Epithelioid Glioblastomas and Anaplastic Epithelioid Pleomorphic Xanthoastrocytomas—Same Entity or First Cousins?

Abstract

Epithelioid glioblastoma (eGBM) and pleomorphic xanthoastrocytoma (PXA) with anaplastically transformed foci (ePXA) show overlapping features. Eleven eGBMs and 5 ePXAs were reviewed and studied immunohistochemically. Fluorescence in situ hybridization for EGFR amplification, PTEN deletion and ODZ3 deletion was also performed, with Ilumina 450 methylome analysis obtained in five cases. The average age for eGBM was 30.9 (range 2-79) years, including five pediatric cases and a M : F ratio of 4.5. The ePXA patients had a M : F ratio of 4 and averaged 21.2 (range 10-38) years in age, including two pediatric cases. Six eGBMs and two ePXAs recurred (median recurrence interval of 12 and 3.3 months, respectively). All tumors were composed of solid sheets of loosely cohesive, "melanoma-like" cells with only limited infiltration. ePXAs showed lower grade foci with classic features of PXA. Both tumor types showed focal expression of epithelial and glial markers, retained INI1 and BRG1 expression, occasional CD34 positivity, and lack of mutant IDH1 (R132H) immunoreactivity. BRAF V600E mutation was present in four eGBMs and four ePXAs. ODZ3 deletion was detected in seven eGBMs and two ePXAs. EGFR amplification was absent. Methylome analysis showed that one ePXA and one eGBM clustered with PXAs, one eGBM clustered with low-grade gliomas, and two eGBMs clustered with pediatric-type glioblastomas. Common histologic, immunohistochemical, molecular and clinical features found in eGBM and ePXA suggest that they are closely related or the same entity. If the latter is true, the nomenclature and WHO grading remains to be resolved.

K27M mutation in H3F3A in ganglioglioma grade I with spontaneous malignant transformation extends the histopathological spectrum of the histone H3 oncogenic pathway

“…By contrast, the rapid relapse and shorter evolution of the second case suggest that because of sampling bias the initial histopathology could have been limited to the low‐grade component of a tumour undergoing an anaplastic transformation. A recently reported case of a BRAF wild type, H3.3K27M ‘glioblastoma’ with ATRX loss of expression and with a ganglioglioma component also fits with the malignant transformation of a H3.3K27M ganglioglioma . On the other hand, one might consider these two cases as ganglioglioma grade I on histopathological grounds.…”

Concurrent TERT promoter and BRAF V600E mutation in epithelioid glioblastoma and concomitant low‐grade astrocytoma

“…Among these, one alteration that mapped onto chromosome 4 was restricted to the E‐GBM area . Recently, a deleted status of the same locus encompassing ODZ3 in an E‐GBM case was reported by Alexandrescu and colleagues …”

A rare case of BRAF V600E‐mutated epithelioid glioblastoma with a sarcomatous component

“…Next, we considered the possibility that our case may be PXA or GG. Several reports have assumed that E‐GBM and PXA are the same entity because of the similarity in the results of histologic and genetic analyses . Moreover, some studies have suggested that BRAF mutations might be related to the epithelioid features of high‐grade gliomas .…”