Revisiting the Role of Epstein-Barr Virus (EBV) in Gastric Cancer: A Case Study of EBV in Normal, Dysplastic, and Malignant Gastric Epithelium

Gastric carcinoma represents a significant global health challenge, with Epstein-Barr virus (EBV) playing a key role in certain subtypes of the disease. However, the exact mechanisms by which EBV contributes to gastric carcinogenesis remain poorly understood. This case report presents a 78-year-old female patient with a history of chronic atrophic gastritis, intestinal metaplasia, and multiple hyperplastic gastric polyps, exhibiting both low- and high-grade dysplasia, who ultimately developed multifocal intramucosal adenocarcinoma and underwent subtotal gastrectomy. The gastrectomy specimen revealed numerous polyps of varying sizes throughout the gastric mucosa. Epstein-Barr encoding region in-situ hybridization testing demonstrated EBV expression not only within the neoplastic gastric epithelium but also in the nonneoplastic epithelium and gastric polyps, an unusual finding further confirmed by polymerase chain reaction testing for EBV DNA. While the role of EBV in some gastric carcinomas is well established, the detection of EBV in nonneoplastic gastric epithelium highlights the possibility that latent EBV infection may contribute to gastric carcinogenesis, particularly in the setting of chronic gastritis and intestinal metaplasia. This case report underscores the need for a deeper understanding of EBV's potential impact on cellular processes, including genome-wide hypermethylation, and calls for further research into the mechanisms underlying EBV-associated gastric carcinoma.