Brain lymphomas of immunocompetent and immunocompromised patients: study of the association with Epstein-Barr virus

The Epstein-Barr virus (EBV) has been described in association with lymphomas of the central nervous system. To test if the association between EBV and central nervous system lymphomas was limited to patients with immunosuppression or whether the association also held for patients who were immunocompetent and to determine the true prevalence of any association, we studied 37 formalin-fixed, paraffin-embedded cases of central nervous system lymphomas occurring in immunocompromised and immunocompetent patients. EBV DNA-RNA in situ hybridization was performed using a 30-base biotinylated antisense oligonucleotide complementary to the EBER1 gene of EBV. Immunohistochemistry was also performed, using a monoclonal antibody to the latent membrane protein of EBV. The most common histologic subtypes of lymphoma were high grade immunoblastic (57%), diffuse large cell (22%), and small, noncleaved, non-Burkitt's (11%). Eighty-six percent of all tumors in our series were of B-cell lineage, as confirmed by CD20 expression, but only 37% of the primary tumors showed restricted CD20 expression. EBV RNA was identified in all or virtually all of the malignant lymphoid cells in 11 of the 37 cases (30%), including 10 primary brain lymphomas and one metastasis from systemic disease. Latent membrane protein expression was identified in 64% of the EBER1-positive cases. All 10 patients who had a history of immunosuppression had tumors that expressed EBV RNA. We confirm the strong association of EBV with brain lymphomas occurring in immunocompromised patients, whether due to AIDS or to the immunosuppression associated with organ transplantation. Our findings also demonstrate a low rate of EBV-positivity in immunocompetent patients.