Morphological and molecular features of astroblastoma, including BRAFV600E mutations, suggest an ontological relationship to other cortical-based gliomas of children and young adults
Open Access
- 14 July 2016
- journal article
- research article
- Published by Oxford University Press (OUP) in Neuro-Oncology
- Vol. 19 (1), 31-42
- https://doi.org/10.1093/neuonc/now118
Abstract
Astroblastomas (ABs) are rare glial tumors showing overlapping features with astrocytomas, ependymomas, and sometimes other glial neoplasms, and may be challenging to diagnose. We examined clinical, histopathological, and molecular features in 28 archival formalin-fixed, paraffin-embedded AB cases and performed survival analyses using Cox proportional hazards and Kaplan–Meier methods. Unlike ependymomas and angiocentric gliomas, ABs demonstrate abundant distinctive astroblastic pseudorosettes and are usually Olig2 immunopositive. They also frequently exhibit rhabdoid cells, multinucleated cells, and eosinophilic granular material. They retain immunoreactivity to alpha thalassemia/mental retardation syndrome X-linked, are immunonegative to isocitrate dehydrogenase-1 R132H mutation, and only occasionally show MGMT promoter hypermethylation differentiating them from many diffuse gliomas. Like pleomorphic xanthoastrocytoma, ganglioglioma, supratentorial pilocytic astrocytoma, and other predominantly cortical-based glial tumors, ABs often harbor the BRAFV600E mutation, present in 38% of cases tested (n = 21), further distinguishing those tumors from ependymomas and angiocentric gliomas. Factors correlating with longer patient survival included age less than 30 years, female gender, absent BRAFV600E, and mitotic index less than 5 mitoses/10 high-power fields; however, only the latter was significant by Cox and Kaplan–Meier analyses (n = 24; P = .024 and .012, respectively). This mitotic cutoff is therefore currently the best criterion to stratify tumors into low-grade ABs and higher-grade anaplastic ABs. In addition to their own characteristic histological features, ABs share some molecular and histological findings with other, possibly ontologically related, cortical-based gliomas of mostly children and young adults. Importantly, the presence of BRAFV600E mutations in a subset of ABs suggests potential clinical utility of targeted anti-BRAF therapy.Keywords
Funding Information
- NIH (K08 NS45077, R01 NS081125)
This publication has 50 references indexed in Scilit:
- The Prognostic Value of BRAF Mutation in Colorectal Cancer and Melanoma: A Systematic Review and Meta-AnalysisPLOS ONE, 2012
- Clinical features and post-surgical outcome of patients with astroblastomaJournal of Clinical Neuroscience, 2011
- Outcomes of Malignant CNS Ependymomas: An Examination of 2408 Cases Through the Surveillance, Epidemiology, and End Results (SEER) Database (1973–2005)Journal of Surgical Research, 2009
- IDH1 Mutations as Molecular Signature and Predictive Factor of Secondary GlioblastomasClinical Cancer Research, 2009
- Brainstem astroblastoma: a case report and review of the literatureSurgical Neurology, 2008
- Angiocentric Neuroepithelial Tumor (ANET): A New Epilepsy‐Related Clinicopathological Entity with Distinctive MRIBrain Pathology, 2005
- Medulloblastomas With Favorable Versus Unfavorable Histology: How Many Small Blue Cell Tumor Types are There in the Brain?Advances in Anatomic Pathology, 2002
- Infiltrative Astrocytomas With Granular Cell Features (Granular Cell Astrocytomas)The American Journal of Surgical Pathology, 2002
- Divergent Differentiation in Pleomorphic XanthoastrocytomaThe American Journal of Surgical Pathology, 1996
- ASTROBLASTOMAS OF THE BRAIN1Acta Psychiatrica Scandinavica, 1930