Lack of IDH1 mutation in astroblastomas suggests putative origin from ependymoglial cells?

Abstract

Astroblastomas are extremely rare neuroepithelial tumors of uncertain histogenesis, affecting children and young adults, and constitute a new addition to the WHO 2000 classification of CNS tumors. We report the largest series of nine cases diagnosed in a single institute over the last 13 years and review published literature. Mean age at presentation was 12.8 years (range: 22 months to 27years). Seven out of nine cases were supratentorial (frontal/frontoparietal - three, parieto-occipital - three, parafalcine - one), one was intraventricular and another was optochaismatic/suprasellar. Five cases were high grade (anaplastic) astroblastomas with Ki-67 labeling index of 8-10%. Immunohistochemical and ultrastructural evidence suggesting origin from cells intermediate between ependymocytes and astrocytes is presented. The histogenetic origin of these tumors remains speculative. But the lack of Isocitrate dehydrogenase 1 (IDH1) mutation as detected by immunohistochemistry in this study, which is similar to ependymomas supports putative origin from ependymoglial cells. Out of the nine cases, recurrence was noted in one case, 12 months after gross total resection with progression to high grade in the recurrent tumor. There is no recommended treatment protocol due to the rarity of this entity and prognostic factors are yet to be established.

Astroblastoma: a distinct tumor entity characterized by alterations of the X chromosome and MN1 rearrangement

“…Because whole genome sequencing or RNA sequencing failed to show MN1 rearrangement, genetic aberrations of ependymomas seem to be different from the data shown in the present study . Therefore, astroblastoma is considered to be distinct from ependymoma in both clinicopathologic and genetic aspects, but there may be some relationship in cellular differentiation and histogenesis .…”

“…The clinical features of the eight cases collected based on the current criteria of astroblastoma were similar to those of the cases reported by Bonnin and Rubinstein (5), Brat et al (7), and others (2,17,19,34). All patients, but one, were children or young adults.…”

“…The chromosomal alterations Brat et al . reported were 20q gain (4 of 7), 19 gain , 9q loss , and 10 loss . Those of Jay et al .…”

“…Their ages ranged from 5 to 60 years (median, 14.5 years; mean, 20.9 years). All tumors affected cerebral hemispheres: frontal lobe (5 cases), occipital , and parietal . The representative symptoms were headache, convulsions, nausea, vomiting, and paralyses.…”

Multimodal molecular analysis of astroblastoma enables reclassification of most cases into more specific molecular entities

“…One next-generation sequencing study of three cases identified mutations in a few genes known to be altered in low-grade gliomas, including BCOR, BCORL1, ERBB3, MYB and ATM, but no recurrent mutations were seen (5). Importantly, this study did not identify mutations in genes that are commonly altered in infiltrating astrocytoma, such as IDH1, ATRX or TP53, thus differentiating astroblastoma genetically from diffuse gliomas and validating previous immunohistochemical findings (2). In another immunohistochemical study of 28 cases, Lehman et al identified BRAF p.V600E mutant protein in 38% of cases, raising the possibility of genetic overlap between astroblastoma and other circumscribed glial neoplasms driven by MAPK pathway alterations such as pleomorphic xanthoastrocytoma, ganglioglioma and pilocytic astrocytoma (19).…”