Endometrial Cancer of the Colon without Colonic Endometriosis in a Patient with Lynch Syndrome

Purpose: Endometrial cancer in the colon is rare. It usually arises from endometriosis, which can be seen by histological examination in proximity to the tumor. Women with Lynch syndrome (LS) are at an increased risk for endometrial cancer. This is the first reported case of endometrial cancer of the colon without colonic endometriosis in a patient with LS. A 55-year-old woman with no significant medical history presented with lower abdominal pain and constipation. Family history was significant for uterine, colon and pancreatic cancers. Computed tomography imaging revealed circumferential thickening of the sigmoid colon. The patient underwent a colonoscopy, which showed sloughing layers of black tissue within a polypoid mass in the sigmoid colon. Biopsies revealed Mullerian clear cell carcinoma, a subtype of endometrial cancer. Immunohistochemical analysis discovered an absence of the MSH6 protein and germline testing revealed a mutation in the MSH6 gene, confirming the diagnosis of LS. The clinical dilemma in this patient was to determine the extent of colon resection. There was the option to perform a sigmoid resection, given that the tumor was of a gynecological origin. On the other hand, patients with LS and colorectal cancer (CRC) usually undergo sub-total colectomy because of the increased risk of developing a metachronous CRC. Given that the patient did not have CRC and had a mutation associated with a lower risk of CRC than other LS mutations, after much deliberation, the patient underwent a sigmoid resection and hysterectomy with bilateral salpingo-oophorectomy. Pathology revealed malignant cells extending the full thickness of the sigmoid colon but no colonic endometriosis. There was endometriosis in the uterus and ovaries but no tumor. Mutations in MSH6 account for 10-20% of LS CRC. Women with LS who have a mutation in the MSH6 gene have a cumulative risk of up to 44% for endometrial cancer, and 20% for CRC over their lifetime. Endometrial cells do not shed onto the sigmoid colon unless there is endometriosis. This is the first case of a patient with LS with endometrial cancer in the colon without endometriosis. A reasonable speculation is that the MSH6 mutation induced malignant transformation of endometriosis, but the endometriosis was outgrown by the tumor mass.