Hematopathology — MCQs

Hematopathology Indian Medical PG Practice Questions and MCQs

Question 221: Crumpled tissue paper appearance of cytoplasm in bone marrow examination is due to the intracellular accumulation of which of the following?

A. Cerebroside
B. Ganglioside
C. Sphingomyelin
D. Glucocerebroside (Correct Answer)

Explanation: ### Explanation **Correct Answer: D. Glucocerebroside** **Mechanism:** The "crumpled tissue paper" appearance is the pathognomonic histological feature of **Gaucher cells**, which are enlarged, lipid-laden macrophages [1]. This appearance is caused by the intracellular accumulation of **glucocerebroside** (also known as glucosylceramide) [1]. This occurs due to a deficiency of the lysosomal enzyme **$eta$-glucocerebrosidase** (acid $eta$-glucosidase). The undigested lipid material forms elongated, fibrillar aggregates within the lysosomes, which push the nucleus to the periphery and create the characteristic striated, wrinkled cytoplasm seen on bone marrow aspirates or biopsies [1], [2]. **Analysis of Incorrect Options:** * **A. Cerebroside:** This is a general term for glycosphingolipids. While glucocerebroside is a type of cerebroside, the specific substrate in Gaucher disease is glucocerebroside. Galactocerebroside, another type, accumulates in **Krabbe disease**. * **B. Ganglioside:** Accumulation of GM2 gangliosides is characteristic of **Tay-Sachs disease**, which presents with a "cherry-red spot" on the macula and "onion-skin" lysosomes, but not crumpled tissue paper cells [3]. * **C. Sphingomyelin:** Accumulation of sphingomyelin occurs in **Niemann-Pick disease** (Type A and B) due to sphingomyelinase deficiency. These cells are characterized as **"Foamy macrophages"** (vacuolated cytoplasm) rather than wrinkled ones. **High-Yield Clinical Pearls for NEET-PG:** * **Gaucher Disease** is the most common lysosomal storage disorder. * **Clinical Triad:** Hepatosplenomegaly (massive), bone involvement (Erlenmeyer flask deformity of the femur, bone crises), and pancytopenia [1]. * **Biomarker:** Elevated serum **Chitotriosidase** levels are used to monitor disease activity and treatment response. * **Staining:** Gaucher cells are **PAS (Periodic Acid-Schiff) positive**. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Genetic Disorders, p. 163. [2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Genetic Disorders, pp. 162-163. [3] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Genetic Disorders, p. 161.

Question 222: Prolonged PT and normal PTT may be seen in which of the following conditions?

A. Thrombocytopenia
B. Disseminated Intravascular Coagulation (DIC)
C. Vitamin K deficiency
D. None of the above (Correct Answer)

Explanation: ### Explanation The correct answer is **None of the above** because the conditions listed either do not affect the coagulation profile in this specific pattern or affect both pathways simultaneously. **1. Understanding the Concept** * **Prothrombin Time (PT)** measures the **Extrinsic** and **Common** pathways (Factors VII, X, V, II, and I). * **Activated Partial Thromboplastin Time (aPTT)** measures the **Intrinsic** and **Common** pathways (Factors XII, XI, IX, VIII, X, V, II, and I). * An isolated prolonged PT with a normal aPTT occurs when there is a deficiency or inhibition specifically of **Factor VII** (the only factor unique to the extrinsic pathway). **2. Analysis of Options** * **Thrombocytopenia (A):** This is a quantitative platelet disorder. It affects primary hemostasis (bleeding time) but has **no effect** on PT or aPTT, as these tests are performed on platelet-poor plasma [1]. * **Disseminated Intravascular Coagulation (B):** DIC involves widespread consumption of all clotting factors and platelets. Therefore, it typically shows **prolongation of both PT and aPTT**, along with low fibrinogen and elevated D-dimers [2]. * **Vitamin K Deficiency (C):** Vitamin K is required for the carboxylation of Factors **II, VII, IX, and X** [3]. While Factor VII has the shortest half-life and is affected first (initially prolonging PT), a clinically significant deficiency usually affects all these factors, leading to **prolongation of both PT and aPTT**. **3. Clinical Pearls for NEET-PG** * **Isolated Prolonged PT:** Think of **Early Liver Disease**, **Early Vitamin K deficiency**, or **Warfarin** therapy (all affect Factor VII first) [3]. * **Isolated Prolonged aPTT:** Think of **Hemophilia A (VIII)**, **Hemophilia B (IX)**, **Von Willebrand Disease**, or **Heparin** therapy. * **Prolonged PT + aPTT:** Think of **Common Pathway** factor deficiencies (X, V, II, I), **Severe Liver Disease**, **DIC**, or **Supratherapeutic Warfarin/Heparin** [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. 666-667. [2] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Problems From Blood And Bone Marrow Disease, pp. 625-626. [3] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Problems From Blood And Bone Marrow Disease, pp. 582-583.

