Fusion Sarcomas: Diagnostic Markers and Detection Methods for Newly Defined Entities
This review characterizes several recently defined fusion-driven sarcoma entities including CIC-DUX4, BCOR-CCNB3, EWSR1-NFATC2, ACTB-GLI1, and NTRK-fusion sarcomas. Each entity is described with its distinctive histopathology, immunohistochemical profile, and clinical behavior. The authors compare detection methodologies including NGS panels, anchored multiplex PCR, comprehensive RNA sequencing, and FISH with dual-fusion probes, providing practical guidance for laboratories integrating fusion testing into sarcoma diagnostics.
The original study
New fusion sarcomas: histopathology and clinical significance of selected entities.
- Authors
- Miettinen M, Felisiak-Golabek A, Luiña Contreras A, Glod J, Kaplan RN, Killian JK, et al.
- Journal
- Human pathology
- Type
- Journal Article, Review
- PMID
- 30633925
Original abstract
Many sarcomas contain gene fusions that can be pathogenetic mechanisms and diagnostic markers. In this article we review selected fusion sarcomas and techniques for their detection. CIC-DUX4 fusion sarcoma is a round cell tumor now considered an entity separate from Ewing sarcoma with a more aggressive clinical course, occurrence in older age, and predilection to soft tissues. It is composed of larger cells than Ewing sarcoma and often has prominent necrosis. Nuclear DUX4 expression is a promising immuno histochemical marker. BCOR-CCNB3 fusion sarcoma is cyclin B3-positive, usually occurs in bone or soft tissue of children, and may mimic a poorly differentiated synovial sarcoma. EWSR1-NFATC2 sarcoma may present in bone or soft tissue. It is typically composed of small round cells in a trabecular pattern in a myxoid matrix resembling myoepithelioma. ACTB-GLI1 fusion sarcoma may mimic a skin adnexal carcinoma, showing focal expression of epithelial markers and S100 protein. NTRK-fusion sarcomas include, in addition to infantile fibrosarcoma with ETV6-NTRK3 fusion, LMNA-NTRK1 fusion sarcoma, a low-grade spindle cell sarcoma seen in peripheral soft tissues in children and young adults. Methods to detect gene fusions include next-generation sequencing panels, anchored multiplex polymerase chain reaction systems to detect partner for a known fusion gene, and comprehensive RNA sequencing to detect virtually all gene fusions. In situ hybridization testing using probes for both fusion partners can be used as an alternative confirmation technique, especially in the absence of satisfactory RNA yield. In addition, fusion protein-related and other immunohistochemical markers can have a high specificity for fusion sarcomas.