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

Abstract

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.

Imaging Conundrum of Granular Cell Astrocytoma: A Case Report

“…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 [Vizcaino 2019].…”

Cytopathological and histopathological features of cerebral granular cell astrocytoma: A case report

“…Granular cell astrocytoma is a variant of infiltrative astrocytoma with a worse prognosis. 4,7 However, an older age was associated with a worse prognosis. 4 In addition, GCA reportedly resulted in genetic alterations in IDH-wildtype glioblastoma.…”

“…Granular cell astrocytoma (GCA) is a rare type of infiltrating astrocytic neoplasm, characterised by histiocyte‐like granular neoplastic cells, with a poor prognosis 1‐3 . Furthermore, its genetic alteration is reportedly similar to that of isocitrate dehydrogenase (IDH)‐wildtype glioblastomas 4 …”

SP1–DLEU1–miR-4429 feedback loop promotes cell proliferative and anti-apoptotic abilities in human glioblastoma

“…According to the World Health Organization (WHO) Pathological Grading Standard (2016 version), glioma is admittedly divided into four grades (I-IV) [35]. Mostly, grade I is identified as benign glioma, while diffuse low-and medium-grade gliomas constitute the WHO grade II and III lesions [36]. Grade IV glioma comprises the primary GBM and the secondary glioblastoma from lower grade glioma [37].…”