Question 223: A 6-month-old child with sickle cell anemia has a chronically enlarged spleen. By 5 years of age, the child's spleen is no longer palpable. The decrease in size is most likely related to which of the following?

A. Chronic infection
B. Hodgkin's lymphoma
C. Infarctions (Correct Answer)
D. Non-Hodgkin's lymphoma

Explanation: **Explanation:** In **Sickle Cell Anemia (SCA)**, the pathophysiology of splenic changes follows a predictable chronological sequence [2]. In early childhood (usually before age 2), the spleen is enlarged (**splenomegaly**) due to the sequestration of sickled red blood cells and reactive hyperplasia of the mononuclear phagocytic system [1][2]. However, as the child grows, repeated episodes of microvascular occlusion occur [3]. The sickled erythrocytes clog the splenic sinusoids, leading to chronic ischemia and multiple **infarctions** [2]. Over time, the splenic parenchyma is replaced by fibrous tissue and calcium/iron deposits (forming **Gandy-Gamna bodies**). By age 5 to 10, the spleen becomes a shrunken, non-functional, fibrotic remnant. This process is known as **Autosplenectomy** [1]. **Analysis of Incorrect Options:** * **A. Chronic infection:** While SCA patients are prone to infections (especially encapsulated organisms), chronic infection typically causes splenomegaly, not a decrease in size [1]. * **B & D. Hodgkin's and Non-Hodgkin's Lymphoma:** These are neoplastic conditions that characteristically cause massive splenomegaly due to infiltration by malignant cells. They do not cause the spleen to disappear. **NEET-PG High-Yield Pearls:** * **Autosplenectomy:** The hallmark of adult/late-childhood SCA [1]. * **Howell-Jolly Bodies:** Their presence on a peripheral blood smear is a classic sign of functional asplenia/autosplenectomy [2]. * **Gandy-Gamna Bodies:** Siderofibrotic nodules (calcium and iron deposits) found in the shrunken spleen of SCA patients. * **Infection Risk:** Due to loss of splenic function, patients are highly susceptible to **encapsulated bacteria** (*S. pneumoniae, H. influenzae, N. meningitidis*) [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. 631-632. [2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Red Blood Cell and Bleeding Disorders, pp. 644-645. [3] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Problems From Blood And Bone Marrow Disease, pp. 598-599.

Question 224: A round cell having fine nuclear chromatin, prominent nucleoli, and fine azurophilic granules. What is this cell?

A. Myeloblast (Correct Answer)
B. Lymphoblast
C. Monoblast
D. None of the above

Explanation: ### Explanation The cell described is a **Myeloblast**, which is the earliest recognizable myeloid precursor in the bone marrow. **1. Why Myeloblast is correct:** The identification of a blast cell relies on nuclear and cytoplasmic features. A myeloblast typically presents as a large cell with a high N:C (nucleus-to-cytoplasm) ratio, **fine (lace-like) nuclear chromatin**, and **2–5 prominent nucleoli** [2]. The presence of **fine azurophilic granules** (primary granules) is the pathognomonic feature that distinguishes it from other blasts. These granules contain myeloperoxidase (MPO), which is the gold standard histochemical marker for myeloid lineage. **2. Why other options are incorrect:** * **Lymphoblast:** These cells usually have **clumped (coarse) chromatin**, inconspicuous or fewer nucleoli, and a scant rim of agranular cytoplasm. Crucially, lymphoblasts **never** contain azurophilic granules or Auer rods. * **Monoblast:** While these are large cells with abundant cytoplasm, they typically feature **folded, indented, or convoluted nuclei** (resembling a brain) and "muddy" or "ground-glass" cytoplasm. While they may have fine granules, the classic description of fine chromatin with prominent nucleoli and distinct azurophilic granules favors the myeloblast. **3. NEET-PG Clinical Pearls:** * **Auer Rods:** If these azurophilic granules coalesce into needle-like structures, they are called Auer rods, which are **diagnostic** of AML (specifically M1, M2, M3, and M4 subtypes) [1]. * **Cytochemistry:** Myeloblasts are **MPO positive** and Sudan Black B positive, whereas lymphoblasts are PAS positive (block-like pattern) and TdT positive. * **FAB Classification:** According to the FAB criteria, a cell must have at least 3% MPO positivity to be classified as a myeloblast. **References:** [1] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Problems From Blood And Bone Marrow Disease, pp. 607-608. [2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. The Heart, pp. 589-590.

