Cup-Like Blasts in B-Lymphoblastic Leukemia with KMT2A Rearrangement: A Rare Morphological Presentation

Blasts with cup-like nuclear morphology (Fig. 1) are classically described in acute myeloid leukemia (AML) with normal karyotype and mutations in NPM1 and/or FLT3-ITD, often demonstrating monocytic differentiation [1, 2]. However, this morphology is rarely associated with B-lineage acute lymphoblastic leukemia (B-ALL). Here, we present a case of a 33-year-old female who presented with fever and menorrhagia. Peripheral blood smear (PS) revealed 80% blasts, several with distinctive cup-shaped nuclei, prompting initial consideration of AML. Flow cytometric immunophenotyping (FCI) demonstrated CALLA-negative B-ALL with aberrant CD15 expression (Fig. 3), a phenotype strongly associated with KMT2A rearrangements [3]. Karyotyping and fluorescence in situ hybridization (FISH) confirmed KMT2A rearrangement (Fig. 2) and excluded IKZF1 deletion, and karyogram confirmed a t(4;11)(q21;q23) with additional abnormalities (Fig. 4. Molecular testing for NPM1 and FLT3-ITD was negative. Additional lineage markers (myeloid and monocytic) were also negative, ruling out a mixed B/myeloid phenotype. This case adds to the limited literature reporting cup-like nuclear morphology in B-ALL, which is typically associated with varied cytogenetic abnormalities, including BCR::ABL1 fusion and hyperdiploidy [3, 4]. The findings emphasize the critical role of FCI and molecular studies in distinguishing AML from B-ALL or mixed phenotype acute leukemias.