A 72-year-old woman with abnormal uterine bleeding underwent an endometrial biopsy. The resultant specimen is shown below.
What is your diagnosis?
The specimen consists of a complex proliferation of epithelial cells forming sheets, glands and papillae. The cells vary from having clear vacuolated to eosinophilic cytoplasm. Cells lining the papillae have enlarged nuclei protruding into the lumina in a "hobnail" configuration.
This is a straightforward example of a uterine clear cell carcinoma. These "type II" uterine adenocarcinomas, like their close counterparts, serous papillary carcinomas, tend to occur in older postmenopausal women and do no typically arise in a setting of endometrial hyperplasia. There is no association with estrogen or progesterone therapy. These tumors are histologically identical to ovarian clear cell carcinomas. They are also identical in microscopic appearance to the DES-associated clear cell carcinomas of the cervicovaginal region, but there is no known association with DES for the uterine tumors. In the past, when DES-associated tumors were more common, distinction of uterine v. cervicovaginal origin could be problematic, but today DES-associated adenocarcinomas are virtually non-existent as the drug was discontinued many years ago.
Uterine clear cell carcinomas make occur in pure form or be associated with papillary serous carcinoma. Distinction between the two is occasionally problematic, but not of great clinical importance. When both tumors have a papillary pattern, the distinction seems to be most difficult as clear cells are less prominent on the papillae. The papillae of clear cell carcinoma typically have hyalinized, densely eosinophilic cores.
Uterine clear cell carcinomas are typically positive for ER and PR, but are less often p53 positive, as compared to serous carcinomas. Clear cell carcinomas should be distinguished from uncommon endometrial metaplasias, including clear cell, hobnail, and papillary syncytial metaplasia. This is usually (but not always) straightforward on the basis of the marked nuclear pleomorphism and mitotic activity in clear cell carcinoma.
It should be noted that the FIGO grading system for uterine endometrioid adenocarcinomas does not apply to clear cell or serous carcinomas. These tumors are, by definition, high-grade neoplasms. Their diagnosis in a curettage specimen will typically lead to retroperitoneal lymph node sampling or dissection, regardless of the depth of myometrial invasion.