Advances in molecular pathobiology of PCNSL - towards clinical implementation of novel diagnostics and therapeutics

Primary central nervous system lymphoma (PCNSL) is a rare aggressive extranodal non-Hodgkin's lymphoma which outcomes remain poor despite therapeutic advances. Recent improvements in our understanding of the molecular diversity of aggressive diffuse large B cell lymphomas suggest that the biological refinement of PCNSL diagnostics may be enabled by an integrated multi-modal approach, augmenting clinical data with modern minimally-invasive liquid biopsy-based assays and multi-omic molecular profiling. Single cell sequencing and spatial imaging technologies dissecting the immune microenvironmental architecture of PCNSL are anticipated to further refine future diagnostics. Concurrently, several innovative strategies featuring immunomodulatory agents, oncogenic kinase inhibitors and immunotherapies including chimeric antigen receptor (CAR) T-cell therapy have emerged. In this review, we provide an update of recent advances in the understanding of the pathobiology of PCNSL focusing on clinically relevant molecular subclassifications, highlight emerging therapeutics, and discuss the translational roadmap to clinical implementation of next-generation diagnostic platforms based on novel technologies.