Journal article
Authors list: Gloss, Stefanie; Jurmeister, Philipp; Thieme, Anne; Schmid, Simone; Cai, Wei Y.; Serrette, Rene N.; Perner, Sven; Ribbat-Idel, Julika; Pagenstecher, Axel; Blaeker, Hendrik; Keber, Ursula; Stadelmann, Christine; Zechel, Sabrina; Johann, Pascal D.; Hasselblatt, Martin; Paulus, Werner; Thomas, Christian; Dohmen, Hildegard; Baumhoer, Daniel; Frank, Stephan; Agaimy, Abbas; Schueller, Ulrich; Vasudevaraja, Varshini; Snuderl, Matija; Liu, Cheng Z.; Pfister, David G.; Jungbluth, Achim A.; Ghossein, Ronald A.; Xu, Bin; Capper, David; Dogan, Snjezana
Publication year: 2021
Pages: 1190-1204
Journal: The American Journal of Surgical Pathology
Volume number: 45
Issue number: 9
ISSN: 0147-5185
eISSN: 1532-0979
Open access status: Green
DOI Link: https://doi.org/10.1097/PAS.0000000000001697
Publisher: Lippincott, Williams & Wilkins
Abstract:
IDH2 R172 mutations occur in sinonasal undifferentiated carcinoma (SNUC), large-cell neuroendocrine carcinoma (LCNEC), sinonasal adenocarcinomas, and olfactory neuroblastoma (ONB). We performed a clinical, pathologic, and genetic/epigenetic analysis of a large IDH2-mutated sinonasal tumor cohort to explore their distinct features. A total 165 sinonasal/skull base tumors included 40 IDH2 mutants studied by light microscopy, immunohistochemistry, and genome-wide DNA methylation, and 125 IDH2 wild-type tumors used for comparison. Methylation profiles were analyzed by unsupervised hierarchical clustering, t-distributed stochastic neighbor embedding dimensionality reduction and assessed for copy number alterations (CNA). Thirty-nine histologically assessable cases included 25 (64.1%) SNUC, 8 (20.5%) LCNEC, 2 (5.1%) poorly differentiated adenocarcinomas, 1 (2.7%) ONB, and 3 (7.7%) IDH2-mutated tumors with ONB features. All cases were high-grade showing necrosis (82.4%), prominent nucleoli (88.9%), and median 21 mitoses/10 HPFs. AE1/AE3 and/or CAM 5.2 were positive in all and insulinoma-associated protein 1 (INSM1) in 80% cases. All IDH2 mutants formed one distinct group by t-distributed stochastic neighbor embedding dimensionality reduction separating from all IDH2 wild-type tumors. There was no correlation between methylation clusters and histopathologic diagnoses. Recurrent CNA included 1q gain (79.3%), 17p loss (75.9%), and 17q gain (58.6%). No CNA differences were observed between SNUC and LCNEC. IDH2 mutants showed better disease-specific survival than SMARCB1-deficient (P=0.027) and IDH2 wild-type carcinomas overall (P=0.042). IDH2-mutated sinonasal tumors are remarkably homogeneous at the molecular level and distinct from IDH2 wild-type sinonasal malignancies. Biology of IDH2-mutated sinonasal tumors might be primarily defined by their unique molecular fingerprint rather than by their respective histopathologic diagnoses.
Citation Styles
Harvard Citation style: Gloss, S., Jurmeister, P., Thieme, A., Schmid, S., Cai, W., Serrette, R., et al. (2021) IDH2 R172 Mutations Across Poorly Differentiated Sinonasal Tract Malignancies Forty Molecularly Homogenous and Histologically Variable Cases With Favorable Outcome, The American Journal of Surgical Pathology, 45(9), pp. 1190-1204. https://doi.org/10.1097/PAS.0000000000001697
APA Citation style: Gloss, S., Jurmeister, P., Thieme, A., Schmid, S., Cai, W., Serrette, R., Perner, S., Ribbat-Idel, J., Pagenstecher, A., Blaeker, H., Keber, U., Stadelmann, C., Zechel, S., Johann, P., Hasselblatt, M., Paulus, W., Thomas, C., Dohmen, H., Baumhoer, D., ...Dogan, S. (2021). IDH2 R172 Mutations Across Poorly Differentiated Sinonasal Tract Malignancies Forty Molecularly Homogenous and Histologically Variable Cases With Favorable Outcome. The American Journal of Surgical Pathology. 45(9), 1190-1204. https://doi.org/10.1097/PAS.0000000000001697
Keywords
ESTHESIONEUROBLASTOMA; genome-wide DNA methylation; IDH2 R172 mutations; olfactory neuroblastoma; sinonasal large-cell neuroendocrine carcinoma; sinonasal undifferentiated carcinoma; SUBGROUPS; UNDIFFERENTIATED CARCINOMA
