B-cell lymphoma following an indolent course over 30 years with immunophenotypic changes at each recurrence

Diffuse large B-cell lymphoma (DLBCL) can undergo stepwise immunophenotypic and molecular evolution over decades, progressing from a germinal Center B-cell-like (GCB)-like phenotype to an activated B-cell -like/non-GCB pattern (MUM1+, CD30+) and ultimately to an aggressive anaplastic variant.The cell-of-origin profile and its associated molecular features are not necessarily static; thus, therapeutic strategies for relapsed DLBCL should be tailored to the current disease state rather than relying on the signature at initial diagnosis.Longitudinal re-evaluation through repeat biopsies is imperative to capture the evolving landscape of the malignancy, ensuring that treatment selection is guided by the most recent pathological and molecular findings.