#00066682

A 59-year-old man presented with leukocytosis (95.0 × 10⁹/L), anemia (hemoglobin, 79 g/L; mean corpuscular volume, 89 femtoliters), thrombocytopenia (platelets, 22 × 10⁹/L), and 94% circulating blasts. Peripheral blood smear demonstrated numerous small to medium-sized blasts with ∼40% exhibiting prominent cuplike nuclear invaginations (panel A, 50× lens objective; inset, 100× lens objective). Flow cytometry of aspirate identified a single blast population (98%) with low side scatter, expressing dim CD45, CD19, CD79a, dim CD22, partial dim CD15, CD38, HLA-DR, and terminal deoxynucleotidyl transferase, but lacking CD10/CD20, consistent with a pro-B immunophenotype. CD34 expression was heterogeneous, with both CD34-positive and CD34-negative blasts forming a bimodal distribution within the same leukemic population (panel B). Biopsy demonstrated a hypercellular marrow (100%) with sheets of blasts, consistent with acute leukemia. Cytogenetics/optical genome mapping demonstrated t(4;11)(q21;q23), KMT2A(MLL)::AFF1 fusion (84% of cells) and CDKN2A/B deletion (53% of cells), confirmed by fluorescence in situ hybridization. A diagnosis of B-lymphoblastic leukemia (B-ALL) with KMT2A rearrangement was rendered.

Cuplike nuclear morphology is classically associated with acute myeloid leukemia with NPM1 mutation but has been described in B-ALL, including DUX4-rearranged and IKZF1-deleted cases, with rare reports in B-ALL harboring t(4;11). This case highlights cuplike nuclei with heterogeneous CD34 expression within a single blast population, illustrating morphologic, immunophenotypic and molecular heterogeneity in KMT2A-rearranged B-ALL.

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