Chronic Leukemias — MCQs
Which of the following is the most common myeloproliferative disorder?
A 45-year-old woman presents with marked splenomegaly, a leukocyte count of 300,000/μL, and a differential count showing a predominance of myelocytes, metamyelocytes, bands, and segmented neutrophils, along with increased basophils and platelets, without anemia. Leukocyte alkaline phosphatase is decreased. Which of the following describes a major characteristic of chronic myeloid leukemia?
A 55-year-old male with fatigue and a palpable spleen is found to have a high white cell count predominantly consisting of mature lymphocytes. What is the most likely diagnosis?
A 68-year-old woman was admitted with a history of weakness for two months. On examination, cervical lymph nodes were found enlarged and the spleen was palpable 2 cm below the costal margin. Her hemoglobin was 10.5 g/dL, platelet count 27 × 10^9/L, and total leukocyte count 40 × 10^9/L, which included 80% mature lymphoid cells with coarse clumped chromatin. Bone marrow revealed a nodular lymphoid infiltrate. The peripheral blood lymphoid cells were positive for CD19, CD5, CD20, and CD23, and negative for CD79B and FMC-7. The histopathological examination of the lymph node in this patient will most likely exhibit effacement of lymph node architecture by?
Which is TRUE about JAK2 V617F mutation?
Before the advent of tyrosine kinase inhibitors, the most effective treatment of chronic myeloid leukemia was:
Which of the following is positive in Follicular lymphoma?
BCR-ABL fusion gene is MOST CHARACTERISTICALLY seen in?
Which among the following statements is wrong?
Tumor cells in chronic lymphocytic leukemia or small lymphoblastic lymphoma (CLL/SLL) arise from which of the following?
Chronic Leukemias Indian Medical PG Practice Questions and MCQs
Question 1: Which of the following is the most common myeloproliferative disorder?
- A. Essential Thrombocythemia (Correct Answer)
- B. Polycythemia rubra vera
- C. CML
- D. Myelofibrosis
Explanation: ***Essential Thrombocythemia*** - **Essential thrombocythemia (ET)** is the **most common myeloproliferative neoplasm**, with an incidence of approximately 1.5-2.4 per 100,000 per year. - It is characterized by **persistent thrombocytosis** (platelet count >450,000/μL) and megakaryocytic proliferation [1]. - Commonly associated with **JAK2 V617F mutation** (~55-60%), **CALR mutations** (~25-30%), and **MPL mutations** (~3-5%) [2]. *Polycythemia rubra vera* - **Polycythemia vera (PV)** is the **second most common** classic MPN, with an incidence of approximately 0.8-2.3 per 100,000 per year. - Characterized by increased red blood cell mass, often with leukocytosis and thrombocytosis [1]. - Strongly associated with **JAK2 V617F mutation** (present in >95% of cases) [2][3]. *CML* - **Chronic myeloid leukemia (CML)** has similar incidence to PV (approximately 1-2 per 100,000 per year). - Defined by the presence of the **Philadelphia chromosome (BCR-ABL1 fusion gene)** [2]. - Treated distinctly with tyrosine kinase inhibitors (TKIs). *Myelofibrosis* - **Primary myelofibrosis (PMF)** is the **least common** of the classic MPNs, with an incidence of approximately 0.3-1.5 per 100,000 per year. - Characterized by bone marrow fibrosis, extramedullary hematopoiesis, and splenomegaly [3]. - Associated with **JAK2, CALR, or MPL mutations** [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. 627-628. [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. 624. [3] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Problems From Blood And Bone Marrow Disease, pp. 614-615.
Question 2: A 45-year-old woman presents with marked splenomegaly, a leukocyte count of 300,000/μL, and a differential count showing a predominance of myelocytes, metamyelocytes, bands, and segmented neutrophils, along with increased basophils and platelets, without anemia. Leukocyte alkaline phosphatase is decreased. Which of the following describes a major characteristic of chronic myeloid leukemia?
