Granular cell astrocytoma: an aggressive IDH-wildtype diffuse glioma with molecular genetic features of primary glioblastoma.
Adult
Aged
Aged, 80 and over
Astrocytoma
/ genetics
Biomarkers, Tumor
/ genetics
Brain Neoplasms
/ pathology
Female
Glioblastoma
/ genetics
Glioma
/ genetics
Granular Cell Tumor
/ genetics
High-Throughput Nucleotide Sequencing
/ methods
Humans
Immunohistochemistry
Isocitrate Dehydrogenase
/ genetics
Kaplan-Meier Estimate
Male
Middle Aged
Mutation
Promoter Regions, Genetic
/ genetics
TERT
GBM
Granular cell
IDH-wildtype
astrocytoma
diffuse glioma
glioblastoma
Journal
Brain pathology (Zurich, Switzerland)
ISSN: 1750-3639
Titre abrégé: Brain Pathol
Pays: Switzerland
ID NLM: 9216781
Informations de publication
Date de publication:
03 2019
03 2019
Historique:
received:
16
08
2018
accepted:
10
09
2018
pubmed:
18
9
2018
medline:
25
7
2019
entrez:
18
9
2018
Statut:
ppublish
Résumé
Granular cell astrocytoma (GCA) is a rare adult infiltrating glioma subtype. We studied a series of 39 GCAs. Median age of presentation was 57.8 years and most cases developed in the frontal or temporal lobes. Tumors included grade II (n = 14), grade III (n = 11), and grade IV (n = 14) by WHO criteria. Granular cell morphology was diffuse in 31 (79%) cases and partial in eight (21%). Immunohistochemistry showed frequent positivity for GFAP (28 of 31), OLIG2 (16 of 16), and CD68 (27 of 30), but HAM56, CD163, and IBA-1 histiocytic markers were all negative (22 of 22). IDH1(R132H) was negative in all the cases tested (16 of 16), while ATRX expression was retained (12 of 12). Cytogenetics demonstrated monosomy 10 (6 of 6) cases, +7 in 4 (of 6), -13q in 4 of 6, and -14 in 4 of 6. Next-generation sequencing demonstrated mutations in PTEN/PIK3 genes in 6/13 (46%), NF1 in 3 of 10 (30%), TP53 in 3 of 13 (23%), PALB2 in 3 of 10 (30%), STAG2 in 3 of 10 (30%), EGFR mutation/amplification in 3 of 13 (23%), and AR in 2 of 10 (20%). CDKN2A/B deletion was identified in 5 of 13 (30%) cases (homozygous deletion in 4). The TERT C228T mutation was identified in 9 of 13 (69%). No mutations were encountered in IDH1, IDH2, CIC, FUBP1, H3F3A, BRAF or ATRX genes. The mean overall survival was 11.3 months. Patients >60 years old at diagnosis had a worse survival than patients <60 years (P = 0.001). There were no statistically significant differences in survival by WHO grade, extent of granular cell change, sex or MIB-1 (P > 0.05). GCA is a variant of IDH-wildtype diffuse glioma with aggressive behavior irrespective of grade and extent of granular cell morphology, and with molecular genetic features corresponding to primary glioblastoma.
Identifiants
pubmed: 30222900
doi: 10.1111/bpa.12657
pmc: PMC6397086
mid: NIHMS989380
doi:
Substances chimiques
Biomarkers, Tumor
0
Isocitrate Dehydrogenase
EC 1.1.1.41
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Pagination
193-204Subventions
Organisme : NCI NIH HHS
ID : P30 CA006973
Pays : United States
Organisme : NCI NIH HHS
ID : T32 CA193145
Pays : United States
Informations de copyright
© 2018 International Society of Neuropathology.
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