Malignant transformation of extraovarian endometriosis is rare, with the carcinogenesis mechanism unclear. To clarify the actionable variants of rare-site endometriosis-associated cancer (RSEAC), we performed whole-exome sequencing for the tumor, in two patients. The intestine was affected in both cases, although the histology was that of clear cell carcinoma and undifferentiated carcinoma, respectively. Therefore, the cases were referred to as endometriosis-associated intestinal tumors (EIATs). Actionable variants (all frameshift mutations) were identified in tumor suppressor genes ARID1A, PTEN, and p53; however, no oncogenic variants were identified. Both cases were microsatellite stable. The patient with undifferentiated carcinoma exhibited hypermutator and homologous recombination deficiency phenotypes. The dominant mutation signatures were signature 30 (small subset of breast cancers) and 19 (pilocytic astrocytoma) in patient 1, and signature 5 (small subset of breast cancers) and 3 (breast, ovarian, and pancreatic cancers) in patient 2. Immunohistochemistry revealed positive CD8 and PD-1 expression in both patients; patient 1 also showed positive PDL-1 expression. Our results suggest that RSEAC is associated with variants of tumor suppressor genes as epigenetic alterations. Mutation signature-based whole-exome sequencing could be useful to select an adjuvant chemotherapy regimen. High CD8 and PD-1 expression in RSEAC suggests that immune checkpoint inhibitors are useful for treatment.
The frequency of malignant transformation in endometriosis is rare; it is estimated to be less than 1%. Malignant transformation mainly occurs in the ovary and rarely in the extragonadal sites. Endometriosis-associated intestinal tumors (EAITs) represent the malignant transformation of gastrointestinal endometriosis; the prevalence of EAITs is 0.77% in Japan. Here, we present a case of endometrioid carcinoma of the rectum arising from rectal endometriosis that was treated by laparoscopic surgery.A 68-year-old woman presented with no symptoms but had a pelvic mass and was referred to our hospital. She had no history of endometriosis and hormone replacement therapy. Tissue biopsy revealed a poorly-differentiated adenocarcinoma, and the immunohistochemical studies showed cytokeratin7+, cytokeratin20-, and estrogen receptor+.Therefore, the tumor was suspected to be of gynecological origin and not primary colon origin. She underwent laparoscopic total hysterectomy, bilateral salpingo-oophorectomy, and low anterior resection with D3 lymphadenectomy. There were no malignant findings in the uterus and ovaries. The tumor was located adjacent to the rectal wall; endometrial glands and stroma were present adjacent to the tumor. We diagnosed her with endometrioid carcinoma arising from endometriosis of the rectum. No metastatic lymph nodes were identified pathologically. The patient received adjuvant chemotherapy postoperatively and has been disease-free for 18 months since the surgery.The basic treatment for EAITs is surgery, and we could treat her through laparoscopy. Laparoscopy, a minimally invasive surgery, is another treatment option for EAITs.
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