ABPath - American Board of Pathology Hematopathology Questions and Answers 1 — Questions and Answers
Question 1: A lymph node biopsy from a 62-year-old male with generalized lymphadenopathy shows a nodular proliferation of crowded follicles composed of centrocytes and centroblasts. Immunohistochemistry is strongly positive for BCL2 in the germinal centers, as well as CD10 and BCL6. Flow cytometry confirms a monoclonal B-cell population. Which of the following cytogenetic abnormalities is most characteristic of this diagnosis?
- t(11;14)(q13;q32)
- t(8;14)(q24;q32)
- t(14;18)(q32;q21) (Correct answer)
- t(9;22)(q34;q11)
Correct answer: t(14;18)(q32;q21)
The clinical presentation, morphology (nodular proliferation of centrocytes and centroblasts), and immunophenotype (CD10+, BCL6+, BCL2+) are classic for Follicular Lymphoma. The characteristic cytogenetic abnormality in the vast majority of follicular lymphomas is the t(14;18)(q32;q21), which juxtaposes the BCL2 gene on chromosome 18 with the immunoglobulin heavy chain (IGH) gene locus on chromosome 14, leading to overexpression of the anti-apoptotic protein BCL2.
Question 2: A 45-year-old female presents with fatigue, easy bruising, and bleeding gums. Her CBC shows pancytopenia with Auer rods seen in numerous promyelocytes. Coagulation studies indicate disseminated intravascular coagulation (DIC). A bone marrow biopsy confirms the diagnosis of acute promyelocytic leukemia (APL). Which genetic translocation is specifically targeted by all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) therapy in this condition?
- BCR-ABL1
- PML-RARA (Correct answer)
- RUNX1-RUNX1T1
- CBFB-MYH11
Correct answer: PML-RARA
Acute promyelocytic leukemia (APL) is defined by the presence of the t(15;17)(q22;q21) translocation, which creates the PML-RARA fusion gene. The resulting fusion protein blocks myeloid differentiation at the promyelocyte stage. All-trans retinoic acid (ATRA) and arsenic trioxide (ATO) are targeted therapies that specifically act on the PML-RARA protein to induce degradation and promote differentiation of the leukemic cells, leading to high rates of remission.
Question 3: Which of the following immunophenotypic profiles, as determined by flow cytometry, is most characteristic of Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL)?
- CD19+, CD5-, CD10+, CD23-
- CD19+, CD5+, CD23+, dim CD20 (Correct answer)
- CD19+, CD103+, CD25+, CD11c+
- CD19+, CD5+, CD10+, Cyclin D1+
Correct answer: CD19+, CD5+, CD23+, dim CD20
The classic immunophenotype for Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) is the co-expression of the B-cell marker CD19 with the T-cell associated marker CD5. Additionally, CLL/SLL cells are typically positive for CD23 and show characteristically dim expression of CD20 and surface immunoglobulin. This pattern helps distinguish it from other B-cell lymphomas, such as mantle cell lymphoma (CD5+, CD23-, bright CD20, Cyclin D1+) and follicular lymphoma (CD5-, CD10+).
Question 4: A 30-year-old male presents with recurrent episodes of dark urine, particularly in the morning, along with fatigue and abdominal pain. Laboratory studies show evidence of intravascular hemolysis (elevated LDH, low haptoglobin) and a CBC reveals pancytopenia. Which test is considered the gold standard for confirming a diagnosis of Paroxysmal Nocturnal Hemoglobinuria (PNH)?
- Direct antiglobulin (Coombs) test
- Osmotic fragility test
- Acidified serum lysis (Ham) test
- High-sensitivity flow cytometry for GPI-anchored proteins (Correct answer)
Correct answer: High-sensitivity flow cytometry for GPI-anchored proteins
Paroxysmal Nocturnal Hemoglobinuria (PNH) is a rare, acquired disorder caused by a mutation in the PIGA gene, leading to a deficiency of glycosylphosphatidylinositol (GPI)-anchored proteins on the surface of blood cells. This makes them susceptible to complement-mediated destruction. High-sensitivity flow cytometry is the current gold standard diagnostic test, as it can accurately detect and quantify the percentage of cells (e.g., granulocytes and erythrocytes) that lack GPI-anchored proteins like CD55 and CD59. The Ham test is historical and has been replaced by flow cytometry.
Question 5: A 68-year-old male is diagnosed with multiple myeloma. According to the International Myeloma Working Group (IMWG) criteria, which of the following findings would be classified as a CRAB feature, indicating myeloma-defining end-organ damage?
- Serum M-protein of 2.5 g/dL
- Bone marrow plasma cell percentage of 15%
- Serum creatinine of 2.5 mg/dL (Correct answer)
- Involved/uninvolved free light chain ratio of 50
Correct answer: Serum creatinine of 2.5 mg/dL
The CRAB criteria are used to define end-organ damage in multiple myeloma and are an indication for initiating therapy. CRAB stands for: C (Calcium elevation >11 mg/dL), R (Renal insufficiency, defined as serum creatinine >2 mg/dL or creatinine clearance <40 mL/min), A (Anemia, hemoglobin <10 g/dL or >2 g/dL below normal), and B (Bone lesions, one or more osteolytic lesions on imaging). A serum creatinine of 2.5 mg/dL clearly meets the 'R' criterion. The other options, while relevant to the diagnosis, do not by themselves constitute a CRAB feature.
Question 6: A bone marrow biopsy from a 65-year-old patient with splenomegaly, anemia, and leukoerythroblastosis shows hypercellularity with prominent proliferation of atypical, clustered megakaryocytes and significant reticulin fibrosis (Grade 2/3). Molecular testing is positive for a CALR mutation. Which of the following is the most likely diagnosis?
- Essential Thrombocythemia (ET)
- Chronic Myeloid Leukemia (CML)
- Primary Myelofibrosis (PMF), fibrotic stage (Correct answer)
- Polycythemia Vera (PV)
Correct answer: Primary Myelofibrosis (PMF), fibrotic stage
The combination of bone marrow findings (atypical megakaryocytic proliferation and significant fibrosis), clinical features (splenomegaly, anemia), peripheral smear findings (leukoerythroblastosis), and the presence of a driver mutation (CALR) are all classic features for Primary Myelofibrosis (PMF), fibrotic stage. While ET can have megakaryocytic proliferation, it lacks significant fibrosis. CML is defined by the BCR-ABL1 fusion, and PV is characterized primarily by erythrocytosis with a JAK2 mutation.
ABPath - American Board of Pathology Hematopathology Questions and Answers 1
A lymph node biopsy from a 62-year-old male with generalized lymphadenopathy shows a nodular proliferation of crowded follicles composed of centrocytes and centroblasts.
Immunohistochemistry is strongly positive for BCL2 in the germinal centers, as well as CD10 and BCL6.
Flow cytometry confirms a monoclonal B-cell population.
Which of the following cytogenetic abnormalities is most characteristic of this diagnosis?