Morphologic and Immunohistochemical Study of Clear Cell Carcinoma of the Uterine Endometrium and Cervix in Comparison to Ovarian Clear Cell Carcinoma

Endometrial clear cell carcinoma (ECCC) and clear cell adenocarcinoma of the cervix (CCAC) are uncommon gynecologic cancers that have morphologic and phenotypic features similar to ovarian clear cell carcinoma (OCCC), but the 3 entities may not be completely identical. This study identified the morphologic and phenotypic characteristics and the differences between ECCC and CCAC in comparison to OCCC. The morphologic features of 16 ECCCs, 7 CCACs, and 22 OCCCs are described. The immunoprofiles of hepatocyte nuclear factor (HNF) 1β, napsin A, estrogen, progesterone, p53, and Ki-67 were assessed. The results confirm that clear cell carcinomas of the gynecologic tract have a similar spectrum of histopathologic features with the exception that ECCCs have focal solid components more often than CCACs and OCCCs and ECCCs have a slightly higher average mitotic index. Similar to OCCCs, both ECCCs and CCACs were positive for HNF1β and napsin A, and rarely expressed estrogen and progesterone. HNF1β was a sensitive marker for clear cell carcinoma at all 3 sites. Napsin A was less sensitive in ECCCs than in OCCCs (56.3% vs. 90.9%, P=0.021). The average Ki-67 index was higher in ECCCs than in OCCCs (52.6% vs. 39.1%) in hotspot scoring, and more ECCC cases had a higher expression (56.3% vs. 22.7%). Diffuse p53 expression, which is associated with TP53 mutation, was observed slightly more often in ECCCs than in OCCCs (25% vs. 9.1%). Our findings revealed morphologic and immunophenotypic similarities and differences among different gynecologic clear cell carcinomas, which may help in improving diagnosis and knowledge of CCC in the female genital tract.