A 54-year-old man presented with mild bruising and fatigue. Complete blood count revealed anemia, neutropenia, thrombocytopenia, and 90% blasts. Bone marrow aspirate showed 90% blasts with frequent Auer rods, including multiple ones within a blast (panel A and insert; original magnification ×1000; Wright-Giemsa stain). Flow cytometry (panel B; FITC, fluorescein isothiocyanate; PE, phycoerythrin) demonstrated that blasts were positive for myeloperoxidase (MPO), CD34, CD117, HLA-DR, CD13, and CD33 and negative for cCD3; a subset of the MPO⁺ blast population (∼40%) was also positive for CD19 (intensity reaches that of normal B cells) and CyCD79a. By immunohistochemistry, CD34⁺ blasts (panel D; original magnification ×400) were MPO⁺ (panel E; original magnification ×400) and also CD79a⁺ and PAX5⁺ (panel F; original magnification ×400) in a subset (panel C; original magnification ×400; hematoxylin and eosin [H&E] stain). Cytogenetic studies revealed add (1)(q32) and add (3)(p25). Results of molecular studies for BCR-ABL1 and RUNX1-RUNX1T1 fusion genes were negative. Next-generation sequencing detected NRAS, TET2, and U2AF1 mutations. The diagnosis of mixed-phenotype acute leukemia (MPAL; B/myeloid) was rendered.

Auer rods are pink needle-shaped structures resulting from an abnormal fusion of azurophilic granules. They are typically found in cells of myeloid lineage in either high-grade myelodysplastic syndrome or acute myeloid leukemia (AML) but are rarely seen in MPAL, especially with multiple Auer rods. This case demonstrates that the presence of Auer rods in acute leukemia does not always signify an AML and emphasizes the importance of evaluating the immunophenotype of the blasts carefully to reach an accurate diagnosis.