeloma (Correct Answer):** Multiple myeloma is a plasma cell dyscrasia characterized by the neoplastic proliferation of a single clone of plasma cells. These cells produce **Osteoclast Activating Factors (OAFs)**, such as IL-6 and RANK-L, which stimulate osteoclasts to resorb bone. This results in the classic **"punched-out" lytic lesions**—well-circumscribed areas of bone destruction without any surrounding reactive sclerosis (osteoblastic activity). On a lateral skull radiograph, these appear as multiple, small, round radiolucencies of varying sizes, often described as a **"pepper pot skull"** or "rain-drop" appearance. **Analysis of Incorrect Options:** * **B. Metastatic disease:** While metastases (e.g., from lung or breast cancer) can cause lytic lesions, they are typically less well-defined, vary significantly in size, and often show some degree of reactive bone formation (sclerosis) at the margins. * **C. Malignancy:** This is a broad category. While Multiple Myeloma is a malignancy, the term is non-specific. In exams, always choose the most specific pathological diagnosis provided. * **D. Medulloblastoma:** This is a primary posterior fossa brain tumor in children. It does not typically present with multiple punched-out skull lesions; if it metastasizes to bone, it usually presents as blastic (sclerotic) lesions. **High-Yield Clinical Pearls for NEET-PG:** * **Diagnostic Triad:** Bone marrow plasmacytosis (>10%), M-protein in serum/urine, and lytic bone lesions. * **Radiology:** Skeletal survey is preferred over Bone Scan (Bone scans are often false-negative because they detect osteoblastic activity, which is absent in Myeloma). * **Bence-Jones Proteins:** Light chains found in urine; they do not show up on a standard dipstick (requires sulfosalicylic acid test). * **CRAB Criteria:** Calcium (elevated), Renal insufficiency, Anemia, Bone lesions.

Question 1

Histologic sections from a rapidly enlarged cervical lymph node in a 35-year-old female reveal a diffuse, monotonous proliferation of small, noncleaved lymphocytes, which are forming a "starry sky" appearance because numerous tingible-body macrophages are present. A touch prep reveals that many of these cells have cytoplasmic vacuoles. Which stain would most likely react with these cytoplasmic vacuoles?

Accepted Answer

Oil red O

Answer

Myeloperoxidase

Answer

Nonspecific esterase

Answer

Chloracetate esterase

Question 2

All are seen in Thalassemia major EXCEPT:

Accepted Answer

Macrocytic anemia

Answer

Transfusion dependency

Answer

Splenoheptatomegaly

Answer

Ineffective erythropoiesis

Question 3

Punctate basophilia is characteristically seen in which condition?

Accepted Answer

Lead poisoning

Answer

Acute myeloid leukaemia

Answer

Chronic myeloid leukaemia

Answer

Megaloblastic anaemia

Question 4

Which of the following immunophenotypic markers is characteristic of mantle cell lymphoma?

Accepted Answer

CD5+, CD23-

Answer

CD5+, CD25-

Answer

CD5+, CD10+

Answer

CD5+, CD23+

Question 5

Leucocyte alkaline phosphatase (LAP) is raised in all conditions except?

Accepted Answer

Chronic myeloid leukemia

Answer

Myelofibrosis

Answer

Essential thrombocythemia

Answer

Polycythemia vera

Question 6

Which subtype of Hodgkin lymphoma is characterized by the lymphohistiocytic variant of Reed-Sternberg cells?

Accepted Answer

Lymphocyte predominant

Answer

Nodular sclerosis

Answer

Lymphocyte rich

Answer

Lymphocyte depleted

Question 7

For a thalassemic patient requiring recurrent transfusions who develops fever and chills after transfusion, what modification of the blood product can decrease the incidence of transfusion reactions?

Accepted Answer

Leukocyte depletion

Answer

Antibiotics

Answer

Irradiation

Answer

Washed RBCs

Question 8

What is the most common cause of hereditary spherocytosis?

Accepted Answer

Ankyrin

Answer

Spectrin

Answer

Glycophorin

Answer

Band 4

Question 9

All of the following are poor prognostic markers of multiple myeloma, except?

Accepted Answer

t(1;14)

Answer

t(14;16)

Answer

1q gain

Answer

t(14;20)

Question 10

Multiple punched-out lesions in the soft skull are characteristic of which condition?

Accepted Answer

Multiple myeloma

Answer

Metastatic disease

Answer

Malignancy

Answer

Medulloblastoma

Hematopathology — MCQs

Hematopathology — MCQs

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