Epstein‐Barr virus‐associated undifferentiated carcinoma with lymphoid stroma of the salivary gland in Japanese patients: Comparison with benign lymphoepithelial lesion

BACKGROUND Undifferentiated carcinoma with lymphoid stroma (UCLS) arising in the salivary gland is a rare tumor, except for its geographic concentration among Eskimo and southern Chinese populations. Five cases of salivary gland UCLS in Japanese patients are presented here and compared with benign lymphoepithelial lesions (BLELs) with regard to their association with Epstein-Barr virus (EBV), p53 expression, and cell proliferative activity. METHODS Formalin fixed, paraffin embedded sections of 5 cases of UCLS selected from 1676 patients with primary tumors of the major salivary gland and 7 cases of BLEL were examined using in situ hybridization for EBV-encoded RNAs (EBERs), along with immunostaining for p53 and Ki-67 (MIB-1). RESULTS The incidence of UCLS was 0.3% among patients with major salivary gland tumors. EBER hybridization signals were strongly expressed in most of the neoplastic cells in all five cases of UCLS, whereas there was no signal in BLEL and surrounding nontumorous salivary gland tissues. All cases of UCLS showed strongly positive immunostaining for p53 in the tumor cell nuclei. By contrast, only one case of BLEL was positively stained for p53 in dysplastic epimyoepithelial cells, which showed focal immunostaining. Cell proliferative activity assessed using the Ki-67 labeling index was significantly higher in tumor cells of UCLS than in epimyoepithelial cells of BLEL. CONCLUSIONS UCLS of the salivary gland is an extremely rare tumor in Japanese patients characterized by consistent association with EBV. Distinction between BLEL and UCLS is possible by examining for evidence of EBV infection, expression of p53, and cell proliferative activity. Cancer 1996;78:695-703.