Original ArticlesImmunohistochemical Characterization of Giant Cell Tumor of Bone Treated With Denosumab Support for Osteoblastic DifferentiationKerr, Darcy A. MD*; Brcic, Iva MD†; Diaz-Perez, Julio A. MD*; Shih, Angela MD‡; Wilky, Breelyn A. MD§; Pretell-Mazzini, Juan MD∥; Subhawong, Ty K. MD¶; Nielsen, G. Petur MD‡; Rosenberg, Andrew E. MD* Author Information Departments of *Pathology ¶Radiology §Department of Medicine, Division of Hematology-Oncology ∥Department of Orthopaedics, Division of Musculoskeletal Oncology, University of Miami Miller School of Medicine, Miami, FL †Department of Pathology, Medical University of Graz, Graz, Austria ‡Department of Pathology, Massachusetts General Hospital, Boston, MA Present address: Darcy A. Kerr, MD, Department of Pathology, Dartmouth-Hitchcock Medical Center, Lebanon, NH; and Geisel School of Medicine at Dartmouth, Hanover, NH. Present address: Breelyn A. Wilky, MD, Department of Medicine, University of Colorado School of Medicine, Aurora, CO. Portions of this work have previously been presented at the United States and Canadian Academy of Pathology 107th Annual Meeting in Vancouver, BC, Canada, March 2018. 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: Darcy A. Kerr, MD, Department of Pathology and Laboratory Medicine, Dartmouth-Hitchcock Medical Center, Borwell Level 4, One Medical Center Drive, Lebanon, NH 03756 (e-mail: [email protected]). The American Journal of Surgical Pathology: January 2021 - Volume 45 - Issue 1 - p 93-100 doi: 10.1097/PAS.0000000000001555 Buy SDC Metrics Abstract Giant cell tumor of bone is a locally aggressive, rarely metastasizing neoplasm. Evidence suggests that the neoplastic cells may be osteoblastic in differentiation. Standard treatment is surgical removal, but medical therapy with denosumab, an inhibitor of receptor activator of nuclear factor-κβ ligand, has become a component of patient management in select cases. Denosumab-treated giant cell tumor of bone (DT-GCTB) shows drastic morphologic changes including the presence of abundant bone. To further determine the relationship of the neoplastic cells to osteoblast phenotype, we performed a morphologic and immunohistochemical study on a series of DT-GCTB. Cases of DT-GCTB were retrieved from surgical pathology files, available slides were reviewed, and immunohistochemistry for H3.3 G34W, SATB2, and p63 was performed. The cohort included 31 tumors from 30 patients (2:3 male:female), ages 15 to 73 years (median=36 y). The morphology of post–denosumab-treated tumors ranged from tumors composed of an abundant bone matrix with few spindle cells to spindle cell-predominant tumors. Five had focal residual classic CGTB, and 2 manifested mild nuclear atypia. The majority expressed all markers: 86.2% for H3.3 G34W, 96.7% for SATB2, and 100% for p63. All markers stained the various tumor components including spindle cells and the cells on the surface of and within the treated tumor bone matrix. Most markers were also positive in reactive-appearing woven bone adjacent to tumor: 84.6% for H3.3 G34W, 100% for SATB2, and 68% for p63. These findings suggest that denosumab treatment of giant cell tumor of bone results in osteoblastic differentiation with bone production. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.