Clear cell carcinoma of the endometrium: a biological and clinical enigma.

Clear cell carcinoma accounts for only 1 to 5.5% of all endometrial carcinomas, and it is often associated with an aggressive clinical behavior and a poor outcome. According to the FIGO Annual Report 2006, 5-year overall survival was 62.5% for patients with this histological type compared with 83.2% for those with endometrioid carcinoma of the endometrium. In contrast to endometrioid carcinoma and uterine papillary serous carcinoma (UPSC), the molecular pathways involved in the development of clear cell carcinoma are still unclear. Literature data on the pattern of failures and the optimal treatment modalities of the clear cell carcinoma are not well defined, largely because most papers have assessed clear cell carcinoma and UPSC together because of their rarity. Patients with clear cell carcinoma often experience relapse in the pelvis, in para-aortic nodes and at distant sites, whereas they do not seem to have a high propensity to fail in the abdomen. Total abdominal hysterectomy and bilateral salpingo-oophorectomy with comprehensive surgical staging is the standard surgical treatment of patients with clear cell carcinoma of the endometrium, whereas pelvic irradiation, with or without brachytherapy and/or para-aortic irradiation, whole-abdomen irradiation, and chemotherapy have been widely employed as postoperative therapy. However, no commonly accepted guidelines are currently available for the management of these patients. An adequate molecular characterization of clear cell carcinoma of the endometrium is strongly warranted in order to identify new biological prognostic variables of the disease and to develop novel molecular targeted therapies.