Clonal Epstein-Barr virus in lymphoepithelioma-like carcinoma of the lung

Lymphoepithelioma of the nasopharynx is an undifferentiated carcinoma with a prominent lymphoid infiltrate. A consistent association with Epstein-Barr virus (EBV) has been demonstrated over the years by a variety of methods. More recently, undifferentiated carcinomas with a similar morphology have been described in other anatomical locations, often of foregut origin. However, for lymphoepithelioma-like carcinoma, the association with EBV has been more tenuous, especially in Western countries. Interestingly, these tumors have shown a geographic distribution similar to nasopharyngeal lymphoepithelioma, with relatively high frequency of EBV positive cases in Asian patients. We report five cases of lymphoepithelioma-like carcinoma arising in the lung. In situ hybridization revealed the presence of EBV in all cases with localization to the epithelial cells only. Southern-blot analysis from two cases revealed the presence of clonal episomal EBV in the tumor tissue. These findings further support the hypothesis that EBV is also associated with lymphoepithelioma-like lung carcinomas and suggest that EBV infection has preceded the clonal expansion of the tumor.