Clear Cell Carcinoma Clear cell carcinoma accounts for less than 5% of all endometrial carcinomas (96,113,114). Clear cell carcinoma usually has a mixed histologic pattern, including papillary, tubulocystic, glandular, and solid types. The cells have highly atypical nuclei and abundant clear or eosinophilic cytoplasm. Often, the cells have a hobnail configuration arranged in papillae with hyalinized stalks (Fig. 35.5).
Clear cell carcinoma characteristically occurs in older women and like serous carcinoma is considered a poor prognosticator. Traditionally clear cell carcinoma was associated with very poor outcomes with overall survival rates varying from 33% to 64%. A multi-institutional review of 99 patients with uterine clear cell carcinoma documented only 1 recurrence (vaginal) in the 22 patients without extrauterine disease subjected to thorough surgical staging (115). Considering all 49 patients with stage I or II disease (regardless of the extent of staging), only 1 hematologic failure was noted. These data argue against the use of systemic therapy in patients with clear cell carcinoma limited to the pelvis, while the 10% vaginal cuff failure suggests that vaginal brachytherapy alone may be sufficient treatment. In contrast, others argued for systemic treatment of patients with stage I disease (116).
Complete surgical staging is important because 52% of patients with clinical stage I clear cell carcinoma have metastatic disease. Patients who undergo a complete cytoreduction appear to have improved progression-free and overall survivals compared to women left with residual disease following surgery (115). Postoperative therapy for patients with advanced disease is platinum-based (116).
Squamous Carcinoma Squamous carcinoma of the endometrium is rare. Some tumors are pure, but most have a few glands. To establish primary origin within the endometrium, there must be no connection with or spread from cervical squamous epithelium. Squamous carcinoma often is associated with cervical stenosis, chronic inﬂammation, and pyometra at the time of diagnosis. This tumor has a poor prognosis, with an estimated 36% survival rate in patients with clinical stage I disease (117).
Simultaneous Tumors of the Endometrium and Ovary
Figure 35.5 Clear cell adenocarcinoma of the endometrium. Back-to-back glands lined by polygonal to columnar cells with distinct cell membrane, abundant granular to clear cytoplasm, and variably sized nuclei (including binucleated and multinucleated forms) with prominent nucleoli (magnification X400). (Provided by Gordana Stevanovic, MD, and Jianyu Rao, MD, Department of Pathology, UCLA.)
Synchronous endometrial and ovarian cancers are the most frequent simultaneously occurring genital malignancies, with a reported incidence of 1.4% to 3.8% (118–122). Most commonly, both the ovarian and endometrial tumor are well-differentiated endometrioid adenocarcinomas of low stage, resulting in an excellent prognosis. Patients often are premenopausal and present with abnormal uterine bleeding. The ovarian cancer usually is discovered as an incidental finding and is diagnosed at an earlier stage because of the symptomatic endometrial tumor, leading to a more favorable outcome. Up to 29% of patients with endometrioid ovarian adenocarcinomas have associated endometrial cancer. If more poorly differentiated, nonendometrioid histologic subtypes are present or if the uterine and ovarian tumors are histologically dissimilar, the prognosis is less favorable. Immunohistochemical studies, ﬂow cytometry, and assessment of molecular DNA patterns to detect loss of heterozygosity may be helpful in distinguishing between metastatic and independent tumors, but the differential diagnosis can usually be determined by conventional clinical and pathologic criteria.