Rapid PCR Test Detects Lymphoma Signature in Brain Tumors During Surgery

A rapid genetic test that detects a mutation highly specific to primary central nervous system lymphoma (PCNSL) could help surgeons distinguish this aggressive brain cancer from other brain tumors while the patient is still on the operating table, according to a new study published in Acta Neurochirurgica.

PCNSL is a fast-growing and aggressive lymphoma that arises within the brain and other parts of the central nervous system. The MYD88 L265P mutation, found in tumor tissue and cell-free DNA in cerebrospinal fluid, is highly specific to PCNSL and therefore serves as a promising molecular fingerprint for the disease.

In the new study, researchers led by Akari Kusakawa and Akihiro Inoue evaluated whether the GeneSoC® system, a microfluidic real-time PCR platform, could detect this mutation quickly enough to be useful both before and during surgery. The team analyzed cerebrospinal fluid obtained preoperatively and tumor tissue collected intraoperatively, then compared the GeneSoC® results against the final histopathological diagnosis established after surgery on paraffin-embedded sections.

The study included 38 patients, 21 men and 17 women, with a median age of 70.5 years and an age range of 14 to 88 years. Their final postoperative diagnoses were 16 cases of PCNSL, 16 glioblastomas, 5 diffuse astrocytomas, and 1 adenocarcinoma, providing a realistic mix of tumors that surgeons must tell apart in practice.

To turn raw PCR output into a usable diagnostic rule, the researchers measured fluorescence intensity at the 50-cycle point and calculated a mutant-to-wild-type (M/W) ratio. From these measurements they derived cut-off values for gene-based diagnosis of PCNSL: 0.27 for tumor specimens and 0.05 for cerebrospinal fluid.

The performance of these thresholds differed between the two sample types. In tumor tissue, the GeneSoC® test showed a sensitivity of 71.4% and a specificity of 100% at the chosen cut-off. For intraoperative diagnosis using tumor tissue, the system achieved a sensitivity of 71.4%, a specificity of 100%, and a positive predictive value of 100%. In other words, when the test flagged a tumor as PCNSL-positive during surgery, that call was correct in every case in this cohort, although the test missed roughly three in ten PCNSL cases.

Diagnosis based on cerebrospinal fluid performed differently. Using the CSF cut-off value, gene analysis with the GeneSoC® system demonstrated a sensitivity of 92.3%, a specificity of 88.9%, and a positive predictive value of 92.3%.

The authors conclude that rapid analysis of the MYD88 mutation with GeneSoC® may serve as a potential marker for early diagnosis of PCNSL.

The study’s scope is worth keeping in perspective. It involved a single cohort of 38 patients with a defined mix of tumor types, and the reported sensitivity, specificity, and predictive values reflect performance against final paraffin-section pathology within that group. The published version is an early-release, peer-reviewed accepted manuscript that remains subject to further edits before the final Version of Record appears.

Even so, the findings point toward a practical shift in neurosurgical workflow: a rapid, mutation-based molecular test that returns results in time to matter. If validated more broadly, combining preoperative CSF testing with intraoperative tissue analysis could shorten the path from first suspicion of PCNSL to the chemotherapy that these patients urgently need.

Subject of Research: Rapid detection of the MYD88 L265P mutation for preoperative and intraoperative diagnosis of primary central nervous system lymphoma

Article Title: 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

Article References: Kusakawa, A., Inoue, A., Miyazaki, Y., Yano, H., Fujii, Y., Taniwaki, M., Ohnishi, T., Watanabe, H., Nakamura, Y., Ohtsuka, S., Shibagaki, K., Matsumoto, S., Shigekawa, S., & Kunieda, T. (2026). 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. Acta Neurochirurgica. https://doi.org/10.1007/s00701-026-07072-2

Image Credits: AI Generated

DOI: 10.1007/s00701-026-07072-2

Keywords: primary central nervous system lymphoma, MYD88 L265P mutation, GeneSoC, rapid PCR, cerebrospinal fluid, intraoperative diagnosis, brain tumors, glioblastoma, molecular diagnostics, neurosurgery, Early, detection