Clonal Epstein-Barr virus in lymphoepithelioma-like carcinoma of the stomach: demonstration of viral genome by in situ hybridization and Southern blot analysis.

Lymphoepithelioma (LE), originally described in the nasopharynx, is an undifferentiated carcinoma with heavy lymphocytic infiltrate. The tumor is common in Southeast Asia, particularly in southern China, where the Epstein-Barr virus (EBV) association has been documented more consistently than in Western countries. Tumors histologically similar to LE have been described also in other anatomical sites, mostly of fore-gut origin, such as salivary gland, tonsil, lung, thymus, and more recently stomach. We are reporting a case of poorly differentiated gastric adenocarcinoma with marked lymphocytic infiltrate resembling LE (LE-like carcinoma) in a Chinese without evidence of nasopharyngeal carcinoma. In situ hybridization for EBV revealed that the tumor cells but not the lymphoid cells harbored the virus. Tumor cells both in syncytial and glandular areas were positive for EBV. By Southern blot analysis EBV was demonstrated in the DNA extracted from the tumor, while the adjacent normal gastric tissue was negative. Moreover, analysis of the EBV termini revealed a clonal episomal form of the virus. Our case further supports the hypothesis that EBV is associated with LE-like gastric carcinoma. It also strongly suggests that EBV infection has preceded, and thus most likely contributed to, the clonal expansion in this tumor.