Qing Zhang, Yingjie Xiu, Junhong Li, Xin Cao
Collision tumors composed of colorectal adenocarcinoma and mantle cell lymphoma are exceptionally rare, and component-resolved molecular characterization is largely lacking. We report a 65-year-old woman who initially presented with rectal adenocarcinoma and underwent radical resection followed by adjuvant capecitabine. Seven months later, she developed generalized lymphadenopathy, and excisional cervical lymph node biopsy confirmed mantle cell lymphoma with Cyclin D1 and SOX11 positivity, t(11;14)(q13;q32) rearrangement, and a Ki-67 proliferation index of approximately 40%. Retrospective review of the original rectal resection specimen identified an occult mantle cell lymphoma component at the tumor margin and within the submucosa, leading to reclassification as a synchronous rectal collision tumor composed of adenocarcinoma and mantle cell lymphoma. Targeted sequencing across four specimens revealed a shared TP53 exon 7 frameshift in the archival composite rectal specimen, the rectal lymphoma component, and the adenocarcinoma component, whereas the nodal lymphoma specimen showed a dominant NOTCH2-truncating profile without a reported pathogenic TP53 alteration. The adenocarcinoma component additionally harbored a truncating APC alteration consistent with colorectal tumorigenesis. These findings support partial molecular overlap together with compartment- and site-specific divergence, while not establishing a common clonal origin. The patient received bendamustine plus rituximab followed by zanubrutinib maintenance and remained in remission at the last follow-up. This case highlights a clinically important diagnostic pitfall, shows how retrospective pathologic review can uncover occult gastrointestinal mantle cell lymphoma in a colorectal resection specimen, and provides multi-specimen molecular evidence of spatial heterogeneity across synchronous bowel and nodal disease.