ABPath - American Board of Pathology Hematopathology 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?

Accepted Answer

t(14;18)(q32;q21)

Answer

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?

Accepted Answer

PML-RARA

Answer

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)?

Accepted Answer

CD19+, CD5+, CD23+, dim CD20

Answer

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)?

Accepted Answer

High-sensitivity flow cytometry for GPI-anchored proteins

Answer

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?

Accepted Answer

Serum creatinine of 2.5 mg/dL

Answer

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.

American Board of Pathology (ABPath) Practice Test

American Board of Pathology (ABPath) Practice Test

ABPath - American Board of Pathology Hematopathology Questions and Answers