Hematopathology — MCQs

A 70-year-old male presented with a 3-month history of generalized weakness. On examination, bilateral axillary lymphadenopathy was noted. Histopathological examination of the enlarged lymph node showed effacement of the lymph node architecture by a diffuse proliferation of small-sized, mature-appearing lymphoid cells. Peripheral blood showed lymphocytosis with the presence of CD5-positive and CD23-positive B-cells. Which of the following is the most likely diagnosis in this patient?

Q406Easy

Burkitt's lymphoma arises from which cell type?

Q407Medium

CD59 deficiency leads to which condition?

Q408Medium

A 55-year-old man presents with a 1-week history of a lump near his shoulder. Physical examination reveals an enlarged, nontender, supraclavicular lymph node and enlargement of the Waldeyer ring of oropharyngeal lymphoid tissue. There is no hepato-splenomegaly. A complete blood count is normal except for findings of mild anemia. A lymph node biopsy specimen shows replacement by a monomorphous population of lymphoid cells that are twice the size of normal lymphocytes, with enlarged nuclei and prominent nucleoli. Immunohistochemical staining and flow cytometry of the node indicate that most lymphoid cells are CD19+, CD10+, CD3-, CD15-, and terminal deoxynucleotidyl transferase negative (TdT-). A BCL6 gene mutation is present. Which of the following is the most likely diagnosis?

Q409Easy

Pure red cell aplasia is associated with which of the following conditions?

Q410Easy

Sickle cell anemia is due to:

Hematopathology Indian Medical PG Practice Questions and MCQs

Question 401: All of the following NHL involve the white pulp of the spleen EXCEPT?

A. Hairy cell leukemia (Correct Answer)
B. Burkitt lymphoma
C. Follicular lymphoma
D. Mantle cell lymphoma

Explanation: In the spleen, the **white pulp** consists of lymphoid tissue (B-cell follicles and T-cell periarteriolar lymphoid sheaths), while the **red pulp** consists of splenic cords and sinuses filled with blood. ### **Why Hairy Cell Leukemia (HCL) is the Correct Answer** Hairy Cell Leukemia is unique among B-cell neoplasms because it characteristically involves the **red pulp** of the spleen [1]. The neoplastic cells infiltrate the splenic cords and sinuses, leading to the obliteration of the white pulp [4]. This diffuse infiltration results in massive splenomegaly and the formation of **"blood cysts"** (pseudosinuses), which are pathognomonic histological features. ### **Analysis of Incorrect Options** Most Non-Hodgkin Lymphomas (NHLs) are derived from lymphocytes that naturally reside in or migrate to the lymphoid follicles of the white pulp: * **Follicular Lymphoma:** Arises from germinal center B-cells; it typically forms nodular aggregates within the **white pulp** [2]. * **Mantle Cell Lymphoma:** Arises from the mantle zone of the lymphoid follicle; it characteristically expands the **white pulp** [3]. * **Burkitt Lymphoma:** A highly aggressive B-cell lymphoma that involves the lymphoid follicles of the **white pulp**. ### **NEET-PG High-Yield Pearls** * **HCL Triad:** Splenomegaly (massive), Pancytopenia, and "Dry tap" on bone marrow aspiration (due to increased reticulin fibers) [1]. * **Monoclonal Marker:** CD103, CD11c, CD25, and **Annexin A1** (most specific). * **Genetic Mutation:** **BRAF V600E** mutation is seen in almost all cases. * **TRAP Stain:** Tartrate-Resistant Acid Phosphatase positive (though being replaced by flow cytometry). * **Treatment of Choice:** Cladribine (2-Chlorodeoxyadenosine). **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, p. 612. [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. [3] 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. [4] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Problems From Diseases Of The Urinary And Male Genital Tracts, pp. 569-570.

Question 402: Which of the following conditions features an intrinsic cell wall defect of red blood cells?