- A. Expansion of mature B lymphocytes in lymph nodes
- B. Low levels of immunoglobulins (hypogammaglobulinemia)
- C. Presence of hairy cells with filamentous projections
- D. Translocation of chromosome 9 and 22 (Philadelphia chromosome) (Correct Answer)
Explanation: ***9;22 translocation*** - The presence of leukocytosis with myelocyte predominance and splenomegaly suggests a myeloproliferative disorder, specifically Chronic Myeloid Leukemia (CML) [2]. - The **9;22 translocation** leading to the BCR-ABL fusion gene is a hallmark of CML, indicating its role in the pathogenesis of the disease [1]. *Expansion of mature B lymphocytes within multiple lymph nodes* - This description is more characteristic of **chronic lymphocytic leukemia (CLL)** or lymphomas rather than CML. - CML primarily affects **myeloid lineage**, not B lymphocytes, and typically does not exhibit marked lymphadenopathy. *Hypogammaglobulinemia* - Hypogammaglobulinemia is associated with disorders that affect antibody production, but is not a major characteristic of CML. - In fact, CML may present with **normal or elevated immunoglobulin levels** at diagnosis. *Neoplastic cells exhibiting hair-like filamentous projections* - This feature describes **hairy cell leukemia**, not CML, which is characterized by myeloid proliferation. - CML presents with atypical myeloblasts and myeloid cells, rather than the unique cellular morphology seen in hairy cell leukemia. **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. 624. [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. 625-626.
Question 3: A 55-year-old male with fatigue and a palpable spleen is found to have a high white cell count predominantly consisting of mature lymphocytes. What is the most likely diagnosis?
- A. Acute lymphoblastic leukemia
- B. Chronic lymphocytic leukemia (Correct Answer)
- C. Myelodysplastic syndrome (ineffective hematopoiesis and cytopenias)
- D. Hairy cell leukemia (characterized by "hairy" appearing cells)
Explanation: ***Chronic lymphocytic leukemia*** - The presence of **fatigue**, a **palpable spleen**, and an elevated white cell count predominantly consisting of **mature lymphocytes** is highly characteristic of CLL [1]. - CLL is a common leukemia in older adults, where **monoclonal B-lymphocytes** accumulate in the blood, bone marrow, and lymphoid organs [1]. *Acute lymphoblastic leukemia* - This leukemia typically presents with **immature lymphocytes (blasts)** and a more aggressive clinical course, often seen in children [2]. - While it causes fatigue and can lead to organomegaly, the predominance of **mature lymphocytes** in the peripheral blood rules out ALL [2]. *Myelodysplastic syndrome (ineffective hematopoiesis and cytopenias)* - This syndrome is characterized by **ineffective hematopoiesis** and **cytopenias** (low blood cell counts), rather than a high white cell count. - It involves dysplasia in one or more myeloid cell lines, and the peripheral smear would show abnormal cell morphology, not a predominance of mature lymphocytes. *Hairy cell leukemia (characterized by "hairy" appearing cells)* - While it presents with **splenomegaly** and can cause fatigue, the characteristic cells have **"hairy" cytoplasmic projections** and are rarely found in high numbers in the peripheral blood initially. - The diagnosis is confirmed by flow cytometry and bone marrow biopsy, and the classic picture often includes **pancytopenia**, not just a high white cell count from mature lymphocytes.
Question 4: A 68-year-old woman was admitted with a history of weakness for two months. On examination, cervical lymph nodes were found enlarged and the spleen was palpable 2 cm below the costal margin. Her hemoglobin was 10.5 g/dL, platelet count 27 × 10^9/L, and total leukocyte count 40 × 10^9/L, which included 80% mature lymphoid cells with coarse clumped chromatin. Bone marrow revealed a nodular lymphoid infiltrate. The peripheral blood lymphoid cells were positive for CD19, CD5, CD20, and CD23, and negative for CD79B and FMC-7. The histopathological examination of the lymph node in this patient will most likely exhibit effacement of lymph node architecture by?
