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.
So-called gastric-type adenocarcinoma and related premalignant lesions have been characterized in the cervix, but similar lesions are not widely recognized in the vagina. We report a series of 11 vaginal glandular lesions exhibiting gastric differentiation, comprising 5 cases of adenocarcinoma and 6 of adenosis. All cases occurred in adults (aged 33 to 69) with no known history of diethylstilboestrol exposure. The vaginal adenocarcinomas exhibited morphologic features identical to gastric-type adenocarcinoma of the cervix, but 1 case additionally demonstrated basaloid and sarcomatoid components, which have not been previously reported in cervical gastric-type adenocarcinoma. Immunohistochemically, the adenocarcinomas were positive for MUC6 (4/5), PAX8 (3/5), CK7 (5/5), CK20 (1/5), CDX2 (5/5), CA19.9 (5/5), CEA (4/5), CA125 (5/5), and hepatocyte nuclear factor 1β (5/5). p16, estrogen receptor, and Napsin A were negative in all cases tested, whereas p53 exhibited mutation-type staining in 3/5 cases. In all 5 adenocarcinomas, a component of adenosis with benign or atypical nuclear features was identified; the adenosis displayed gastric morphology in 4 cases and tuboendometrial morphology in 1. The 6 cases of pure vaginal adenosis (without associated adenocarcinoma) all contained gastric-type mucinous glands together with tuboendometrial glands in 2 cases. There was focal intestinal differentiation with goblet cells in all 6 cases and neuroendocrine cells with eosinophilic granules in 3. Cytologic atypia was observed in 4/6 cases of pure vaginal adenosis. Immunohistochemically, the gastric-type adenosis (10 cases) was positive for MUC6 (10/10), estrogen receptor (5/10), PAX8 (8/10), CK7 (9/9), CK20 (2/9), CDX2 (5/9), CA19.9 (8/9), CEA (6/9), CA125 (6/9), hepatocyte nuclear factor 1β (10/10), and Napsin A (1/10). p53 exhibited wild-type immunoreactivity in all 10 cases, whereas p16 was negative in all cases tested. Scattered individual chromogranin-positive cells were present in all 5 cases of pure adenosis tested. Follow-up was available in 4 of the adenocarcinoma cases, with 3 patients dead of disease within 1 to 3 years and 1 patient alive with disease at 1 year. The morphologic and immunohistochemical findings in our study suggest a close relationship between vaginal gastric-type adenocarcinoma and adenosis exhibiting gastric differentiation. This probably represents a distinct pathway of vaginal gastric-type carcinogenesis analogous to that occurring in the cervix. We propose that gastric-type adenocarcinoma be recognized as a distinct histologic subtype of vaginal adenocarcinoma while vaginal adenosis of gastric-type represents a novel subtype of adenosis that requires further study to clarify its biological potential.
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