Hematopathology Practice Questions

Q: What is the most common beta thalassemia gene mutation worldwide?

IVS-1-110 (G→A) mutation. ***IVS-1-110 (G→A) mutation*** - This mutation at **intron 1 position 110** (Guanine to Adenine substitution) is considered the most common single gene defect causing **beta thalassemia** worldwide, particularly prevalent in the **Mediterranean region** (Greece, Cyprus, Turkey). [1] - It leads to an alteration in the **splicing of mRNA**, resulting in reduced or absent production of the **beta-globin chain**. [1] - **Note:** The most common mutation varies by geographic population; in the **Indian subcontinent**, IVS-1-5 (G→C) is most prevalent. *IVS-1-1 (G→T) mutation* - This mutation, involving a **Guanine to Thymine** substitution at **intron 1 position 1**, is a common cause of **beta thalassemia** in the **Indian subcontinent** and Mediterranean regions. [1] - It affects RNA splicing and is the second most common mutation in India after IVS-1-5 (G→C). *Codon 39 (C→T) mutation* - This mutation, a **nonsense mutation** where Cytosine is replaced by Thymine at **codon 39**, is prevalent in the **Mediterranean and Middle East** populations. [2] - It results in a **premature stop codon**, leading to a complete absence of functional beta-globin chain (β⁰ thalassemia). [2] *Large gene deletion* - While large deletions can occur and cause **beta thalassemia**, particularly certain forms of **β⁰ thalassemia**, they are generally less frequent compared to point mutations. [1] - Deletions more commonly cause **alpha thalassemia** rather than beta thalassemia, although some deletions do affect the beta-globin gene cluster. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Red Blood Cell and Bleeding Disorders, pp. 646-647. [2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Genetic Disorders, pp. 147-148.

Q: A 15-year-old girl presented with weakness for 2 months, accompanied by pallor and icterus on examination, with a palpable spleen. Laboratory examination findings include reticulocytosis, increased mean corpuscular hemoglobin concentration (MCHC), and a positive osmotic fragility test. The Coombs test is negative. What is the diagnosis?

Hereditary spherocytosis. ***Hereditary spherocytosis*** - The combination of **reticulocytosis**, **macrocytic anemia (increased MCV)**, and **positive osmotic fragility test** indicates spherocytes, which are typical in hereditary spherocytosis [1]. - The **negative Coombs test** further supports this diagnosis by ruling out autoimmune hemolytic anemia (AIHA) [2]. *AIHA* - AIHA is characterized by a **positive Coombs test** due to the presence of autoantibodies, which is not the case here [2]. - It typically presents with **normocytic anemia** rather than macrocytic changes like in hereditary spherocytosis. *G-6-PD deficiency anemia* - G-6-PD deficiency usually presents with **episodic hemolysis** and often shows **bite cells**, but the osmotic fragility would not be positive in this scenario. - Symptoms often occur after certain triggers (e.g., infections, drugs), differing from the chronic symptoms noted in this patient [3]. *Iron deficiency anemia* - Iron deficiency anemia typically shows **microcytic hypochromic cells**, with a **low MCV** and **MCHC**, which is inconsistent with the findings of increased MCV and reticulocytosis here. - It doesn't cause a positive osmotic fragility test. **References:** [1] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Problems From Blood And Bone Marrow Disease, pp. 597-598. [2] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Problems From Blood And Bone Marrow Disease, pp. 602-603. [3] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Red Blood Cell and Bleeding Disorders, pp. 641-642. [4] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Red Blood Cell and Bleeding Disorders, pp. 640-641.

Q: Which test quantifies fetal hemoglobin in maternal blood using acid elution?

Kleihauer-Betke test. ***Kleihauer-Betke test*** - This test uses **acid elution** to quantify **fetal hemoglobin (HbF)**, which is resistant to acid, allowing it to remain in red cells while adult hemoglobin (HbA) elutes out. - It's primarily used to detect and quantify **fetomaternal hemorrhage**, guiding the dose of Rh immune globulin [2]. *Hemoglobin electrophoresis* - This method separates different **hemoglobin types** based on their electrical charge, useful for diagnosing hemoglobinopathies like sickle cell disease or thalassemia [1]. - While it can identify HbF, it is not the primary method for quantifying small amounts of fetal blood in maternal circulation after acid elution. *Complete Blood Count* - Provides information on red blood cell count, hemoglobin concentration, hematocrit, and other indices, but does not specifically quantify **fetal hemoglobin**. - It's a general screen for anemia or other blood disorders, not designed for differential hemoglobin analysis. *Peripheral Blood Smear* - Allows for microscopic examination of blood cell morphology, identifying abnormal red cell shapes or inclusions and estimating the proportions of different cell types. - It does not quantify specific types of hemoglobin, nor does it involve acid elution to differentiate fetal from adult red cells. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Red Blood Cell and Bleeding Disorders, pp. 649-650. [2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Diseases of Infancy and Childhood, pp. 469-470.

