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Endometrial Gastric (Gastrointestinal)-type Mucinous Lesions

Report of a Series Illustrating the Spectrum of Benign and Malignant Lesions

Wong, Richard Wing-Cheuk FRCPA*; Ralte, Angela FRCPath; Grondin, Katherine MD, PhD; Talia, Karen L. FRCPA§; McCluggage, W. Glenn FRCPath

The American Journal of Surgical Pathology: September 26, 2019 - Volume Publish Ahead of Print - Issue - p
doi: 10.1097/PAS.0000000000001381
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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.

*Department of Clinical Pathology, Pamela Youde Nethersole Eastern Hospital, Chai Wan, Hong Kong

Department of Pathology, Queen Elizabeth Hospital, Gateshead Health NHS Foundation Trust, Gateshead

Department of Pathology, Belfast Health and Social Care Trust, Belfast, UK

Department of Pathology, CHU de Québec-Université Laval, Quebec City, QC, Canada

§VCS Pathology, VCS Foundation, Carlton, Vic., Australia

Conflicts of Interest and Source of Funding: The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article.

Correspondence: Richard Wing-Cheuk Wong, FRCPA, Department of Clinical Pathology, Pamela Youde Nethersole Eastern Hospital, 3 Lok Man Road, Chai Wan, Hong Kong (e-mail: wwc091@ha.org.hk).

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