Departments of Pathology.
Department of Pathology, Northwestern University, Chicago, IL.
Appl Immunohistochem Mol Morphol. 2020 Mar;28(3):e26-e30. doi: 10.1097/PAI.0000000000000553.
Lynch syndrome is an autosomal dominant disorder, caused by an abnormality in DNA mismatch repair genes and characterized by the development of a variety of cancers. Upper urinary tract urothelial carcinoma is well characterized in Lynch syndrome; however, support for the inclusion of bladder urothelial carcinoma is limited, except for MSH2 mutation carriers. Urologic adenocarcinoma has not been documented in Lynch syndrome. Here we report, to the best of our knowledge, the first case of bladder adenocarcinoma, synchronous with uterine endometrioid dedifferentiated endometrioid adenocarcinoma in a patient with Lynch syndrome. We present a 47-year-old woman with an MLH1 gene mutation (G133X 397G>T) who presented with menorrhagia. Eleven family members have this mutation, 6 with carcinoma: 5 colorectal and 1 with a gynecologic primary of unknown type. Colonoscopy and endoscopy were unremarkable. Positron emission and computed tomography revealed a 3 cm anterior dome bladder mass without additional extrauterine disease or uterine connection. She underwent partial cystectomy, laparoscopic hysterectomy, bilateral salpingo-oophorectomy, and lymphadenectomy. The uterus demonstrated a dedifferentiated endometrioid adenocarcinoma, immunohistochemically positive for vimentin, ER, CK7, MSH2, MSH6, and p53 (focally) and negative for CEA, CDX2, CK20, β-catenin, MLH1, and PMS2. The bladder demonstrated a well-differentiated, enteric-type adenocarcinoma without muscularis propria invasion, positive for CEA, CDX2, CK20, p53, MSH2, and MSH6 and negative for vimentin, ER, CK7, MLH1, and PMS2. Eleven nodes were negative for carcinoma. The morphologic, immunohistochemical, and clinical findings support synchronous bladder adenocarcinoma, enteric type, and uterine dedifferentiated endometrioid adenocarcinoma, in a patient with Lynch syndrome.
林奇综合征是一种常染色体显性遗传疾病，由 DNA 错配修复基因异常引起，其特征是多种癌症的发展。上尿路上皮尿路上皮癌在林奇综合征中表现良好；然而，除 MSH2 突变携带者外，对膀胱癌的支持有限。在林奇综合征中尚未记录到尿路上皮腺癌。在这里，我们报告了迄今为止已知的首例林奇综合征患者的膀胱腺癌病例，该患者同时患有子宫内膜样去分化子宫内膜样腺癌。我们报告了一名 47 岁的女性患者，她携带 MLH1 基因突变（G133X 397G>T），表现为月经过多。有 11 名家庭成员携带该突变，其中 6 名患有癌症：5 名结直肠癌和 1 名妇科原发性肿瘤类型未知。结肠镜和内窥镜检查无异常。正电子发射和计算机断层扫描显示 3cm 前穹窿膀胱肿块，无额外的子宫外疾病或与子宫相连。她接受了部分膀胱切除术、腹腔镜子宫切除术、双侧输卵管卵巢切除术和淋巴结切除术。子宫表现为去分化的子宫内膜样腺癌，免疫组化阳性表达 vimentin、ER、CK7、MSH2、MSH6 和 p53（局灶性），阴性表达 CEA、CDX2、CK20、β-catenin、MLH1 和 PMS2。膀胱表现为分化良好的肠型腺癌，无固有肌层浸润，阳性表达 CEA、CDX2、CK20、p53、MSH2 和 MSH6，阴性表达 vimentin、ER、CK7、MLH1 和 PMS2。11 个淋巴结均无癌。形态学、免疫组化和临床发现支持林奇综合征患者同时发生膀胱腺癌、肠型和子宫内膜样去分化子宫内膜样腺癌。
