Endometrial cancer arising in adenomyosis versus endometrial cancer coexisting with adenomyosis: are these two different entities?

Abstract

Purpose: While adenomyosis is one of the most common benign histologic findings in hysterectomy specimens of endometrial cancer, demographics of endometrial cancer arising in adenomyosis (EC-AIA) has not been well elucidated. The aim of this study is to evaluate histopathological findings and disease-free survival (DFS) of EC-AIA in comparison to endometrial cancer coexisting with adenomyosis (EC-A).

Methods: EC-AIA cases were identified via a systematic literature search (n = 46). EC-A cases were identified from a historical cohort that underwent hysterectomy-based surgical staging in two institutions (n = 350). Statistical comparisons of the two groups were based on univariate and multivariate analyses.

Results: The EC-AIA group was significantly older than the EC-A group (58.9 versus 53.8, p = 0.002). As to tumor characteristics, 63.6% of EC-AIA cases reported tumor within the myometrium without endometrial extension. The EC-AIA group was significantly associated with more non-endometrioid histology (23.9 versus 14.8%; p = 0.002) and deep myometrial tumor invasion (51.6 versus 19.4%; p < 0.001) than EC-A. Tumor grade, stage, and nodal metastasis risk were similar (all, p > 0.05). In a univariate analysis, the EC-AIA group had a significantly decreased DFS compared to EC-A (5-year rates, 72.2 versus 85.5%, p = 0.001). After controlling for age, histology, tumor grade, and stage, EC-AIA remained an independent prognostic factor associated with decreased DFS compared to EC-A (adjusted-hazard ratio 2.87, 95% confidence interval 1.44-5.70, p = 0.031).

Conclusion: Our study demonstrated that EC-AIA has distinct tumor characteristics and a poorer survival outcome compared to EC-A. This suggests a benefit of recognition of this unique entity as an aggressive variant of endometrial cancer.

Keywords: Adenomyosis; Endometrial cancer; Endometriosis-associated cancer; Prognosis; Survival.

Fig. 1

Schema for study design. Prior studies examined (i) endometrial cancer coexisting with adenomyosis (EC-A) compared to endometrial cancer without adenomyosis (EC w/o A), (ii) endometrial cancer arising in adenomyosis (EC-AIA) compared to endometrial cancer regardless of adenomyosis status. However, the relation between EC-AIA and EC-A is still unknown. EC-AIA defined as follows: (1) the carcinoma must not be situated in the endometrium or elsewhere in the pelvis, (2) the carcinoma must be seen to arise from the epithelium of adenomyosis and not to have invaded from another source, (3) endometrial stromal cells should be surrounding the aberrant glands to support the diagnosis of adenomyosis

Fig. 2

Disease-free survival in case-control cases. Log-rank test for p values. Kaplan-Meier method for survival curves for a DFS for all cases, b OS for all cases, and c DFS for stage I