Question 225: Which of the following coagulation factors is deficient in classical hemophilia?

A. VIII (Correct Answer)
B. IX
C. X
D. XII

Explanation: **Explanation:** **Classical Hemophilia**, also known as **Hemophilia A**, is an X-linked recessive bleeding disorder caused by a deficiency or dysfunction of **Coagulation Factor VIII** [1], [2]. Factor VIII serves as a critical cofactor for Factor IXa in the "tenase complex," which activates Factor X in the intrinsic pathway of the coagulation cascade. A deficiency leads to impaired secondary hemostasis, resulting in characteristic deep-tissue bleeding and hemarthrosis [1]. **Analysis of Options:** * **Option A (Factor VIII):** Correct. This is the most common hereditary disease associated with serious bleeding [2]. * **Option B (Factor IX):** Incorrect. Deficiency of Factor IX causes **Hemophilia B** (also known as Christmas Disease) [2]. While clinically indistinguishable from Hemophilia A, it is less common. * **Option C (Factor X):** Incorrect. Factor X deficiency (Stuart-Prower deficiency) is a rare autosomal recessive disorder that affects the common pathway. * **Option D (Factor XII):** Incorrect. Factor XII (Hageman factor) deficiency is unique because it causes a **prolonged PTT in vitro** but does **not** cause clinical bleeding in vivo; instead, it may be associated with an increased risk of thrombosis. **High-Yield Clinical Pearls for NEET-PG:** * **Inheritance:** Both Hemophilia A and B are **X-linked recessive** (primarily affecting males) [1], [2]. * **Lab Findings:** Characterized by **Prolonged aPTT** with a **Normal PT and Bleeding Time**. * **Mixing Study:** The prolonged aPTT will **correct** when mixed with normal plasma (distinguishes it from Factor VIII inhibitors). * **Treatment:** Recombinant Factor VIII concentrate. Cryoprecipitate can be used if concentrates are unavailable (contains Factor VIII, Fibrinogen, and vWF). **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Red Blood Cell and Bleeding Disorders, pp. 670-671. [2] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Problems From Blood And Bone Marrow Disease, pp. 622-623.

Question 226: Stored blood as compared to fresh blood has:

A. More 2,3 DPG
B. High extracellular K+ (Correct Answer)
C. High extracellular hemoglobin
D. Increased platelets

Explanation: **Explanation:** The storage of blood leads to a series of biochemical and morphological changes collectively known as the **"Storage Lesion."** **1. Why Option B is Correct:** During storage at 1–6°C, the **Na+/K+ ATPase pump** on the red blood cell (RBC) membrane becomes sluggish due to the cold temperature and gradual depletion of ATP. This prevents the pump from maintaining the ionic gradient, causing potassium to leak out of the RBCs into the plasma. Consequently, **extracellular K+ levels increase** significantly over time. This is clinically vital because rapid transfusion of stored blood can lead to **hyperkalemia**, potentially causing cardiac arrhythmias. **2. Why Other Options are Incorrect:** * **Option A:** **2,3-DPG levels decrease** during storage. 2,3-DPG is essential for oxygen release to tissues; its depletion causes a "left shift" in the oxygen dissociation curve (increased oxygen affinity). * **Option C:** While some hemolysis occurs, **high extracellular hemoglobin** is not the primary characteristic change compared to the significant rise in potassium, unless the blood is expired or damaged. * **Option D:** Platelets are highly sensitive to cold. They lose their viability and function within 48–72 hours of storage at 1–6°C. Therefore, stored blood has **decreased/non-functional platelets.** **Clinical Pearls for NEET-PG:** * **pH:** Decreases (becomes acidic) due to lactic acid accumulation. * **Sodium:** Decreases (moves into the RBC). * **Factors V and VIII:** These are labile clotting factors and their levels decrease in stored blood. [1] * **Citrate Toxicity:** Massive transfusion of stored blood can lead to **hypocalcemia** because the citrate anticoagulant binds to the patient's ionized calcium. **References:** [1] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Problems From Blood And Bone Marrow Disease, pp. 625-626.

