DNA Methylation Profiling Confirms a Challenging Glioblastoma, Atypical Mesenchymal Type Which Mimics Intracranial Mesenchymal Tumor

Abstract

Abstract Introduction/Objective Brain tumors exhibit distinct DNA methylation patterns that reflect their cellular origin, molecular subtype, and clinical behavior. DNA methylation signatures provide valuable insights into tumor heterogeneity, evolution, and treatment response, guiding personalized therapeutic strategies. Our case, glioblastoma, atypical mesenchymal type confirmed by DNA methylation profile and it reflects the clonal evolution of the glioblastoma metaplasia with minimal glial component which was histologically challenging. Methods/Case Report A 56-year-old gentleman presented with headaches. MRI brain demonstrated a heterogeneous enhancing mass with areas of central necrosis in the left temporal lobe, measuring approximately 49 x 34 mm, with surrounding T2 FLAIR hyperintensity extending into the left basal ganglia, causing compression of the left lateral ventricle and uncal herniation. He underwent left-sided craniotomy for tumor resection. Microscopic examination revealed hypercellular spindle cell neoplasm, forming fascicles. Brisk mitotic activity and geographic necrosis were evident. GFAP highlighted narrow margins of the tumor which could represent the entrapped glial tissue. CD99 stained the tumor cells, Other immunohistochemical stains for spindle cell work up, like S100, EMA, PR STAT6 and desmin were all negative. A diagnosis of intracranial mesenchymal tumor /sarcoma was considered. Methylation profiling results showed class calibrated scores of 0.9741, compatible with Glioblastoma, IDH-wildtype, atypical mesenchymal type with a cytogenetic profile including gain of chromosome 7 (including EGFR) and loss of chromosome 10 (including PTEN), and loss of CDKN2A/B. Results (if a Case Study enter NA) NA Conclusion Although histopathological examination and immunohistochemical study are fundamental in diagnosing brain tumors, the rapid development of cytogenetic and molecular diagnostic modalities has significantly contributed to diagnostic accuracy and the potential for targeted treatment. Particularly, DNA methylation profiling has proven valuable in diagnosing morphologically challenging cases with prognostic value. Eventually, DNA methylation profiling will be adopted as a major cancer diagnostic criterion and will become a standard procedure performed at major academic centers.