Gastric Pit Dysplasia in Adjacent Gastric Mucosa in 414 Gastric Cancers

Abstract

Despite wide acceptance of the chronic gastritis-intestinal metaplasia-dysplasia-carcinoma sequence, especially for intestinal-type gastric adenocarcinoma, the precise nature of the subtle precursor lesions of gastric cancer remains to be delineated. For example, pit dysplasia with surface foveolar maturation is not well defined, nor is its prevalence and biological characteristics well characterized. We have evaluated the surrounding gastric mucosa of 414 gastric cancers for the presence of gastric pit dysplasia. We investigated its relationship with various clinicopathological and immunophenotypic features of gastric adenocarcinoma, as well as the severity and extent of any surrounding gastritis and intestinal metaplasia. p53 expression and Ki-67 proliferation index were also evaluated. We have found that 21.0% (n=87) of gastric cancer cases showed pit dysplasia in adjacent gastric mucosa. Gastric cancers with pit dysplasia were significantly associated with older age, male sex, body/fundic location, and intestinal histologic type (P<0.05). Interestingly, gastric mucin-containing intestinal metaplasia (incomplete intestinal metaplasia) was highly associated with adenocarcinoma with pit dysplasia (P=0.000). In addition, MUC6 expression in gastric adenocarcinoma was associated with pit dysplasia (P=0.036). p53 overexpression and increased Ki-67 proliferation index were more evident in gastric pit dysplasia compared with adjacent gastric mucosa. We suggest that gastric pit dysplasia is an important candidate precursor of gastric adenocarcinoma and may represent another morphologic step in the pathogenesis of gastric adenocarcinoma, especially of intestinal type. More detailed prospective studies are needed to determine the precise significance of these findings.

Non-adenomatous forms of gastro-oesophageal epithelial dysplasia: an under-recognised entity?

“…Goblet cells may also be present. In this form of dysplasia, there is no surface epithelial involvement 18. In addition to these features, architectural abnormalities such as branching, budding, crowding and irregularly shaped glands are also identified.…”

“…These features are equivalent to low-grade and high-grade dysplasia without involvement of the surface epithelium. Pit dysplasia is found to be associated in 21% of the cases with intestinal-type gastric adenocarcinomas of the body/fundus with elevated morphology and immunoreactivity for MUC6 18. Pit dysplasia also shows p53 overexpression and increased Ki67 proliferation index 18…”

Gastric dysplasia: update and practical approach

“…However, subtle budding, branching, and crowding may be seen. 61,62 Pit dysplasia has been reported in association with older age, male sex, elevated morphology, and MUC6 expression. Importantly, these changes have been reported adjacent to bona fide neoplasia in 49%e72% of cases.…”

“…Importantly, these changes have been reported adjacent to bona fide neoplasia in 49%e72% of cases. 62,63 Use of immunohistochemistry…”

Negative pathology after endoscopic resection of gastric epithelial neoplasms: importance of pit dysplasia

“…GED is defined according to its architectural and cytological abnormalities along the full length of the pit and the surface epithelium, and is categorized into adenomatous (or intestinal), foveolar (or gastric), and hybrid types based on its morphological characteristics [9-11]. However, several recent studies reported pit or crypt dysplasia, which exhibited dysplasia or atypical glandular or crypt lesions with surface maturation in Barrett esophagus [12,13] and the stomach [14-16]. With respect to the discrepancy that can occur between forceps biopsy and ER specimens, pit dysplasia (PD) might be diagnosed as GED in forceps biopsy and as a negative pathology after ER, and this could explain why NPD is sometimes found in ER specimens.…”