Endometriosis-associated ovarian neoplasia

Abstract

This article reviews the most relevant pathological and molecular features of ovarian tumours that are associated with endometriosis. Endometriosis is a common condition, affecting 5-15% of all women, and it has been estimated that 0.5-1% of cases are complicated by neoplasia. The most common malignant tumours in this setting are endometrioid adenocarcinoma and clear cell adenocarcinoma, each accounting for approximately 10% of ovarian carcinomas in Western countries. A minority of cases are associated with Lynch syndrome. These carcinomas are often confined to the ovaries at presentation in which case they have relatively favourable outcomes. However, high-stage tumours, particularly clear cell carcinomas, generally have a poor prognosis and this partly reflects relative resistance to current treatment. Histological diagnosis is straightforward in the majority of cases but some variants, for example endometrioid carcinomas with sex cord-like appearances or oxyphil cells, may create diagnostic difficulty. Similarly, clear cell carcinomas can show a range of architectural and cytological patterns that overlap with other tumours, both primary and metastatic, involving the ovaries. Endometriosis-associated borderline tumours are less common, and they often show mixed patterns of differentiation (seromucinous tumours). Atypical endometriosis may represent an intermediate step in neoplastic progression and some of these lesions demonstrate immunohistological and molecular alterations similar to those observed in endometriosis-related tumours. ARID1A mutations are relatively common in all of these tumours, but each has additional characteristic molecular alterations which are likely to be of increasing clinical relevance as targeted therapies are developed. Less is known of the pathogenesis of rarer endometriosis-associated ovarian tumours including endometrioid stromal sarcoma, mesodermal (Müllerian) adenosarcoma, and carcinosarcoma. This article also briefly reviews the issue of synchronous endometrioid carcinomas of the endometrium and the ovary, including the most recent developments on pathogenesis.

Keywords: Endometriosis; clear cell; endometrioid; immunohistochemistry; molecular; tumour.