High-Grade Myoepithelial Carcinoma with EWSR1 :: CREB1 Fusion in the Submandibular Gland of a Young Man: Salivary or Soft Tissue Type?

Myoepithelial carcinoma is an uncommon malignant tumor of neoplastic myoepithelial cells. Myoepithelial carcinoma may arise in salivary glands or within soft tissues, and myoepithelial carcinomas of salivary and soft tissue types are generally regarded as distinct. Fusions involving EWSR1 are a molecular hallmark of soft tissue myoepithelial carcinomas; however, salivary myoepithelial carcinomas typically lack these fusions. We report an unusual high-grade myoepithelial carcinoma arising in the submandibular gland of a man in his 20s, initially diagnosed as extraskeletal Ewing sarcoma due to an EWSR1 rearrangement identified by fluorescence in situ hybridization (FISH). The resection specimen demonstrated a round cell tumor with multiple growth patterns and high-grade features. No benign pleomorphic adenoma component was identified. Tumor cells were positive for pankeratin, S100, and SOX10, and were only weakly positive for CD99. Next-generation sequencing unearthed an EWSR1 :: CREB1 fusion, which has been identified in a handful of diverse soft tissue neoplasms. While EWSR1 signal rearrangements by FISH have been described, a bona fide fusion involving EWSR1 is novel, if this tumor does indeed represent a myoepithelial carcinoma of salivary origin. No primary salivary tumors with a CREB1 fusion partner have been described. We highlight the possibility that myoepithelial carcinoma may arise within the major salivary glands, and that definitive distinction between salivary myoepithelial carcinoma and soft tissue myoepithelial carcinoma is quite difficult, even with molecular data.