Soft Tissue Special Issue: Biphenotypic Sinonasal Sarcoma: A Review with Emphasis on Differential Diagnosis


Biphenotypic sinonasal sarcoma is an anatomically restricted low-grade malignant neoplasm with dual neural and myogenic differentiation composed of a monotonous population of spindled cells with herringbone/fascicular architecture. These tumors demonstrate a unique immunoprofile with relatively consistent S100-protein and actin expression in conjunction with more variable desmin, myogenin and myoD1 staining. SOX10 is uniformly negative. Genetically, the majority of tumors harbor PAX3-MAML3 fusions, with alternate PAX3 partners including FOXO1, NCOA1, NCOA2 and WWTR1. Although the differential diagnosis of BSNS is broad, careful morphologic inspection together with targeted ancillary studies is often sufficient to arrive at the correct diagnosis. As these tumors have significant local recurrence rates but lack metastatic potential, awareness and accurate diagnosis of this rare and newly described neoplasm is critical for appropriate management.

This is a preview of subscription content, log in to check access.

Access options

Buy single article

Instant unlimited access to the full article PDF.

US$ 39.95

Price includes VAT for USA

Subscribe to journal

Immediate online access to all issues from 2019. Subscription will auto renew annually.

US$ 99

This is the net price. Taxes to be calculated in checkout.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7


  1. 1.

    Lewis JT, Oliveira AM, Nascimento AG, et al. Low-grade sinonasal sarcoma with neural and myogenic features: a clinicopathologic analysis of 28 cases. Am J Surg Pathol. 2012;36:517–25.

  2. 2.

    Andreasen S, Bishop JA, Hellquist H, et al. Biphenotypic sinonasal sarcoma: demographics, clinicopathological characteristics, molecular features, and prognosis of a recently described entity. Virchows Arch. 2018;473:615–26.

  3. 3.

    Fritchie KJ, Jin L, Wang X, et al. Fusion gene profile of biphenotypic sinonasal sarcoma: an analysis of 44 cases. Histopathology. 2016;69:930–6.

  4. 4.

    Huang SC, Ghossein RA, Bishop JA, et al. Novel PAX3-NCOA1 fusions in biphenotypic sinonasal sarcoma With focal rhabdomyoblastic differentiation. Am J Surg Pathol. 2016;40:51–9.

  5. 5.

    Jo VY, Marino-Enriquez A, Fletcher CDM, et al. Expression of PAX3 distinguishes biphenotypic sinonasal sarcoma from histologic mimics. Am J Surg Pathol. 2018;42:1275–85.

  6. 6.

    Kakkar A, Rajeshwari M, Sakthivel P, et al. Biphenotypic sinonasal sarcoma: a series of six cases with evaluation of role of beta-catenin immunohistochemistry in differential diagnosis. Ann Diagn Pathol. 2018;33:6–10.

  7. 7.

    Le Loarer F, Laffont S, Lesluyes T, et al. Clinicopathologic and molecular features of a series of 41 biphenotypic sinonasal sarcomas expanding their molecular spectrum. Am J Surg Pathol. 2019;43:747–54.

  8. 8.

    Rooper LM, Huang SC, Antonescu CR, et al. Biphenotypic sinonasal sarcoma: an expanded immunoprofile including consistent nuclear beta-catenin positivity and absence of SOX10 expression. Hum Pathol. 2016;55:44–50.

  9. 9.

    Wang X, Bledsoe KL, Graham RP, et al. Recurrent PAX3-MAML3 fusion in biphenotypic sinonasal sarcoma. Nat Genet. 2014;46:666–8.

  10. 10.

    Wong WJ, Lauria A, Hornick JL, et al. Alternate PAX3-FOXO1 oncogenic fusion in biphenotypic sinonasal sarcoma. Genes Chromosom Cancer. 2016;55:25–9.

  11. 11.

    Cannon RB, Wiggins RH, Witt BL, et al. Imaging and outcomes for a new entity: low-grade sinonasal sarcoma with neural and myogenic features. J Neurol Surg Rep. 2017;78:e15–9.

  12. 12.

    Wang Q, Fang WH, Krupinski J, et al. Pax genes in embryogenesis and oncogenesis. J Cell Mol Med. 2008;12:2281–94.

  13. 13.

    Lang D, Lu MM, Huang L, et al. Pax3 functions at a nodal point in melanocyte stem cell differentiation. Nature. 2005;433:884–7.

  14. 14.

    Medic S, Ziman M. PAX3 across the spectrum: from melanoblast to melanoma. Crit Rev Biochem Mol Biol. 2009;44:85–97.

  15. 15.

    Nakazaki H, Reddy AC, Mania-Farnell BL, et al. Key basic helix-loop-helix transcription factor genes Hes1 and Ngn2 are regulated by Pax3 during mouse embryonic development. Dev Biol. 2008;316:510–23.

  16. 16.

    Heffner DK, Gnepp DR. Sinonasal fibrosarcomas, malignant schwannomas, and "Triton" tumors. A clinicopathologic study of 67 cases. Cancer. 1992;70:1089–101.

  17. 17.

    Hellquist HB, Lundgren J. Neurogenic sarcoma of the sinonasal tract. J Laryngol Otol. 1991;105:186–90.

  18. 18.

