Hematopathology Practice Questions

Q: A 27-year-old pregnant female in her first trimester presents to the OPD for a regular antenatal checkup. During blood type screening, potential ABO incompatibility is discussed. The healthcare provider explains that certain antibody types are less concerning than others during pregnancy. ABO incompatibility does not occur due to which antibody in her case?

IgM. ***IgM***- The predominant natural antibodies against **ABO antigens** (anti-A and anti-B) are of the **IgM class**, which are large pentameric molecules. These **IgM antibodies** generally cannot cross the placenta due to their size, meaning they do not reach the fetal circulation and cause significant hemolytic disease of the newborn (HDN). *IgA*- IgA is predominantly found in secretions (mucous membranes, breast milk) and is not generally involved in causing **hemolytic disease of the newborn (HDN)**, as it does not cross the placenta in significant amounts. This antibody class is not the primary mechanism of incompatibility, as the most common non-transmissible antibodies are IgM. *IgG*- **IgG is the only class** of immunoglobulin that efficiently crosses the placenta into the fetal circulation, meaning that any present **IgG anti-A or anti-B antibodies** are the ones responsible for causing **fetal red cell hemolysis** in ABO incompatibility. Though ABO HDN is usually less severe than Rh HDN, the pathology depends entirely on the presence of IgG. *IgD*- IgD antibodies are primarily expressed on the surface of naïve **B lymphocytes** and are involved in B cell activation and signaling. They are not involved in **red blood cell agglutination** or placental transfer relevant to ABO incompatibility.

Q: Basophilic stippling of red blood cells is most characteristically seen in which of the following conditions?

Lead poisoning. ***Lead poisoning*** - Lead inhibits several enzymes in the heme synthesis pathway and also inhibits **ribonuclease**, which is responsible for degrading residual ribosomal RNA (rRNA) in reticulocytes [1]. This leads to aggregation of ribosomes, appearing as coarse blue granules known as **basophilic stippling**. - While also seen in conditions like thalassemias and sideroblastic anemia, coarse basophilic stippling is a classic and highly characteristic finding in lead poisoning. *Iron deficiency anaemia* - The characteristic peripheral smear findings are **microcytic** and **hypochromic** red blood cells, which appear smaller and paler than normal [2]. - **Pencil cells** (elliptocytes) and **thrombocytosis** (an increased platelet count) are also commonly observed, but basophilic stippling is not a typical feature [2]. *Megaloblastic anemia* - This anemia, due to **vitamin B12** or **folate** deficiency, is characterized by **macro-ovalocytes** (large, oval red blood cells) and **hypersegmented neutrophils** on the peripheral smear [3]. - Other inclusions like **Howell-Jolly bodies** may be present, but basophilic stippling is not the defining feature. *Hereditary spherocytosis* - This is a genetic disorder affecting red blood cell membrane proteins, leading to the formation of **spherocytes** – small, round RBCs lacking central pallor. - The key findings are spherocytes on the smear and an increased **mean corpuscular hemoglobin concentration (MCHC)**, not basophilic stippling. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Infectious Diseases, pp. 418-419. [2] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Problems From Blood And Bone Marrow Disease, pp. 590-591. [3] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Problems From Blood And Bone Marrow Disease, pp. 594-595.

Q: Bernard-Soulier syndrome is caused by a defect in which of the following platelet glycoproteins?

GpIb/IX complex. ***GpIb/IX complex***- Bernard-Soulier syndrome (BSS) is a rare, autosomal recessive bleeding disorder caused by a quantitative or qualitative defect in the **platelet GpIb/IX/V complex** [1].- This complex acts as the essential high-affinity receptor for **von Willebrand factor (vWF)**, mediating initial **platelet adhesion** to the injured vessel wall, which is impaired in BSS [1], [2].*GpIIb/IIIa*- A defect in **GpIIb/IIIa** (integrin $\alpha_{IIb}\beta_3$) causes **Glanzmann thrombasthenia**, which presents with impaired **platelet aggregation**, not adhesion [1].- GpIIb/IIIa is the receptor for **fibrinogen**, which is necessary to link aggregating platelets [1], [2].*GpIa/IIa*- **GpIa/IIa** (integrin $\alpha_2\beta_1$) is primarily a receptor for **collagen** on the platelet surface, mediating adhesion in parallel with GpIb/vWF.- While important for hemostasis, defects in this receptor generally cause only mild bleeding and not the characteristic **giant platelets** or severe adhesion defect seen in BSS.*GpIV*- **GpIV** (also known as CD36) is a scavenger receptor that binds to **thrombospondin** and sometimes collagen.- Platelet defects related to GpIV are rare and usually involve mild aggregation defects, distinct from the severe adhesion failure defined by BSS. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Red Blood Cell and Bleeding Disorders, pp. 668-669. [2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Hemodynamic Disorders, Thromboembolic Disease, and Shock, p. 128.

