Somatic Cancer Driver Mutation Analysis in Endometriosis with Tumor-Like Presentations

Endometriosis manifests as ectopic endometrial tissue outside the uterine cavity. This common disease can sometimes appear at unusual anatomical sites or within the intestinal tract, growing as a lesion and mimicking cancer. Such tumor-like endometriosis lesions are relatively uncommon and biologically intriguing. This study is a retrospective case series of 14 patients presenting with tumor-like endometriosis at a single institution between 2011 and 2022. Unlike conventional endometriosis, these tumor-like lesions were generally sizable and clinically presented as a groin mass, aorta wall, omentum, bowel wall, and lymph nodes, all of which raised suspicion for malignancy, despite eleven (78.6%) of the 14 cases having a history or clinical signs of endometriosis. Laser capture microdissection was used to isolate epithelial cells from endometriotic glands in tissue sections prepared from formalin-fixed paraffin-embedded blocks, and the microdissected epithelium was analyzed for cancer-driver mutations. A total of 11 cancer-driver mutations were identified in 6 (43%) of the 14 patients, with four patients harboring multiple mutations. Recurrent mutations included KRAS-activating mutations in four cases and ARID1A-inactivating mutations in two cases. Additional mutations involved PIK3CA, CTNNB1, CHD4, MYD88, and STAG1. The mutation frequency in cancer driver genes within this cohort was comparable to that observed in conventional endometriosis located in pelvic tissues, ovaries, and fallopian tubes, suggesting that these mutations may have roles beyond their canonical tumor-promoting functions in tumor-like endometriosis.