Original ArticlesClinical Utility of Anchored Multiplex Solid Fusion Assay for Diagnosis of Bone and Soft Tissue TumorsChebib, Ivan MD*; Taylor, Martin S. MD, PhD*; Nardi, Valentina MD*; Rivera, Miguel N. MD*; Lennerz, Jochen K. MD, PhD*; Cote, Gregory M. MD, PhD†; Choy, Edwin MD, PhD†; Lozano Calderón, Santiago A. MD, PhD‡; Raskin, Kevin A. MD‡; Schwab, Joseph H. MD‡; Mullen, John T. MD§; Chen, Yen-Lin E. MD∥; Hung, Yin P. MD, PhD*; Nielsen, Gunnlaugur P. MD*; Deshpande, Vikram MBBS*Author Information *James Homer Wright Pathology Laboratories †Department of Internal Medicine, Division of Hematology/Oncology Departments of ‡Orthopedic Oncology §Surgical Oncology ∥Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA Conflicts of Interest and Source of Funding: The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article. Correspondence: Ivan Chebib, MD, James Homer Wright Pathology Laboratories, WRN2 55 Fruit Street, Boston, MA 02139 (e-mail: [email protected]). The American Journal of Surgical Pathology: August 2021 - Volume 45 - Issue 8 - p 1127-1137 doi: 10.1097/PAS.0000000000001745 Buy SDC Metrics Abstract 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. Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.