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A 77-year-old woman presented with symptomatic anemia (hemoglobin, 66 g/L) and 10% circulating medium-to-large blasts with high nuclear-to-cytoplasmic ratios, prominent nucleoli, intensely basophilic cytoplasm, and punched-out vacuoles, resembling Burkitt-like cells (panel A; May-Grünwald Giemsa [MGG] stain, 50× objective). Bone marrow aspirate demonstrated 70% blasts with a striking starry-sky appearance (panel B; MGG stain, 20× objective). Flow cytometry identified CD34⁺ blasts expressing CD13, CD33, CD117, CD15, and HLA-DR, with absent myeloperoxidase and no surface or cytoplasmic CD3, CD19, or CD79a. Cytogenetic analysis revealed a complex monosomal karyotype, including monosomies of chromosomes 3 and 11; trisomy 6; interstitial deletions of 5q and 15q; and a large marker chromosome (panel C), which fluorescence in situ hybridization demonstrated to originate from a massive intrachromosomal homogeneously staining region at 11q23, consistent with high-level KMT2A amplification (panel D); targeted molecular profiling additionally identified an ASXL1 mutation (variant allele frequency, 38%), supporting the diagnosis of acute myeloid leukemia with myelodysplasia-related changes (AML-MRC).

Although cytoplasmic vacuolization in marrow blasts has been associated with myelodysplastic changes in AML, this case is distinctive for Burkitt-like circulating blasts. Although typically associated with lymphoid malignancies, a starry-sky pattern in myeloid blasts may signal high-level KMT2A amplification, a rare feature in older patients with complex monosomal karyotypes. Recognition of this constellation is critical, as KMT2A amplification denotes genomic instability and dismal prognosis.

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