Cytogenetic and Molecular Characterization of IDH-Wildtype Glioblastomas and Grade 4 IDH-Mutant Astrocytomas with Unusual Histology

Jared T. Ahrendsen, Robert S. Freund, Nancy Hsu, Christine Bryke, Hemant Varma*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish (US)
Pages (from-to)996-1001
Number of pages6
JournalJournal of neuropathology and experimental neurology
Issue number12
StatePublished - Dec 1 2022


  • Genomic haploidization
  • Glioblastoma
  • Unusual histology

ASJC Scopus subject areas

  • General Medicine


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