Epstein-Barr virus detection in non-Hodgkin's lymphoma of the oral cavity: An immunocytochemical and in situ hybridization study

Objective. The purpose of this study was to histologically characterize a series of oral non-Hodgkin's lymphomas (NHLs) and to investigate latent and lytic Epstein-Barr virus (EBV) infection in these. Study design. The revised European-American Lymphoma classification system(41) was used to categorize 58 cases of oral NHL, which included 9 immunosuppression-related NHLs. EBV infection was determined by in situ hybridization for Epstein-Barr virus-encoded RNA and by immunohistochemistry for the EBV antigens latency membrane protein, Epstein-Barr nuclear antigen-2 (EBNA2) and Z EBV replication activator protein. Results. Most tumors were B-cell lymphomas (78%), but the proportion of T-cell lymphomas was surprisingly high (22%). The most common histologic subtypes were diffuse large B-cell lymphomas (45%), peripheral T-cell lymphomas (19%), and follicle center lymphomas (14%). Two thirds of the known immunosuppression-related NHLs were T-cell lymphomas. All of the immunosuppression-related tumors were EBV-infected, whereas the EBV infection rate in the NHLs of the remaining patients presumed to be immunocompetent was only 9%. Most EBV-positive tumors expressed neither of the latent antigens (ie, latency membrane protein and Epstein-Barr nuclear antigen-2), and coexpression of the 2 was observed only in immunosuppressed patients. Z EBV replication activator protein expression, which is indicative of replicative infection, occurred only in immunosuppressed individuals. Conclusions. Diffuse large B-cell lymphomas were the most common histologic subtype of oral NHLs, but T-cell lymphomas were relatively common and frequently occurred in states of immunosuppression. EBV may play a limited role in the initiation of lymphoma in the immunocompetent patient, but the virus may be of importance in progression of the disease in those patients with more aggressive tumors, as immunosuppression occurs.