Q: All are true about polycythemia vera except one.

Increased erythropoietin. ***Increased erythropoietin*** - Polycythemia vera is characterized by **low erythropoietin levels** due to the autonomous proliferation of erythroid progenitor cells in the bone marrow [3]. - The disease is associated with a **JAK2 mutation**, which leads to erythrocytosis independent of erythropoietin stimulation [2,3]. *Increased LAP Score* - The LAP (leukocyte alkaline phosphatase) score is often **increased** in polycythemia vera due to increased leukocyte activity. - This test helps differentiate it from **essential thrombocythemia**, which typically has a normal or low LAP score. *Decreased erythropoietin* - Polycythemia vera generally exhibits **decreased erythropoietin levels** because of the negative feedback from increased red blood cell mass [3]. - Patients typically show a lack of normal response to hypoxia, which is observed in secondary causes of erythrocytosis [3]. *Increased ESR* - The erythrocyte sedimentation rate (ESR) can be **increased** in polycythemia vera due to elevated levels of multiple proteins in the blood. - This non-specific marker often reflects **inflammation** or other hematological conditions. **References:** [1] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Problems From Blood And Bone Marrow Disease, pp. 614-615. [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. 626-627. [3] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Red Blood Cell and Bleeding Disorders, pp. 663-664.

Q: Which of the following is not a B-cell marker?

CD 34. ***CD 19*** - CD 19 is a core B-cell marker crucial for B-cell development and differentiation in the immune response [1]. - It is universally present on all B-cell lineages, making it a reliable marker for identifying B-cells [1]. *CD 10* - CD 10, also known as the common acute lymphoblastic leukemia antigen (CALLA), is not exclusive to B-cells but can be found in **various cell types**, including early B-cells and T-cells [1]. - It is primarily used as a marker in certain leukemias rather than a definitive B-cell marker. *CD 34* - CD 34 is a marker for **hematopoietic stem cells** and progenitor cells, not specifically for B-cells. - While it can indicate early stages of B-cell lineages, it is not utilized as a definitive marker for B-cells themselves. *CD 20* - CD 20 is a well-established marker found on the surface of **mature B-cells** and is often targeted in therapies for B-cell malignancies [1]. - It plays a critical role in B-cell activation and differentiation, thus confirming it as a B-cell marker [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, p. 598.

Q: Classical markers for Hodgkin's disease are

CD 15 and CD 30. ***CD 15 and CD 30*** - These are **classical markers** specific for Reed-Sternberg cells, which are characteristic of Hodgkin's lymphoma [1][2]. - The presence of both markers is essential for **diagnosing Hodgkin's disease** and differentiating it from non-Hodgkin lymphomas [1]. *CD 20 and CD 30* - **CD 20** is primarily associated with B-cell non-Hodgkin lymphomas and is not a classical marker for Hodgkin's disease. - Hodgkin's lymphoma typically does not express **CD 20**, making this combination inappropriate for diagnosis. *CD 15 and CD 20* - While **CD 15** is a classical marker for Hodgkin's, **CD 20** is linked to B-lineage cells, which are not prominently present in Hodgkin's disease. - Diagnosis relies on the presence of **CD 30** alongside **CD 15**, highlighting the key difference. *CD 15 and CD 22* - Although **CD 15** is associated with Hodgkin's disease, **CD 22** is not a marker indicative of this lymphoma type. - **CD 22** is more relevant to B-cell malignancies; thus, it is not part of the classical markers for Hodgkin's lymphoma. **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. 614-616. [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. 616.

Q: A 10-year-old boy presents with a palpable mass in the abdomen. On imaging, the para-aortic lymph nodes are found to be enlarged. A biopsy from the lymph node shows a starry sky appearance. What is the likely underlying abnormality?

cMYC gene translocation. ***Translocation involving cMYC gene*** - The **starry sky appearance** in a lymph node biopsy is often associated with **Burkitt lymphoma** [2], which is caused by a translocation involving the cMYC gene [1]. - This translocation leads to **overexpression of cMYC** [1], promoting rapid cellular proliferation characteristic of this aggressive lymphoma. *Translocation involving BCR-ABL genes* - This abnormality is associated with **Chronic Myeloid Leukemia (CML)**, not lymphoma, and does not present with a **starry sky appearance**. - In CML, the hallmark finding is the presence of **Philadelphia chromosome** and myeloid cell overproduction. *Rb tumor suppressor gene mutation* - Rb gene mutations are typically noted in **retinoblastoma** or osteosarcoma, not in lymphomas presenting with a starry sky pattern. - These tumors often have different clinical presentations and do not typically involve lymph nodes as a primary finding. *Tumor suppressor gene Tp53 mutation* - Mutations in the Tp53 gene are commonly involved in **various cancers**, including sarcomas and breast cancer, but are not linked to the **starry sky appearance** seen in lymphomas. - While critical for **cell cycle regulation**, Tp53 mutations do not directly correlate with the typical findings in Burkitt lymphoma. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Neoplasia, pp. 324-325. [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.

