Hematopathology Practice Questions

Q: Which gene is commonly overexpressed in follicular lymphoma?

Bcl-2. ***Bcl- 2*** - Follicular lymphoma is characteristically associated with the **overexpression of Bcl-2** [1][2], which prevents apoptosis and contributes to oncogenesis [1][3]. - It is a result of the **t(14;18)** translocation, leading to the fusion of the Bcl-2 gene with the immunoglobulin heavy chain locus [1][2][3]. *Bcl-6* - While Bcl-6 is involved in the pathogenesis of some lymphomas, including **diffuse large B-cell lymphoma** [4], it is not a defining feature of follicular lymphoma. - Its positivity in follicular lymphoma cases does not correlate with the diagnosis. *None of the above* - This option is incorrect as there is a clear association with **Bcl-2** [1][2], which is pivotal in the pathology of follicular lymphoma. - Saying "none of the above" overlooks the critical marker essential for diagnosis. *Bcl-1* - Bcl-1 is primarily linked to **mantle cell lymphoma**, not follicular lymphoma, making it an unsuitable choice. - It is associated with **t(11;14)** translocations and has a different role in lymphoid malignancies compared to Bcl-2. **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. 602-604. [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. Neoplasia, pp. 310-311. [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. 604.

Q: Which disease is characterized by the absence of the CD59 protein?

Paroxysmal Nocturnal Hemoglobinuria (PNH). ***PNH*** - CD59 is a **glycoprotein** that inhibits the formation of the membrane attack complex of the complement system, which is deficient in **Paroxysmal Nocturnal Hemoglobinuria (PNH)** [1][2]. - The presence of CD59 deficiency leads to **hemolysis** and manifestations like **dark urine**, especially in the morning [1]. *BRR* - Refers to **Bloom-Richardson Grade** in breast cancer pathology, not related to CD59. - It focuses more on **histological features** rather than specific **markers** like CD59. *PTEN* - PTEN is a **tumor suppressor gene** associated with various cancers, particularly in **Cowden syndrome** and **PTEN hamartoma syndrome**. - It does not relate to the **CD59 deficiency** found in PNH. *Cowden syndrome* - Cowden syndrome is linked to mutations in the **PTEN gene**, leading to numerous hamartomas and an increased risk for breast and thyroid cancers. - It does not exhibit any relationship with **CD59**, which is specifically associated with PNH. **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. [2] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Problems From Blood And Bone Marrow Disease, pp. 601-602.

Q: Which of the following statements about sideroblastic anemia is correct?

Prussian blue staining reveals ringed sideroblasts. ***Prussian blue staining reveals ringed sideroblasts*** - Sideroblastic anemia is characterized by the presence of **ringed sideroblasts** in the bone marrow, which are erythroblasts with iron granules accumulating in a ring around the nucleus. - These iron deposits are visible with **Prussian blue staining**, confirming the diagnosis. *Severity of the disease is influenced by ALA synthase activity* - While defects in **heme synthesis** can cause sideroblastic anemia, the severity is not primarily or solely determined by **ALA synthase activity**. - Sideroblastic anemias involve diverse genetic and acquired causes, affecting various enzyme steps and pathways, not just specifically ALA synthase. *All of the options are false* - This statement is incorrect because the presence of **ringed sideroblasts** seen with Prussian blue staining is a hallmark diagnostic feature of sideroblastic anemia, making that option true. - This option would only be true if all other statements were false, which is not the case here. *Pyridoxine supplementation is the definitive treatment for all types of sideroblastic anemia* - **Pyridoxine (vitamin B6)** is a cofactor for some enzymes in the heme synthesis pathway, and about one-third of congenital sideroblastic anemias respond to it. - However, it is not a definitive treatment for **all types of sideroblastic anemia**, especially acquired forms or those with specific genetic mutations not responsive to pyridoxine.

Q: Which of the following statements is false regarding beta thalassemia major?

