Narrative review: biomarkers, a hope towards early diagnosis in primary CNS lymphoma

Primary central nervous system lymphoma (PCNSL) arises in the central nervous system and remains confined into the brain, an organ with singular biological and immunological characteristics, where the structured lymphoid tissue is not normally present. Early diagnosis represents one of the main tasks for clinicians approaching PCNSL patients, because it would allow both a reduction of the risk of cerebral damage due to the presence of lymphomatous tissue and a limited time of use of steroid therapy, that raises a higher risk of immunosuppression. To date, diagnostic stereotactic biopsy is required in the most of the cases with suspicious PCNSL, however the use of less invasive and alternative diagnostic procedures would limit the surgery related-risks and morbidities, that are described in 8% of the cases. The PCNSL molecular profile and biological characteristics are poorly known, and the researchers’ efforts have been focused on studying these aspects only in the last years. In particular, the progressive knowledge on the genomic and molecular profile of lymphomatous cells and their microenvironment have helped to better characterize the pathophysiology of PCNSL. However, their diagnostic predictive and prognostic roles still remain unclear and have not yet been applied into the clinical practice. In this review we have reported the important advances on the knowledge of the main biomarkers detectable on biological fluids [blood, cerebrospinal fluid (CSF) and vitreous humor] that include genomic fragments, cytokines and their receptors, surface molecules. These biomarkers demonstrated a potential role in the early diagnosis of PCNSL, particularly when they are detected in combination, and some of them showed to have a prognostic value and a role in monitoring