Here, we report a juvenile (18-year-old male) case of
epilepsy-associated,
isocitrate dehydrogenase wild-type/
histone 3 wild-type diffuse
glioma with a rare BRAF mutation and a focal atypical feature resembling diffuse
astrocytoma. The patient presented with refractory
temporal lobe epilepsy. Subsequently, magnetic resonance imaging revealed a hyperintense lesion in the right temporal lobe on fluid attenuated inversion recovery images. The patient underwent right lateral temporal lobectomy and amygdalohippocampectomy. Histopathologically, the
tumor showed isomorphic, diffuse, infiltrative proliferation of glial
tumor cells and intense CD34 immunoreactivity. The
tumor cells were immunonegative for
isocitrate dehydrogenase 1 (IDH1) R132H and BRAF V600E. Notably, the
tumor cells showed the lack of nuclear staining for α-
thalassemia/
mental retardation syndrome, X-linked (ATRX). In addition, the Ki-67 labeling index, using a
monoclonal antibody MIB-1, was elevated focally at
tumor cells with p53 immunoreactivity. Molecular analyses identified a BRAFA598T mutation, the first case reported in a
glioma. BRAFA598T is predicted to result in loss of
kinase action; however, inactive mutants can stimulate
mitogen-activated protein kinase kinase (
MEK)-
extracellular signal-regulated kinase (ERK) signaling through CRAF activation. Thus, according to the recent update of the consortium to inform molecular and practical approaches to
central nervous system tumor taxonomy (cIMPACT-NOW update 4), our case is also compatible with diffuse
glioma with the
mitogen-activated protein kinase (MAPK) pathway alteration. Thorough immunohistochemical and molecular studies are necessary for diagnosis of
epilepsy-associated, diffuse
gliomas. Partial resemblance in histopathological and molecular genetic features to diffuse
astrocytoma also calls for attention.