Fusion-positive soft tissue tumors: A selective review

Even for experts, the diagnosis of soft tissue tumors remains challenging, owing to their rarity, striking diversity, and sometimes subtle morphological differences. Over the past decade, however, significant advances have been made in our collective understanding of the molecular genetic pathogenesis of these rare lesions, especially with the discovery that many are characterized by the presence of characteristic gene fusions, which can be exploited for diagnostic purposes. This review article focuses on four fusion-driven soft tissue tumors which illustrate different aspects of our evolving understanding of these tumors: (1) NUTM1-rearranged sarcoma, a prototypical example of a novel, clinically significant entity defined almost entirely by molecular genetics; (2) SRF-rearranged myoid neoplasm, an entity whose recognition greatly clarifies our understanding of pediatric "leiomyosarcomas;" (3) superficial FET-ETS neurocristic tumor, a very recently described, clinically benign entity sharing identical fusion events with often-lethal Ewing sarcoma; and (4) an evolving family of glomoid/myoid neoplasms harboring EWSR1::WT1 fusions, but clearly differing from desmoplastic small round cell tumor. These examples illustrate the complexity of fusion-driven soft tissue tumors and the importance of integrating molecular genetic testing with other clinicopathological data, rather than viewing it in isolation.