Bone marrow iron is depleted. ***Bone marrow iron is depleted*** - In beta thalassemia major, patients typically experience **iron overload** due to repeated blood transfusions, leading to **depleted iron stores** in the bone marrow. - This finding contrasts with conditions where iron stores are preserved or increased, highlighting the pathology of thalassemia. *Growth and development is impaired* - While children with beta thalassemia major may experience growth delay, this statement is **not universally true** for all patients. - Factors such as treatment and iron overload management can influence growth and development outcomes. *Red cell count <4 x 10'2/L* - Normal red cell counts can occur in some patients, particularly in **transfusion-dependent cases**. - Thus, it is not a definitive characteristic of beta thalassemia major, as levels can vary. *Levels of HbA2 < 3.5%* - In beta thalassemia major, HbA2 levels are often **increased**, usually exceeding 3.5% [1]. - This distinguishes it from beta thalassemia trait, where HbA2 is elevated but not to the same extent as in major [1].

Q: Which of the following genes is most commonly mutated in Juvenile myelomonocytic leukemia (JMML)?

PTPN11. ***PTPN11*** - **PTPN11** encodes the SHP2 protein, a non-receptor protein tyrosine phosphatase that plays a crucial role in the **RAS-MAPK signaling pathway**. - **Germline or somatic mutations** in PTPN11 are found in approximately **35% of JMML cases**, making it the **most commonly mutated gene** in this disorder. - These gain-of-function mutations lead to constitutive activation of RAS signaling, driving the myeloproliferative phenotype characteristic of JMML. - PTPN11 mutations are also associated with **Noonan syndrome**, and patients with Noonan syndrome have an increased risk of developing JMML. *KRAS* - **KRAS** is a proto-oncogene encoding a GTPase in the RAS-MAPK pathway. Mutations cause constitutive activation and uncontrolled cell proliferation. - KRAS mutations are found in approximately **15-20% of JMML cases**, making it the **second most common** genetic alteration in this disease. - While definitely associated with JMML, KRAS mutations are **less frequent than PTPN11 mutations**. *PTEN* - **PTEN** is a tumor suppressor gene regulating the PI3K-AKT pathway, involved in various cancers including Cowden syndrome and endometrial cancer. - PTEN mutations are **not associated with JMML** pathogenesis. *APC* - The **APC gene** is a tumor suppressor in the Wnt signaling pathway, critical for colon epithelial regulation. - APC mutations cause **familial adenomatous polyposis (FAP)** and colorectal cancer, but are **not implicated in JMML**.

Q: TEL-AML1 fusion is associated with?

ALL. ***ALL*** - The **TEL-AML1 fusion gene** (also known as ETV6-RUNX1) is a common chromosomal abnormality found in approximately 25% of cases of **B-cell precursor acute lymphoblastic leukemia (ALL)**, particularly in children. - This fusion creates an abnormal protein that interferes with normal blood cell development, leading to the uncontrolled proliferation of immature lymphocytes characteristic of ALL. *CLL* - **Chronic lymphocytic leukemia (CLL)** is a cancer of mature lymphocytes, specifically B cells, and is not associated with the TEL-AML1 fusion. - Typical genetic abnormalities in CLL include deletions or mutations in chromosomes 13q, 17p, 11q, and trisomy 12. *CML* - **Chronic myeloid leukemia (CML)** is characterized by the presence of the **Philadelphia chromosome (BCR-ABL1 fusion gene)**, which results from a translocation between chromosomes 9 and 22. - CML is a myeloproliferative neoplasm affecting myeloid stem cells, distinct from the lymphoid origin of ALL. *AML* - **Acute myeloid leukemia (AML)** involves the myeloid lineage and is associated with various chromosomal translocations and mutations, but **TEL-AML1 fusion is not characteristic of AML**. - Common genetic alterations in AML include t(8;21), inv(16), t(15;17) (PML-RARA), and mutations in FLT3, NPM1, or CEBPA.

