The developing spectrum of gastric-type cervical glandular lesions

Abstract

Adenocarcinoma of the cervix is less common than squamous cell carcinoma, although its relative prevalence is increasing. Oncogenic (high-risk) human papillomavirus (HPV) infection is implicated in the development of approximately 90% of all cervical adenocarcinomas. Of the remaining non-HPV associated tumours, the most frequent is gastric-type adenocarcinoma (GAS), which is recognised by the World Health Organization as a form of mucinous adenocarcinoma of the cervix. Minimal deviation adenocarcinoma (MDA) of mucinous type (adenoma malignum) is considered an extremely well differentiated variant of GAS and is encompassed within the category of GAS. The concept of gastric-type cervical glandular lesions has emerged over recent decades and our understanding of the full spectrum of benign, premalignant and malignant lesions is still evolving. Established benign lesions, which are rare, include simple gastric metaplasia and lobular endocervical glandular hyperplasia (LEGH) (complex gastric metaplasia). Postulated premalignant lesions comprise atypical LEGH and gastric-type adenocarcinoma in situ (gAIS); these are probably related lesions for which the umbrella term 'gAIS' has been proposed. The term 'gastric-type' derives from the morphological resemblance of the glandular epithelium to that seen in the stomach and pancreaticobiliary tree; intestinal metaplasia with goblet cells and neuroendocrine cells are present in some cases. A gastric immunophenotype has been demonstrated using markers of pyloric gland mucin, MUC6 and HIK1083. Uncommonly, gastric-type cervical glandular lesions involve multiple sites in the female genital tract and it may be problematic to discern whether these represent independent synchronous or metastatic lesions. There is also an association between gastric-type cervical lesions and Peutz-Jeghers syndrome. Awareness of the spectrum of gastric-type lesions is important, as the diagnostic features of both gAIS and GAS, particularly well differentiated examples, may be subtle, and p16 immunohistochemistry is usually negative. GAS has a much poorer prognosis than HPV-associated cervical adenocarcinoma, with propensity for presentation at advanced stage and wide dissemination to unusual sites such as the ovary, omentum and peritoneum. Although uncommon, GAS is likely to increase in relative prevalence with the introduction of HPV vaccination and precursor lesions will not be detected by primary HPV-based screening programs.

Cervical adenocarcinoma: integration of HPV status, pattern of invasion, morphology and molecular markers into classification

“…14 Not infrequently, intestinal type goblet cells and neurosecretory granules can also be present, imparting a truly gastrointestinal morphology and phenotype. 15 GEA lacks the numerous floating mitoses and apoptotic bodies of HPVA adenocarcinomas, although mitotic figures can be seen at high magnification in small numbers. Overall, GEA morphologically resemble pancreatobiliary adenocarcinomas, and should be considered in the differential diagnosis when such a tumour is encountered in the cervix (Figure 3).…”

“…described the cytoplasm of these tumours as being more foamy than clear, similar to adenocarcinomas of the prostate and pancreas . Not infrequently, intestinal type goblet cells and neurosecretory granules can also be present, imparting a truly gastrointestinal morphology and phenotype . GEA lacks the numerous floating mitoses and apoptotic bodies of HPVA adenocarcinomas, although mitotic figures can be seen at high magnification in small numbers.…”

Cervical Adenocarcinomas: A Heterogeneous Group of Tumors With Variable Etiologies and Clinical Outcomes

“…Parallel to our increased understanding of invasive gastric type endocervical adenocarcinoma, our understanding of preinvasive endocervical lesions with gastric phenotype has also evolved. [41][42][43][44][45][46][47] Currently, it is postulated that GEA might develop from a series of precursor lesions that begin with gastric metaplasia at one end of the spectrum, and proceed through LEGH, atypical LEGH, gastric type adenocarcinoma in situ, and finally to invasive carcinoma. There are several previously described entities that now fall into the category of noninvasive gastric lesions in the cervix in addition to LEGH and atypical LEGH.…”

Immunohistochemical expression of HIK1083 and MUC6 in endometrial carcinomas

“…These aggressive, chemotherapy‐refractory, non‐human papillomavirus‐associated neoplasms may show a morphological spectrum, with appearances ranging from well‐differentiated tumours (minimal deviation adenocarcinoma) to poorly differentiated lesions that lack glandular architecture and show severe nuclear atypia. These tumours may be associated with a presumed non‐obligate precursor lesion termed lobular endocervical glandular hyperplasia, and recent literature has described gastric‐type adenocarcinoma in situ , further expanding the spectrum of precursor lesions for this aggressive subtype of EA …”