Q: 2-year-old with fever, lymphadenopathy and H&E shows hallmark cells. The diagnosis of anaplastic large cell lymphoma was made. Most likely translocation?

t(2;5). ***Correct: t(2;5)*** - This is the **most common and classic translocation** found in systemic **Anaplastic Large Cell Lymphoma (ALCL)**, especially in children [1] - Occurs in approximately **60-85% of systemic ALCL cases** - Fuses the **NPM (Nucleophosmin)** gene on chromosome 5 with the **ALK** gene on chromosome 2 [1] - Results in constitutively active **ALK tyrosine kinase** that drives cell proliferation [1] - **ALK-positive ALCL** has a better prognosis, particularly in pediatric patients [1] *Incorrect: t(8;14)* - This is the hallmark translocation of **Burkitt Lymphoma (BL)**, not ALCL [2] - Juxtaposes the **MYC oncogene** on chromosome 8 to the **IgH promoter** on chromosome 14 [2] - Burkitt Lymphoma presents with rapidly growing masses and characteristic **"starry sky"** microscopic appearance [3] - Distinct from ALCL's hallmark cells (large cells with eccentric horseshoe/kidney-shaped nuclei) *Incorrect: t(8;22)* - A variant translocation associated with **Burkitt Lymphoma (BL)** [2] - Translocates **MYC gene** to the **kappa light chain locus** on chromosome 22 [2] - Results in MYC overexpression, which is pathognomonic for Burkitt Lymphoma - Not associated with Anaplastic Large Cell Lymphoma *Incorrect: t(14;18)* - Characteristic translocation of **Follicular Lymphoma (FL)** - Leads to overexpression of the **BCL2 anti-apoptotic protein** - Follicular Lymphoma is typically seen in adults and is a **B-cell lymphoma** - ALCL is a **T-cell/null-cell lymphoma**, making this translocation irrelevant **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. 565-566. [2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Neoplasia, pp. 324-325. [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.

Q: Which CD markers are typically positive in Chronic Lymphocytic Leukaemia (CLL)?

CD19, CD20, CD23, CD5. CD19, CD20, CD23, CD5 [1] - Chronic Lymphocytic Leukemia (CLL) is a malignancy of mature B-lymphocytes, which typically express the pan-B-cell markers CD19 and CD20 (often dimly), along with CD23 [1]. - A hallmark of CLL is the aberrant co-expression of the T-cell marker CD5 [2], which is crucial for differentiating it from other B-cell lymphomas. The peripheral smear in the image shows mature lymphocytes and a characteristic smudge cell, supporting the diagnosis of CLL [1]. CD3, CD5, CD8 - This profile is characteristic of a T-cell malignancy, as CD3 is a pan-T-cell marker and CD8 is a marker for cytotoxic T-cells [2]. - While CD5 is present in CLL, its combination with CD3 and CD8 excludes a B-cell disorder like CLL. CD10, CD19, CD22 - This combination of markers is more suggestive of other B-cell neoplasms like Follicular Lymphoma or Burkitt Lymphoma, which are characteristically CD10 positive [2]. - Typical CLL is negative for CD10 and positive for CD5 and CD23, which are key distinguishing features [1]. CD13, CD33, CD117 - These are markers associated with the myeloid lineage. CD13 and CD33 are classic myeloid antigens often seen in Acute Myeloid Leukemia (AML). - CD117 (c-kit) is a marker for hematopoietic progenitors and is also frequently positive in AML, making this immunophenotype inconsistent with a lymphoid neoplasm. **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] 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. 598.

Q: A young boy presents with joint swelling after a fall. Lab investigations show normal PT and raised aPTT. What is the most likely diagnosis?

Hemophilia. ***Hemophilia***- The presentation of joint swelling after trauma (suggesting **hemarthrosis**) in a young boy is highly characteristic of hemophilia, which is an X-linked recessive disorder [1].- Hemophilia A (Factor VIII deficiency) or B (Factor IX deficiency) affects the **intrinsic coagulation pathway**, leading to an isolated prolongation of the **aPTT** while the PT remains normal. *Von Willebrand Disease*- VWD primarily causes defects in **platelet adhesion** and mild to moderate mucocutaneous bleeding (e.g., epistaxis, menorrhagia), not typically severe spontaneous hemarthrosis [1].- While severe VWD can lower Factor VIII and mildly prolong aPTT, it generally presents differently and often affects both males and females (autosomal pattern) [2].*Iron Deficiency Anaemia (IDA)*- IDA is a nutritional deficiency resulting in **microcytic, hypochromic anemia** and is not a primary bleeding disorder.- It does not involve defects in the coagulation cascade; therefore, PT and aPTT levels would be within the **normal reference range**.*Platelet function disorder*- These disorders (e.g., Glanzmann's or Bernard-Soulier) affect **primary hemostasis** (platelet plug formation), leading mainly to mucocutaneous bleeding [2].- In platelet disorders, the **PT and aPTT** are typically normal, as the coagulation cascade (secondary hemostasis) is intact.

