Case Report: Synchronous colorectal adenocarcinomas with discordant mismatch repair status: a case of lynch-like syndrome and serrated pathway association

Objective Synchronous colorectal cancers (SCRCs) with discordant mismatch repair (MMR) status present unique clinical and therapeutic challenges. This case report describes a rare instance of synchronous ascending colon and rectal adenocarcinomas arising from distinct tumorigenic pathways (Lynch-like syndrome and serrated pathway). We aim to explore the mechanism underlying MMR status heterogeneity, and emphasize the clinical value of lesion-specific molecular profiling combined with regional metastatic lymph node MMR phenotyping for individualized treatment of this condition. Methods A 67-year-old female with secondary peritonitis was enrolled. The patient underwent sequential imaging, colonoscopy, and histopathological examination, which confirmed synchronous double primary colorectal adenocarcinomas. Systematic molecular analyses were performed, including MMR immunohistochemistry (IHC), BRAF V600E mutation testing, germline next-generation sequencing (NGS) targeting MMR-related genes, and MLH1 promoter methylation testing via enzyme conversion NGS. MMR phenotyping of regional metastatic lymph nodes was performed to assess the invasive potential of each lesion and guide adjuvant treatment. The patient received adjuvant CAPEOX-based chemoradiotherapy and was followed up for 24 months. Results Histopathology confirmed two synchronous primary adenocarcinomas: the ascending colon tumor was poorly differentiated adenocarcinoma with deficient MMR (dMMR; MLH1-, PMS2-; MSH2+, MSH6+), BRAF V600E wild-type, and negative MLH1 promoter methylation in both tumor tissue and peripheral blood; the rectal tumor was moderately-to-poorly differentiated adenocarcinoma with proficient MMR (pMMR; MLH1+, PMS2+, MSH2+, MSH6+), adjacent to a sessile serrated lesion (SSL). Germline NGS revealed no pathogenic MMR gene variants, consistent with a diagnosis of Lynch-like syndrome (LLS). Regional metastatic lymph nodes showed a pMMR phenotype, consistent with the rectal primary tumor, indicating higher metastatic potential of the rectal lesion. No recurrence or metastasis was observed at the 24-month follow-up, with satisfactory patient quality of life. Conclusion Lesion-specific molecular characterization combined with regional lymph node MMR phenotyping is critical for the precise management of SCRCs with discordant MMR status. This case provides a referable diagnostic workflow and surgical decision-making framework for this rare clinical scenario, supporting risk-adapted individualized therapy for molecularly heterogeneous colorectal cancer.