Q: Where are Dutcher bodies typically seen?

Bone marrow. ***Bone marrow*** - **Dutcher bodies** are **intranuclear inclusions** of immunoglobulin, characteristically seen in **plasma cells** within the bone marrow. - Their presence is a classic morphological feature of **Waldenström macroglobulinemia** and other lymphoproliferative disorders. *Brain* - The brain is not the typical site for finding Dutcher bodies; structures like **Lewy bodies** (Parkinson's disease) or **neurofibrillary tangles** (Alzheimer's disease) are seen here. - Dutcher bodies are specifically associated with plasma cell abnormalities and **B-cell lymphomas**. *Spleen* - While the spleen can be involved in various hematological malignancies, Dutcher bodies are not primarily identified within splenic tissue but rather in the **plasma cells** of the **bone marrow**. - Splenic pathology typically involves changes in spleen size and cellular architecture, not intranuclear inclusions like Dutcher bodies. *Liver* - The liver is not the primary site for the detection of Dutcher bodies. Liver pathology might show infiltration by malignant cells in some systemic diseases, but not these specific inclusions within hepatocytes or other liver cells. - **Councilman bodies** (apoptotic hepatocytes in viral hepatitis) are an example of liver-specific microscopic findings.

Q: Which oncogene is associated with Burkitt's lymphoma?

C-MYC. ***C-MYC*** - Burkitt's lymphoma is associated with the translocation involving the **C-MYC gene**, which drives cell proliferation [1]. - This oncogene is typically involved in the **t(8;14)** translocation, linking C-MYC to the immunoglobulin heavy chain locus [1]. *ALK* - The **ALK gene** is primarily associated with anaplastic large cell lymphoma and is not linked to Burkitt's lymphoma. - ALK rearrangements lead to mutations that result in uncontrolled growth in other lymphomas, but not in Burkitt's. *BCL-1, IgH* - **BCL-1** (also known as CCND1) is associated with mantle cell lymphoma and is linked to the **t(11;14)** translocation, not Burkitt's. - It primarily involves cyclin D1 overexpression in the tumor pathogenesis distinct from Burkitt's behavior. *BCL-2, IgH* - The **BCL-2 gene** is commonly associated with follicular lymphoma and contributes to anti-apoptotic functions, unrelated to Burkitt's. - Burkitt's typically shows rapid proliferation and high apoptosis, unlike the mechanisms driven by BCL-2. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Neoplasia, pp. 324-325.

Q: Left shift in Arneth's count is seen in?

Septicemia. ***Septicemia*** - A **left shift** indicates a higher proportion of **immature neutrophils (bands or metamyelocytes)** in the blood, which is a hallmark of the body rapidly producing white blood cells to fight severe bacterial infections like **septicemia**. - This response is due to overwhelming bacterial load and systemic inflammation, prompting the bone marrow to release less mature neutrophils into circulation. *Megaloblastic anemia* - Characterized by **hypersegmented neutrophils** (a right shift), not a left shift, due to impaired DNA synthesis and delayed nuclear maturation. - The primary defect is in red blood cell production, although white blood cell morphology can also be affected. *Liver disease* - Liver disease does not typically cause a left shift in the Arneth count; instead, it can lead to various hematological abnormalities, including **anemia**, **thrombocytopenia**, or altered coagulation factors. - Neutrophil counts might fluctuate, but a sustained left shift is not a characteristic feature. *TB* - Tuberculosis usually causes a mild to moderate **neutrophilic leukocytosis** and sometimes a **monocytosis**, but a significant **left shift** is not a characteristic feature unless there is a severe acute exacerbation or secondary bacterial infection. - Chronic infections like TB are more often associated with changes like monocytosis or lymphocytosis.

Q: Richter's syndrome refers to which of the following malignant transformations?