Question 227: Presence of Birbeck granules in histopathological examination suggests which of the following?

A. Plasmacytoma.
B. Burkett lymphoma.
C. Langerhan cells histiocytosis. (Correct Answer)
D. All of the above.

Explanation: **Explanation:** **Langerhans Cell Histiocytosis (LCH)** is the correct answer. Birbeck granules are the pathognomonic ultrastructural hallmark of Langerhans cells [1]. On Electron Microscopy (EM), these are pentalaminar, rod-shaped cytoplasmic organelles with a central striated line and a bulbous end, giving them a characteristic **"Tennis Racket" appearance** [1]. These granules contain **Langerin (CD207)**, a protein involved in capturing and internalizing antigens [1]. **Why other options are incorrect:** * **Plasmacytoma:** This is a neoplastic proliferation of plasma cells. Histology shows "clock-face" nuclei and perinuclear halos (Golgi zone). Immunophenotype is positive for CD138 and CD38, not Birbeck granules. * **Burkitt Lymphoma:** This is a high-grade B-cell lymphoma characterized by a **"Starry Sky" appearance** (tingible body macrophages against a background of small malignant lymphocytes) [2]. It is associated with the t(8;14) translocation and c-MYC overexpression. **High-Yield Clinical Pearls for NEET-PG:** * **Immunohistochemistry (IHC) Markers for LCH:** CD1a (most specific), **S100** (sensitive), and **CD207 (Langerin)**. * **Clinical Presentation:** Can range from a solitary bone lesion (Eosinophilic Granuloma) to multisystem involvement (Letterer-Siwe disease). * **Hand-Schüller-Christian Disease:** A classic triad of LCH consisting of bone lesions (calvarium), exophthalmos, and diabetes insipidus. * **Radiology:** "Punched-out" lytic lesions in the skull are a frequent finding. **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. 629-630. [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.

Question 228: Polycythemia vera may transform into which of the following myeloid neoplasms?

A. Acute lymphoblastic leukemia (ALL)
B. Acute myeloid leukemia (AML) (Correct Answer)
C. Chronic myeloid leukemia (CML)
D. Renal cell carcinoma

Explanation: **Explanation:** Polycythemia Vera (PV) is a chronic myeloproliferative neoplasm (MPN) characterized by the clonal expansion of multipotent hematopoietic progenitor cells, primarily driven by the **JAK2 V617F mutation**. **Why AML is the correct answer:** The natural history of PV involves two major late-stage complications: 1. **Spent Phase (Post-PV Myelofibrosis):** Characterized by extensive bone marrow fibrosis and extramedullary hematopoiesis [2]. 2. **Leukemic Transformation:** PV can progress into **Acute Myeloid Leukemia (AML)** or Myelodysplastic Syndrome (MDS) [1]. This transformation occurs in approximately 5–15% of patients, often following the "spent phase." The blast cells in this transformation are of myeloid lineage because PV is a disease of the myeloid stem cell. **Why incorrect options are wrong:** * **Acute Lymphoblastic Leukemia (ALL):** PV is a myeloid stem cell disorder. While rare cases of lymphoid transformation exist in other MPNs, the classic and expected transformation for PV is AML. * **Chronic Myeloid Leukemia (CML):** CML is defined by the *BCR-ABL1* fusion gene (Philadelphia chromosome). PV and CML are distinct MPNs; one does not typically transform into the other. * **Renal Cell Carcinoma (RCC):** RCC is a solid tumor of the kidney. While RCC can cause **secondary polycythemia** (via ectopic erythropoietin production), PV does not transform into RCC. **High-Yield Clinical Pearls for NEET-PG:** * **JAK2 V617F Mutation:** Present in >95% of PV cases (Exon 14) and nearly all remaining cases (Exon 12). * **Low Serum Erythropoietin (EPO):** A key diagnostic marker to differentiate PV (Primary) from secondary polycythemia (High/Normal EPO). * **Pruritus:** Classically occurs after a hot shower (aquagenic pruritus) due to mast cell degranulation. * **Treatment:** Phlebotomy and Hydroxyurea are mainstays; Ruxolitinib (JAK inhibitor) is used in resistant cases. **References:** [1] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Problems From Blood And Bone Marrow Disease, pp. 613-614. [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. 628-629.

Question 229: Von Willebrand factor protects which coagulation factor from premature degradation?

