Endometrial clear cell carcinoma: An update on recent concepts

Endometrial clear cell carcinoma is an uncommon endometrial cancer that is biologically, clinically, and pathologically distinct from the more common endometrioid and serous carcinomas. The differential diagnosis for endometrial clear cell carcinoma includes benign and nonneoplastic lesions, as well as a variety of neoplastic processes that may potentially display clear cells. Resolution of this differential diagnosis in a given case of putative endometrial clear cell carcinoma requires the recognition that (1) the diagnosis of endometrial clear cell carcinoma in the gynecologic tract is based more on the presence of the classic architectural patterns of this entity than the presence of clear cells, (2) clear cells are not unique to clear cell carcinomas, and (3) clear cell carcinomas need not display a prominent complement of clear cells and occasionally display a significant population of cells with oxyphilic cytoplasm. Stage is an important prognostic factor in endometrial clear cell carcinoma. Accordingly, the identification of precancerous lesions and the application of an intervention before the development or progression of the malignancy may contribute to improved outcomes in patients with this cancer. A spectrum of lesions that have been frequently identified adjacent to endometrial carcinomas with a clear cell component (clear cell endometrial glandular dysplasia and clear cell endometrial intraepithelial carcinoma) may represent precursor lesions to the malignancy. We present herein a case of endometrial clear cell carcinoma associated with these precursor lesions and evaluate the current state of knowledge on various clinicopathologic aspects of endometrial clear cell carcinoma.