Early detection of a MYD88 mutation with the GeneSoC® rapid PCR system in brain tumors facilitates preoperative and intraoperative diagnosis of primary central nervous system lymphoma

Primary central nervous system lymphoma (PCNSL) rapidly grows and is aggressive. Early diagnosis and initiation of the most appropriate chemotherapy are critical for an optimal outcome. The MYD88 L265P mutation is highly specific to PCNSL. We investigated the usefulness of early detection of the MYD88 L265P mutation using a microfluidic real-time PCR system (GeneSoC®) in tumor tissue and cerebrospinal fluid (CSF) for determination of the surgical plan and for possibly improved diagnostic accuracy during surgery. CSF obtained preoperatively and tumor tissue collected intraoperatively were analyzed using GeneSoC®. The reliability of data obtained from this system was evaluated by comparison with the final histopathological diagnosis of the tumor. In addition, fluorescence intensity at the 50-cycle point was measured to calculate the mutant-to-wild-type (M/W) ratio in the CSF, which served as a cut-off value of the M/W ratio in CSF and tumor tissues. Thirty-eight patients (21 men, 17 women; median age 70.5 years; range, 14–88 years) were included. Postoperative final pathological diagnoses based on paraffin-embedded sections were: 16 PCNSLs, 16 glioblastomas, 5 diffuse astrocytomas, and 1 adenocarcinoma. Cut-off values for gene-based diagnosis of PCNSL using the GeneSoC® system were determined based on the M/W ratios of 0.27 for tumor specimens and 0.05 for CSF. Sensitivity and specificity for these cut-off values in tumor tissues were 71.4% and 100%, respectively. Using these cut-off values, gene analysis with the GeneSoC® system demonstrated a sensitivity of 71.4%, specificity of 100%, and positive predictive value of 100% for intraoperative diagnosis using tumor tissue, and a sensitivity of 92.3%, specificity of 88.9%, and positive predictive value of 92.3% for CSF–based diagnosis. Rapid analysis of the MYD88 mutation by GeneSoC® may identify a potential marker for early diagnosis of PCNSL, which can facilitate intraoperative decision-making and earlier therapeutic intervention.