The early recognition and diagnosis of neoplastic meningitis

The diagnosis and monitoring of leptomeningeal metastases (LM) from solid tumors are challenging, and the combination of neurological symptoms, MRI findings, and cerebrospinal fluid (CSF) cytology does not always allow to achieve a definitive diagnosis.

This review summarizes the studies that have investigated CSF liquid biopsy to improve the initial diagnosis of LM in case the CSF cytology is negative or only suspicious for tumor cells, and monitoring of tumor response following targeted therapies or immunotherapy. In this regard, the early detection of LM recurrence and the development of resistant mutations are critical issues. Moreover, the early identification of subgroups of patients with a higher risk of LM progression, as well as the correlation of LM burden with survival, are discussed.

There is an urgent need of prospective studies to monitor longitudinally LM using CSF liquid biopsy and investigate the role of CTC, ctDNA or novel assays. The optimal setting for the longitudinal CSF and blood collection can be clinical trials focused on the molecular diagnosis of LM as well as the response and monitoring following targeted agents.