Anti-H3F3A monoclonal antibody, clone 22E9 [Alexa Fluor® 488]

Epithelioid glioblastoma (e-gbm) is a recently described variant of glioblastoma (GBM) which is associated with short survival and now added as a provisional entity to WHO 2016 classification of CNStumors. About half of these tumors show characteristic BRAF-V600E mutation. However, unlike conventional GBMs, e-gbm lack specific diagnostic and prognostic markers. Hence, we aimed to molecularly characterize these tumors. An extensive review of literature was performed.In a multi-institutional effort, all the cases of glioblastoma of year 2017 were reviewed. Cases with predominant epithelioid morphology were analysed. Seven cases of e-gbm (adults:4 and pediatric: 3) were identified. Duration of symptoms varied from 2 weeks to one month. Radiologically, all cases were supratentorial, contrast enhancing with solid and cystic appearance. Majority of the cases were immunopositive for GFAP (71%), EMA (71%), S100 (71%) and vimentin (85%). All the cases showed ATRX, INI-1 and H3K27me3 expression. BRAFV600Emutation was seen in 28% of cases. TERT mutation was seen in 40% cases, while one case showed EGFR amplification. H3F3A mutations and PTEN deletions were seen in none. Although e-gbms are rare, epithelioid morphology of a CNS tumor in a young adult or children with areas of necrosis needs thorough histomorphological and genetic workup.

BACKGROUND: In the revised World Health Organization 2016 classification of central nervous system tumors, "diffuse midline glioma, H3 K27M-mutant" has been added as a new diagnostic entity. However, some confusion exists concerning this diagnostic entity because H3 K27M-mutant diffuse midline glioma is diagnosed with grade IV regardless of morphologic phenotype. Furthermore, the significance of H3 K27M mutation in tumors that aren't typical "diffuse midline glioma, H3 K27M-mutant," such as those with an unusual location and nontypical histology, remains unclear. CASE DESCRIPTION: To elucidate further such unusual tumors, we describe here a rare case of pediatric low-grade glioma located in the tectum, which was morphologically a pilocytic astrocytoma (PA) with genetically H3 K27M mutation but no microvascular proliferation, necrosis, mitoses, or other genetic alterations, insofar as we were able to observe. At the latest follow-up, 28 months after surgery, radiotherapy, and chemotherapy, the patient was found to be free from any neurologic deficits and MRI demonstrated that the tumor was stable without tumor regrowth. This case might be identified as "diffuse midline glioma, H3 K27M-mutant", grade IV, when applying only the current World Health Organization 2016 classification. In addition, we discuss the morphologically benign gliomas harboring the H3 K27M mutation based on the literature. - CONCLUSIONS: We describe here a rare case and present a short literature review of circumscribed/nondiffuse gliomas, particularly in PA with H3 K27M mutation. However, the significance of H3 K27M mutation for PA remains unclear, so further studies and clinical data are needed to elucidate the biology and optimal treatment of such tumors.