A. Factor II
B. Factor V
C. Factor VIII (Correct Answer)
D. Factor X

Explanation: **Explanation:** **1. Why Factor VIII is correct:** Von Willebrand Factor (vWF) serves two primary roles in hemostasis: it facilitates platelet adhesion to subendothelial collagen and acts as a **carrier protein for Factor VIII (FVIII)** [1] in the circulation. In the absence of vWF, FVIII is highly unstable and undergoes rapid proteolytic degradation by activated Protein C and Factor Xa. By binding to FVIII, vWF increases its half-life from approximately 1–2 hours to 12 hours. This explains why patients with severe Von Willebrand Disease (vWD) often have secondary deficiencies of Factor VIII, leading to a prolonged Activated Partial Thromboplastin Time (aPTT). **2. Why other options are incorrect:** * **Factor II (Prothrombin):** This is a vitamin K-dependent factor synthesized in the liver. Its stability is not dependent on vWF. * **Factor V:** While Factor V shares structural homology with Factor VIII, it does not bind to vWF. It circulates freely or is stored within platelet alpha-granules. * **Factor X:** This factor is part of the common pathway and is activated by the tenase complex. It does not require a carrier protein for stabilization in the plasma. **3. Clinical Pearls for NEET-PG:** * **Synthesis:** vWF is synthesized in **endothelial cells** (stored in **Weibel-Palade bodies**) and **megakaryocytes** (stored in **alpha-granules** [1] of platelets). * **Ristocetin Cofactor Assay:** This is the gold standard for testing vWF function; ristocetin induces vWF to bind to platelet GP Ib/IX/V receptors. * **Treatment:** Desmopressin (DDAVP) is used in Type 1 vWD as it triggers the release of vWF and Factor VIII from endothelial stores. * **Inheritance:** Most forms of vWD are Autosomal Dominant, making it the most common inherited bleeding disorder. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Red Blood Cell and Bleeding Disorders, pp. 669-670.

Question 230: Leucocyte alkaline phosphatase (LAP) is raised in which of the following conditions?

A. Myelofibrosis
B. Essential thrombocythemia
C. Polycythemia
D. Chronic myeloid leukemia (Correct Answer)

Explanation: **Explanation:** The **Leucocyte Alkaline Phosphatase (LAP) score** (also known as the Neutrophil Alkaline Phosphatase/NAP score) measures the activity of the enzyme alkaline phosphatase within the secondary granules of mature neutrophils. **Correct Answer: D. Chronic Myeloid Leukemia (CML)** In CML, the LAP score is characteristically **decreased** (often near zero) [1]. This occurs because the malignant neutrophils produced in CML are functionally defective and lack the enzyme. Therefore, a low LAP score is a classic diagnostic marker used to differentiate CML from a Leukemoid reaction (where the score is high) [1]. **Analysis of Options:** * **A, B, and C (Myelofibrosis, Essential Thrombocythemia, Polycythemia Vera):** These are all Chronic Myeloproliferative Neoplasms (MPNs) [2]. Unlike CML, the LAP score in these conditions is typically **normal or elevated**. Specifically, in Polycythemia Vera, a high LAP score is a common finding [1]. **High-Yield Clinical Pearls for NEET-PG:** * **Decreased LAP Score:** Seen in CML, Paroxysmal Nocturnal Hemoglobinuria (PNH), Hypophosphatasia, and Sideroblastic Anemia. * **Increased LAP Score:** Seen in **Leukemoid Reaction** (most common cause), Pregnancy, Polycythemia Vera, and during acute infections or treatment with G-CSF. * **The "CML vs. Leukemoid" Rule:** This is a favorite exam topic. If a patient has a massive shift to the left (high WBC count): * High LAP = Leukemoid Reaction. * Low LAP = CML. * **Note on CML:** The LAP score may normalize or increase if a patient with CML develops an infection or enters a **Blast Crisis**. **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. 624-629. [2] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Problems From Blood And Bone Marrow Disease, pp. 614-615.

Practice by Chapter

Anemias: Classification and Approach

Practice Questions

Hemolytic Anemias

Practice Questions

Myeloproliferative Neoplasms

Practice Questions

Myelodysplastic Syndromes

Practice Questions

Acute Leukemias

Practice Questions

Chronic Leukemias

Practice Questions

Lymphomas and Lymphoid Neoplasms

Practice Questions

Plasma Cell Disorders

Practice Questions

Bleeding Disorders

Practice Questions

Thrombotic Disorders

Practice Questions

Want unlimited practice?

Get full access to all questions, explanations, and performance tracking.

Start For Free