[IDH-mutant adult-type diffuse gliomas: a clinicopathological analysis of 1 301 cases]

Objective: To investigate the clinicopathological characteristics of IDH-mutant adult-type diffuse gliomas. Methods: Adult-type diffuse gliomas with IDH1 (R132) or IDH2 (R172) mutation confirmed by Sanger sequencing and 1p/19q FISH testing were collected at the West China Hospital of Sichuan University between January 2021 and June 2025. The correlations among patient sex, age, lesion location, IDH mutation type, tumor type, and WHO grade were retrospectively analyzed. Results: Among the 1 301 patients, 722 (55.5%) were male and 579 (44.5%) were female, with a male-to-female ratio of 1.25∶1.00. The patient age was 41 (33, 51) years. There were 9 patients (0.7%) aged≤18 years, 1 140 (87.6%) aged 19-55 years, and 152 (11.7%) aged>55 years. There were observed in 1 271 cases (97.7%) of supratentorial tumor and 17 cases (1.3%) of infratentorial tumor, while the location was unknown in 13 cases (1.0%). IDH1 (R132) mutations were identified in 1 244 cases, with R132H being the most common (1 211 cases, 93.1%), while non-R132H IDH1 mutations were detected in 33 cases (2.5%) and IDH2 mutations in 57 cases (4.4%). Among the 1 301 cases, 711 cases (54.7%) were astrocytoma, with WHO grades 2, 3, and 4 comprising 364 cases (51.2%), 116 cases (16.3%), and 231 cases (32.5%), respectively. Oligodendrogliomas accounted for 590 cases (45.3%), with WHO grade 2 in 372 cases (63.1%), and WHO grade 3 in 218 cases (36.9%). Patient sex was associated with WHO grade (r=0.078, P=0.014), but not age, location, tumor type, or IDH mutation type. Male patients outnumbered females across all grades, with the proportion of males increasing with higher tumor grades. Patient age was associated with IDH mutation type and tumor type (r=-0.072, 0.199, P=0.001), but not location or WHO grade. Compared to patients>18 years, those≤18 years were more likely to harbor non-R132H IDH1 mutations, whereas IDH2 mutations were observed only in patients>18 years. Patients over 65 years exhibited exclusively IDH1 R132H mutation. The proportion of oligodendroglioma patients increased with age (r=0.199, P=0.001). Tumor location was associated with IDH mutation type and tumor type (r=0.118, -0.077,P<0.05), but not with WHO grade. Compared to supratentorial tumors, non-R132H IDH1 mutations were significantly more common in infratentorial tumors (χ²=74.285, P=0.001), while IDH2 mutations rarely occurred infratentorially. Oligodendrogliomas were rarely found in infratentorial locations. IDH mutation type was associated with tumor type (r=0.118, P=0.001), but not with WHO grade. The incidence of non-R132H IDH1 mutations was significantly higher in astrocytoma than oligodendroglioma. The proportion of IDH2 mutations was significantly higher in oligodendrogliomas than astrocytoma (χ²=50.661, P<0.001). Conclusions: IDH mutations predominantly occur in adults, with an average age range of 25-55 years, although there are also rare pediatric cases. IDH-mutant gliomas are most located in the supratentorial region, particularly in the frontal lobe, and predominantly with IDH1 R132H mutation. Patients aged >65 years exclusively exhibit IDH1 R132H mutations. Compared to supratentorial tumors, non-R132H IDH1 mutations are significantly more frequent in infratentorial tumors. IDH2-mutant gliomas almost exclusively occur in adults and in supratentorial locations, with a significantly higher proportion in oligodendrogliomas than astrocytoma.