© 2007 Informa UK Ltd. First described by Hendrickson et al1 in 1982, uterine papillary serous carcinoma (UPSC) is an aggressive histologic subtype of endometrial cancer that has distinct clinical and pathologic characteristics and accounts for a disproportionate number of recurrences and deaths.2 While this subtype comprises <10% of cases of endometrial cancer, it accounts >50% of recurrences and deaths due to this disease.1 These tumors occur more frequently in the absence of hyperestrogenism and endometrial hyperplasia, and most arise from atrophic endometrium. The 5-year overall survival rate for patients with stage I UPSC is 45-70% and that for patients with stage III or IV disease is 7-37%.3-9 CLINICOPATHOLOGIC FEATURES While prognostic markers for typical endometrial carcinoma (i.e. endometrioid endometrial carcinoma, EEC) are well characterized, only limited information is available that allows us to predict clinical behavior for patients with UPSC. Traditional pathologic criteria (lymphovascular space invasion (LVSI), depth of myometrial invasion, and lymph node involvement) are not predictive of metastatic disease or site of recurrence for UPSC. However, stage, lymph node status, LVSI, and depth of uterine invasion are predictors of survival. Several investigators have confirmed that depth of myometrial invasion and LVSI are significant pathologic determinants of a poor prognosis.6,10,11 Significantly, it is not uncommon for patients with no myometrial invasion to have distant disease at the time of initial diagnosis. Up to 40% of patients with no myometrial invasion will have advanced disease at the time of surgical staging. Therefore, complete surgical evaluation, including lymph node dissection and omental biopsy, is indicated at the time of initial surgery. In addition, mixed adenocarcinomas with serous components portend a clinical course similar to that of pure UPSC. Therefore, patients with either endometrioid carcinoma or clear cell carcinoma with serous components should be treated as if they have UPSC.6,8 Unlike most other gynecologic tumors, patients with stage IA tumors may have unusually aggressive disease. In the study by Gehrig et al,12 6 had stage IA UPSC and were given adjuvant therapy, and 2 went on to have documented vaginal recurrences. In the study by Carcangiu et al8 of 13 patients with stage IA UPSC, all except 1 received adjuvant therapy, and 2 of the 13 patients had recurrences in the abdomen 9 months after their initial diagnosis. One had received adjuvant whole_abdominal radiotherapy, and the other had received adjuvant platinum-based chemotherapy. In the large retrospective series of 129 patients from the MD Anderson Cancer Center, 20% of patients with stage IA disease had recurrent disease.6.