Clinicopathologic and Molecular Features of a Series of 41 Biphenotypic Sinonasal Sarcomas Expanding Their Molecular Spectrum

Am J Surg Pathol. 2019 Jun;43(6):747-754. doi: 10.1097/PAS.0000000000001238.

Abstract

Biphenotypic sinonasal sarcoma (BSNS) is a locally aggressive tumor occurring in the sinonasal region. It harbors both myogenic and neural differentiation and is characterized by PAX3 rearrangement with MAML3 as the most frequent fusion partner, but the partner of PAX3 remains unidentified in a subset of cases. About 70 cases have been reported so far. In this study, we report a series of 41 cases with clinical, pathologic, and molecular description. Twenty-five (61%) patients were female individuals, and the median age was 49 years. Tumors arose predominantly in the nasal cavity and ethmoidal sinuses. Local recurrences occurred in 8 cases of the 25 (32%). Histologic features were characteristic of BSNS, with 5 cases showing focal rhabdomyoblastic differentiation. Immunohistochemistry showed a constant positivity of S100 protein and PAX3 and negativity of SOX10. MyoD1 was focally positive in 91% of cases, whereas only 20% were positive for myogenin. Molecular analysis showed a PAX3-MAML3 transcript in 37 cases (90%). RNA sequencing was performed in the 4 negative cases for PAX3-MAML3 fusion, and it showed that 1 case harbored a PAX3-FOXO1 fusion, as previously described in the literature, and 2 novel fusions: PAX3-WWTR1 fusion in 2 cases and PAX3-NCOA2 fusion in 1 case. RNA sequencing results were confirmed by fluorescence in situ hybridization, reverse transcription-polymerase chain reaction, and Sanger sequencing. The PAX3-NCOA2-positive case showed focal rhabdomyoblastic differentiation. In conclusion, we report 2 novel fusions (PAX3-WWTR1 and PAX3-NCOA2) in BSNS and show that MyoD1 is more sensitive than myogenin for demonstrating myogenic differentiation in this tumor.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor* / analysis
  • Biomarkers, Tumor* / genetics
  • Cell Differentiation
  • Female
  • Gene Fusion
  • Genetic Predisposition to Disease
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization, Fluorescence
  • Male
  • Middle Aged
  • MyoD Protein / analysis
  • Nasal Cavity* / chemistry
  • Nasal Cavity* / pathology
  • Nuclear Receptor Coactivator 2 / genetics
  • Oncogene Proteins, Fusion / genetics
  • PAX3 Transcription Factor / genetics
  • Paired Box Transcription Factors / genetics
  • Paranasal Sinus Neoplasms* / chemistry
  • Paranasal Sinus Neoplasms* / genetics
  • Paranasal Sinus Neoplasms* / pathology
  • Paranasal Sinus Neoplasms* / therapy
  • Paranasal Sinuses* / chemistry
  • Paranasal Sinuses* / pathology
  • Phenotype
  • Prospective Studies
  • Retrospective Studies
  • Sarcoma* / chemistry
  • Sarcoma* / genetics
  • Sarcoma* / pathology
  • Sarcoma* / therapy
  • Trans-Activators / genetics
  • Transcriptional Coactivator with PDZ-Binding Motif Proteins

Substances

  • Biomarkers, Tumor
  • MAML3 protein, human
  • MyoD Protein
  • MyoD1 myogenic differentiation protein
  • NCOA2 protein, human
  • Nuclear Receptor Coactivator 2
  • Oncogene Proteins, Fusion
  • PAX3 Transcription Factor
  • PAX3 protein, human
  • PAX3-FOXO1A fusion protein, human
  • Paired Box Transcription Factors
  • Trans-Activators
  • Transcriptional Coactivator with PDZ-Binding Motif Proteins
  • WWTR1 protein, human