IMMUNOPHENOTYPE: Primary CNS lymphomas (PCNSL) are usually diffuse large B-cell type and express pan B-cell markers such as CD20, CD22, CD79a, and PAX5, and monotypic immunoglobulin (usually IgM). Pan T-cell markers are generally negative in the tumor and show non-neoplastic reactive T-cells in the background (as depicted here with CD3 immunostain). HIV-associated PCNSLs are immunoblastic type (>90% immunoblasts) and are positive for BCL2, latent membrane protein (LMP-1), and Epstein-Barr nuclear antigen and negative for BCL6. GENETICS: Immunoglobulin heavy- and light-chain genes are clonally rearranged in PCNSL. Majority of the PCNSLs in immunocompromised patients are positive for EBV-coded small RNA (EBER) by in-situ hybridization. Image courtesy of: Dr. Luciano de Souza Queiroz, Dept. of Pathology, Faculty of Medical Sciences, State University of Campinas (UNICAMP), Campinas, São Paulo State, BRAZIL.