- A. A monomorphic lymphoid proliferation with admixed proliferation centers (Correct Answer)
- B. A polymorphous population of lymphocytes, plasma cells, eosinophils and scattered large binucleated cells
- C. A predominantly follicular pattern with variably-sized follicles effacing nodal architecture
- D. A diffuse proliferation of medium to large lymphoid cells with high mitotic rate
Explanation: ***A monomorphic lymphoid proliferation with admixed proliferation centers*** - The clinical and laboratory findings suggest **chronic lymphocytic leukemia (CLL)** [1], characterized by a predominance of **mature lymphoid cells** [2] and a nodular infiltrate in the bone marrow. - Histopathological examination would typically show a **monomorphic proliferation** of small, mature lymphocytes [1], which efface the lymph node architecture. *A diffuse proliferation of medium to large lymphoid cells with high mitotic rate.* - This description aligns more with **aggressive lymphomas**, such as diffuse large B-cell lymphoma, rather than CLL. - CLL is characterized by **low mitotic activity** and predominantly small, mature lymphocytes [2], not medium to large cells. *A predominantly follicular pattern with variably-sized follicles effacing nodal architecture* - This finding is typical of **follicular lymphoma**, where the architecture features multiple follicles rather than a monomorphic infiltrate. - The malignant cells in CLL do not form **follicular patterns** but rather disrupt the normal architecture with a more uniform appearance [1]. *A polymorphous population of lymphocytes, plasma cells, eosinophils and scattered large binucleated cells* - A polymorphous pattern suggests a **reactive lymphadenopathy** or conditions such as Hodgkin lymphoma, which show mixed cellularity. - CLL is characterized by **uniformity** in cell type [1] with little to no diversity in the lymphocyte population, making this option unsuitable. **References:** [1] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Problems From Blood And Bone Marrow Disease, pp. 612-613. [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. 602.
Question 5: Which is TRUE about JAK2 V617F mutation?
- A. Seen in ET.
- B. Rare in CML.
- C. Common in PV but not specific.
- D. Seen in PV, ET, and PMF but rare in CML. (Correct Answer)
Explanation: ***Seen in PV, ET, and PMF but rare in CML.*** - The **JAK2 V617F mutation** is a hallmark of classic Philadelphia chromosome-negative **myeloproliferative neoplasms (MPNs)**, including **polycythemia vera (PV)** (~95%), **essential thrombocythemia (ET)** (~50-60%), and **primary myelofibrosis (PMF)** (~50-60%) [1]. - It is **rare in chronic myeloid leukemia (CML)**, which is defined by the **BCR-ABL1 fusion gene** [1]. - This option provides the **most comprehensive and accurate** description of JAK2 V617F distribution across myeloproliferative disorders. *Seen in ET.* - While the **JAK2 V617F mutation** is indeed found in approximately 50-60% of patients with **essential thrombocythemia (ET)**, this statement is **incomplete** [2]. - It fails to mention the mutation's presence in other MPNs (PV and PMF) and its rarity in CML, making it a partial truth rather than the best answer. *Rare in CML.* - This statement is **medically accurate** - JAK2 V617F is indeed **rare in CML**, as CML is characterized by the **BCR-ABL1 translocation** [1]. - However, this option is **incomplete** as it omits crucial information about the mutation's presence in PV, ET, and PMF. - Knowing where the mutation IS found is more clinically useful than only knowing where it's rare. *Common in PV but not specific.* - This statement is **technically correct** - the **JAK2 V617F mutation** is found in about 95% of patients with **polycythemia vera (PV)**, making it very **common** in this condition [2]. - The phrase "**not specific**" is also accurate because the mutation is found in other MPNs (ET and PMF), not exclusively in PV [1]. - However, this option is less complete than the correct answer because it doesn't describe the full distribution pattern across all major MPNs or mention its rarity in CML. **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. 624. [2] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Problems From Blood And Bone Marrow Disease, pp. 614-615.
