Cytogenetic and Molecular Characterization of IDH-Wildtype Glioblastomas and Grade 4 IDH-Mutant Astrocytomas with Unusual Histology. Issue 12 (18th October 2022)

• Record Type: Journal Article
• Authors: Ahrendsen, Jared T; Freund, Robert S; Hsu, Nancy; Bryke, Christine; Varma, Hemant
• Is Part Of: Journal of neuropathology and experimental neurology. Volume 81:Issue 12(2022)
• Page Start: 996
• Page End: 1001
• Publication Date: 2022-10-18
• Subjects: Genomic haploidization -- Glioblastoma -- Unusual histology; Neurology -- Diseases -- Periodicals; Neurology -- Diseases -- Physiopathology -- Periodicals; 616.8047
• DOI: 10.1093/jnen/nlac091
• Languages: English
• ISSNs: 0022-3069

Abstract

Abstract: Glioblastoma (GBM) is a highly heterogenous tumor. Though several well-defined histological patterns of GBMs are known, these are infrequent, and the molecular correlates of several of these histological patterns are not well understood. We identified 31 adult-type infiltrating grade 4 gliomas with unusual histology in our institutional archives from 2016 to 2020, including tumors with a preponderant component of giant cell (n = 15), gemistocytes (n = 6), spindle cells (n = 5), small cells (n = 3), and ependymoma-like features (n = 2). We performed molecular and cytogenetic profiles of IDH-wildtype GBMs with unusual histology and compared to 48 tumors with conventional histology. We found that the majority (85%) of giant cell GBM had increased numbers of whole chromosome loss and genomic haploidization compared to conventional GBMs and other variants. Furthermore, we identified a genetically confirmed GBM with prominent ependymal features, indicating that glial tumors with ependymal features should be considered in the differential diagnosis of GBM. We also identified 6 IDH-mutant grade 4 astrocytomas with unusual histology and similar molecular and cytogenetic profiles to conventional appearing grade 4 IDH-mutant astrocytomas. These findings emphasize the role of molecular/cytogenetic analyses in the diagnostic clarification of GBMs with unusual histological patterns, refine the classification of unusual GBMs, and potentially pave the way for personalized therapies.