Burkitt in disguise: clonal transformation of incidentally detected gallbladder diffuse large B-cell lymphoma in a liver transplant recipient

Post-transplant lymphoproliferative disorders (PTLDs) typically arise months to years after solid-organ transplantation and are frequently driven by Epstein–Barr virus (EBV). However, EBV-negative monomorphic PTLDs are increasingly recognized as an alternative pathogenesis. We report a case of a 64-year-old man who underwent liver transplantation and was found to have a minute focus of diffuse large B-cell lymphoma (DLBCL) in the resected gallbladder. Given the absence of residual disease and the patient’s postoperative frailty, close observation was chosen. Three months later, the patient developed an aggressive clinical relapse characterized by Burkitt-like features, including massive effusions and gastric wall thickening. Retrospective analysis using a 398-gene panel (DISCAVar) revealed that both the initial and recurrent lesions shared an IGH::MYC rearrangement, while the recurrent tumor acquired additional Burkitt lymphoma (BL)-associated mutations (TP53, TCF3, CCND3, DDX3X) absent in the original lesion. These alterations spanned all three molecular subgroups of BL and suggest rapid clonal evolution from a pre-existing MYC-positive clone under post-transplant immunosuppression. Despite treatment with dose-modified EPOCH, the patient’s condition deteriorated, and he died 108 days after treatment initiation. This case underscores the value of longitudinal molecular analysis in understanding the pathogenesis of EBV-negative PTLD and identifying high-risk clones before clinical transformation.