Mesenchymal sinonasal tumors
2025-04-08 Paola Dal Cin, PhD Affiliation1.Brigham and Women's Hospital , Harvard Medical School, Boston , MA (USA)
Keywords
Soft tissue tumors , CTNNB1 aberrations, PAX3 rearrangements, TBXT duplication,Classification
Definition
Primary soft tissue tumors arising in the sinonasal tract are rare. Some tumor types are relatively more common in this area, such as schwannoma and rhabdomyosarcoma. 1 There are 3 unique spindle cell neoplasms with unique histological and molecular profiles, that arise in nasal cavity/paranasal sinuses: sinonasal tract angiofibroma (STA) (commonly known as juvenile nasopharyngeal angiofibroma), glomangiopericytoma (GPC), and biphenotypic sinonasal sarcoma (BSNS). These entities are overall indolent behavior with frequent recurrences, especially in cases of incomplete excision. Genetically, abnormal expression pattern of Beta-catenin frequently found in these tumors underlying CTNNB1 aberrations frequently seen in both STA and GPC entities, 2 while mainly PAX3 rearrangements hare seen in BSNS.
Chordoma, a rare malignant tumor of the bone, originated from the remnants of the primitive notochord, and typically presents in the skull base. Multiple genetic events are reported in chordoma, including duplications in the TBXT gene (encoding brachyury). 3
| Mesenchymal sinonasal tumors | Genetic marker(s) | ||
|---|---|---|---|
| Sinonasal tract angiofibroma (STA) | Histologically benign,but locally aggressive and potentially destructive lesion predominantly affects male adolescents. Frequent CTNNB1 abnormalities have been described in STA , commonly known as juvenile nasopharyngeal angiofibroma (JNA), as mutations, but also interstitial deletions and amplifications.2 No APC aberrations were reported in sporadic cases, but altered APC expression particularly noted in FAP-associated STA.4 and copy number aberrations involvin APC locus have been also reported .5 The advancement of genome technologies and analytical tools has provided evidence that a diverse range of genetic factors contributing to STA e.g., includes genomic alterations, tumor suppressor genes, oncogenes, growth factors, and hormonal influences.2 | ||
| The development of STA is believed to be hormonally driven, because the relatively high prevalence of STA in young men and its onset typically during the years of sexual maturation. Whole-exome sequencing (WES) analysis on males with STA revealed revealed a high prevalence of mutations in 14 genes within the protein-coding, male-specific region of the Y-chromosome of young males with USP9Y and UTY been the most frequent mutated genes, followed by KDM5D, DDX3Y, and TSPY4. 6 | |||
| Sinonasal glomangiopericytoma (SGP) | Recurrent missense mutations in exon 3 of CTNNB1 in the majority of the these lesions affecting older individuals with a slight female preponderance. 7,8 MIR143::NOTCH fusion, commonly observed in glomus tumors, has not been detected in SGP. 3 | ||
| Biphenotypic sinonasal sarcoma (BSNS) | BNSN cases mainly harbor PAX3::MAML3/t(2;4) (q35;q31.1) rearrangement 9. Other partner genes have been reported FOXO1, NCOA1 and NCOA2, rarely FOXO6 and WWTR1 . 2,10,11 A PAX7::PPARGC1A fusion was seen in a single case. 12 Confident distinction between monophasic synovial sarcoma and BSNS can be achived using immunohistochemical stain specifically targeted to the SS18-SSX fusion protein product. 13 | ||
| Skull base chordoma | Duplications in the TBXT gene (encoding brachyury}, deletions CDKN2A/ CDKN2B, and LYST, SETD2, and PBRM1 mutations are consistently observed, also accompanied by chromosomal changes, particularly LOH at 3p and 13q14 RB1 and LOH at 9p, which correlates with reduced overall survival. 3 |
Article Bibliography
| Reference Number | Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|---|
| 1 | 26472693 | 2016 | Soft tissue tumors of the sinonasal tract. | Johncilla M et al |
| 2 | 39489557 | 2024 | Spindle Cell Neoplasms Unique to the Sinonasal Tract. | Perez AN et al |
| 3 | 38376625 | 2024 | Integrated Molecular and Histological Insights for Targeted Therapies in Mesenchymal Sinonasal Tract Tumors. | Hoch CC et al |
| 4 | 18227724 | 2008 | Wnt pathway, angiogenetic and hormonal markers in sporadic and familial adenomatous polyposis-associated juvenile nasopharyngeal angiofibromas (JNA). | Ponti G et al |
| 5 | 26572152 | 2016 | Identification of CTNNB1 mutations, CTNNB1 amplifications, and an Axin2 splice variant in juvenile angiofibromas. | Wemmert S et al |
| 6 | 39297564 | 2024 | Comprehensive Analysis of Juvenile Nasopharyngeal Angiofibromas via Whole-Exome Sequencing. | Kumari K et al |
| 7 | 29736797 | 2018 | β-catenin (CTNNB1) mutation and LEF1 expression in sinonasal glomangiopericytoma (sinonasal-type hemangiopericytoma). | Suzuki Y et al |
| 8 | 30206803 | 2019 | Glomangiopericytoma of the Nasal Cavity with CTNNB1 p.S37C Mutation: A Case Report and Literature Review. | Kono M et al |
| 9 | 24859338 | 2014 | Recurrent PAX3-MAML3 fusion in biphenotypic sinonasal sarcoma. | Wang X et al |
| 10 | 30829729 | 2019 | Clinicopathologic and Molecular Features of a Series of 41 Biphenotypic Sinonasal Sarcomas Expanding Their Molecular Spectrum. | Le Loarer F et al |
| 11 | 31950469 | 2020 | Soft Tissue Special Issue: Biphenotypic Sinonasal Sarcoma: A Review with Emphasis on Differential Diagnosis. | Gross J et al |
| 12 | 37378830 | 2023 | Biphenotypic Sinonasal Sarcoma with a Novel PAX7::PPARGC1 Fusion: Expanding the Spectrum of Gene Fusions Beyond the PAX3 Gene. | Bhele S et al |
| 13 | 32141887 | 2020 | A Novel SS18-SSX Fusion-specific Antibody for the Diagnosis of Synovial Sarcoma. | Baranov E et al |
Citation
Paola Dal Cin, PhD
Mesenchymal sinonasal tumors
Atlas Genet Cytogenet Oncol Haematol. 2025-04-08
Online version: http://atlasgeneticsoncology.org/solid-tumor/209320/mesenchymal-sinonasal-tumors
