Pathology of Epstein-Barr virus-associated gastric carcinoma and its relationship to prognosis

Among Epstein-Barr virus (EBV)-associated neoplasms, EBV-associated gastric carcinoma (EBVaGC) is the most common tumor worldwide. In contrast to the predominant site of occurrence of EBV-negative gastric carcinoma in the antrum, EBVaGC occurs most frequently in the proximal stomach, including the cardia, fundus and body. Microscopically, EBVaGC can be subclassified into three histological subtypes according to the host cellular immune responses: lymphoepithelioma-like carcinoma, carcinoma with Crohn's disease-like lymphoid reaction, and conventional-type adenocarcinoma. Recent studies have shown that patients with the lymphoepithelioma-like carcinoma subtype of EBVaGC have the best overall and disease-free survival, followed by Crohn's disease-like reactions, which in turn have better survival than patients with conventional-type adenocarcinoma. Histologic subclassifications of EBVaGCs are based on the differing degree and pattern of inflammatory response and the extent of desmoplasia. Because these subclassifications appear to be a powerful prognostic parameter, further research into the underlying mechanisms of the cellular immune reaction in these pathologic subtypes of EBVaGCs may play a key role in understanding the innate immune response of patients with this highly aggressive carcinoma.