Among brain tumors, the BRAFV600E mutation is frequently associated with pleomorphic xanthoastrocytomas (PXAs) and gangliogliomas (GGs). This oncogenic mutation is also detected in ~5 % of other pediatric low-grade gliomas (LGGs) including pilocytic astrocytomas (PAs) and diffuse astrocytomas. In the current multi-institutional study of 56 non-PXA/non-GG diencephalic pediatric LGGs, the BRAFV600 mutation rate is 36 %. V600-mutant tumors demonstrate a predilection for infants and young children (<age 3) and have a higher tendency for multicentricity. On neuroimaging, BRAFV600-mutant tumors appear as nodular, yet infiltrative contrast-enhancing masses. Morphologic examination reveals a monophasic, predominantly compact and partially infiltrative architecture. Due to the lack of classic morphologic features associated with PAs, pilomyxoid astrocytomas (PMAs), or diffuse astrocytomas, 75 % of the BRAFV600-mutant tumors could not be definitively classified on initial histopathologic evaluation. At a median follow-up of 55 months, the 5-year progression-free survival (PFS) rate for BRAFV600-mutant diencephalic low-grade astrocytomas (LGAs) was 22 ± 12 %, shorter than BRAFV600-WT PAs (52 ± 13 %) but higher than PMAs (10 ± 6 %). Of note, long-term PFS was observed in several adolescent patients with BRAFV600-mutant tumors. In children aged 0–12 years, 5-year PFS rate and median PFS in BRAFV600-mutant LGAs are 9 ± 9 % and 19 months (95 % CI 3–37 months), respectively. The PFS is comparable to that in BRAFV600-WT PMAs (5-year PFS rate: 10 ± 9 %; median PFS: 15 months, 95 % CI 3–32 months; p = 0.96) and significantly shorter than BRAFV600-WT PAs (5-year PFS rate: 46 ± 13 %; median PFS: 51 months, 95 % CI 20–∞ months; p < 0.05). In summary, diencephalic BRAFV600-mutant pediatric LGAs are associated with unique clinicopathologic features and have a more aggressive clinical course, especially in children under age 13. The low rate of CDKN2A deletion also suggests that these tumors are molecularly distinct from secondary pediatric high-grade gliomas.
- Low-grade glioma
- Pilocytic astrocytoma
- Pilomyxoid astrocytoma
ASJC Scopus subject areas
- Pathology and Forensic Medicine
- Clinical Neurology
- Cellular and Molecular Neuroscience