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

Le Loarer, François, MD, PhD*,†,‡; Laffont, Sophie, MD*; Lesluyes, Tom, MSc†,‡,§; Tirode, Franck, PhD∥,¶; Antonescu, Cristina, MD#; Baglin, Anne-Catherine, MD**; Delespaul, Lucile, MSc†,‡,§; Soubeyran, Isabelle, MD, PhD*,‡; Hostein, Isabelle, PhD*; Pérot, Gaëlle, PhD*; Chibon, Frédéric, PhD‡,§; Baud, Jessica, PhD; Le Guellec, Sophie, MD††; Karanian, Marie, MD∥,¶,‡‡; Costes-Martineau, Valérie, MD§§; Castain, Claire, MD∥∥; Eimer, Sandrine, MD∥∥; Le Bail, Brigitte, MD†,∥∥; Wassef, Michel, MD**; Coindre, Jean-Michel, MD*,†,‡

The American Journal of Surgical Pathology: June 2019 - Volume 43 - Issue 6 - p 747–754
doi: 10.1097/PAS.0000000000001238
Original Articles

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.

*Department of Pathology, Institut Bergonie


∥∥Department of Pathology, CHU de Bordeaux, Bordeaux

Université de Bordeaux, Institut Bergonié, Talence

§Cancer Research Center of Toulouse

††Department of Pathology, Institut Claudius Regaud, Institut Universitaire du Cancer Toulouse-Oncopole, Toulouse

INSERM 1052, CNRS 5286, Cancer Research Center of Lyon, University of Lyon, Université Claude Bernard Lyon 1

Department of Translational Research and Innovation, Centre Leon Berard

‡‡Department of Pathology, Centre Leon Berard, Lyon

**Department of Pathology, Hôpital Lariboisiere, Paris

§§Department of Pathology, CHU de Montpellier, Montpellier, France

#Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY

F.L.L. and S.L. contributed equally

M.W. and J.-M.C.: supervised the work.

Conflicts of Interest and Source of Funding: The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article.

Correspondence: Jean-Michel Coindre, MD, Institut Bergonié, 276 cours de I'Argonne, 33000 Bordeaux, France (e-mail:

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