Specific association of Epstein-Barr virus with lymphoepithelial carcinoma among tumors and tumorlike lesions of the salivary gland.

The Epstein-Barr virus (EBV)-encoded RNAs in situ localization procedure is a convenient, highly sensitive, and highly specific technique that is applicable to routinely fixed, paraffin-embedded tissue sections; this technique can be used for the study of the association and, hence, the possible causal role of EBV in tumors. This study was performed to elucidate whether EBV plays a role in the pathogenesis of tumors that arise in the salivary glands, since the salivary gland is known to be a reservoir for EBV replication. Cases that were selected included 61 examples of various benign and malignant neoplasms, as well as tumorlike conditions of the major and minor salivary glands. Only the five cases of lymphoepithelial carcinoma (so-called malignant lymphoepithelial lesion) and the single case of metastatic nasopharyngeal undifferentiated carcinoma showed staining with EBV-encoded RNAs, whereas negative findings were found in all of the other cases. In the cases with positive results, all of the neoplastic epithelial cells showed strong nuclear signals, but the lymphoid cells were negative. The consistent association of EBV with lymphoepithelial carcinoma of the salivary gland suggests that the virus probably plays a causal role in this tumor, at least in the Asian population, whereas there is no evidence for a causal role of EBV in other primary tumors of the salivary gland.