Strategies for Classifying Endometrial Carcinoma with Clear Cells

Clear cell carcinomas (CCC) is one of the rarest forms of endometrial carcinoma. In one series of 852 consecutive endometrial carcinomas managed at a single academic center, only 3 (0.35%) were considered to be CCC (1). Although CCC is rare, it features frequently in the differential diagnosis of endometrial neoplasms, primarily because one of the morphologic features of CCC the presence of clear cells is not specific to the histotype. CCC is considered a high grade histotype, hence the necessity of their separation from low grade endometrial carcinomas. However, CCC should also be distinguished from other high grade histotypes because there may be prognostic (2-4) and therapeutic differences (3,5), and due to the possibility that CCC is associated with a comparatively increased risk of thromboembolic events (6,7). Additionally, erroneous pathologic classifications of non-CCC histotypes as CCC not only represents a significant impediment to scientific advancement on both histotypes, but also may deny some patients eligibility for potentially life-saving clinical trials to which they should qualify. Presented herein is an approach to the pathologic classification of endometrial carcinomas with clear cells, with an emphasis on the distinction of CCC from its potential histologic mimics.