Primary lymphoma of the central nervous system: just DLBCL or not?

Primary lymphoma of the central nervous system (PCNSL), defined as diffuse large B-cell lymphoma (DLBCL) confined to the central nervous system (CNS), has recently gained attention due to its increased incidence, which is mainly due to theAIDS epidemic and has been observed in some but not all series addressing immunocompetent patients.1 As morphology does not distinguish between PCNSL and extracerebral DLBCL, the question arose whether PCNSL constitutes a distinct lymphoma entity—as considered by the new WHO Classification of Tumors of Haematopoietic and Lymphoid Tissues. This is supported by the remarkably poorer prognosis of PCNSL compared with extracerebral DLBCL (Table S1, available on the Blood website; see the Supplemental Materials link at the top of the online article). This clinical observation provides the rationale for intense scientific efforts to elucidate the biology of PCNSL. Three major issues need to be addressed to understand the nature of PCNSL and to develop specific therapeutic regimens: (1) the histogenetic origin of the tumor cells; (2) the transforming events; and (3) the role of the microenvironment of the CNS.