Pediatric Lynch syndrome: Clinical, genotypic, and left-sided patterns of colorectal cancer

To characterize the clinical, histopathologic, and molecular-genetic characteristics of Lynch syndrome (LS)-associated gastrointestinal disease in the pediatric population.

We conducted a scoping review, systematically searching PubMed and Embase® (from inception to October 16, 2025) and using controlled vocabulary and keywords, with additional screening of reference lists and conference abstracts. We included reports of gastrointestinal manifestations of LS in individuals <21 years or pediatric subsets within mixed-age cohorts; no language, date, or geographic restrictions were applied. Titles/abstracts and full texts were independently screened. Data were abstracted for demographics, presentation, gastrointestinal phenotype, tumor characteristics, mismatch repair immunohistochemistry, genotype, management, and outcomes. Findings were summarized descriptively.

Forty-eight pediatric LS patients (age 12-21 years, mean 16; 26 male) were included. Gastrointestinal manifestations included colorectal cancer (CRC) (n = 44), adenomatous polyps (n = 5), gastric adenocarcinoma (n = 1), and jejunal adenocarcinoma (n = 1). CRCs were predominantly left-sided (71%) and advanced at diagnosis (66% stage III/IV). Right-sided tumors were more common (3:1) in males whereas left-sided tumors were evenly distributed. MMR gene variants were reported in 37 patients, dominated by MLH1 (54%) and MSH2 (32%), with fewer MSH6 and PMS2 variants (14%). Histology included conventional (69%), mucinous (22%), medullary (6%), and signet-ring (3%) adenocarcinoma.

LS confers risk for pediatric colorectal adenoma and cancer. CRC in this population manifests predominantly as left-sided, advanced-stage CRC, driven by loss-of-function variants in MLH1 and MSH2. These findings contrast with the right-sided predominant adult LS and suggest age-specific biology. Increased awareness and further research are needed to inform age-appropriate surveillance strategies.