Concurrent endometrial carcinoma following hysterectomy for atypical endometrial hyperplasia

Abstract

Objective

To evaluate the prevalence of concurrent endometrial carcinoma in women diagnosed with atypical endometrial hyperplasia (AEH) by endometrial biopsy.

Study design

We retrospectively analyzed the medical records of 126 patients who underwent hysterectomies for AEH diagnosed by endometrial biopsy from 1999 to 2008. AEH was initially diagnosed by dilatation and curettage (98 cases) or endometrial biopsy with a Z-sampler (24 cases). The remaining four cases were diagnosed by hysteroscopic polypectomy. The results of the endometrial biopsies were graded on an ordinal scale and were compared with pathologic features obtained at the hysterectomy.

Results

In patients preoperatively diagnosed with AEH by biopsy, hysterectomy specimens revealed a rate of simple or complex endometrial hyperplasia without atypia of 27% with AEH and normal proliferative phases found in 54.7 and 7.9% of specimens, respectively. The incidence of endometrial carcinoma was considerably high (13/126, 10.3%). Eleven of 13 cases were confined to the endometrium and the remaining two were located at the adenomyosis without myometrial invasion. All patients with endometrial carcinoma displayed coexisting atypical complex hyperplasia following hysterectomy.

Conclusions

Biopsy specimens showing AEH, particularly atypical complex hyperplasia, are associated with a risk of coexisting endometrial carcinoma. When considering management strategies for women with a biopsy diagnosis of AEH, clinicians should take into account the considerable rate of concurrent endometrial cancer and the discrepancy with pathologic diagnosis. Treatment modalities may differ depending on population as the rates of concurrent endometrial cancer with AEH and myometrial invasion vary by geographical location.

Introduction

Endometrial hyperplasia is classified into four categories according to the World Health Organization (WHO) system, including simple hyperplasia, complex hyperplasia, simple hyperplasia with atypia, and complex hyperplasia with atypia [1]. While the Endometrial Collaborative Group has proposed a new term, endometrial intraepithelial neoplasia (EIN), for superior reproducibility, this classification has not yet undergone the necessary prospective evaluation or assessment of reproducibility [2]. Miller et al. classified endometrial hyperplasia based on the WHO classification system with additional qualifying comments that could potentially identify patients at high risk for endometrial cancer. The intent was to better predict increased risk for coexistent carcinomas that may require surgical staging. However, several limitations, including the retrospective nature and the absence of expert pathologic review, compromise its utility [3]. Atypical endometrial hyperplasia (AEH) has a well-known role in the progression to endometrial carcinoma, providing the link from proliferative endometrium to well-differentiated adenocarcinoma. Although they fall along the same spectrum, the diagnosis of AEH versus endometrial carcinoma carries different significance, as endometrial carcinoma requires a different clinical approach compared with its predecessor. Despite the significance of the differentiation between AEH and carcinoma, a pathologic review by the Gynecologic Oncology Group (GOG) in 2006 failed to demonstrate diagnostic consistency [4]. In the study, the diagnosis agreement between the referral and the study groups was only 39%, suggesting that morphological differences may be nearly indistinguishable.

Many previous studies have reported that approximately 17–52% of cases of AEH may be associated with coexistent endometrial carcinoma [4], [5], [6], [7], [8], [9], [10], [11]. Moreover, the rate of concurrent endometrial carcinoma following hysterectomy is increasing, and therefore, in recent studies the rates are even higher, reaching 40–50% [4], [11]. In order to ensure appropriate management and patient safety, it is essential to have a better understanding of the rate of concurrent endometrial carcinoma among women with AEH as diagnosed by endometrial biopsy. The purpose of this study was to examine the relationship between the diagnoses of AEH by endometrial sampling and endometrial carcinoma with the postoperative pathology reports from hysterectomy specimens serving as the definitive results.