Morphological characteristics of Epstein-Barr virus-related early gastric carcinoma: a case-control study

A strong association between Epstein-Barr virus (EBV) and gastric carcinoma has been demonstrated by the uniform presence of EBV in all carcinoma cells, episomal monoclonality, elevated antibodies, and a unique 'lace pattern' in the mucosa. The present study is concerned with morphological changes of intramucosal carcinoma and submucosal invasion, reactive lymphocytes, and with atrophy and intestinal metaplasia of the surrounding mucosa. Fifty-two EBV-positive early gastric carcinomas were matched by age, sex, and site of tumor with 103 EBV-negative carcinomas, all of which had previously been examined by serial cut-sections of the tumors and surrounding mucosa. Epstein-Barr virus involvement was strongly associated with lace pattern morphology as demonstrated previously, and with lymphocytic infiltration in and around the tumor nests in the mucosa. The infiltrating lymphocytes in the tumor nests were mainly composed of CD8+ T lymphocytes. Lymphoepithelioma (LE)-like carcinoma, was observed in the submucosal portions of 13 of 31 EBV-positive cases with such invasions, including 12 of 29 with lace pattern morphology in the mucosa. The majority of the surrounding gastric mucosa showed moderate to severe atrophy with marked depletion of parietal cells, complete-type intestinal metaplasia in EBV-positive cases, and Helicobacter pylori (H. pylori) infection for both EBV-positive and EBV-negative cases. It is suggested that EBV infection may occur in the atrophic gastric epithelial cells associated with intestinal metaplasia and H. pylori infection, leading to the development of carcinoma. Such cancers show lace pattern and marked lymphocytic reaction in the mucosa, with some tendency for histological change and lymphocytic reaction during the invasive process without lymph node metastasis.