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IDH2 R172 Mutations Across Poorly Differentiated Sinonasal Tract Malignancies Forty Molecularly Homogenous and Histologically Variable Cases With Favorable Outcome

Gloss S, Jurmeister P, Thieme A, Schmid S, Cai WY, Serrette RN, Perner S, Ribbat-Idel J, Pagenstecher A, Blaeker H, Keber U, Stadelmann C, Zechel S, Johann PD, Hasselblatt M, Paulus W, Thomas C, Dohmen H, Baumhoer D, Frank S, Agaimy A, Schueller U, Vasudevaraja V, Snuderl M, Liu CZ, Pfister DG, Jungbluth AA, Ghossein RA, Xu B, Capper D, Dogan S (2021)

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Publication Type: Journal article

Publication year: 2021

Journal

Book Volume: 45

Pages Range: 1190-1204

Journal Issue: 9

DOI: 10.1097/PAS.0000000000001697

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.

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APA:

Gloss, S., Jurmeister, P., Thieme, A., Schmid, S., Cai, W.Y., Serrette, R.N.,... Dogan, S. (2021). IDH2 R172 Mutations Across Poorly Differentiated Sinonasal Tract Malignancies Forty Molecularly Homogenous and Histologically Variable Cases With Favorable Outcome. American Journal of Surgical Pathology, 45(9), 1190-1204. https://doi.org/10.1097/PAS.0000000000001697

MLA:

Gloss, Stefanie, et al. "IDH2 R172 Mutations Across Poorly Differentiated Sinonasal Tract Malignancies Forty Molecularly Homogenous and Histologically Variable Cases With Favorable Outcome." American Journal of Surgical Pathology 45.9 (2021): 1190-1204.

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