Case Report: Concordance of cerebrospinal fluid-derived circulating tumor DNA with tumor tissue in spinal glioblastoma associated with Lynch syndrome

Abstract

Background Spinal glioblastoma (GBM) is an exceptionally rare entity and poses significant diagnostic challenges due to a substantial risk of neurological morbidity with surgical biopsy. Tissue-based analyses are frequently limited by sampling constraints and tumor heterogeneity. Conventional diagnostic modalities, including MRI and cerebrospinal fluid (CSF) cytology, often lack specificity and sensitivity. Commercially available CSF liquid biopsy platforms offer a minimally invasive approach for detecting tumor-derived cell-free DNA (cfDNA) to enable genomic profiling. Methods We report a case of a 37-year-old male with spinal GBM who underwent prospective CSF cfDNA analysis using Belay Summit™ and GTC Liquid Trace™, yielding a provisional diagnosis of GBM and raising suspicion for Lynch syndrome. Results Subsequent tissue-based molecular profiling with Tempus™ confirmed the diagnosis of GBM, while germline testing via Ambry Genetics™ established Lynch syndrome. Conclusion Based on the findings of mismatch repair deficiency and Lynch syndrome, the decision to proceed with immunotherapy was made. CSF cfDNA is a promising ancillary tool for guiding therapy in difficult-to-biopsy cases.