Observations on the Origin of Ovarian Cortical Inclusion Cysts in Women Undergoing Risk-Reducing Salpingo-Oophorectomy

Abstract

Aims

Evidence suggests that up to 70% of high-grade serous ovarian carcinomas (HGSCs) potentially arise from fallopian tube fimbriae, and that many of the remaining cases arise from within the ovary in cortical inclusion cysts (CICs) 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 post-ovulation. However, this proposal is controversial. We therefore conducted a study of CICs in women, most of them BRCA1/2 mutation carriers, undergoing risk-reducing salpingo-oophorectomy at our institution from 2000-2014.

Methods and results

We used immunohistochemistry for Paired Box gene 8 (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 likely 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.

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