Risk factor analysis of recurrence in low-grade endometrial adenocarcinoma

Prognosis of endometrial adenocarcinoma is favorable; however, the risk of recurrence ranges from 7% to 13%. Recurrence has been related to age, tumor type, International Federation of Gynecology and Obstetrics grade, depth of invasion, and lymphovascular invasion (LVI); however, morphologic features that would predict the site of recurrence have not been established. In this multi-institutional study, we reviewed 589 patients with International Federation of Gynecology and Obstetrics grades 1 or 2 endometrial adenocarcinoma, endometrioid type. Cox proportional hazard analysis was used to identify univariate and multivariate risk factors for recurrence and survival. Univariate analysis revealed features of tumors that recurred only in the vagina: low nuclear grade; superficial myoinvasion; minimal to no LVI; and minimal myoinvasion with microcystic, elongated, and fragmented (MELF) pattern; low nuclear grade and superficial myoinvasion persisted on multivariate analysis. Features of tumors that recurred at other sites included large size, deep myoinvasion, tumor necrosis, 1 or more LVI foci, LVI foci distant/deeper than invasive tumor front, MELF myoinvasion pattern, lower uterine segment and cervical stromal involvement, pelvic and/or paraaortic lymph node metastases at presentation, and higher grade of tumor in the metastatic foci, whereas increased percentage of solid component and lower percentage of mucinous features were marginally associated. Tumors with recurrences only in vagina had different features than tumors that recurred at other sites. The presence of tumor necrosis, MELF foci at the invasive tumor front, and the percentage of solid component and mucinous features could be helpful in grading endometrioid adenocarcinomas, if a 2-tier rather than a 3-tier grading system is accepted in the future.