Ovarian clear cell carcinoma with plasma cell-rich inflammatory stroma: A clear cell carcinoma subgroup with distinct clinicopathological features

Abstract

Aims: Ovarian clear cell carcinoma has a unique stroma. Although a hyalinized or mucoid stroma is more common, the stroma sometimes shows a dense inflammatory infiltrate, simulating a dysgerminoma. The aim of this study was to analyse the character and significance of the inflammatory stroma. Methods and results: Twelve of 60 (20%) clear cell carcinomas showed an inflammatory stroma. The inflammatory stroma and hyalinized/mucoid stroma were mutually exclusive. Inflammatory cells were predominantly composed of CD138-positive plasma cells. As compared with the non-inflammatory cases, the epithelial component frequently showed a solid growth pattern and immunoreactivity for cyclooxygenase-2, one of the critical proinflammatory enzymes (P < 0.005). These findings were repeated after heterotransplantation of three clear cell carcinoma cell lines into athymic nude mice. In particular, xenografts of one cell line (JHOC-5) were infiltrated by mature plasma cells, indicating that plasma cell differentiation was stimulated by JHOC-5 cells, independently of T lymphocytes. Clinicopathologically, the frequency of International Federation of Gynaecology and Obstetrics stage III was higher in the cases with an inflammatory stroma than in those without it (P < 0.01). Conclusions: Clear cell carcinomas with an inflammatory stroma constitute a distinct clinicopathological subgroup. It is strongly suggested that tumour cells themselves are responsible for inducing inflammation and stimulating plasma cell differentiation in a paracrine manner.