Biphenotypic Sinonasal Sarcomas with Recurrent PAX3::FOXO6 Gene Fusion

Area of Science:

• Oncology
• Genetics
• Pathology

Background:

• Biphenotypic sinonasal sarcoma (BSNS) is a rare tumor characterized by neural and myogenic marker expression.
• PAX3 gene fusions are common in BSNS, with partners like MAML3, NCOA1, NCOA2, FOXO1, FOXO6, WWTR1, and YAP1.
• Understanding these genetic alterations is crucial for accurate diagnosis and classification.

Purpose of the Study:

• To report two additional cases of BSNS harboring PAX3::FOXO6 gene fusions.
• To contribute to the variant classification of BSNS.
• To provide further evidence supporting the role of PAX3::FOXO6 in BSNS.

Main Methods:

• Histopathological examination of two BSNS cases.
• Immunohistochemical analysis for specific protein markers (beta-catenin, SMA, S100).
• RNA sequencing to identify gene fusions, specifically PAX3::FOXO6.

Main Results:

• Both cases presented as unencapsulated infiltrative spindle cell neoplasms consistent with BSNS.
• Immunohistochemistry showed variable results for beta-catenin, SMA, and S100 protein expression.
• RNA sequencing confirmed the presence of PAX3::FOXO6 (exon 7::exon 2) fusion in both patients.

Conclusions:

• BSNS can be distinguished from other sinonasal entities by location, morphology, and immunophenotype.
• Genetic evaluation, particularly identifying PAX3 fusions, is essential in challenging cases.
• The findings support PAX3::FOXO6 as a recurrent fusion in BSNS, aiding in its classification.