Application of WHO CNS Fifth Edition Criteria for Glioblastoma Multiforme Diagnosis: A single center study

Abstract

Abstract Introduction/Objective The fifth edition of the WHO classification of the tumors of the central nervous system (WHO CNS 5) published in 2021 introduced major changes that incorporate molecular diagnostics in CNS tumor classification along with histology and immunohistochemistry. Glioblastomas (GBM) were diagnosed based on the histologic features of diffuse and astrocytic glioma in adults, if there is microvascular proliferation and /or necrosis. Isocitrate dehydrogenase 1 (IDH) R132 H immunohistochemical stain expression and /or mutation analysis results were used to further classify GBMs as IDH mutant or IDH wild type. In WHO CNS 5 all IDH mutant diffuse astrocytic tumors are considered a single type (Astrocytoma, IDH mutant) and graded 2, 3, or 4. Glioblastoma IDH wild type is diagnosed in the setting of an IDH wild type diffuse and astrocytic glioma with microvascular proliferation or necrosis or TERT promoter mutation or EGFR gene amplification or +7/-10 chromosome copy number changes. In this study, we analyze how the change in diagnostic criterion would affect the classification of GBMs diagnosed in our institution retrospectively. Methods/Case Report The pathology database was searched for all diffuse gliomas diagnosed as GBM between 01/2019 and 12/2021. Age of the patient, gender, location of tumor, histologic features, IDH status and molecular alterations ( Onkosight Advanced solid tumor panel, 50 genes) were reviewed. Results (if a Case Study enter NA) A total of 74 adult high grade glial neoplasms were identified out of which 25 were GBMs. The age of the patients ranged from 40 to 87 years. 14 were men and 11 were females. All tumors had histologic features of GBM such as necrosis and microvascular proliferation. 24 (96%) tumors were IDH negative by immunohistochemistry and mutation analysis, and 1 (4%) was IDH strongly positive by immunohistochemistry. Molecular studies were not performed on this tumor. Conclusion 96% of GBMS diagnosed during the time period conformed to the WHO CNS 5 diagnostic criteria. The one IDH positive tumor would be reclassified as diffuse astrocytoma, IDH mutant, Grade 4. Like previous WHO classifications, WHO CNS 5 is a work in progress attempting to introduce new knowledge into the classification hoping to provide practical guidance to pathologists and neuro-oncologists and to benefit the patients with CNS tumors.