Pathogenesis of Ovarian Clear Cell Adenofibroma, Atypical Proliferative (Borderline) Tumor, and Carcinoma: Clinicopathologic Features of Tumors with Endometriosis or Adenofibromatous Components Support Two Related Pathways of Tumor Development

摘要

The clinicopathologic features of 472 ovarian epithelial clear cell neoplasms (4 adenofibromas [AFs], 41 atypical proliferative [borderline] tumors [APTs], and 427 carcinomas [CAs]) were studied in order to elucidate the morphologic steps involved in the pathogenesis of these tumors and determine whether clear cell CA is a type I or type II tumor in the dualistic model of ovarian carcinogenesis. Thirty-three percent of the CAs had an adenofibromatous background [CA(AF+)], and 67% did not [CA(AF-)]. Endometriosis was found in all types of tumors, but tumors arising in endometriotic cysts were more frequent with CA(AF-)s (pI) and were higher grade compared to CA(AF+)s or CA(AF-) with endometriosis (p-values, <0.0001 to 0.0071). All AFs and APTs were stage I compared to 79% of CA(AF+)s. An increase in mean tumor size correlated with each respective tumor category from AF (6.8 cm) to CA(AF+) [12.9 cm]. Notable nuclear atypia was absent in all AFs but was focally present in 27% of APTs and in the adenofibromatous background of 24% of the CA(AF+)s. An increase in the proportion of carcinoma in the CA(AF+)s correlated with an increase in grade and advanced stage. In summary, ovarian clear cell CA appears to develop along two pathways, both of which are related to endometriosis. We speculate that, in one, epithelial atypia arises in an endometriotic cyst and then evolves into clear cell CA, and, in the other, non-cystic endometriosis induces a fibromatous reaction resulting in the formation of AF, which then develops into APT and subsequently a clear cell CA. The absence of endometriosis or adenofibromatous components in CC(AF-)s may be due to overgrowth and obliteration by the invasive carcinoma. Finally, the findings in this study support the view that both types of clear cell CA [CC(AF+) and CC(AF-)] are more closely related to type I tumors.