A variety of lymphomas can involve the central nervous system (CNS) at different phases of their evolution, both in immunocompetent and immunocompromised individuals. They represent a heterogeneous group of malignancies, with variable clinical and behavioral characteristics, and require different therapeutic approaches. In this chapter, the therapeutic management of these malignancies will be analyzed separately in three main entities: primary CNS lymphomas (PCNSL), secondary CNS lymphomas (SCNSL), and other, less common, forms of CNS lymphomas.

Histopathology

Primary diffuse large B-cell lymphoma (DLBCL) of the CNS shows diffuse parenchymal growth with dense cuffing in perivascular spaces. The latter is best appreciated towards the periphery of the tumor. Large areas of necrosis may be present, especially in those treated with steroids prior to biopsy. Towards the periphery of the tumor the neoplastic cells are often admixed with astrocyte gliosis. Cytologically, the neoplastic cells resemble those of DLBCL encountered elsewhere. Similarly, the immunophenotype of primary CNS DLBCL is similar to those outside the CNS and is positive for B-cell markers (CD20, CD79a, and PAX-5). Strong IRF4/MUM1 staining is seen in 90% of cases. CD10 is expressed by a minority of cases, while many express BCL-6. BCL-2 is often expressed. As these lymphomas (by definition) occur in immunocompetent patients, Epstein–Barr virus (EBV) is generally absent.

Many lymphomas involving the CNS in immunocompromised patients are EBV-positive and show features of DLBCL, many with an immunoblastic morphology. Burkitt lymphoma, a common lymphoma in the immunocompromised patient, may involve the CNS.