Endometrial Gastric (Gastrointestinal)-type Mucinous Lesions

Abstract

With the recent elucidation of gastric-type lesions in the female genital tract (especially in the cervix), occasional cases of endometrial adenocarcinoma displaying gastric (gastrointestinal) differentiation have been reported, but they are currently not recognized as a distinct pathologic entity. We report 9 cases of endometrial mucinous lesions which exhibit gastric (gastrointestinal)-type features by morphology and immunohistochemistry, including 4 adenocarcinomas and 5 benign mucinous lesions, in patients aged 32 to 85. The adenocarcinomas showed gastric-type morphology in all 4 cases and goblet cells in 1, with a component of benign gastric-type mucinous glands in 1 case. Immunohistochemically, the adenocarcinomas were positive for CK7 (4/4), CEA (4/4), MUC6 (3/3), PAX8 (3/4), CK20 (2/4), CDX2 (2/4), and estrogen receptor (1/4). They were negative for Napsin A (0/3), with mutation-type p53 staining in 2/4 cases, block-type p16 positivity in 1/4, and scattered chromogranin-positive cells in 1/2. Targeted next-generation sequencing revealed nonsense mutation in RB1 gene for the case with block-positive p16. Follow-up was available in all adenocarcinoma cases and indicated aggressive behavior; 2 patients were dead of disease at follow-up of 7 months to 3 years, 1 was alive with progression at 9 months, and 1 was alive without disease at 7 months. The benign mucinous lesions (including the benign component in 1 adenocarcinoma) exhibited gastric-type morphologic features in 5/6 cases, goblet cells in 5/6, and Paneth-like neuroendocrine cells in 1/6. These benign mucinous lesions were associated with an endometrial polyp in 5/6 cases. Cytologic atypia was present in 2/6 cases and a lobular architecture resembling cervical lobular endocervical glandular hyperplasia in 4/6. Immunohistochemically, the benign mucinous lesions were positive for CK7 (5/5), CDX2 (5/6), estrogen receptor (4/5), MUC6 (4/5), CK20 (3/5), PAX8 (3/5), and CEA (2/4), with scattered chromogranin-positive cells in 4/4 cases; in all cases tested Napsin A was negative, p53 was wild-type and p16 was negative. We propose the term “endometrial gastric (gastrointestinal)-type adenocarcinoma” for this distinctive group of rare aggressive endometrial carcinomas. We believe that benign or atypical gastric (gastrointestinal)-type mucinous lesions are putative precursors for these adenocarcinomas, comparable to recognized premalignant gastric-type lesions in the cervix and the vagina. Future recognition and reporting of these gastric-type endometrial mucinous lesions will help delineate their pathogenesis and clinical significance.

New Pathological and Clinical Insights in Endometrial Cancer in View of the Updated ESGO/ESTRO/ESP Guidelines

“…GTEC is an uncommon mucinous neoplasm which resembles endocervical gastric-type adenocarcinoma. GTEC has also been termed “gastrointestinal-type” carcinoma, given the spectrum of gastric and intestinal differentiation that may be found in these lesions [ 74 ]. While mucinous carcinoma is now considered as a type of differentiation of endometrioid carcinoma, GTEC is considered as a separate entity [ 4 ].…”

Endometrial Carcinomas with Intestinal-Type Metaplasia/Differentiation: Does Mismatch Repair System Defects Matter? Case Report and Systematic Review of the Literature

“…In the case reported by us, the intestinal component of tumor showed intestinal-type morphology, while gastric-type tumor-differentiation and benign endometrial lesions with gastric-type metaplasia were not found. In addition, according to Wong et colleagues, a typical endometrioid component should be absent by definition in endometrial gastric (gastro-intestinal)-type adenocarcinomas, while it was present in in our case [8].…”

“…Endometrial carcinomas exhibiting gastric-type differentiation had been recently elucidated by Wong et al colleagues. They present overlapping morphological and clinical features (aggressive behavior) with gastric-type adenocarcinoma of the cervix and vagina; interestingly, one of the reported cases by the authors showed benign gastric-type mucinous glands in the background endometrium, reminiscent of in situ and lobular endocervical glandular hyperplasia (LEGH) and gastric-type vaginal adenosis [8]. In the case reported by us, the intestinal component of tumor showed intestinal-type morphology, while gastric-type tumor-differentiation and benign endometrial lesions with gastric-type metaplasia were not found.…”

“…Rare variants of mucinous differentiation were described in ECs, including gastric-type and intestinal-type [8,9]. Gastric (gastrointestinal)-type differentiation in malignant ECs has been recently elucidated by Wong and Colleagues who proposed diagnostic criteria for its recognition.…”

“…Gastric (gastrointestinal)-type differentiation in malignant ECs has been recently elucidated by Wong and Colleagues who proposed diagnostic criteria for its recognition. According to the authors, gastric (gastrointestinal)-type mucinous carcinomas represent a rare and aggressive subtype of EC with specific morphological and immunohistochemical features, including the absence of an endometrioid component [8].…”