HPV-negative Gastric Type Adenocarcinoma In Situ of the Cervix: A Spectrum of Rare Lesions Exhibiting Gastric and Intestinal Differentiation

Karen L. Talia, Colin J. R. Stewart, Brooke E. Howitt, Marisa R. Nucci, W. Glenn McCluggage

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37 Citations (Scopus)


In recent years, a number of benign and malignant cervical glandular lesions exhibiting gastric differentiation have been described but premalignant gastric-type lesions have not been well characterized. We report a series of 9 cases of a rare form of cervical adenocarcinoma in situ (AIS) distinguished by gastric and sometimes intestinal differentiation and lack of association with human papillomavirus (HPV) infection. The lesions occurred in women aged 25 to 73 years (mean age 51 y). All cases were located at (or just proximal to) the cervical transformation zone and there was extension to the lower uterine segment in 3 cases, 2 of which also involved the endometrium. In all cases, the normal cervical glandular architecture was largely preserved but in 5 cases there was a mild degree of increased intraglandular architectural complexity. The glandular epithelium ranged from almost purely gastric in type (4 cases) to mixed gastric and intestinal (5 cases), with varying proportions of intermixed goblet cells. In contrast to the basophilic cytoplasm of normal endocervical glands, the gastric-type epithelium was typically predominantly composed of cells with eosinophilic or pale pink cytoplasm, but conspicuous foamy or clear cell cytoplasm was present in some cases. Nuclear atypia was present in all cases but was considered low-grade in 8. High-grade features such as marked nuclear pleomorphism and hyperchromasia were evident in only 1 case. Mitotic activity and apoptotic bodies were present but both were noted to be less frequent than in usual type (HPV-related) AIS. Immunohistochemically, there was usually positive staining with CK 7 (7/7 cases) and MUC 6 (7/8 cases) and some cases were positive with CK 20 (3/7), CDX2 (5/9), PAX 8 (5/9) and CEA (2/6). Estrogen receptor and progesterone receptor were usually negative, although Estrogen receptor was positive in 3 of 9 cases. p16 was negative or exhibited mosaic-type staining (nonblock staining) in all cases and there was mutation-type p53 staining in 2 of 9 cases. HPV molecular testing was negative in all 4 cases tested. We believe this unusual subtype of AIS, which we term gastric-type AIS (gAIS), represents a precursor to gastric-type adenocarcinoma of the cervix and suggest that gAIS and so-called atypical lobular endocervical glandular hyperplasia are related entities within a spectrum of premalignant gastric-type lesions for which we propose the umbrella term gAIS. The malignant potential and optimal management of gAIS are currently unknown but in one of our cases a gastric-type adenocarcinoma developed 6 years after removal of a cervical polyp which contained gAIS. The introduction of HPV vaccination will result in a relative increase in incidence of premalignant and malignant cervical glandular lesions exhibiting gastric differentiation and these will not be detected by HPV-based screening programs.

Original languageEnglish
Pages (from-to)1023-1033
Number of pages11
JournalThe American Journal of Surgical Pathology
Issue number8
Publication statusPublished - Aug 2017
Externally publishedYes


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