Endometrial intraepithelial neoplasia with secretory differentiation: diagnostic features and underlying mechanisms

Abstract

Endometrial intraepithelial neoplasia (EIN) with secretory differentiation and ordinary EIN occurring in a secretory context are rare but recognized findings. We determined how often secretory differentiation in EIN was associated with evidence of circulating progestins in the background endometrium, and studied clinical characteristics and clinical outcomes of affected patients. We selected 41 patients with secretory differentiation in either the EIN itself (n ¼ 31) and/or background endometrium (n ¼ 38). Most (90%, 28/31) secretory EINs were associated with circulating progestins. Rare exceptions were observed, suggesting that secretory EIN may occur as a hormone-independent phenomenon. Circulating progestins are not sufficient, however, to induce EIN secretory differentiation, as 26% (10/38) of EIN within a secretory background were of the ordinary (nonsecretory) type. EIN patients with secretory endometrium in the background are younger (averaging 45 years) than the aggregate group of all patients with EIN (53 years in previously published studies) and are often premenopausal with a cyclical source of endogenous progestins. Involution of EIN during follow-up was more frequent (81%, 17/21) for those with a secretory background at the time of initial EIN diagnosis compared with historical averages (25%, 36/142). These results suggest a potential role for endogenous progesterone, as well as therapeutic progestins, in modulating EIN outcomes. Modern Pathology (2013) 26, 868-873; doi:10.1038/modpathol.2012.231; published online 18 January 2013 Keywords: endometrial cancer; endometrial intraepithelial neoplasia; secretory Endometrial intraepithelial neoplasia (EIN) is a clonal proliferation of endometrial glands, considered to be a premalignant condition due to its strong association with concurrent and/or subsequent endometrioid (type I) adenocarcinoma of the endometrium. Indeed, a diagnosis of EIN is associated with a 27% likelihood of having ('concurrent') adenocarcinoma within 1 year, and carrying a 45-fold increased risk for a future (after 1 year) diagnosis of adenocarcinoma. 1 Diagnosis of EIN requires strict application of histological criteria, including size (at least 1 mm in greatest linear dimension), architecture (area of glands exceeds area of endometrial stroma) and cytology (difference in nuclear and cytoplasmic appearance between the abnormal and background endometrium). [2][3][4] Exclusion of cancer, as well as benign conditions mimicking EIN, is an important part of accurate diagnosis.Accurate and sensitive diagnosis of EIN in reproductive age women can be challenging when a secretory background is present. Secretory-phase endometrium displays changes that may morphologically overlap with EIN. 2 In normal mid-late secretory endometrium the gland to stroma ratio is increased, nuclei become enlarged and round, and large expanses of secretory superficial endometrium are offset from basal areas lacking secretory changes. Furthermore, when EIN does occur within the context of a secretory environment,...

Endometrial Intraepithelial Neoplasia (EIN) In An Endometrial Polyp

“…Endometrial intraepithelial neoplasia (EIN) is a monoclonal proliferation of the endometrial glands, which is considered to be a premalignant condition due to its strong association with concurrent and/or subsequent endometrioid adenocarcinoma of the endometrium [1,2]. The risk factors for the development of EIN include exposure to oestrogens without opposing progestins, obesity, diabetes, and rare hereditary conditions.…”