Granular cell astrocytoma: an aggressive IDH IDH ‐wildtype diffuse glioma with molecular genetic features of primary glioblastoma

摘要

Abstract Granular cell astrocytoma ( GCA ) is a rare adult infiltrating glioma subtype. We studied a series of 39 GCA s. 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), OLIG 2 (16 of 16), and CD 68 (27 of 30), but HAM 56, CD 163, and IBA ‐1 histiocytic markers were all negative (22 of 22). IDH 1(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 / PIK 3 genes in 6/13 (46%), NF 1 in 3 of 10 (30%), TP 53 in 3 of 13 (23%), PALB 2 in 3 of 10 (30%), STAG 2 in 3 of 10 (30%), EGFR mutation/amplification in 3 of 13 (23%), and AR in 2 of 10 (20%). CDKN 2A/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 IDH 1 , IDH 2 , CIC , FUBP 1 , 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.