Abstract
The aim of this study was to assess the relationship between endometrial metaplastic/reactive changes (EMRCs) and endometrial neoplastic lesions. Twenty cases of “simple” (without architecture complexity) EMRCs coexistent with endometrial malignant/premalignant lesions, twenty cases of neoplasia-unassociated EMRCs, and eight cases of complex metaplastic lesions were assessed by immunohistochemistry. EMRCs coexisted with endometrioid carcinoma (n = 12), atypical endometrial hyperplasia (n = 3), serous carcinoma (n = 2), and clear cell carcinoma (n = 3). Neoplasia-associated EMRCs showed a mean Ki67 labeling index of 12.6% (range 0–30%); with nuclear atypia in 16/20 (80%) cases; diffuse p16 expression in 15/20 (75%) cases; and heterogeneous ER, PR, and vimentin expression. Compared to the associated neoplasia, EMRCs showed a lower Ki67 expression (p < 0.001) and higher p16 expression (p < 0.001). No EMRC case showed mitotic activity, PTEN loss, MMR deficiency, nuclear β-catenin, p53-mutant pattern, Napsin A, or AMACR expression. No significant differences were found between neoplasia-associated and neoplasia-unassociated EMRCs. Complex metaplastic lesions showed a lower Ki67 expression than EMRCs (p = 0.044) and PTEN loss in 5/8 cases, even in the absence of nuclear atypia. In conclusion, neoplasia-associated simple EMRCs may show evident atypia and a worrisome immunophenotype, but no data support their involvement in endometrial carcinogenesis. Architectural complexity appears as a crucial factor to identify precancerous lesions.
Highlights
The uterine endometrium is a unique tissue undergoing different phases of hormonal stimulation and may show several different types of altered differentiation, such as tubal, squamous, morular, and mucinous
Twenty endometrial metaplastic/reactive changes (EMRCs) associated with endometrioid carcinoma (n = 10), atypical endometrial hyperplasia (n = 5), clear cell carcinoma (n = 3), and serous carcinoma (n = 2) were identified (Figure 1)
Ki67 levels were heterogeneous, with LI varying from 0% to 30%; the mean LI level was significantly lower in EMRC than in associated neoplasia; in two cases, the Ki67 LI of EMRCs was equal to or higher than that of the coexistent neoplasia (Figure 3a)
Summary
The uterine endometrium is a unique tissue undergoing different phases of hormonal stimulation and may show several different types of altered differentiation, such as tubal, squamous, morular, and mucinous. EMRCs are often found in association with endometrial carcinomas [1] These features have prompted researchers to assess whether some EMRCs may represent premalignant lesions. To the best of our knowledge, no study assessed whether simple EMRCs associated with endometrial carcinoma may represent premalignant lesions. The aim of this study was to assess the relationship between EMRCs and endometrial neoplastic lesions. This was carried out by (i) reviewing the morphological and immunohistochemical features of simple EMRCs associated with endometrial neoplasia, (ii) comparing EMRCs to the associated neoplasia and the background endometrium, and (iii) comparing neoplasia-associated EMRCs to neoplasia-unassociated EMRCs and to complex metaplastic lesions
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