Long-Term Outcomes of IDH2-Mutant Sinonasal Carcinomas Compared With IDH2-Wild Type Sinonasal Undifferentiated Carcinoma

Why clinicians should know about it

• Picked for Otorhinolaryngology (paper of the day, 12 October 2026): IDH2‑mutant sinonasal carcinoma shows improved survival outcomes

Abstract

BACKGROUND: Sinonasal carcinomas are aggressive and often locally invasive at presentation, with no universally accepted treatment approach. Histopathologic IDH2-mutant status appears to be associated with improved treatment response and survival. However, the clinical significance of histopathologic classification among IDH2-mutant sinonasal carcinomas, as well as that of IDH2 mutation status within SNUC, remains unclear and long-term clinical outcome data are limited. METHODS: Records from a prospectively maintained skull-base database at a large, tertiary care hospital system from 1986 to 2024 were reviewed. Patients with a diagnosis of SNUC or sinonasal tumor of any histopathology positive for IDH2 R172 mutation were identified. SMARCB1-deficient, SMARCA4-deficient, NUT sinonasal carcinomas, and other small round cell mimickers were excluded. After histopathologic confirmation, 22 IDH2-mutant SNUC, 14 IDH2-mutant non-SNUC, and 8 IDH2-wildtype SNUC cases were amenable to comprehensive clinicopathologic data review. A presence of IDH2 R172 and pathogenic TP53 mutations was determined by molecular testing and/or by immunohistochemistry. RESULTS: The median age at diagnosis was 58 years and 61% of patients were male. The majority of patients presented with T4b disease (41% of IDH2-mutant SNUC; 57% of IDH2-mutant non-SNUC; 75% of IDH2-wildtype SNUC; p = 0.3). There was no significant difference in the proportion of patients presenting with orbital invasion (55% IDH2-mutant SNUC; 64% IDH2-mutant non-SNUC; 75% of IDH2-wildtype SNUC; p = 0.7) or intracranial invasion (82% IDH2-mutant SNUC; 79% IDH2-mutant non-SNUC; 75% of IDH2-wildtype SNUC; p = 0.7). On histopathology, there was no significant difference in perineural invasion and margin status between the three subgroups (p > 0.6). A greater proportion of IDH2-mutant non-SNUCs had TP53 mutations (67%) than IDH2-mutant SNUC (31%) and IDH2-wildtype SNUC (29%) (p = 0.13). Across the cohort, 41% of patients received neoadjuvant chemotherapy, with a partial response by RECIST criteria in 94% of patients across the subgroups. Median follow-up was 28 months (IQR 11-64 months). 5-year DSS of 73% in IDH2-mutant SNUC, 75% in IDH2-mutant non-SNUC and 80% in IDH2-wildtype SNUC (p = 0.78). 5-year RFS was 53% in IDH2-mutant SNUC, 48% in IDH2-mutant non-SNUC and 43% in IDH2-wildtype SNUC (p = 0.78). CONCLUSION: Upfront assessment of IDH2 mutation status in sinonasal carcinoma patients may be warranted to select patients for clinical trials with IDH-inhibitors. However, no significant differences in the extent of disease at presentation or response to induction chemotherapy were observed according to histopathologic classification among IDH2-mutant sinonasal carcinomas or IDH2 mutation status within SNUC. Larger series are required to determine the prognostic significance of IDH2 mutation status in sinonasal carcinoma patients.

Abstract as published, via PubMed.