Chika Noriyasu, Murakami Tetsuo, Kamae Nao, Suzuki Okihide, Mori Yoshiko, Sakimoto Takehiko, Ishiguro Toru, Kumagai Yoichi, Eguchi Hidetaka, Ishibashi Keiichiro, Mochiki Erito, Okazaki Yasushi, Iwama Takeo, Ishida Hideyuki
Dept. of Digestive Tract and General Surgery, Saitama Medical Center, Saitama Medical University.
Gan To Kagaku Ryoho. 2020 Dec;47(13):1909-1912.
The proband was a 77-year-old man who had been admitted to a local hospital for fecal occult blood. He was diagnosed with descending colon carcinoma, T4a, N1, M0, Stage Ⅲb, and rectal adenoma. He had undergone surgeries for rectal cancer at 52 years of age and cecum colon cancer at 57 years of age. Regarding his family history, 5 first-degree and 3 second- degree relatives had a history of gastrointestinal and gynecological cancers, thus meeting 2 of the 5 criteria of the revised Bethesda guidelines. The microsatellite-instability(MSI)test performed using preoperative biopsy tissues demonstrated high-frequency MSI(MSI-H). Hartmann's procedure was performed for MSI-H colon cancer under a strong suspicion of Lynch syndrome. Pathological findings were consistent with descending colon carcinoma, tub2, pT3, pN0, M0, pStage Ⅱa. He was then referred to our hospital. We performed the immunohistochemistry(IHC)analysis of the mismatch repair protein using surgical specimens. The IHC analysis revealed defective expression of the MSH2/MSH6 protein. We found a pathogenic variant in the mismatch repair gene, MSH2(c.1510+2T>G), through genetic testing and finally diagnosed the patient with Lynch syndrome. After disclosure of the results to the proband, 7 relatives underwent genetic testing for the MSH2 variant. Four relatives had the same variant and were also diagnosed with Lynch syndrome. They subsequently underwent surveillance for Lynch syndrome-associated cancers. In 2 variant carriers with a history of early colorectal cancer, an early colon cancer was identified and successfully resected endoscopically. Surveillance for Lynch syndrome-associated cancer is ongoing for the proband and variant carriers.
先证者是一名77岁男性，因粪便潜血入住当地医院。他被诊断为降结肠癌，T4a，N1，M0，Ⅲb期，以及直肠腺瘤。他曾在52岁时接受过直肠癌手术，57岁时接受过盲肠癌手术。关于他的家族史，5名一级亲属和3名二级亲属有胃肠道和妇科癌症病史，因此符合修订后的贝塞斯达指南5条标准中的2条。使用术前活检组织进行的微卫星不稳定性（MSI）检测显示为高频MSI（MSI-H）。由于高度怀疑林奇综合征，对MSI-H结肠癌进行了哈特曼手术。病理结果与降结肠癌、tub2、pT3、pN0、M0、pⅡa期一致。随后他被转诊至我院。我们使用手术标本对错配修复蛋白进行了免疫组织化学（IHC）分析。IHC分析显示MSH2/MSH6蛋白表达缺陷。通过基因检测，我们在错配修复基因MSH2中发现了一个致病变异（c.1510+2T>G），最终诊断该患者为林奇综合征。在向先证者披露结果后，7名亲属接受了MSH2变异的基因检测。4名亲属有相同变异，也被诊断为林奇综合征。他们随后接受了林奇综合征相关癌症的监测。在2名有早期结直肠癌病史的变异携带者中，发现了早期结肠癌并成功进行了内镜切除。先证者和变异携带者的林奇综合征相关癌症监测正在进行中。
