Morphological and molecular features of astroblastoma, includingBRAFV600Emutations, suggest an ontological relationship to other cortical-based gliomas of children and young adults

Abstract

Background. Astroblastomas (ABs) are rare glial tumors showing overlapping features with astrocytomas, ependymomas, and sometimes other glial neoplasms, and may be challenging to diagnose. Methods. We examined clinical, histopathological, and molecular features in 28 archival formalin-fixed, paraffinembedded AB cases and performed survival analyses using Cox proportional hazards and Kaplan-Meier methods. Results. 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 BRAF V600E 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 BRAF V600E , and mitotic index less than 5 mitoses/10 highpower 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.

A comprehensive analysis identifies BRAF hotspot mutations associated with gliomas with peculiar epithelial morphology

“…While this paper was under revision, Lehman et al . reported that 38% of analyzed ABs showed the BRAF V600E mutation, which strongly supports our data here.…”

Targeted fusion analysis can aid in the classification and treatment of pediatric glioma, ependymoma, and glioneuronal tumors

“…On reresection, his tumor was consistent with anaplastic ependymoma histologically and tested positive for MN1‐CXXC5 fusion. Given the presence of this alteration, the diagnosis was amended to astroblastoma, which are rare glial tumors histologically defined by astrocytic cells with broad thick processes arranged around blood vessels . Astroblastoma can be difficult to differentiate from ependymoma and other tumors with perivascular pseudorosettes.…”

“…These findings led to the review of molecular findings in histologically defined astroblastomas, a large proportion of which were shown to have MN1 alterations. The current understanding is that although astroblastoma histology is not specific to any particular tumor entity, a large number show MN1 alterations and cluster best with CNS high‐grade neuroepithelial tumors . A recent study of MN1‐altered tumors with astroblastoma histology showed good prognosis unlike that expected for PNET.…”

“…These fusions were observed in a subset of tumors previously defined as PNET. Although many MN1 ‐fused tumors showed a nonspecific primitive neuroectodermal (PNET‐like) morphology, a subset had classic features of astroblastoma, an entity previously histologically characterized by the presence of perivascular pseudorosettes composed of tumor cells with thick broad processes extending to a central blood vessel, often with hyalinized walls . These findings led to the review of molecular findings in histologically defined astroblastomas, a large proportion of which were shown to have MN1 alterations.…”

BRAF V600E‐mutated central nervous system tumor with divergent morphological feature – Anaplastic pleomorphic xanthoastrocytoma‐like and astroblastoma‐like

“…Further, the mutated cases can be potential candidates for targeted therapy. Recently, BRAF V600E mutation has also been documented in approximately 38% of cases of astroblastoma, which is a histomorphological entity as per WHO classification and have an unpredictable biological behavior . No hallmark genetic alteration associated with astroblastoma has been described till now.…”