gastrointestinal disorders
Lynch Syndrome
Diagnosis of Lynch Syndrome
Detailed family history Clinical criteria followed by testing for microsatellite instability (MSI) or with immunohistochemistry (IHC) Genetic testing for confirmation The specific diagnosis of Lynch syndrome is confirmed by genetic testing. However, deciding who to test is difficult because, unlike Familial Adenomatous Polyposis , there is no typical phenotypic appearance. Thus, suspicion of Lynch syndrome requires a detailed family history, which should be obtained in all younger patients identified with colorectal cancer (CRC). To meet the Amsterdam II criteria for Lynch syndrome, all three of the following historical elements must be present ( Diagnosis references ): Three or more relatives with CRC or a Lynch syndrome–associated cancer CRC involving at least two generations At least one case of CRC before age 50 model) and other criteria (eg, the Bethesda criteria [ Diagnosis references ]) are used by some health care professionals. Patients meeting these criteria should have their tumor tissue tested either for MSI or with IHC to detect proteins responsible for DNA mismatch repair; however, most commercial and hospital pathology laboratories now routinely do this test on all colorectal adenocarcinoma specimens. The 2015 American Gastroenterological Associationguidelinesrecommend that tumors of all patients with CRC should be tested either with IHC or for MSI. If MSI or IHC is positive, genetic testing (germline testing) for specific Lynch syndrome mutations is indicated. Patients with Lynch syndrome should have surveillance colonoscopy every 1 to 2 years. Patients with confirmed Lynch syndrome require ongoing screening for other cancers. For Endometrial Cancer , annual endometrial aspiration or transvaginal ultrasound is recommended. For First-degree relatives of patients with Lynch syndrome should have genetic testing. If no genetic testing has been done, they should have colonoscopy every 1 to 2 years beginning in their 20s, and annually after age 40. Female first-degree relatives should be tested annually for endometrial and ovarian cancer. 1.Vasen HF, Watson P, Mecklin JP, Lynch HT. New clinical criteria for hereditary nonpolyposis colorectal cancer (HNPCC, Lynch syndrome) proposed by the International Collaborative group on HNPCC.Gastroenterology116(6):1453–1456, 1999. doi: 10.1016/s0016-5085(99)70510-x 2.Umar A, Boland CR, Terdiman JP, et al: Revised Bethesda guidelines for hereditary nonpolyposis colorectal cancer (Lynch syndrome) and microsatellite instability.J Natl Cancer Inst96(4):261–268, 2004. doi: 10.1093/jnci/djh034 