Clear Cell Carcinoma of Ovary and Uterus

Clear cell carcinomas of the female genital tract are rare tumours with a fearsome reputation for having poor responses to conventional platinum-based chemotherapy and poor prognosis. However, it is now clear that early-stage ovarian clear cell carcinoma has an excellent prognosis and may not require any adjuvant therapy. In addition, radiotherapy may also have a key role to play in adjuvant management of clear cell tumours. Identification of patients who truly do not need adjuvant chemotherapy is important. The past 3 years has seen a significant improvement in our understanding of clear cell carcinoma biology—in particular, the role of mutations in the chromatin remodelling gene ARID1A as key drivers that are common to clear cell carcinomas of ovarian and endometrial origin. Moreover, gynaecological clear cell carcinomas appear to share many features with renal clear cell tumours, suggesting a common pathogenesis. This raises the possibility of clinical trials that include patients with clear cell tumours from different organs of origin. Dissecting the role of disordered chromatin organisation in clear cell carcinoma pathogenesis is a key priority. Finally, the role of endometriosis and the attendant chronic inflammation are recognised. The inflammatory cytokine interleukin-6 appears to play a key role in clear cell carcinoma biology and is an excellent potential therapeutic target.