Q: The most common translocation in acute promyelocytic leukemia (APML) is:

t(15;17). ***t (15:17)*** - The most common translocation in **acute promyelocytic leukemia (APML)** is the **t(15;17)**, which fuses the promyelocytic leukemia (PML) gene with the promyelocyte-retinoic acid receptor (RARA) gene [1]. - This genetic alteration is associated with a **specific clinical presentation** of APML, including bleeding diathesis and a high risk of coagulopathy [2]. *t (8:14)* - This translocation is commonly associated with **Burkitt lymphoma**, not APML. - It involves the **MYC gene**, leading to uncontrolled cell division, which is unrelated to the pathophysiology of APML. *t (8:21)* - Associated with **acute myeloid leukemia (AML)**, particularly the M2 subtype. - This translocation involves the **RUNX1 (AML1) gene** and does not pertain to APML's characteristic genetic changes. *t (9:22)* - Known as the **Philadelphia chromosome**, it is implicated in **chronic myeloid leukemia (CML)** and some types of ALL (acute lymphoblastic leukemia). - This translocation involves the **BCR-ABL fusion gene** which is distinctly different from the genetic abnormalities found in APML. **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. 620-622. [2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Neoplasia, p. 326.

Question 1

Which type of leukemia is associated with the Philadelphia chromosome?

Accepted Answer

Chronic Myeloid Leukemia (CML)

Answer

Acute Myeloid Leukemia (AML)

Answer

Acute Lymphoblastic Leukemia (ALL)

Answer

Chronic Lymphocytic Leukemia (CLL)

Question 2

What is the most common beta thalassemia gene mutation worldwide?

Accepted Answer

IVS-1-110 (G→A) mutation

Answer

Large gene deletion

Answer

IVS-1-1 (G→T) mutation

Answer

Codon 39 (C→T) mutation

Question 3

A 15-year-old girl presented with weakness for 2 months, accompanied by pallor and icterus on examination, with a palpable spleen. Laboratory examination findings include reticulocytosis, increased mean corpuscular hemoglobin concentration (MCHC), and a positive osmotic fragility test. The Coombs test is negative. What is the diagnosis?

Accepted Answer

Hereditary spherocytosis

Answer

Iron deficiency anemia

Answer

Autoimmune hemolytic anemia (AIHA)

Answer

G6PD deficiency anemia

Question 4

Which test quantifies fetal hemoglobin in maternal blood using acid elution?

Accepted Answer

Kleihauer-Betke test

Answer

Complete Blood Count

Answer

Hemoglobin electrophoresis

Answer

Peripheral Blood Smear

Question 5

All are true about polycythemia vera except one.

Accepted Answer

Increased erythropoietin

Answer

Decreased erythropoietin

Answer

Increased LAP Score

Answer

Increased blood viscosity

Question 6

Which of the following is not a B-cell marker?

Accepted Answer

CD 34

Answer

CD 10

Answer

CD 20

Answer

CD 19

Question 7

Classical markers for Hodgkin's disease are

Accepted Answer

CD 15 and CD 30

Answer

CD 15 and CD 20

Answer

CD 20 and CD 30

Answer

CD 15 and CD 22

Question 8

A 10-year-old boy presents with a palpable mass in the abdomen. On imaging, the para-aortic lymph nodes are found to be enlarged. A biopsy from the lymph node shows a starry sky appearance. What is the likely underlying abnormality?

Accepted Answer

cMYC gene translocation

Answer

Mutation in the Rb tumor suppressor gene

Answer

BCR-ABL gene translocation

Answer

Mutation in the Tp53 tumor suppressor gene

Question 9

Which of the following statements is true regarding eosinophilic granuloma?

Accepted Answer

Eosinophilic granuloma is associated with Langerhans cell histiocytosis.

Answer

Eosinophilic granuloma primarily affects adults.

Answer

Eosinophilic granuloma is characterized by a predominant neutrophilic infiltrate.

Answer

Eosinophilic granuloma is a benign condition that resolves spontaneously.

Question 10

The most common translocation in acute promyelocytic leukemia (APML) is:

Accepted Answer

t(15;17)

Answer

t(8;21)

Answer

t(8;14)

Answer

t(9;22)

Hematopathology — MCQs

Hematopathology — MCQs

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