Primary central nervous system lymphoma: advances in its pathogenesis, molecular markers and targeted therapies

Purpose of reviewPrimary central nervous system lymphoma (PCNSL) is a rare subtype of diffuse large B-cell lymphoma (DLBCL) located in the CNS with a less favorable prognosis. Recent information addressing the disease molecular heterogeneity is paving the way for tailored treatment strategies. This article reviews current work on the pathogenesis of the disease, potential biomarkers, and treatments.Recent findingsPrevious molecular classifications of PCNSL, built on DLBCL heterogeneity, did not properly address its intrinsic variability. Recent evidence has shown the existence of four different molecular PCNSL subtypes with associated multiomic characteristics, including prognostic relevance. Several studies have identified the tumor microenvironment (TME) as a driving prognostic factor in PCNSL. Therapy efforts continue mainly into targeting either the NF-kappa beta (nuclear factor kappa-light-chain enhancer of activated B cells) pathway or modulating the TME through immunomodulatory drugs (lenalidomide) or immunotherapy (antiprogrammed cell death 1/programmed cell death 1 ligand 1).Despite the increasing understanding of PCNSL pathogenesis with recent studies, future efforts are still needed to yield diagnostic biomarkers to detect either PCNSL or its molecular subtypes and hence ease routine clinical use.

Automated summary

Recent studies have revealed four distinct molecular subtypes of PCNSL with prognostic relevance, highlighting the importance of the tumor microenvironment (TME) as a driving prognostic factor. Therapeutic efforts are focused on targeting the NF-kappa beta pathway or modulating the TME through immunomodulatory drugs or immunotherapy. Further research is needed to develop diagnostic biomarkers for detecting PCNSL and its molecular subtypes in routine clinical use.