Multidisciplinary approach to a case of Lynch syndrome with colorectal, ovarian, and metastatic liver carcinomas

Abstract

Lynch syndrome is an autosomal dominant disorder with an estimated prevalence of 3 % of all colorectal cancers. It is attributed to germline mutations in DNA mismatch repair (MMR) genes, which confer increased susceptibility to cancers of the colorectum, endometrium, stomach, small intestine, hepatobiliary system, kidney, urinary bladder, brain, and ovary. We report a thought-provoking Lynch syndrome case with a family history and simultaneous tumors in the colon, pelvis, and liver. These findings made diagnosis and treatment complicated. However, the multidisciplinary approaches followed by a medical oncologist, gynecologist, surgeon, radiologist, and pathologist led to a favorable outcome. This patient had two primary cancers of the colon and ovary, and systemic metastases of colon cancer. The loss of MSH6 protein expression was proven by immunohistochemical examination, but the germline MSH6 mutation was not detected by DNA sequence analysis. Regarding this discrepancy, some possibilities, e.g., genomic rearrangements and epigenetic modifications, which can be missed by conventional sequence analysis, were considered. Theoretically, Lynch syndrome cases with MSH6 impairment exhibit late onset and low penetrance compared to other major cases with MLH1 or MSH6 mutations. Irinotecan hydrochloride (CPT-11) has favorable effects on MMR-deficient tumor cells with high microsatellite instability, although its clinical benefit remains controversial. In this case, the first-line chemotherapy bevacizumab + FOLFIRI regimen has been effective for over a year in the partial response state. We discuss the diagnostic, therapeutic, pathological, and molecular biological characteristics of this intriguing case, indicating the importance of family history, histological assessment, and molecular biological etiology in Lynch syndrome cases presenting a complicated phenotype.