Changes in the ovarian microenvironment due to physiologic and iatrogenic aging

Abstract

Low-grade endometrial endometrioid adenocarcinomas (LGEECa) can recur in the vagina (VRec), pelvic and abdominal region (PARec), or distant sites (DMet). Tumor size, histopathologic features, and lymph node involvement at presentation have been linked to the development of these recurrences. However, the amount of information on risk factors to predict site of recurrence is limited. Methods: In this multi-institutional study, we analyzed data from 589 patients with FIGO grades 1 and 2 LGEECa and found 116 patients with VRec, PARec, or DMet. They were compared with 187 age-matched controls with negative lymph nodes, no adjuvant treatment, and no recurrences; mean follow-up times were 44 and 59 months, respectively. Cox proportional hazards analysis was used to identify univariable and multivariable risk factors for each type of recurrence (P b .05). Results: Forty-one patients had VRec, 33 had PARec (pelvic soft tissue, 14; abdominal tissue, 9; liver capsule, 5; retroperitoneum, 3; colorectal wall, 2), and 42 had DMet (lung, 19; lymph nodes, 17; bone and soft tissue, 5; brain, 1) as the initial site of recurrence. Univariate and multivariate analysis of histopathologic features are summarized in Table 1. In addition, features associated with vaginaonly recurrence included superficial myometrial invasion (P = .002); low nuclear grade (P = .03); lymphovascular invasion (LVI) adjacent to tumor, but not deeper than invasive tumor front (P b .001); less than 5% microcystic elongated and fragmented pattern (MELF) at invasive tumor front (P = .014); and no pelvic lymph node metastasis at presentation (P = .019). These features were not significantly different from controls. Conclusions: (1) Features of LGEECa that predicted VRec included superficialy invasive, low nuclear grade tumors with minimal MELF, minimal or no LVI, and no lymph node metastasis. These features were more closely related with tumors that did not recur than with recurrent tumors. (2) LGEECa with PARec differed from those with VRec, because the tumors were larger and deeply invasive and MELF at invasive tumor front, suggesting a different dissemination route than tumors with VRec. (3) Significant predictor features of LGEECa with DMet included intraglandular tumor necrosis, cell clusters at the invasive front and adjacent to areas of LVI, and cervical stromal involvement. The latter feature might be indicative of venous rather of lymphatic invasion.