Pathology of clear cell carcinoma of the ovary: A basic view based on cultured cells and modern view from comprehensive approaches

Clear cell carcinoma (CCC) is a distinct histologic type of ovarian carcinoma. CCC is more frequent in Japan than in the Western world. CCC is chemo-resistant and often associated with paraneoplastic thromboembolism. Histologically, CCC is characterized by both cancer cells and stromas, being concordant with the cytological features. Clear cells contain abundant glycogen. Hepatocyte nuclear factor-1β is a specific marker of CCC, and is likely to be involved in glucose metabolism. Extracellular matrix (ECM)-deposited stroma and plasma cell-rich inflammatory stroma are characteristic stromas of CCC. Studies using CCC cell lines showed that CCC cells produce ECMs and stimulate plasma cell differentiation in a paracrine manner. Most CCCs, as well as endometrioid carcinomas, originate from ovarian endometriosis. This is supported by molecular genetic data, although it remains unclear why different histologic types originate from the same precursor. CCC and endometrioid carcinoma are Lynch syndrome-associated ovarian carcinomas. Recent comprehensive studies indicate that CCC is distinct not only in terms of histology but also in genomics, epigenomics and transcriptomics. This review summarizes the pathology of ovarian CCC along with a basic view based on cultured cells, and refers to recent genetic and omic data.