Question 6: Before the advent of tyrosine kinase inhibitors, the most effective treatment of chronic myeloid leukemia was:
- A. Chemotherapy
- B. Hydroxyurea and interferon
- C. Haploidentical bone marrow transplant
- D. Allogeneic bone marrow transplant (Correct Answer)
Explanation: ***Allogeneic bone marrow transplant*** - Before the advent of TKIs, **allogeneic hematopoietic stem cell transplantation (HSCT)** was the only curative treatment for CML [1]. - It involved replacing the patient's diseased bone marrow with healthy stem cells from a genetically matched donor, thereby eradicating the **Philadelphia chromosome-positive clone** [1]. *Haploidentical bone marrow transplant* - While a form of HSCT, **haploidentical transplants** were typically used as a backup option when a fully matched donor was unavailable due to higher risks of **graft-versus-host disease (GVHD)** and rejection. - It was not considered the most effective or preferred treatment before TKIs, being reserved for specific challenging cases. *Chemotherapy* - **Conventional chemotherapy** for CML, such as busulfan or hydroxyurea, primarily aimed at reducing the white blood cell count and controlling symptoms. - It was **palliative** and did not offer a cure or significantly prolong survival in the long term, unlike allogeneic HSCT [1]. *Hydroxyurea and interferon* - **Hydroxyurea** is a cytoreductive agent, and **interferon-alpha** was used to induce hematologic and cytogenetic responses in CML patients. - Although they provided some benefit in controlling the disease and improving survival compared to no treatment, they rarely achieved a cure and were associated with significant side effects, making them less effective than allogeneic HSCT [1].
Question 7: Which of the following is positive in Follicular lymphoma?
- A. Cyclin D1 (Bcl-1)
- B. Bcl-2 protein (Correct Answer)
- C. Bcl-10 signaling protein
- D. Bcl-6 transcription factor
Explanation: ***Bcl-2 protein*** - The characteristic **t(14;18) chromosomal translocation** in follicular lymphoma leads to the **overexpression of the Bcl-2 protein**, which promotes cell survival by inhibiting apoptosis [1], [4]. - This constitutive activation makes the tumor cells resistant to programmed cell death, contributing to their accumulation [2]. - **Bcl-2 positivity is highly specific for follicular lymphoma** among lymphomas, making it the most diagnostically useful marker [3]. *Cyclin D1 (Bcl-1)* - **Cyclin D1** overexpression is characteristic of **Mantle Cell Lymphoma**, typically due to a **t(11;14) translocation**. - It plays a role in cell cycle progression rather than directly inhibiting apoptosis in the same manner as Bcl-2. *Bcl-10 signaling protein* - **Bcl-10** is involved in **NF-ΙB activation**, particularly in certain types of **MALT lymphoma** and other lymphoid neoplasms. - It is not a primary diagnostic marker for follicular lymphoma. *Bcl-6 transcription factor* - **Bcl-6** is a germinal center marker and is **positive in most follicular lymphomas** since they are germinal center-derived B-cell neoplasms. - However, Bcl-6 is also expressed in other germinal center-derived lymphomas like **DLBCL of germinal center subtype**, making it **less specific** than Bcl-2 [3], [5]. - While both Bcl-2 and Bcl-6 can be positive in follicular lymphoma, **Bcl-2 overexpression due to t(14;18) is the defining molecular hallmark** and most diagnostically specific feature [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. 602-604. [2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Neoplasia, pp. 310-311. [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. [4] 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. [5] 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.
Question 8: BCR-ABL fusion gene is MOST CHARACTERISTICALLY seen in?
- A. CML (Correct Answer)
- B. AML
- C. Chronic Lymphocytic Leukemia (CLL)
- D. Acute Lymphoblastic Leukemia (ALL)
Explanation: ***CML*** - The **BCR-ABL gene mutation** is characteristic of **Chronic Myeloid Leukemia (CML)**, resulting from a translocation between chromosomes 9 and 22 [1]. - This mutation leads to the production of the **BCR-ABL fusion protein**, which promotes cell proliferation and inhibits apoptosis [1]. *AML* - Acute Myeloid Leukemia (AML) does not typically exhibit the **BCR-ABL fusion gene**; rather, it is associated with various other genetic mutations. - Key features of AML include **myeloblast proliferation** and it presents with different cytogenetic abnormalities like **FLT3 or NPM1 mutations**. *CLL* - Chronic Lymphocytic Leukemia (CLL) is characterized by the accumulation of **mature lymphocytes**, not the **BCR-ABL mutation**. - It is often associated with mutations such as **TP53** and **NOTCH1**, distinct from myeloid malignancies. *ALL* - Acute Lymphoblastic Leukemia (ALL) is primarily linked with **chromosomal translocations** involving **the TCF3** gene or others, but not specifically with **BCR-ABL**. - In ALL, **lymphoid progenitor cells** proliferate, whereas CML is primarily a **myeloid process** associated with the BCR-ABL gene [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. 624-625.
