IDH1/2 Mutations in Sinonasal Undifferentiated Carcinomas

Sinonasal undifferentiated carcinoma (SNUC) is a rare, poorly defined sinonasal epithelial neoplasm from which several genetically defined entities are emerging. IDH1/2 mutations were recently identified in a subset of SNUC. However, the ideal method for the detection of these mutations remains to be established. Cases diagnosed as SNUC between 2010 and 2020 were retrieved. Immunohistochemistry was performed using IDH1/2 mutant-specific antibody MsMab-1. Quantitative real-time polymerase chain reaction (qPCR) was performed on genomic DNA extracted from formalin-fixed paraffin-embedded tissue using 2 kits to detect IDH1/2 mutations. Sanger sequencing was performed in a subset of cases. Thirty-eight cases of SNUC were identified, 18 of which showed IDH1/2 mutations by qPCR (47.4%). IDH2 R172K and R140x were most frequent, each seen in 6 cases (33.3%). Sanger sequencing identified IDH1/2 mutations in 4 out of 21 cases (19%) and did not detect mutations identified by qPCR in 7 cases. On immunohistochemistry, strong IDH positivity was present in 2 cases (5.3%), 1 of which had IDH2 mutation, while no mutation was detected in the other. Our results demonstrating IDH2 R172K and IDH2 R140x variants are a novel finding in SNUC. Immunohistochemistry and Sanger sequencing have low sensitivity for detection of IDH1/2 mutations, and qPCR-based assays may be utilized, particularly in resource-limited settings where access to sophisticated sequencing techniques are difficult.