Clinical Utility of Anchored Multiplex Solid Fusion Assay for Diagnosis of Bone and Soft Tissue Tumors

Am J Surg Pathol. 2021 Aug 1;45(8):1127-1137. doi: 10.1097/PAS.0000000000001745.


Sarcoma diagnosis has become increasingly complex, requiring a combination of morphology, immunohistochemistry, and molecular studies to derive specific diagnoses. We evaluated the role of anchored multiplex polymerase chain reaction-based gene fusion assay in sarcoma diagnostics. Between 2015 and 2018, bone and soft tissue sarcomas with fusion assay results were compared with the histologic diagnosis. Of 143 sarcomas tested for fusions, 43 (30%) had a detectable fusion. In review, they could be classified into 2 main categories: (1) 31 tumors with concordant morphologic and fusion data; and (2) 12 tumors where the fusion panel identified an unexpected rearrangement that played a significant role in classification. The overall concordance of the fusion assay results with morphology/immunohistochemistry or alternate confirmatory molecular studies was 83%. Collectively, anchored multiplex polymerase chain reaction-based solid fusion assay represents a robust means of detecting targeted fusions with known and novel partners. The predictive value of the panel is highest in tumors that show a monomorphic cell population, round cell tumors, as well as tumors rich in inflammatory cells. However, with an increased ability to discover fusions of uncertain significance, it remains essential to emphasize that the diagnosis of bone and soft tissue neoplasms requires the integration of morphology and immunohistochemical profile with these molecular methods, for accurate diagnosis and optimal clinical management of sarcomas.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Bone Neoplasms / diagnosis*
  • Bone Neoplasms / genetics
  • Child
  • Female
  • High-Throughput Nucleotide Sequencing / methods*
  • Humans
  • Male
  • Middle Aged
  • Multiplex Polymerase Chain Reaction / methods*
  • Sarcoma / diagnosis*
  • Sarcoma / genetics
  • Soft Tissue Neoplasms / diagnosis*
  • Soft Tissue Neoplasms / genetics
  • Young Adult