Observations on the origin of ovarian cortical inclusion cysts in women undergoing risk‐reducing salpingo‐oophorectomy

摘要

Aims Evidence suggests that up to 70% of high‐grade serous ovarian carcinomas ( HGSC s) arise potentially from fallopian tube fimbriae, and that many of the remaining cases arise from within the ovary in cortical inclusion cysts ( CIC s) with a Müllerian phenotype (Müllerian‐CICs). It has been proposed that Müllerian‐CICs arise either from metaplasia of mesothelial ovarian surface epithelium ( OSE ) entrapped within the ovary after ovulation or from normal tubal cells entrapped postovulation. However, this proposal is controversial. We therefore conducted a study of CIC s in women, most of them BRCA1/2 mutation carriers, undergoing risk‐reducing salpingo‐oophorectomy at our institution from 2000 to 2014. Methods and results We used immunohistochemistry for PAX8, a Müllerian marker, and calretinin, a mesothelial marker to classify CIC cells. In 499 CICs from 59 women, 72.3% were positive for PAX8 (PAX8 + ): ≥10% of CIC cells positive; 43.5% positive for calretinin (calretinin + ). The proportion of PAX8 + CICs increased from 62.9% in premenopausal to 80.5% in postmenopausal patients. The proportion of calretinin + CICs decreased from 52.6% to 35.6%, respectively. There was significant overlap of PAX8 and calretinin positivity: 82 (16.4%) CICs were PAX8 + /calretinin + ; 43 (40.2%) of these 82 demonstrated PAX8 + /calretinin + in the same cells. Conclusions These results, and the increased ratio of PAX8 + to calretinin + CICs from premenopausal to postmenopausal, show that many PAX8 + CICs probably arise from metaplasia of OSE‐derived CICs. The proportion of PAX + /calretinin ? CICs arising from OSE‐derived CICs is unclear, but our results strongly support the proposal that many Müllerian‐CICs arise from OSE via metaplasia.