The major consideration in this category is primary brain lymphoma. These B-cell lymphomas arise in the CNS, usually are multicentric (at least microscopically), and rarely metastasize systemically. Characteristically, they develop late in HIV-1 infection when blood CD4+ lymphocytes are low, i.e., in the same setting as major opportunistic infections. Indeed, the tumor cells are nearly always positive for Epstein-Barr virus (EBV), which likely plays an important role in their genesis.

Recently, this association has been exploited diagnostically using PCR DNA amplification to detect EBV sequences in CSF. Radiation therapy usually results in tumor regression, and some patients do well, although more generally the prognosis is poor, principally because other complications develop; the role of chemotherapy is uncertain, but aggressive treatment is often not possible because of reduced bone marrow reserves. Systemic lymphoma can also spread to the CNS, although usually to the leptomeninges rather than brain parenchyma.

Although Kaposi’s sarcoma has been reported to metastasize to brain, this is exceedingly rare.