Treatment initiation by positive liquid biopsy alone in primary central nervous system lymphoma: A retrospective analysis of a multi-institutional study

Abstract Background The gold standard for the diagnosis of primary central nervous system lymphoma (PCNSL) remains surgical biopsy, but it carries the risk of complications, and operability depends on the size and location of the lesion or the patient’s condition. Previously, we have reported the reliable detection of MYD88 L265P-mutant droplets in cerebrospinal fluid (CSF) cell-free DNA (cfDNA) of PCNSL using droplet digital PCR (ddPCR). In the present study, we conducted a multi-institutional study to diagnose and initiate treatment for PCNSL by liquid biopsy alone without a surgical biopsy. Methods We analyzed 10 patients from 5 institutions who were deemed difficult to biopsy surgically and were subsequently treated based on the detection of MYD88 L265P-mutant droplets in their CSF cfDNA. CSF was obtained by lumbar puncture at each institution, cfDNA was extracted at Niigata University, and ddPCR was performed to detect MYD88 L265P-mutant droplets. Results Surgical biopsy was not performed in 8 patients because the lesions were located in deep locations, such as the brainstem, and in 2 patients because of low performance status and/or advanced age. MYD88 L265P-mutant droplets were detected in all cases. Treatment response was observed in all cases. In a patient with chronic renal failure, liquid biopsy was helpful to rule out possible relapse. Conclusions Liquid biopsy for the diagnosis of PCNSL has the potential to replace surgical biopsy with a less-invasive method and early diagnosis, leading to early treatment and possibly better outcomes. Further large-scale studies are warranted to establish the reliability of this approach.