Endometrial metaplasias and reactive changes: a spectrum of altered differentiation

Abstract

Endometrial metaplasias and changes (EMCs) are conditions frequently overlooked and misdiagnosed. The aim of this review is to update current issues and provide a classification with a practical clinicopathological approach. Hormonal or irritative stimuli are the main inducing factors of EMCs, although some metaplasias have a mutational origin. EMCs vary from reactive, degenerative lesions to those able to associate with malignancy or those having a preneoplastic potential. The most common types of EMCs are ciliated tubal metaplasia (CTM) and mucinous metaplasia (MM), which occur in simple and complex glands, and possibly these architectural changes hold the same prognostic significance as they do in hyperplastic endometrioid lesions. Immunohistochemically, CTM is positive for LhS28, bcl-2, PAX2 and p16

Frequent KRAS mutation in complex mucinous epithelial lesions of the endometrium

“…1 Very rarely, mucinous changes of the endometrium exhibit intestinal-type differentiation with cellular brush border, goblet cells and neuroendocrine cells, although this is more common in the cervix where it is frequently associated with an endocervical neoplastic process. 2 In fact, intestinal differentiation was not observed in any of the endometrial mucinous lesions in this study. The architectural patterns of mucinous metaplasia vary widely from simple epithelial pattern to variable degrees of complexity including epithelial branching, budding, papillation, cribriforming or microglandular formation.…”

“…They commonly coexist in the same biopsy specimen 3,8 and frequently are associated with pathologic conditions including polyps, endometritis, hyperplasia and adenocarcinoma. [1][2][3][16][17][18] Mucinous change represents approximately 24% of endometrial metaplasia and is characterized by the presence of epithelial cells that have a distinctive watery blue appearance (endocervical-type epithelium) as a result of cytoplasmic accumulation of PAS-positive diastaseresistant mucin material. 1 Very rarely, mucinous changes of the endometrium exhibit intestinal-type differentiation with cellular brush border, goblet cells and neuroendocrine cells, although this is more common in the cervix where it is frequently associated with an endocervical neoplastic process.…”

“…1,2 Mucinous metaplasia, including both the typical endocervical and the rare intestinal types, is particularly relevant as it is not infrequently encountered in an endometrial biopsy or curettage specimen of menopausal or postmenopausal patients and is more likely associated with additional aggressive endometrial lesions. However, the frequent disparity between the cytological atypia and architectural alterations in a mucinous lesion, especially in a small, fragmented biopsy may lead to significant diagnostic challenges of interpretation to guide patient management.…”

“…However, the frequent disparity between the cytological atypia and architectural alterations in a mucinous lesion, especially in a small, fragmented biopsy may lead to significant diagnostic challenges of interpretation to guide patient management. 2,3 Type I endometrial adenocarcinomas frequently show mucinous differentiation, a subset of which are classified as mucinous adenocarcinoma when the tumor contains 50% or more mucinous component. The latter diagnosis also includes the low-grade mucinous adenocarcinoma 4 and microglandular variant of endometrioid adenocarcinoma.…”

“…The latter diagnosis also includes the low-grade mucinous adenocarcinoma 4 and microglandular variant of endometrioid adenocarcinoma. [5][6][7] It has been hypothesized that subtypes of endometrial mucinous metaplasia are biologically related to endometrial adenocarcinoma as precursor lesions, and different classification systems have been proposed based solely on morphological grounds to predict the risk of subsequent endometrial cancer, 2,3,8,9 particularly mucinous adenocarcinoma. 10 Endometrial mucinous lesions have been recently proposed to be classified into simple and papillary/complex groups, based on the presence or absence of intraglandular papillary tufts or complex glandular architecture.…”