Question 9: Which among the following statements is wrong?
- A. M components are detected in chronic myeloid leukemia. (Correct Answer)
- B. In 20% of myelomas, only light chains are produced.
- C. Light chains are synthesized in slight excess normally in plasma cells.
- D. Qualitative assessment of M component can be done by electrophoresis.
Explanation: ***M components are detected in chronic myeloid leukemia.*** - This statement is **incorrect**. M-components (monoclonal proteins) are characteristic of **plasma cell dyscrasias** such as multiple myeloma, MGUS, and Waldenström macroglobulinemia [1]. - **Chronic myeloid leukemia (CML)** is a myeloproliferative neoplasm involving the granulocytic cell line, not plasma cells. CML does not produce M-components unless there is a **coincidental and unrelated plasma cell disorder**. - M-components arise from clonal proliferation of plasma cells producing a single type of immunoglobulin, which is not a feature of CML pathophysiology [2]. *Qualitative assessment of M component can be done by electrophoresis.* - This statement is correct. **Serum protein electrophoresis (SPEP)** is the primary tool for qualitative detection of M-components. - It provides qualitative information by demonstrating the presence of a monoclonal spike and its migration pattern in the gamma, beta, or alpha regions. - While SPEP also provides quantitative data (size/concentration), **immunofixation electrophoresis (IFE)** is subsequently used for specific typing of the heavy chain (IgG, IgA, IgM) and light chain (kappa or lambda). *In 20% of myelomas, only light chains are produced.* - This statement is correct. Approximately **15-20% of multiple myeloma cases** produce only monoclonal light chains without intact heavy chains [1]. - These are called **light chain myelomas**, and the light chains (Bence Jones proteins) are detected in urine and serum [2]. *Light chains are synthesized in slight excess normally in plasma cells.* - This statement is correct. Normal plasma cells produce a **slight excess of light chains** compared to heavy chains to ensure proper immunoglobulin assembly. - The excess free light chains are normally cleared by the kidneys, maintaining a balanced serum free light chain ratio (kappa/lambda ratio of 0.26-1.65). **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. 606-609. [2] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Problems From Blood And Bone Marrow Disease, pp. 616-617.
Question 10: Tumor cells in chronic lymphocytic leukemia or small lymphoblastic lymphoma (CLL/SLL) arise from which of the following?
- A. Naive B cell
- B. Mature B cell (Correct Answer)
- C. Centrocytes of germinal center
- D. Progenitor B-cell
Explanation: ***Mature B cell*** - CLL/SLL is characterized by the accumulation of **monoclonal B lymphocytes** that are morphologically mature but functionally incompetent. [1] - These malignant cells exhibit a mature immunophenotype, expressing **CD5, CD19, CD20 (dim), and CD23**, indicating their origin from a post-germinal center or memory B cell lineage. [1] *Naive B cell* - Naive B cells are typically found circulating in the blood and lymph nodes; while they are B cells, the specific immunophenotype and genomic features of CLL/SLL cells point to a more differentiated origin. - Although CLL/SLL cells express some markers of naive B cells, their overall profile, particularly the expression of **CD23**, is more consistent with a mature or activated B cell stage. [1] *Centrocytes of germinal center* - Malignancies arising from centrocytes of germinal centers often include **follicular lymphoma**, which presents with distinct clinical and immunophenotypic features from CLL/SLL. - Centrocytes are typically involved in somatic hypermutation and class switching, processes relevant to later stage B cell development, but not the direct origin of CLL/SLL. *Progenitor B-cell* - Progenitor B-cells are early developmental stages of B cells, and their malignant transformation leads to conditions like **B-cell acute lymphoblastic leukemia (B-ALL)**. [1] - B-ALL presents with immature blast cells and a different immunophenotype (e.g., lack of CD23), distinct from the mature lymphoid cells seen in CLL/SLL. [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. 596-598.
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