PMC4919599_01
Histological features of biphenotypic sinonasal sarcoma. The tumor consists of a highly cellular submucosal proliferation (A) of uniform spindle cells with bland nuclear features (B), arranged in short fascicles, with bone invasion (C) and no mitotic figures or necrotic areas. D, Multifocal expression of S100 protein, smooth muscle actin (SMA), and scattered myogenin (MYOG) demonstrating focal rhabdomyoblastic differentiation. Diffuse expression and nuclear accumulation of beta-catenin (beta-CAT) indicates activation of Wnt signaling.
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F1
Histologically, the tumor was a homogeneous and highly cellular proliferation of uniform spindle cells, arranged in short fascicles, with bland, elongated nuclei and scant cytoplasm (Fig. 1A). S100 protein, smooth muscle actin, and desmin. Scattered cells expressed myogenin, corresponding to focal rhabdomyoblastic differentiation (Fig. 1B). Accordingly, immunohistochemistry demonstrated nuclear accumulation of beta-catenin, indicating activation of Wnt signaling (Fig. 1D).
A, Break-apart FISH demonstrating split of 5' (red) and 3' (green) ends of one copy of FOXO1. B, RT-PCR demonstrates presence of PAX3-FOXO1 fusion transcript in biphenotypic sinonasal sarcoma (SNS) and alveolar rhabdomyosarcoma (RMS, control). No PAX3-MAML3 fusion transcript was detected using two independent previously published sets of primers. GAPDH served as control. C, Predicted exon structure and transcript Sanger sequencing demonstrating an in-frame fusion between exon 7 of PAX3 and exon 2 of FOXO1.
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F2
Rearrangement of the FOXO1 locus in chromosome 13q14 was demonstrated by fluorescence in situ hybridization (FISH) using a break-apart probe (Fig. 2A). RT-PCR, followed by Sanger sequencing, demonstrated an in-frame fusion between exon 7 of PAX3 and exon 2 of FOXO1 (Fig. 2B and 2C). In contrast, PAX3-MAML3 gene fusion was absent (Fig. 2B).