Gastric Epithelial Carcinogenesis: From Atrophic Gastritis, Intestinal Metaplasia, and Dysplasia to Invasive Adenocarcinoma

Abstract

Atrophic gastritis and intestinal metaplasia, often in the setting of Helicobacter pylori infection, are associated with higher risk of gastric adenocarcinoma. According to the Correa model, the pathway of gastric carcinogenesis is triggered by chronic inflammation, which leads to atrophic gastritis, intestinal metaplasia, gastric dysplasia, and gastric carcinoma. Histopathologic assessment of atrophic gastritis suffers from low interobserver concordance, but staging with the Operative Link for Gastritis Assessment system effectively stratifies risk of gastric carcinoma. Intestinal metaplasia is a more highly reproducible diagnosis and can be classified with multiple systems including the Operative Link for Gastric Intestinal Metaplasia. Gastric epithelial dysplasia and invasive carcinoma are most commonly classified using the Vienna system among Western countries. The 2 tiers of dysplasia (low and high grade) are distinguished by severity of cytologic atypia, complexity of glandular architecture, loss of nuclear polarity, and degree of mitotic activity. However, grading of dysplasia on biopsy specimens suffers from high interobserver variability, as well as relatively poor correlation to Vienna system classification on subsequent resections. Intramucosal carcinoma is distinguished from high-grade dysplasia by neoplastic invasion into the lamina propria or muscularis mucosae. Grade of intraepithelial neoplasm and depth of invasive carcinoma remain central to guiding treatment decisions, while clinical approaches to surveillance and therapy continue to evolve.