B- and T-Lymphocyte Distribution in Benign and Malignant Lymphoepithelial Lesions of the Parotid Gland: Correlation with Epstein-Barr Virus Expression and a Proposed Mechanism of Malignant Transformation

Abstract

Epstein-Barr virus expression in malignant lymphoepithelial lesions (LEL) of the parotid gland has been well established. The virus is occasionally expressed in benign LEL, especially in immunocompromised hosts. The pathogenesis of the disease as it relates to virus expression and lymphocyte subsets has not been clearly defined. In this study, we attempted to identify B- and T-lymphocyte distribution in the lesions as it relates to EBV expression in LELs of the parotid gland. Formalin-fixed paraffin-embedded sections of 18 cases of LEL of the parotid gland were immunohistochemically tested for the distribution of B- and T-lymphocytes in the lesions, using the antibodies L-26 (CD 20) for B-lymphocytes and UCHL-1 (CD-45RO) for T-lymphocytes. The sections were also tested by in situ hybridization for EBV mRNA expression, using the EBER-1 probe specific for EBV-1 gene. The 18 lesions included seven malignant LEL, seven benign LEL and four benign lymphoepithelial cysts. All malignant LELs showed a high and diffuse level of epithelial expression of EBV mRNA. Of the 11 benign lesions, only one case showed focal epithelial expression of EBV mRNA. This was a case of benign LEL in an HIV-positive male. All the benign lesions, except that expressing EBV mRNA, showed a T-/B-lymphocyte ratio averaging 2:1. All cases expressing EBV mRNA, including the case of benign LEL in the HIV-positive patient, showed a T-/B-lymphocyte ratio averaging 1:3. Our findings suggest that a T-lymphocyte-mediated immune response may play an essential role in suppressing proliferation of EBV in benign LEL of the parotid gland. This immune mechanism may be significantly disturbed in the malignant lesions, leading to uncontrolled viral replication and carcinogenesis.