Q: For testing blood clotting/coagulation parameters, blood is collected in which color-coded vacutainer tube?

Blue. ***Blue*** - The blue-coded vacutainer contains **Sodium Citrate** (3.2% or 3.8%), which is the required anticoagulant for performing coagulation studies, such as **PT** (Prothrombin Time) and **aPTT** (Activated Partial Thromboplastin Time) [1]. - **Sodium Citrate** works by binding and sequestering **calcium ions** (Factor IV), thereby reversibly preventing the coagulation cascade from proceeding until calcium is added back in the lab [1]. *Red* - The Red top tube typically contains **no anticoagulant** (or a clot activator) and is used to obtain **serum** after the blood clots naturally. - It is utilized for chemistry, serology, and blood bank tests, where the natural clotting process is required or coagulation factors are not needed. *Green* - The Green top tube contains **Heparin** (Lithium or Sodium Heparin), which inhibits clotting by augmenting the activity of **antithrombin III** [2]. - Although it provides plasma, it is unsuitable for routine coagulation assays because heparin itself significantly interferes with most coagulation factor tests. *Gray* - The Gray top tube contains **Potassium Oxalate** as an anticoagulant and **Sodium Fluoride** as a preservative. - It is specifically reserved for **glucose** and sometimes **lactate** measurements, as sodium fluoride inhibits enolase, thereby preventing glycolysis (glucose breakdown) by blood cells. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Hemodynamic Disorders, Thromboembolic Disease, and Shock, pp. 128-130. [2] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Problems From Blood And Bone Marrow Disease, pp. 583-584.

Q: What defect is seen in Bernard Soulier syndrome?

Deficiency of GpIb receptors. ***Deficiency of GpIb receptors***- **Bernard-Soulier syndrome (BSS)** is an autosomal recessive disorder caused by defective or deficient **Glycoprotein Ib (GpIb)** [1]; this receptor is necessary for platelet adhesion to the subendothelium via **von Willebrand factor (vWF)** [1], [2]. - This defect results in dysfunctional primary **hemostasis**, causing bleeding and characteristic findings like **giant platelets** (macrothrombocytopenia) and mild to severely prolonged **bleeding time**. *Deficiency of GpIIb/IIIa receptor*- Deficiency or dysfunction of the **GpIIb/IIIa receptor** (fibrinogen receptor) causes **Glanzmann thrombasthenia** [1], which impairs platelet aggregation, not initial adhesion. - In Glanzmann thrombasthenia, platelets fail to aggregate in response to most agonists (like ADP or thrombin), but the initial adhesion mediated by GpIb is preserved [1]. *Deficiency of von Willebrand factor*- Deficiency of **von Willebrand factor (vWF)** causes **von Willebrand disease (vWD)**, the most common inherited bleeding disorder. - vWF is the ligand that links GpIb on the platelet to the exposed collagen in the vessel wall [2]; its deficiency is distinct from the receptor deficiency seen in BSS. *Deficiency of ADP receptors*- Deficiency of **ADP receptors** (specifically the P2Y12 receptor) impairs the signal transduction critical for sustained platelet aggregation and granule release [2]. - While affecting primary hemostasis, this congenital receptor deficiency is separate from BSS and is rarely reported; the most common interference with this receptor is therapeutic (**clopidogrel**). **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Red Blood Cell and Bleeding Disorders, pp. 668-669. [2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Hemodynamic Disorders, Thromboembolic Disease, and Shock, p. 128.

Q: Which gene mutation is most commonly associated with Burkitt's lymphoma?

C-myc. ***C-myc*** - Burkitt's lymphoma is characterized by the **t(8;14) translocation** in 80% of cases [1] - This translocation juxtaposes the **C-myc oncogene (chromosome 8)** with the **immunoglobulin heavy chain locus (chromosome 14)** [1] - Results in **constitutive overexpression of C-myc**, driving uncontrolled cell proliferation [1] - This is a **pathognomonic molecular feature** of Burkitt's lymphoma [1] - Variants include t(2;8) and t(8;22) involving immunoglobulin light chain loci [1] *p53* - Tumor suppressor gene involved in many cancers - Not the characteristic mutation defining Burkitt's lymphoma - May be involved in disease progression but not the hallmark feature *Rb* - Retinoblastoma gene, another tumor suppressor - Associated with retinoblastoma and osteosarcoma - Not characteristic of Burkitt's lymphoma *p21* - Cyclin-dependent kinase inhibitor (CDKN1A) - Involved in cell cycle regulation - Not the defining genetic alteration in Burkitt's lymphoma **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Neoplasia, pp. 324-325.

