IDH2 Mutation Analysis in Undifferentiated and Poorly Differentiated Sinonasal Carcinomas for Diagnosis and Clinical Management

Am J Surg Pathol. 2020 Mar;44(3):396-405. doi: 10.1097/PAS.0000000000001420.

Abstract

A large number of tumor types arise from the mucosa of the sinonasal cavities. Although presenting clinically distinct behavior, due to poorly differentiated histologic features, they can be difficult to classify correctly. Our aim was to investigate whether IDH2 and IDH1 mutations may be specific to a subset of undifferentiated and poorly differentiated sinonasal carcinomas. A total of 125 tumor samples of 7 different histologic subtypes were analyzed for IDH mutations by sequencing and mutant-specific immunohistochemistry, and the results were correlated to clinical and follow-up data. The highest incidence of IDH2 mutations occurred in sinonasal undifferentiated carcinoma, with 11/36 (31%) cases affected. However, also, 1/9 neuroendocrine carcinomas, 2/4 high-grade non-intestinal-type adenocarcinomas, and 1/8 poorly differentiated squamous cell carcinomas carried the IDH2 mutation, whereas 1/48 intestinal-type adenocarcinomas harbored an IDH1 mutation. Immunohistochemical analysis of mutant IDH1/2 produced a number of false-negative results, but also 1 false-positive tumor was found. Disease-specific survival was more favorable in IDH2-mutant versus wild-type cases. Our data suggest that IDH-mutant sinonasal cancers, independent of their histologic subtype, may represent a distinct tumor entity with less aggressive clinical behavior. Clinically, patients with these mutations may benefit from specific IDH-guided therapies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / genetics*
  • Carcinoma / diagnosis*
  • Carcinoma / genetics
  • Carcinoma / pathology
  • Carcinoma / therapy
  • DNA Mutational Analysis
  • Female
  • Follow-Up Studies
  • Humans
  • Isocitrate Dehydrogenase / genetics*
  • Male
  • Maxillary Sinus Neoplasms / diagnosis*
  • Maxillary Sinus Neoplasms / genetics
  • Maxillary Sinus Neoplasms / pathology
  • Maxillary Sinus Neoplasms / therapy
  • Middle Aged
  • Mutation*
  • Prognosis
  • Young Adult

Substances

  • Biomarkers, Tumor
  • IDH2, human
  • Isocitrate Dehydrogenase
  • IDH1 protein, human

Supplementary concepts

  • Sinonasal undifferentiated carcinoma