A 59-year-old man presented with oral bleeding. Peripheral blood showed leukocytosis (59.6 × 109/L; 83% blasts). Bone marrow biopsy revealed markedly increased immature cells (panel A; hematoxylin and eosin stain, ×40 objective, original magnification ×400). Aspirate smear showed blasts with round to irregular nuclei, fine chromatin, and small amount of cytoplasm; no obvious Auer rods were identified (panel B; Wright and Giemsa stains, ×100 objective, original magnification ×1000). The blasts were positive for myeloperoxidase (panel C; cytochemical stain, ×100 objective, original magnification ×1000). Flow cytometry showed the blasts (CD34+CD117+HLA-DR) coexpressed myeloid (myeloperoxidase, CD13, and CD33) and T-lineage (cytoplasmic CD3, CD2, and CD7) markers, suggestive of mixed-phenotype acute leukemia (MPAL), T/myeloid (panels D-E; red cells in panel D are blasts, and blue cells in panel D are T and B cells in the background). However, his D-dimer level was markedly increased (>20 μg/mL fibrinogen equivalent units; normal range 0-0.4), accompanied by a decreased fibrinogen level, concerning for acute promyelocytic leukemia (APL). Fluorescence in situ hybridization confirmed PML/RARA rearrangement (panel F, yellow arrows; original magnification ×1000). Molecular studies revealed an internal tandem duplication and a D835 point mutation of the FLT3 gene. He was diagnosed with microgranular APL.

APL is a hematologic emergency due to its high mortality rate. Cytoplasmic CD3 expression, the T-lineage defining marker, is extremely rare in APL. Atypical morphology and immunophenotype can pose a diagnostic challenge on APL. A diagnosis of MPAL requires exclusion of recurrent cytogenetic abnormities such as t(15;17). Clinical features of APL should prompt immediate testing for the PML-RARA translocation even if atypical immunophenotypic features are present, since early detection of APL may help lower the risk of early death in this disease.

A 59-year-old man presented with oral bleeding. Peripheral blood showed leukocytosis (59.6 × 109/L; 83% blasts). Bone marrow biopsy revealed markedly increased immature cells (panel A; hematoxylin and eosin stain, ×40 objective, original magnification ×400). Aspirate smear showed blasts with round to irregular nuclei, fine chromatin, and small amount of cytoplasm; no obvious Auer rods were identified (panel B; Wright and Giemsa stains, ×100 objective, original magnification ×1000). The blasts were positive for myeloperoxidase (panel C; cytochemical stain, ×100 objective, original magnification ×1000). Flow cytometry showed the blasts (CD34+CD117+HLA-DR) coexpressed myeloid (myeloperoxidase, CD13, and CD33) and T-lineage (cytoplasmic CD3, CD2, and CD7) markers, suggestive of mixed-phenotype acute leukemia (MPAL), T/myeloid (panels D-E; red cells in panel D are blasts, and blue cells in panel D are T and B cells in the background). However, his D-dimer level was markedly increased (>20 μg/mL fibrinogen equivalent units; normal range 0-0.4), accompanied by a decreased fibrinogen level, concerning for acute promyelocytic leukemia (APL). Fluorescence in situ hybridization confirmed PML/RARA rearrangement (panel F, yellow arrows; original magnification ×1000). Molecular studies revealed an internal tandem duplication and a D835 point mutation of the FLT3 gene. He was diagnosed with microgranular APL.

APL is a hematologic emergency due to its high mortality rate. Cytoplasmic CD3 expression, the T-lineage defining marker, is extremely rare in APL. Atypical morphology and immunophenotype can pose a diagnostic challenge on APL. A diagnosis of MPAL requires exclusion of recurrent cytogenetic abnormities such as t(15;17). Clinical features of APL should prompt immediate testing for the PML-RARA translocation even if atypical immunophenotypic features are present, since early detection of APL may help lower the risk of early death in this disease.

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