Liquid Biopsy and Other Non-Invasive Diagnostic Measures in PCNSL

Simple Summary Primary central nervous system lymphoma (PCNSL) is an uncommon disease accounting for around 3% of primary CNS tumors. PCNSL exhibits aggressive clinical behavior and has an overall poor prognosis. The clinical presentation is variable, and there are no specific symptoms. Despite progress in radiographic neuroimaging, stereotactic brain biopsy remains obligatory for definitive diagnosis. Advanced standard diagnostics, including CSF cytology and flow cytometry, have limited sensitivity. Accordingly, there is an urgent need to improve the diagnostic tools for PCNSL, including novel non-invasive procedures. The aim of this review is to present and discuss modern methods that have the potential to contribute standard clinical diagnostics within the next few years. Primary central nervous system lymphoma is a rare but highly aggressive form of non-Hodgkin lymphoma that remains confined to the CNS neuroaxis. The diagnosis of PCNSL requires a high level of suspicion as clinical presentation varies depending on the involved CNS areas. Neurological symptoms and MRI findings may mimic gliomas, demyelinating lesions, or infectious and granulomatous diseases. Almost all PCNSL patients undergo invasive surgical procedures for definite diagnosis. Stereotactic biopsy is still the gold standard in achieving a diagnostic accuracy of 73-97%. Both the potential procedural morbidity and mortality, as well as the time to definite histopathologic diagnosis resulting in delays of treatment initiation, have to be considered. On the contrary, minimally invasive procedures, such as MRI, CSF cytology, and flow cytometry, still have limited value due to inferior specificity and sensitivity. Hence, novel diagnostic approaches, including mutation analyses (MYD88) in circulating tumor DNA (ctDNA) and the determination of microRNAs (miR-21, miR-19b, and miR-92) as well as cytokine levels (IL10 and IL6) in blood, cerebrospinal fluid (CSF), and vitreous fluid (VRF), move into the focus of investigation to facilitate the diagnosis of PCNSL. In this review, we outline the most promising approaches that are currently under clinical consideration.

Automated summary

Primary central nervous system lymphoma (PCNSL) is a rare and highly aggressive form of non-Hodgkin lymphoma that requires a high level of suspicion for diagnosis due to its variable clinical presentation. While stereotactic brain biopsy remains the gold standard for diagnosis, potential procedural risks and delays in treatment initiation need to be considered. Novel diagnostic approaches, such as mutation analyses in circulating tumor DNA and determination of microRNAs and cytokine levels in body fluids, are being investigated to improve PCNSL diagnosis.