Q: A child diagnosed with von Willebrand disease requires an understanding of the role of von Willebrand factor (vWF). What does von Willebrand factor primarily combine with?

Glycoprotein Ib. ***Glycoprotein Ib***- vWF bridges exposed subendothelial **collagen** to the platelet surface receptor **Glycoprotein Ib (GPIb)**, which is crucial for initiating platelet **adhesion** during primary hemostasis [1], [2].- A deficiency in vWF (von Willebrand disease) or a defect in GPIb (Bernard-Soulier syndrome) impairs this initial binding step [1], [3].*Platelet factor 3*- Platelet factor 3 (PF3) refers to the **phospholipid surface** (cell membrane) of activated platelets, which serves as a necessary platform for the assembly of clotting factors (e.g., the **tenase** and **prothrombinase** complexes) in secondary hemostasis.- Although critical for clotting, PF3 does not represent the primary receptor that vWF binds to on the platelet surface.*ADP*- **Adenosine diphosphate (ADP)** is a chemical mediator released from platelet dense granules that acts to amplify platelet **activation** and promote **aggregation** (by activating P2Y12 and P2Y1 receptors) [1].- ADP is involved after initial adhesion and promotes platelet-platelet interactions (aggregation) via GP IIb/IIIa receptors, not the binding of vWF (adhesion) via GPIb [1], [3].*Prothrombin*- **Prothrombin (Factor II)** is a circulating zymogen that converts to thrombin (Factor IIa) in the common coagulation pathway, leading to the formation of **fibrin** (secondary hemostasis).- While vWF stabilizes **Factor VIII** (another coagulation factor), it does not primarily bind or activate Prothrombin; its main direct platelet interaction is with GPIb [2]. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Hemodynamic Disorders, Thromboembolic Disease, and Shock, p. 128. [2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Red Blood Cell and Bleeding Disorders, pp. 669-670. [3] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Red Blood Cell and Bleeding Disorders, pp. 668-669.

Question 1

A 27-year-old pregnant female in her first trimester presents to the OPD for a regular antenatal checkup. During blood type screening, potential ABO incompatibility is discussed. The healthcare provider explains that certain antibody types are less concerning than others during pregnancy. ABO incompatibility does not occur due to which antibody in her case?

Accepted Answer

IgM

Answer

IgG

Answer

IgD

Answer

IgA

Question 2

Basophilic stippling of red blood cells is most characteristically seen in which of the following conditions?

Accepted Answer

Lead poisoning

Answer

Megaloblastic anemia

Answer

Hereditary spherocytosis

Answer

Iron deficiency anaemia

Question 3

Bernard-Soulier syndrome is caused by a defect in which of the following platelet glycoproteins?

Accepted Answer

GpIb/IX complex

Answer

GpIV

Answer

GpIa/IIa

Answer

GpIIb/IIIa

Question 4

2-year-old with fever, lymphadenopathy and H&E shows hallmark cells. The diagnosis of anaplastic large cell lymphoma was made. Most likely translocation?

Accepted Answer

t(2;5)

Answer

t(14;18)

Answer

t(8;22)

Answer

t(8;14)

Question 5

Which CD markers are typically positive in Chronic Lymphocytic Leukaemia (CLL)?

Accepted Answer

CD19, CD20, CD23, CD5

Answer

CD10, CD19, CD22

Answer

CD13, CD33, CD117

Answer

CD3, CD5, CD8

Question 6

A young boy presents with joint swelling after a fall. Lab investigations show normal PT and raised aPTT. What is the most likely diagnosis?

Accepted Answer

Hemophilia

Answer

Von Willebrand Disease

Answer

Platelet function disorder

Answer

Iron Deficiency Anaemia (IDA)

Question 7

For testing blood clotting/coagulation parameters, blood is collected in which color-coded vacutainer tube?

Accepted Answer

Blue

Answer

Gray

Answer

Red

Answer

Green

Question 8

What defect is seen in Bernard Soulier syndrome?

Accepted Answer

Deficiency of GpIb receptors

Answer

Deficiency of GpIIb/IIIa receptor

Answer

Deficiency of ADP receptors

Answer

Deficiency of von Willebrand factor

Question 9

Which gene mutation is most commonly associated with Burkitt's lymphoma?

Accepted Answer

C-myc

Answer

p53

Answer

Rb

Answer

p21

Question 10

A child diagnosed with von Willebrand disease requires an understanding of the role of von Willebrand factor (vWF). What does von Willebrand factor primarily combine with?

Accepted Answer

Glycoprotein Ib

Answer

Prothrombin

Answer

ADP

Answer

Platelet factor 3

Hematopathology — MCQs

Hematopathology — MCQs

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