Diffuse Gliomas of the Brainstem and Cerebellum in Adults Show Molecular Heterogeneity

Kathryn L. Eschbacher, Cristiane M. Ida, Derek R. Johnson, Mohammed A. Alvi, Sarah M. Jenkins, Michael W. Ruff, Panagiotis Kerezoudis, Bryan J. Neth, Romela M. Pasion, David J. Daniels, Sani H. Kizilbash, Aditya Raghunathan

Research output: Contribution to journalArticlepeer-review


Posterior fossa (PF) diffuse gliomas in pediatric patients frequently harbor the H3 K27M mutation. Among adults, PF diffuse gliomas are rare, with limited data regarding molecular features and clinical outcomes. We identified 28 adult PF diffuse glioma patients (17 males; median: 50 y, range: 19 to 78 y), with surgery performed at our institution (13 brainstem; 15 cerebellum). Histologic subtypes included anaplastic astrocytoma (n=21), glioblastoma (n=6), and diffuse astrocytoma (n=1). Immunohistochemistry was performed for H3 K27M (n=26), IDH1-R132H (n=28), and ATRX (n=28). A 150-gene neuro-oncology-targeted next-generation sequencing panel was attempted in 24/28, with sufficient informative material in 15 (51.7%). Tumors comprised 4 distinct groups: driver mutations in H3F3A (brainstem=4; cerebellum=2), IDH1 (brainstem=4; cerebellum=4), TERT promotor mutation (brainstem=0; cerebellum=3), and none of these (n=5), with the latter harboring mutations of TP53, PDGFRA, ATRX, NF1, and RB1. All TERT promoter-mutant cases were IDH-wild-type and arose within the cerebellum. To date, 20 patients have died of disease, with a median survival of 16.3 months, 1-year survival of 67.5%. Median survival within the subgroups included: H3F3A=16.4 months, IDH mutant=113.4 months, and TERT promoter mutant=12.9 months. These findings suggest that PF diffuse gliomas affecting adults show molecular heterogeneity, which may be associated with patient outcomes and possible response to therapy, and supports the utility of molecular testing in these tumors.

Original languageEnglish (US)
Pages (from-to)1082-1090
Number of pages9
JournalAmerican Journal of Surgical Pathology
Issue number8
StatePublished - Aug 2021


  • adult glioma
  • brainstem
  • cerebellum
  • diffuse glioma

ASJC Scopus subject areas

  • Anatomy
  • Surgery
  • Pathology and Forensic Medicine


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