258 AML with t(8;21) and B-lineage Marker Expression: A Diagnostic Crossroad

Introduction/Objective Acute myeloid leukemia (AML) with t(8;21)(q22;q22) is a distinct subtype characterized by RUNX1-RUNX1T1 fusion. Although AML typically expresses myeloid markers, aberrant expression of B-lineage markers can occur, complicating diagnosis by mimicking mixed-phenotype acute leukemia (MPAL). Accurate diagnosis requires integration of morphology, immunophenotyping, and cytogenetic findings to guide appropriate treatment. Methods/Case Report A 35-year-old hypertensive male presented with worsening fatigue and anemia. Complete blood count showed anemia (Hb 7.0 g/dL), leukocytosis (WBC 14.26 × 109/L), and thrombocytopenia (platelets 59 × 109/L). Peripheral smear revealed 39% blasts with occasional Auer rods. Bone marrow aspirate was hypercellular, showing 21% blasts with high nuclear-to-cytoplasmic ratio and fine chromatin. Trephine biopsy confirmed blast infiltration with residual trilineage hematopoiesis. Immunohistochemistry showed blasts positive for MPO, CD117, focal CD34, TdT, and unexpectedly, B-cell markers CD19, CD79a, and PAX5. Cytogenetic analysis detected t(8;21)(q22;q22) translocation confirming AML with RUNX1-RUNX1T1 fusion. Results The presence of B-lineage markers raised suspicion for MPAL. However, cytogenetic confirmation of t(8;21) established the diagnosis of AML with aberrant B-cell antigen expression. Conclusion This case highlights the diagnostic challenge posed by aberrant B-lineage marker expression in AML with t(8;21). It emphasizes the critical role of integrating morphology, immunophenotyping and cytogenetics for accurate classification per WHO guidelines, ensuring appropriate treatment strategies.