A. Paroxysmal Nocturnal Hemoglobinuria
B. Sickle cell disease
C. Hereditary spherocytosis (Correct Answer)
D. All of the above

Explanation: ### Explanation **Correct Answer: C. Hereditary spherocytosis** **1. Why Hereditary Spherocytosis (HS) is correct:** Hereditary Spherocytosis is the classic example of an **intrinsic defect of the RBC membrane (cell wall)** [1]. It is caused by mutations in genes encoding vertical membrane-cytoskeleton anchoring proteins—most commonly **Ankyrin** (most frequent), followed by Spectrin, Band 3, and Protein 4.2 [1]. These defects lead to a loss of membrane surface area, forcing the RBC to assume a spherical shape (spherocyte) [1],[2]. These rigid cells are sequestered and destroyed in the splenic cords (extravascular hemolysis) [1],[2]. **2. Why the other options are incorrect:** * **A. Paroxysmal Nocturnal Hemoglobinuria (PNH):** While PNH is an intrinsic/intracorpuscular defect, it is not a structural "cell wall" defect. It is an **acquired stem cell mutation** in the *PIGA* gene, leading to a deficiency of GPI-anchored proteins (CD55 and CD59) that protect the cell from complement-mediated lysis. * **B. Sickle Cell Disease:** This is a **hemoglobinopathy**, not a primary membrane defect [3]. The intrinsic defect lies in the qualitative abnormality of the hemoglobin molecule (valine substituted for glutamic acid at the 6th position of the beta-globin chain), which causes polymerization and secondary membrane damage [3]. **3. NEET-PG High-Yield Pearls:** * **Gold Standard Test for HS:** Eosin-5-maleimide (EMA) binding test (Flow cytometry). * **Screening Test:** Osmotic Fragility Test (increased fragility) [2]. * **MCHC:** Characteristically **increased** (>36 g/dL) in HS due to relative dehydration of the spherocyte. * **Treatment of Choice:** Splenectomy (usually deferred until after age 5-6 to reduce sepsis risk) [2]. * **Complication:** Pigment gallstones (calcium bilirubinate) due to chronic hemolysis [2]. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Red Blood Cell and Bleeding Disorders, pp. 640-641. [2] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Problems From Blood And Bone Marrow Disease, pp. 597-598. [3] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Problems From Blood And Bone Marrow Disease, pp. 598-599.

Question 403: What is the primary treatment for Kostmann's syndrome?

A. Anti-thymocyte globulin and cyclosporin
B. Anti-thymocyte globulin, cyclosporin, and GM-CSF
C. G-CSF (Correct Answer)
D. GM-CSF

Explanation: **Explanation:** **Kostmann’s Syndrome** (Severe Congenital Neutropenia) is an autosomal recessive disorder characterized by a maturation arrest of neutrophil precursors in the bone marrow at the **promyelocyte stage**. This leads to absolute neutrophil counts (ANC) frequently below 200/µL, making patients highly susceptible to life-threatening pyogenic infections. 1. **Why G-CSF is Correct:** The primary goal of treatment is to increase the production and maturation of neutrophils. **Granulocyte Colony-Stimulating Factor (G-CSF)**, such as Filgrastim, is the mainstay of therapy. It bypasses the maturation arrest, significantly increases the ANC, and reduces the frequency of infections. While Hematopoietic Stem Cell Transplant (HSCT) is the only definitive cure, G-CSF is the standard primary medical management. 2. **Why Other Options are Incorrect:** * **Options A & B:** Anti-thymocyte globulin (ATG) and Cyclosporin are immunosuppressive therapies used primarily for **Aplastic Anemia**, where the pathology is T-cell mediated destruction of stem cells [1]. Kostmann’s is a genetic maturation defect, not an autoimmune process. * **Option D:** While GM-CSF (Granulocyte-Macrophage CSF) can stimulate production, it is less effective than G-CSF and is associated with more systemic side effects (like fever and bone pain) without the same targeted efficacy for neutrophil maturation in this specific syndrome. **Clinical Pearls for NEET-PG:** * **Genetics:** Most commonly associated with mutations in the **ELANE gene** (autosomal dominant) or **HAX1 gene** (autosomal recessive/classic Kostmann). * **Bone Marrow Finding:** Characterized by "maturation arrest" at the **promyelocyte/myelocyte stage**. * **Malignancy Risk:** Patients have a significantly increased risk of developing **Acute Myeloid Leukemia (AML)** or Myelodysplastic Syndrome (MDS) [2]. * **Differentiate:** Unlike Cyclic Neutropenia (which occurs every 21 days), Kostmann’s presents with persistent, severe neutropenia from birth. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Red Blood Cell and Bleeding Disorders, p. 662. [2] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Problems From Blood And Bone Marrow Disease, pp. 613-614.

