Advances in liquid diagnostics for primary central nervous system lymphoma: a narrative review

Primary central nervous system lymphoma (PCNSL) is an aggressive malignancy, which is challenging to diagnose, often leading to delays in treatment initiation. The gold standard for diagnosis is brain biopsy, an invasive technique with a risk of neurologic compromise, and in some cases, biopsy may not be feasible or safe. Thus, there have been significant efforts to develop less invasive methods of diagnosis, particularly utilizing cerebrospinal fluid (CSF). Liquid diagnostics is an emerging area of research in many types of cancer, particularly central nervous system (CNS) tumors. Standard CSF cytology and flow cytometry lack sufficient sensitivity; however, the identification of specific biomarkers, particularly genomic variants such as the MYD88 L265P mutation, which can be detected in circulating tumor DNA (ctDNA), has demonstrated increasing promise as a diagnostic tool for PCNSL. Here, we review key advancements in the field of liquid diagnostics for PCNSL, and their potential to reform the approach to diagnosis.