Novel case of cytoplasmic CD3 positive, surface CD4 positive high-grade B-cell lymphoma with MYC rearrangement.

High-grade B-cell lymphoma, not otherwise specified (HGBCL-NOS), is an aggressive mature B-cell neoplasm whose diagnosis remains challenging due to significant morphologic overlap with diffuse large B-cell lymphoma and Burkitt lymphoma, and the absence of defining molecular alterations. Aberrant antigen expression can further complicate diagnoses and may result in lineage ambiguity. We report a unique case of HGBCL-NOS with MYC rearrangement demonstrating aberrant cytoplasmic CD3 and surface CD4 expression, leading to an initial misdiagnosis as a T-cell lymphoma at an outside hospital. A 50-year-old man with a previous diagnosis of peripheral T-cell lymphoma presented to our institution with central nervous system symptoms and a persistent bladder mass. Evaluation by bladder biopsy and cerebrospinal fluid flow cytometry revealed a high-grade B-cell neoplasm with diffuse CD10 and CD79a expression, patchy CD20 positivity, strong PAX5 expression, lambda light-chain restriction, Ki-67 approaching 100%, and flow cytometry confirmed expression of cytoplasmic CD3 and dim surface CD4 expression in a clonal B-cell population. Fluorescence in situ hybridization demonstrated a t(8;14)(q24;q32) MYC::IGH rearrangement without BCL2 or BCL6 rearrangements. This extremely rare phenotype has not previously been described. This case expands the spectrum of aberrant immunophenotypes reported in both B-cell lymphomas and HGBCL-NOS and highlights the importance of comprehensive lineage assessment in lymphomas with unusual antigen expression.