Question 404: Patients with Immune Thrombocytopenic Purpura (ITP) have antibodies to which of the following?

A. Platelet ADP
B. Platelet membrane cholesterol
C. Platelet membrane glycoproteins (Correct Answer)
D. Platelet membrane lipids

Explanation: ### Explanation **Correct Option: C. Platelet membrane glycoproteins** Immune Thrombocytopenic Purpura (ITP) is an acquired autoimmune disorder characterized by the premature destruction of platelets [2]. The underlying pathophysiology involves the production of **IgG autoantibodies** directed against specific antigens on the platelet surface [1]. The most common targets are **Platelet Membrane Glycoproteins**, specifically **GpIIb/IIIa** and **GpIb/IX** [2]. Once these antibodies bind to the glycoproteins, the "opsonized" platelets are recognized by the Fc receptors on splenic macrophages and subsequently sequestered and destroyed in the **spleen**. **Why Incorrect Options are Wrong:** * **A. Platelet ADP:** ADP is a substance stored within the dense granules of platelets and released during activation to recruit more platelets. It is not a surface antigen targeted by autoantibodies in ITP. * **B & D. Platelet membrane cholesterol/lipids:** While lipids and cholesterol are structural components of the cell membrane, they are generally not immunogenic in the context of ITP. Autoantibodies in ITP are highly specific to proteinaceous receptors (glycoproteins). **High-Yield Clinical Pearls for NEET-PG:** * **Bone Marrow Finding:** Characterized by **increased Megakaryocytes** (compensatory hyperplasia) with many "young" or immature forms [2, 4]. * **Spleen:** The spleen is the site of both antibody production and platelet destruction; however, it is usually **not enlarged** (splenomegaly points toward other diagnoses) [1]. * **Treatment:** First-line therapy includes **Corticosteroids** or IVIG [3]. Splenectomy is considered for refractory cases [3]. * **Associated Conditions:** Secondary ITP can be associated with SLE, HIV, Chronic Lymphocytic Leukemia (CLL), or Hepatitis C [2]. **References:** [1] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Problems From Blood And Bone Marrow Disease, pp. 620-621. [2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Red Blood Cell and Bleeding Disorders, pp. 665-666. [3] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Red Blood Cell and Bleeding Disorders, pp. 666-667.

Question 405: A 70-year-old male presented with a 3-month history of generalized weakness. On examination, bilateral axillary lymphadenopathy was noted. Histopathological examination of the enlarged lymph node showed effacement of the lymph node architecture by a diffuse proliferation of small-sized, mature-appearing lymphoid cells. Peripheral blood showed lymphocytosis with the presence of CD5-positive and CD23-positive B-cells. Which of the following is the most likely diagnosis in this patient?

A. Burkitt leukemia
B. Hodgkin lymphoma
C. Chronic lymphocytic leukemia (CLL) (Correct Answer)
D. Diffuse large B-cell lymphoma (DLBCL)

Explanation: ### Explanation The clinical presentation and immunophenotype point definitively to **Chronic Lymphocytic Leukemia (CLL) / Small Lymphocytic Lymphoma (SLL)**. **Why CLL is the correct answer:** 1. **Clinical Profile:** CLL typically affects elderly patients (median age ~70) and often presents with generalized lymphadenopathy and lymphocytosis [2]. 2. **Morphology:** The "diffuse proliferation of small, mature-appearing lymphoid cells" with effacement of architecture is the classic histopathological description of SLL/CLL [1]. 3. **Immunophenotype (High Yield):** The pathognomonic marker for CLL is the co-expression of **CD5** (normally a T-cell marker) and **CD23** on B-cells (CD19/CD20+) [1]. This "aberrant" expression is the gold standard for differentiating it from other B-cell lymphomas. **Why other options are incorrect:** * **Burkitt Leukemia:** Characterized by medium-sized cells with high mitotic activity and a "starry-sky" appearance [3]. It is CD5 negative and CD10 positive. * **Hodgkin Lymphoma:** Histology would show Reed-Sternberg (RS) cells in a polymorphic inflammatory background, not a diffuse proliferation of small mature lymphocytes [4]. * **Diffuse Large B-cell Lymphoma (DLBCL):** As the name suggests, cells are large (3-4x the size of a small lymphocyte) with prominent nucleoli and high proliferation indices, unlike the "small, mature" cells described here. **NEET-PG High-Yield Pearls:** * **Smudge Cells:** Characteristically seen on peripheral smears of CLL patients due to the fragility of the neoplastic lymphocytes [1]. * **Richter Transformation:** The progression of CLL/SLL into a high-grade DLBCL (occurs in ~5-10% of cases). * **Prognostic Markers:** ZAP-70 and CD38 expression, or unmutated IgHV genes, indicate a poorer prognosis. * **Cytogenetics:** Deletion 13q is the most common (good prognosis); Deletion 17p (TP53) is the worst. **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, p. 602. [2] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Problems From Blood And Bone Marrow Disease, pp. 612-613. [3] 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, p. 606. [4] 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, p. 618.

