Epstein-Barr Virus Infection Is Predictive of CNS Involvement in Systemic AIDS-Related Non-Hodgkin’s Lymphomas

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Abstract
PURPOSE: This study aimed at correlating Epstein-Barr virus (EBV) infection of systemic AIDS-related non-Hodgkin lymphomas (AIDS-NHL) with the development of a CNS localization of the tumor. PATIENTS AND METHODS: Demographic, epidemiologic, clinical, histologic, and virologic features were collected for all systemic AIDS-NHL patients included in the study (n = 50). Pathologic specimens were classified according to the working formulation for NHL and the Revised European-American Lymphoma classification. EBV infection in tumor tissue samples was studied by EBV small encoded RNA in situ hybridization; EBV-DNA detection in CSF was carried out by nested polymerase chain reaction using Epstein-Barr nuclear antigen-1–specific primers. In addition, selected EBV-positive lymphomas were subjected to a detailed characterization of EBV molecular heterogeneity. RESULTS: Eleven patients had a CNS involvement at some point during their clinical history (four at diagnosis and seven at relapse). Thirty patients (11 with CNS involvement and 19 without) harbored EBV infection of the tumor. Sensitivity, specificity, and positive and negative predictive values of EBV-DNA detection in CSF for CNS involvement by lymphoma were 90%, 100%, 100%, and 97.6%, respectively. Factors significantly predictive of CNS involvement were EBV infection of the tumor (P = .003), an extranodal disease at diagnosis other than CNS (P = .006), and a non-CNS relapse (P = .01). In four cases of CNS involvement, EBV-DNA in CSF preceded any other sign of disease by a mean of 35 days. CONCLUSION: These results show that EBV infection of the tumor clone significantly increases the risk of CNS involvement by systemic AIDS-NHL, without regard of specific molecular features. The detection of EBV-DNA in the CSF of AIDS-NHL patients may select cases with higher risk of CNS involvement and, therefore, may prove useful in the therapeutic stratification of these tumors.