A 78-year-old man with no prior history of hematologic disorders presented with rapidly progressive dyspnea. The clinical examination was unremarkable. Initial laboratory investigations revealed anemia (76 g/L), thrombocytopenia (50 × 109/L), and lymphocytosis (7 × 109/L), with no eosinophilia. Blood smear review showed 35% blasts with atypical morphology, described as having a pseudo-lymphoid or mature lymphoid appearance, characterized by a distinct blocky chromatin pattern and occasional nucleoli, resembling mature lymphocytes (panel A, May-Grünwald Giemsa stain, 50× objective; and panel B, May-Grünwald Giemsa stain, 63× objective). Flow cytometry showed CD34+ blasts with CD13+, CD33+, CD117+, CD15+, TdT+, HLA-DR+, aberrant CD7+, CD56+, and negative for myeloperoxidase, surface/cytoplasmic CD3, CD19, and CD79a. Bone marrow aspirate showed 60% blasts, confirming acute myeloid leukemia (AML). Cytogenetic analysis revealed deletions of 5q and 11q, and a t(4;12)(q12;p13) in all metaphases (panel C, partial karyotype, G-banding), confirming AML with myelodysplasia-related changes and a molecularly proven SRSF2 mutation (variant allele frequency, 45%). Fluorescence in situ hybridization (FISH) demonstrated an ETV6 gene rearrangement (panel D) in all interphase nuclei; however, the fusion partner remained unidentified. Subsequent RNA sequencing identified an in-frame ETV6::CHIC2 fusion, with no evidence supporting the initially presumed ETV6::PDGFRA fusion based on FISH analysis.
This case of AML, with its atypical morphology mimicking lymphoid features, exemplifies the diagnostic challenges posed by nonclassical presentations and the necessity of integrated morphological, immunophenotypic, and genetic assessment.
For additional images, visit the ASH Image Bank, a reference and teaching tool that is continually updated with new atlas and case study images. For more information, visit https://imagebank.hematology.org.
This feature is available to Subscribers Only
Sign In or Create an Account Close Modal