In the third case, where the interval spanned multiple decades, the GG was found to be positive for both BRAF p.V600E immunohistochemistry (IHC) and for the KIAA1549-BRAF fusion.
It is recognized that IDH mutation negative, low-grade epilepsy associated tumors (LEAT) can show diffuse growth patterns and lack the diagnostic hallmarks of either classical dysembryoplastic neuroepithelial tumors (DNT) or typical ganglioglioma.
Their tumors showed distinctive features of ganglioglioma with low Ki-67 index (2%-4%), positive for the BRAF<sup>V600E</sup> mutation, but negative forIDH1/2 mutations.
Activation of the MAP Kinase (MAPK) pathway caused by the BRAFV600E mutation or the KIAA1549-BRAF fusion has been reported in pediatric GG and PA, respectively.
In this multi-institutional study, 98 cases originally diagnosed as ganglioglioma were analyzed for IDH1 mutations, 86 of which had follow-up data available.
Together, this study highlights that ganglioglioma is characterized by genetic alterations that activate the MAP kinase pathway, with only a small subset of cases that harbor additional pathogenic alterations such as CDKN2A deletion.
To identify potential molecular features predictive of brainstem ganglioglioma's clinical outcomes, a retrospective cohort of 28 World Health Organization (WHO) grade I brainstem gangliogliomas was analysed for BRAF V600E, IDH1 R132H, and IDH2R172K mutations, TERT C228T/C250T promoter mutation, H3F3A K27M mutation and MGMT methylation.
It is recognized that IDH mutation negative, low-grade epilepsy associated tumors (LEAT) can show diffuse growth patterns and lack the diagnostic hallmarks of either classical dysembryoplastic neuroepithelial tumors (DNT) or typical ganglioglioma.
Desmoplastic infantile astrocytoma/ganglioglioma (DIA/DIG) is a rare primary neuroepithelial brain tumour typically affecting paediatric patients younger than 24 months.
Activation of the MAP Kinase (MAPK) pathway caused by the BRAFV600E mutation or the KIAA1549-BRAF fusion has been reported in pediatric GG and PA, respectively.
Desmoplastic infantile astrocytoma/ganglioglioma (DIA/DIG) is a rare primary neuroepithelial brain tumour typically affecting paediatric patients younger than 24 months.
Direct analysis demonstrated loss of p19 expression and p53 mutation in the malignant areas, highly suggestive of these alterations being involved in the malignant progression of the ganglioglioma.
The present case is unusual in four aspects: (i) it arose from a low-grade ganglioglioma in the absence of previous radiation or chemotherapy, which is the fourth reported case; (ii) the original tumor showed a high proliferative index on flow cytometry but a low Ki-67 labeling index, implying that the application of flow cytometry might play a certain role in predicting biological and clinical behavior of low grade gangliogliomas; (iii) p53 mutation and deletion appeared in the secondary glioblastoma, which was not shown in the original well-differentiated ganglioglioma; and (iv) the transformed glioblastoma showed p16 inactivation detected by methylation and deletion, which are relatively uncommon genetic events in secondary glioblastomas.
The selective detection of the TSC2 mutation within the glial component of a ganglioglioma suggests that the glioma portion has undergone clonal evolution in this case.
Ganglioglioma and pleomorphic xanthoastrocytoma were the histologic types with the strongest association with CD34 positivity with an odds ratio of 9.2 and 10.4, respectively, compared with dysembryoplastic neuroepithelial tumors.
We also review current literature data on involvement of parkin, DJ1 and PINK1 in the regulation of mTOR, the pathway probably contributing to the development of GG.
We identified novel ALK fusions in a neuroblastoma (BEND5-ALK) and an astrocytoma (PPP1CB-ALK), novel BRAF fusions in an astrocytoma (BCAS1-BRAF) and a ganglioglioma (TMEM106B-BRAF), and a novel PAX3-GLI2 fusion in a rhabdomyosarcoma.