    Gil Z, Fliss DM, Voskoboimik N, et al. Two novel translocations, t(2;4)(q35;q31) and t(X;12)(q22;q24), as the only karyotypic abnormalities in a malignant peripheral nerve sheath tumor of the skull base. Cancer Genet Cytogenet. 2003;145:139–43.

  19. 19.

    Ducatman BS, Scheithauer BW, Piepgras DG, et al. Malignant peripheral nerve sheath tumors. A clinicopathologic study of 120 cases. Cancer. 1986;57:2006–21.

  20. 20.

    Lee W, Teckie S, Wiesner T, et al. PRC2 is recurrently inactivated through EED or SUZ12 loss in malignant peripheral nerve sheath tumors. Nat Genet. 2014;46:1227–32.

  21. 21.

    Rohrich M, Koelsche C, Schrimpf D, et al. Methylation-based classification of benign and malignant peripheral nerve sheath tumors. Acta Neuropathol. 2016;131:877–87.

  22. 22.

    Schaefer IM, Fletcher CD, Hornick JL. Loss of H3K27 trimethylation distinguishes malignant peripheral nerve sheath tumors from histologic mimics. Mod Pathol. 2016;29:4–13.

  23. 23.

    Cleven AH, Sannaa GA, Briaire-de Bruijn I, et al. Loss of H3K27 tri-methylation is a diagnostic marker for malignant peripheral nerve sheath tumors and an indicator for an inferior survival. Mod Pathol. 2016;29:582–90.

  24. 24.

    Le Guellec S, Macagno N, Velasco V, et al. Loss of H3K27 trimethylation is not suitable for distinguishing malignant peripheral nerve sheath tumor from melanoma: a study of 387 cases including mimicking lesions. Mod Pathol. 2017;30:1677–87.

  25. 25.

    Pekmezci M, Cuevas-Ocampo AK, Perry A, et al. Significance of H3K27me3 loss in the diagnosis of malignant peripheral nerve sheath tumors. Mod Pathol. 2017;30:1710–9.

  26. 26.

    Asano N, Yoshida A, Ichikawa H, et al. Immunohistochemistry for trimethylated H3K27 in the diagnosis of malignant peripheral nerve sheath tumours. Histopathology. 2017;70:385–93.

  27. 27.

    Prieto-Granada CN, Wiesner T, Messina JL, et al. Loss of H3K27me3 expression is a highly sensitive marker for sporadic and radiation-induced MPNST. Am J Surg Pathol. 2016;40:479–89.

  28. 28.

    Agaram NP, LaQuaglia MP, Alaggio R, et al. MYOD1-mutant spindle cell and sclerosing rhabdomyosarcoma: an aggressive subtype irrespective of age. A reappraisal for molecular classification and risk stratification. Mod Pathol. 2019;32:27–36.

  29. 29.

    Cavazzana AO, Schmidt D, Ninfo V, et al. Spindle cell rhabdomyosarcoma. A prognostically favorable variant of rhabdomyosarcoma. Am J Surg Pathol. 1992;16:229–35.

  30. 30.

    Carter CS, East EG, McHugh JB. Biphenotypic sinonasal sarcoma: a review and update. Arch Pathol Lab Med. 2018;142:1196–201.

  31. 31.

    Lasota J, Felisiak-Golabek A, Aly FZ, et al. Nuclear expression and gain-of-function beta-catenin mutation in glomangiopericytoma (sinonasal-type hemangiopericytoma): insight into pathogenesis and a diagnostic marker. Mod Pathol. 2015;28:715–20.

  32. 32.

    Haller F, Bieg M, Moskalev EA, et al. Recurrent mutations within the amino-terminal region of beta-catenin are probable key molecular driver events in sinonasal hemangiopericytoma. Am J Pathol. 2015;185:563–71.

  33. 33.

    Doyle LA, Vivero M, Fletcher CD, et al. Nuclear expression of STAT6 distinguishes solitary fibrous tumor from histologic mimics. Mod Pathol. 2014;27:390–5.

  34. 34.

    Agaram NP, Zhang L, Sung YS, et al. Recurrent NTRK1 gene fusions define a novel subset of locally aggressive lipofibromatosis-like neural tumors. Am J Surg Pathol. 2016;40:1407–16.

  35. 35.

    Suurmeijer AJH, Dickson BC, Swanson D, et al. A novel group of spindle cell tumors defined by S100 and CD34 co-expression shows recurrent fusions involving RAF1, BRAF, and NTRK1/2 genes. Genes Chromosom Cancer. 2018;57:611–21.

  36. 36.

    Davis JL, Lockwood CM, Stohr B, et al. Expanding the spectrum of pediatric NTRK-rearranged mesenchymal tumors. Am J Surg Pathol. 2019;43:435–45.

  37. 37.

    Hung YP, Fletcher CDM, Hornick JL. Evaluation of pan-TRK immunohistochemistry in infantile fibrosarcoma, lipofibromatosis-like neural tumour and histological mimics. Histopathology. 2018;73:634–44.

Download references

Author information

Correspondence to Karen Fritchie.

Ethics declarations

Conflict of interest

The authors have no conflicts to disclose.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Gross, J., Fritchie, K. Soft Tissue Special Issue: Biphenotypic Sinonasal Sarcoma: A Review with Emphasis on Differential Diagnosis. Head and Neck Pathol (2020).

Download citation


  • Sinonasal
  • Sarcoma
  • PAX3
  • MAML3
  • Soft tissue