Bengtsson Daniel, Joost Patrick, Aravidis Christos, Askmalm Stenmark Marie, Backman Ann-Sofie, Melin Beatrice, von Salomé Jenny, Zagoras Theofanis, Gebre-Medhin Samuel, Burman Pia
Department of Clinical and Experimental Medicine, Linköping University, 58183 Linköping, Sweden.
Department of Internal Medicine, Kalmar County Hospital, 39185 Kalmar, Sweden.
J Clin Endocrinol Metab. 2017 Nov 1;102(11):3928-3932. doi: 10.1210/jc.2017-01401.
Lynch syndrome (LS) is a cancer-predisposing syndrome caused by germline mutations in genes involved in DNA mismatch repair (MMR). Patients are at high risk for several types of cancer, but pituitary tumors have not previously been reported.
A 51-year-old man with LS (MSH2 mutation) and a history of colon carcinoma presented with severe Cushing disease and a locally aggressive pituitary tumor. The tumor harbored a mutation consistent with the patient's germline mutation and displayed defect MMR function. Sixteen months later, the tumor had developed into a carcinoma with widespread liver metastases. The patient prompted us to perform a nationwide study in LS.
A diagnosis consistent with a pituitary tumor was sought for in the Swedish National Patient Registry. In 910 patients with LS, representing all known cases in Sweden, another two clinically relevant pituitary tumors were found: an invasive nonsecreting macroadenoma and a microprolactinoma (i.e., in total three tumors vs. one expected).
Germline mutations in MMR genes may contribute to the development and/or the clinical course of pituitary tumors. Because tumors with MMR mutations are susceptible to treatment with immune checkpoint inhibitors, we suggest to actively ask for a family history of LS in the workup of patients with aggressive pituitary tumors.
林奇综合征（LS）是一种由参与DNA错配修复（MMR）的基因种系突变引起的癌症易感综合征。患者患多种癌症的风险很高，但此前尚未有垂体瘤的报道。
一名51岁患有LS（MSH2突变）且有结肠癌病史的男性，因严重库欣病和局部侵袭性垂体瘤就诊。该肿瘤存在与患者种系突变一致的突变，并显示出MMR功能缺陷。16个月后，肿瘤发展为伴有广泛肝转移的癌。该患者促使我们在LS患者中开展一项全国性研究。
在瑞典国家患者登记处寻找与垂体瘤一致的诊断。在代表瑞典所有已知病例的910例LS患者中，又发现了另外两例具有临床意义的垂体瘤：一例侵袭性无分泌大腺瘤和一例微泌乳素瘤（即总共发现三例肿瘤，而预期为一例）。
MMR基因的种系突变可能有助于垂体瘤的发生发展和/或临床进程。由于具有MMR突变的肿瘤对免疫检查点抑制剂治疗敏感，我们建议在侵袭性垂体瘤患者的检查中积极询问LS家族史。
