Unveiling Commonalities: Exploring Shared Characteristics in Clear Cell Carcinomas of the Gynecologic Tract.

Abstract

Clear cell carcinomas arising from the gynecological tract (including from the ovary, endometrium, cervix, vulva or vagina) represent rare but clinically significant entities with intriguing overlapping characteristics. Epidemiologically, clear cell carcinomas exhibit a predilection for women of Asian ethnicity and are often associated with a previous or synchronous diagnosis of endometriosis. Pathologically, despite originating from different primary organs, clear cell carcinomas of the gynecological tract show a similar morphological and immunophenotypic features on traditional histopathology, such as the expression of Napsin A and HNF1b on immunohistochemistry, without the expression of WT1. Well-described molecular characteristics of these cancers include recurrent mutations in genes such as ARID1A, PIK3CA, and/or PTEN, although significant variations exist across the different anatomical sites. Therapeutically, optimal management remains challenging due to the relative rarity of clear cell carcinomas and limited subtype-specific clinical trials. Surgery remains the cornerstone of treatment, often complemented by systemic chemotherapy. However, promising drugs targeting angiogenesis or the immune microenvironment have emerged in recent years, leading to clinical successes and are likely to reshape the therapeutic landscape of gynecological clear cell carcinoma. This review summarizes the commonalities and disparities in terms of epidemiology, pathology, molecular features and therapeutic approach, amongst clear cell carcinomas of different anatomical origin, offering a foundation for further research and dedicated therapeutic interventions for these malignancies.