Novel PAX3-NCOA1 fusions in biphenotypic sinonasal sarcoma with focal rhabdomyoblastic differentiation

Shih Chiang Huang, Ronald A. Ghossein, Justin A. Bishop, Lei Zhang, Tse Ching Chen, Hsuan Ying Huang, Cristina R. Antonescu

Research output: Contribution to journalArticlepeer-review

51 Scopus citations


Sarcomas arising in the sinonasal region are uncommon and encompass a wide variety of tumor types, including the newly described biphenotypic sinonasal sarcoma (BSNS), which is characterized by a monomorphic spindle cell proliferation with dual neural and myogenic phenotypes. Most BSNSs harbor a pathognomonic PAX3-MAML3 fusion driven by t(2;4)(q35;q31.1), whereas the alternative fusion partner gene remains unidentified in a subset of PAX3-rearranged cases. As NCOA1 on 2p23 is a known partner in PAX3-related fusions in other tumor types (ie, alveolar rhabdomyosarcoma), we investigated its status by fluorescence in situ hybridization (FISH) and reverse transcription polymerase chain reaction assays in 2 BSNS cases showing only PAX3 gene rearrangements. Novel PAX3-NCOA1 fusions were identified in these 2 index cases showing an inv(2)(q35p23) by FISH and confirmed by reverse transcription polymerase chain reaction. Five additional BSNS cases with typical morphology were studied by FISH, revealing a PAX3-MAML3 fusion in 4 cases and only PAX3 rearrangement in the remaining case without abnormalities in MAML3 or NCOA1 gene. Except for 1 case with surface ulceration, all other tumors lacked increased mitotic activity or necrosis, and all cases immunohistochemically coexpressed S100 protein and actin, but lacked SOX10 reactivity. Interestingly, the 2 PAX3-NCOA1-positive cases showed desmin reactivity and displayed a small component of rhabdomyoblastic cells, which were not seen in the more common PAX3-MAML3 fusion cases. In conclusion, we report a novel PAX3-NCOA1 fusion in BSNS, which appears to be associated with focal rhabdomyoblastic differentiation and should be distinguished from PAX3-NCOA1-positive alveolar rhabdomyosarcoma or malignant Triton tumor. SOX10 immunohistochemistry is a useful marker in distinguishing BSNS from peripheral nerve sheath tumors.

Original languageEnglish (US)
Pages (from-to)51-59
Number of pages9
JournalAmerican Journal of Surgical Pathology
Issue number1
StatePublished - Jan 1 2016


  • biphenotypic sinonasal sarcoma
  • low-grade sinonasal sarcoma with neural and myogenic features
  • MAML3
  • NCOA1
  • PAX3

ASJC Scopus subject areas

  • Anatomy
  • Pathology and Forensic Medicine
  • Surgery


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