TY - JOUR
T1 - A clinicopathologic study of diencephalic pediatric low-grade gliomas with BRAF V600 mutation
AU - Ho, Cheng Ying
AU - Mobley, Bret C.
AU - Gordish-Dressman, Heather
AU - VandenBussche, Christopher J.
AU - Mason, Gary E.
AU - Bornhorst, Miriam
AU - Esbenshade, Adam J.
AU - Tehrani, Mahtab
AU - Orr, Brent A.
AU - LaFrance, Delecia R.
AU - Devaney, Joseph M.
AU - Meltzer, Beatrix W.
AU - Hofherr, Sean E.
AU - Burger, Peter C.
AU - Packer, Roger J.
AU - Rodriguez, Fausto J
N1 - Funding Information:
We would like to thank Dr. Peter Phillips for providing critical clinical information and Ms. Ashley Tipton for excellent technical assistance. This work was supported in part by the Lauren’s First and Goal and the Pilocytic/Pilomyxoid fund (to FJR).
Publisher Copyright:
© 2015, Springer-Verlag Berlin Heidelberg.
PY - 2015/10/26
Y1 - 2015/10/26
N2 - 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 (V600-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.
AB - 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 (V600-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.
KW - BRAF
KW - Diencephalic
KW - Hypothalamic
KW - Low-grade glioma
KW - Pilocytic astrocytoma
KW - Pilomyxoid astrocytoma
KW - V600E
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U2 - 10.1007/s00401-015-1467-3
DO - 10.1007/s00401-015-1467-3
M3 - Article
C2 - 26264609
AN - SCOPUS:84942363595
SN - 0001-6322
VL - 130
SP - 575
EP - 585
JO - Acta neuropathologica
JF - Acta neuropathologica
IS - 4
ER -