Question 406: Burkitt's lymphoma arises from which cell type?

A. T cell
B. B cell (Correct Answer)
C. Pre B cell
D. NK cell

Explanation: Burkitt’s Lymphoma is a highly aggressive, high-grade Non-Hodgkin Lymphoma (NHL) that originates from **mature B cells** located in the **germinal center** of lymphoid follicles [1]. This is evidenced by the expression of B-cell markers such as CD19, CD20, CD22, and surface IgM, along with germinal center markers like CD10 and BCL6. * **Why B cell is correct:** The malignancy is characterized by the translocation of the *MYC* proto-oncogene (usually $t(8;14)$), which moves the *MYC* gene to the immunoglobulin heavy chain (IgH) locus, leading to constitutive expression of Myc protein and rapid B-cell proliferation. * **Why Pre-B cell is incorrect:** Pre-B cells are immature precursors found in the bone marrow [1]. Malignancies arising from these cells are termed B-lymphoblastic leukemia/lymphoma (B-ALL), not Burkitt’s. * **Why T cell and NK cell are incorrect:** While T-cell and NK-cell lymphomas exist (e.g., Mycosis Fungoides or Extranodal NK/T-cell lymphoma), Burkitt’s is strictly a B-cell lineage malignancy [1]. **High-Yield Clinical Pearls for NEET-PG:** * **Morphology:** Classic **"Starry sky appearance"** (tingible body macrophages containing apoptotic debris against a background of dark neoplastic B cells). * **Cytogenetics:** $t(8;14)$ is most common; $t(2;8)$ and $t(8;22)$ are variants. * **Variants:** 1. *Endemic (African):* Strongly associated with EBV; typically involves the jaw [2]. 2. *Sporadic (Non-African):* Often involves the ileocecal region. 3. *Immunodeficiency-associated:* Often seen in HIV patients [2]. * **Proliferation Index:** Ki-67 index is typically **>99%**, reflecting its extremely rapid doubling time. **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. 596-598. [2] 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. 595-596.

Question 407: CD59 deficiency leads to which condition?

A. Chediak Higashi disease
B. Thrombotic Thrombocytopenic Purpura (TTP)
C. Paroxysmal Nocturnal Hemoglobinuria (PNH) (Correct Answer)
D. Burkitt's Lymphoma

Explanation: **Explanation:** **Paroxysmal Nocturnal Hemoglobinuria (PNH)** is an acquired clonal hematopoietic stem cell disorder caused by a somatic mutation in the **PIGA gene**. This mutation leads to a deficiency of Glycosylphosphatidylinositol (GPI) anchors. Without these anchors, complement-regulatory proteins like **CD59** (Membrane Inhibitor of Reactive Lysis/MIRL) and **CD55** (Decay Accelerating Factor/DAF) cannot bind to the red blood cell membrane [1]. CD59 specifically inhibits the formation of the **Membrane Attack Complex (MAC)**. Its deficiency renders RBCs hypersensitive to complement-mediated lysis, resulting in intravascular hemolysis [1]. **Analysis of Incorrect Options:** * **Chediak Higashi disease:** An autosomal recessive disorder caused by mutations in the **LYST gene**, leading to defective vesicle fusion and giant lysosomal granules in neutrophils. It is not related to complement regulation. * **Thrombotic Thrombocytopenic Purpura (TTP):** Caused by a deficiency of the von Willebrand factor-cleaving protease, **ADAMTS13**, leading to microangiopathic hemolytic anemia (MAHA) and hyaline thrombi. * **Burkitt's Lymphoma:** A high-grade B-cell neoplasm associated with **c-MYC** translocation [t(8;14)] and Epstein-Barr Virus (EBV), characterized by a "starry sky" appearance on histology. **High-Yield Clinical Pearls for NEET-PG:** * **Gold Standard Diagnosis:** Flow cytometry showing absence of CD55 and CD59 on RBCs and granulocytes [1]. * **Classic Triad:** Hemolytic anemia, pancytopenia, and venous thrombosis (often in unusual sites like the Budd-Chiari syndrome) [1]. * **Treatment:** **Eculizumab**, a monoclonal antibody that targets the C5 complement component, preventing MAC formation. * **Screening Test:** Ham’s test (Acidified serum test) and Sucrose lysis test (now largely replaced by flow cytometry). **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Red Blood Cell and Bleeding Disorders, pp. 650-651.