CLL evolving into aggressive lymphoma. ***CLL evolving into aggressive lymphoma*** - **Richter's transformation** specifically describes the malignant transformation of Chronic Lymphocytic Leukemia (CLL) into a more aggressive form of B-cell non-Hodgkin lymphoma, most commonly **diffuse large B-cell lymphoma (DLBCL)**. - This transformation is characterized by a rapid clinical decline, palpable lymphadenopathy, and splenomegaly, with a distinct change in morphology and immunophenotype of the malignant cells. *Hairy cell leukemia evolving to AML* - Hairy cell leukemia (HCL) is a chronic lymphoproliferative disorder that rarely transforms into secondary malignancies; however, transformation into **acute myeloid leukemia (AML)** is not a hallmark of HCL and is not referred to as Richter's syndrome. - HCL is characterized by pancytopenia and distinctive hairy-looking lymphocytes, distinct from the progression pattern seen in Richter's. *Blast crisis in CML* - **Blast crisis** is the terminal phase of chronic myeloid leukemia (CML), where the number of myeloid blasts in the blood or bone marrow increases to >20%. - This is a progression of CML, a myeloproliferative neoplasm, and is distinct from the lymphoid transformation described by Richter's syndrome. *Splenic infiltration in NHL* - While non-Hodgkin lymphoma (NHL) can involve the spleen, **splenic infiltration** itself does not describe a malignant transformation syndrome like Richter's. - Richter's syndrome describes a transformation *from* CLL *to* a more aggressive lymphoma, not just a site of involvement for NHL.

Question 1

Which gene is commonly overexpressed in follicular lymphoma?

Accepted Answer

Bcl-2

Answer

Bcl-1

Answer

Bcl-6

Answer

None of the options

Question 2

Which disease is characterized by the absence of the CD59 protein?

Accepted Answer

Paroxysmal Nocturnal Hemoglobinuria (PNH)

Answer

Atypical Hemolytic Uremic Syndrome (aHUS)

Answer

Hereditary Spherocytosis

Answer

Autoimmune Hemolytic Anemia

Question 3

Which of the following statements about sideroblastic anemia is correct?

Accepted Answer

Prussian blue staining reveals ringed sideroblasts

Answer

All of the options are false

Answer

Severity of the disease is influenced by ALA synthase activity

Answer

Pyridoxine supplementation is the definitive treatment for all types of sideroblastic anemia

Question 4

Which of the following statements is false regarding beta thalassemia major?

Accepted Answer

Bone marrow iron is depleted

Answer

Growth and development is impaired

Answer

Red cell count is typically low

Answer

Levels of HbA2 are typically increased

Question 5

Which of the following genes is most commonly mutated in Juvenile myelomonocytic leukemia (JMML)?

Accepted Answer

PTPN11

Answer

KRAS

Answer

PTEN

Answer

APC

Question 6

TEL-AML1 fusion is associated with?

Accepted Answer

ALL

Answer

CLL

Answer

CML

Answer

AML

Question 7

Where are Dutcher bodies typically seen?

Accepted Answer

Bone marrow

Answer

Brain

Answer

Spleen

Answer

Liver

Question 8

Which oncogene is associated with Burkitt's lymphoma?

Accepted Answer

C-MYC

Answer

BCL-1 (IgH)

Answer

BCL-2 (IgH)

Answer

Anaplastic Lymphoma Kinase (ALK)

Question 9

Left shift in Arneth's count is seen in?

Accepted Answer

Septicemia

Answer

Megaloblastic anemia

Answer

Liver disease

Answer

TB

Question 10

Richter's syndrome refers to which of the following malignant transformations?

Accepted Answer

CLL evolving into aggressive lymphoma

Answer

Hairy cell leukemia evolving to AML

Answer

Blast crisis in CML

Answer

Splenic infiltration in NHL

Hematopathology — MCQs

Hematopathology — MCQs

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