A Case of Lynch Syndrome with MSH2 Likely Pathogenic Variant Who Developed Rectal Cancer Due to Methylation of MLH1

The proband is a 47-year-old woman who underwent a posterior total pelvic exenteration for Stage Ⅲb rectal cancer. Microsatellite instability(MSI)test and immunohistochemistry(IHC)for mismatch repair(MMR)proteins using the resected tumor tissue showed MSI-High and loss of MLH1/PMS2 expression. In addition, although BRAF V600E variant was not identified, MLH1 methylation was detected. Therefore, this patient was diagnosed as having sporadic deficient MMR(MSI-High) rectal cancer. However, the possibility of Lynch syndrome could not be ruled out because of her family history and young age of onset, then we performed a multigene panel testing including MMR genes. Subsequently, a likely pathogenic variant of MSH2(c.2260A>G)was identified. This case suggests that MLH1-methylated rectal cancer can develop in patients with Lynch syndrome and that multigene panel test using next-generation technology would be useful for searching hereditary cancer predisposition syndromes such as Lynch syndrome even in patients with sporadic dMMR colorectal cancer.