Question 408: A 55-year-old man presents with a 1-week history of a lump near his shoulder. Physical examination reveals an enlarged, nontender, supraclavicular lymph node and enlargement of the Waldeyer ring of oropharyngeal lymphoid tissue. There is no hepato-splenomegaly. A complete blood count is normal except for findings of mild anemia. A lymph node biopsy specimen shows replacement by a monomorphous population of lymphoid cells that are twice the size of normal lymphocytes, with enlarged nuclei and prominent nucleoli. Immunohistochemical staining and flow cytometry of the node indicate that most lymphoid cells are CD19+, CD10+, CD3-, CD15-, and terminal deoxynucleotidyl transferase negative (TdT-). A BCL6 gene mutation is present. Which of the following is the most likely diagnosis?

A. Acute lymphoblastic lymphoma
B. Chronic lymphadenitis
C. Diffuse large B-cell lymphoma (Correct Answer)
D. Hodgkin lymphoma

Explanation: The clinical presentation and histopathology point towards **Diffuse Large B-Cell Lymphoma (DLBCL)**, the most common type of non-Hodgkin lymphoma (NHL) [3]. **Why DLBCL is correct:** 1. **Morphology:** The biopsy shows a "monomorphous population" of cells that are "twice the size of normal lymphocytes" with "prominent nucleoli." This describes **centroblasts** or **immunoblasts**, the hallmark of large cell lymphoma. 2. **Immunophenotype:** The cells are **CD19+** (B-cell origin) and **CD10+** (Germinal center origin). Crucially, they are **TdT negative**, which excludes immature blasts (seen in ALL) [2]. 3. **Genetics:** The presence of a **BCL6 mutation** (seen in 30% of cases) is highly characteristic of DLBCL [1], [3]. 4. **Clinical:** Involvement of the **Waldeyer ring** and rapid nodal enlargement are classic clinical features of NHL, specifically DLBCL. **Why other options are incorrect:** * **Acute Lymphoblastic Lymphoma (ALL):** While these are "blasts," they are **TdT positive** (a marker of immaturity) and typically affect children/adolescents [2]. * **Chronic Lymphadenitis:** This would show a pleomorphic (mixed) reactive cell population (plasma cells, histiocytes) and preserved lymph node architecture, not a monomorphous large-cell replacement. * **Hodgkin Lymphoma:** Characterized by **Reed-Sternberg cells** (large cells with "owl-eye" nuclei) in a reactive background. RS cells are typically **CD15+ and CD30+**, but **CD19 negative**. **NEET-PG High-Yield Pearls:** * **DLBCL** is the most common NHL in adults; it is aggressive but potentially curable with R-CHOP chemotherapy [1]. * **Waldeyer Ring involvement** is a strong clinical clue for NHL over Hodgkin Lymphoma. * **BCL6** is the most commonly involved genetic locus in DLBCL [3]. * **CD10+** expression in DLBCL indicates a "Germinal Center B-cell (GCB)" subtype, which generally has a better prognosis than the "Activated B-cell (ABC)" subtype [1]. **References:** [1] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Problems From Diseases Of The Urinary And Male Genital Tracts, pp. 563-564. [2] 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, p. 606. [3] 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, p. 604.

Question 409: Pure red cell aplasia is associated with which of the following conditions?

