P14.10.AMYD88L265P MUTATION IN THE DIAGNOSIS OF PRIMARY CENTRAL NERVOUS SYSTEM LYMPHOMA (PCNSL): CORRELATION BETWEEN TUMOUR TISSUE AND CEREBROSPINAL FLUID (CSF) BY LIQUID BIOPSY
Authors: Bruno F , Bertero L , Ferrero S , Cavallo F , Clerico M , Drandi D , Ferrante M , Mangherini L , Ricci A A , Manini C , Pronello E , Palmiero R , Pellerino A , Garbossa D , Soffietti R , Bruno B , Rudà R 
Published: September 2023

BACKGROUND

Primary Central Nervous System Lymphomas (PCNSLs) harbour MYD88L265P activating mutations in up to 70% of patients. Whether detection of MYD88L265P by liquid biopsy may be an accurate, non-invasive procedure for diagnosis and disease monitoring of PCNSL patients is a matter of debate. The aims of our study were to assess the feasibility of MYD88L265P detection in the tumour tissue, cerebrospinal fluid (CSF), and peripheral blood of patients with PCNSL, and to investigate its use as a potential disease biomarker. Patients and

METHODS

We prospectively collected data from patients who presented with suspected PCNSL at our Institution. After informed consent, CSF was obtained by lumbar puncture (LP) to analyse cytology, B cells immune-phenotype, and MYD88L265P mutation status. MYD88L265P mutation was analysed by droplet digital PCR in the CSF and peripheral blood of all patients, and in tumour tissue of those undergoing biopsy.

RESULTS

From May 2016 to March 2023, 29 patients were included. Median age was 71.0 years. 11 patients (37.9%) had multifocal lesions, and 13 (44.8%) had a positive brain FDG-PET. All patients underwent LP at diagnosis. Overall, MYD88L265P mutation was detected in the CSF and in the blood in 18 (62.1%) and 10 (34.5%) patients, respectively, whereas CSF cytology was informative in 8 patients (27.6%), and CSF immune-phenotype in 11 (37.9%). 18 patients (61.1%) underwent biopsy (the remaining did not due to high surgical risks), and MYD88L265 mutation was assessed in tumour tissue in 14/18 (77.8%) patients. Overall, 13/14 (92.8%) harboured the MYD88L265 mutation in the tumour tissue, of whom 8/13 (61.5%) and 6/13 (46.1%) had also positive CSF and blood, respectively. The only patient with MYD88- wildtype gene (MYD88wt) in the tumour tissue had also the MYD88wt gene in the CSF and blood. Interestingly, in 4/11 (36.4%) patients who did not undergo biopsy and with negative CSF cytology and immune-phenotype, the presence of the MYD88L265P mutation in the CSF was highly suggestive for the diagnosis of PCNSL. Multifocal lesions by FDG-PET and CSF positive cytology did not correlate with the presence of MYD88L265P mutation either in the CSF or in the blood. Patients with CSF MYD88L265P mutation tended to show positive CSF immune-phenotype positivity as compared to MYD88wt (50.0% vs 18.0%, p = 0.087). Overall, the presence of MYD88L265P mutation did not correlate with progression-free survival or overall survival.

CONCLUSION

In our series, the presence of the MYD88L265P mutation was found in the majority (92.8%) of tissue biopsies, and was confirmed in the CSF in 61.5% of patients. This suggests that liquid biopsy of CSF may be helpful for PCNSL at diagnosis. The study is still ongoing to confirm these data, and to clarify in a larger cohort of patients whether liquid biopsy of MYD88L265P mutation might have a role in monitoring response to treatments and predict the outcome.