A. Thymoma (Correct Answer)
B. Renal cell carcinoma
C. Hepatocellular carcinoma
D. Prostate carcinoma

Explanation: **Explanation:** **Pure Red Cell Aplasia (PRCA)** is a rare hematological syndrome characterized by a severe reduction in erythroid precursors in the bone marrow, leading to isolated anemia with normal white cell and platelet counts [1]. **Why Thymoma is the Correct Answer:** The strongest clinical association with acquired PRCA is **Thymoma** (seen in approximately 10–15% of thymoma patients). The underlying mechanism is **autoimmune-mediated destruction** of erythroid progenitor cells. It is believed that T-cells or IgG antibodies directed against erythropoietin or erythroblasts are produced due to the loss of self-tolerance associated with thymic tumors. Surgical removal of the thymoma (thymectomy) can lead to remission of PRCA in many cases. **Why Other Options are Incorrect:** * **Renal Cell Carcinoma (RCC) & Hepatocellular Carcinoma (HCC):** These tumors are classically associated with **Paraneoplastic Erythrocytosis** (Polycythemia), not aplasia. They often secrete ectopic Erythropoietin (EPO), which stimulates red blood cell production. * **Prostate Carcinoma:** While it can cause anemia of chronic disease or leucoerythroblastic anemia (due to bone marrow metastasis), it has no specific association with PRCA. **High-Yield Clinical Pearls for NEET-PG:** * **Other Associations of PRCA:** Parvovirus B19 infection (especially in patients with underlying hemolytic anemias like Sickle Cell), SLE, and drugs (e.g., Phenytoin, Isoniazid) [1]. * **Diamond-Blackfan Anemia:** This is the **congenital** form of PRCA, often presenting in infancy with craniofacial anomalies and thumb deformities [1]. * **Diagnostic Hallmark:** Bone marrow biopsy showing <0.5% erythroblasts but normal granulopoiesis and megakaryopoiesis. **References:** [1] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Problems From Blood And Bone Marrow Disease, pp. 595-596.

Question 410: Sickle cell anemia is due to:

A. Addition
B. Deletion
C. None
D. Point mutation (Correct Answer)

Explanation: **Explanation:** Sickle cell anemia is a classic example of a **point mutation**, specifically a **missense mutation** [1]. It occurs due to a single nucleotide substitution in the **$\beta$-globin gene** located on **chromosome 11** [1]. 1. **Why Point Mutation is Correct:** The molecular defect involves the substitution of **Adenine (A) by Thymine (T)** at the 6th codon of the $\beta$-globin chain (GAG $\rightarrow$ GTG). This results in the replacement of the amino acid **Glutamic acid** (polar/hydrophilic) with **Valine** (non-polar/hydrophobic) [2]. Under deoxygenated conditions, this hydrophobic valine causes hemoglobin molecules (HbS) to polymerize, leading to the characteristic "sickling" of RBCs [3]. 2. **Why Other Options are Incorrect:** * **Addition/Deletion:** These are "frameshift mutations" if they involve 1-2 nucleotides. They typically lead to a completely non-functional protein or a premature stop codon. While some forms of Thalassemia can result from deletions (especially $\alpha$-Thalassemia), Sickle Cell Anemia is strictly a single-base substitution. 3. **High-Yield Clinical Pearls for NEET-PG:** * **Inheritance:** Autosomal Recessive. * **Diagnosis:** **Hb Electrophoresis** is the gold standard (HbS moves slower than HbA toward the anode). * **Screening Test:** Solubility test (using sodium dithionite) or Sickling test (using sodium metabisulfite). * **Protective Effect:** Heterozygotes (Sickle cell trait) are protected against *Plasmodium falciparum* malaria. * **Morphology:** Look for "Sickle cells" and **Howell-Jolly bodies** (indicating functional asplenia) on a peripheral smear [4]. * **Complication:** Auto-splenectomy (shrunken, fibrotic spleen) usually occurs by adulthood due to repeated infarctions [4]. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Cellular Responses to Stress and Toxic Insults: Adaptation, Injury, and Death, pp. 50-51. [2] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Problems From Blood And Bone Marrow Disease, pp. 598-599. [3] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Red Blood Cell and Bleeding Disorders, pp. 643-644. [4] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Red Blood Cell and Bleeding Disorders, pp. 644-645.

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Anemias: Classification and Approach

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Hemolytic Anemias

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Lymphomas and Lymphoid Neoplasms

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Plasma Cell Disorders

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