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Chondroblastoma Expresses RANKL by RNA In Situ Hybridization and May Respond to Denosumab Therapy. Am J Surg Pathol 2020 12;44(12):1581-1590



Pubmed ID




Scopus ID

2-s2.0-85091274697   3 Citations


Lesions of bone featuring osteoclast-like giant cells comprise a diverse group of entities, including giant cell tumor (GCT) of bone, chondroblastoma, and aneurysmal bone cyst, among others. The receptor activator of nuclear factor-I?B ligand (RANKL) has been implicated in the pathogenesis of GCT of bone and may play a role in the pathogenesis of other giant cell-rich lesions as well. In addition, RANKL inhibitors (denosumab) have also been shown to have some efficacy in treating some giant cell-rich lesions. Herein, we examine RANKL expression by RNA in situ hybridization in a total of 84 osseous lesions with a focus on chondroblastoma, GCT, fibrous dysplasia, and aneurysmal bone cyst. The lesions were tested for RANKL expression using a chromogenic RNA in situ hybridization assay. RANKL expression was identified in 24/25 (96%) GCT, 24/26 (92%) chondroblastomas, 6/7 (86%) aneurysmal bone cysts, and 3/16 (19%) patients with fibrous dysplasia. RANKL expression was statistically lower in chondroblastoma and aneurysmal bone cyst compared with GCT. RANKL reactivity in fibrous dysplasia was exclusively seen in the 3 cases with osteoclast-type giant cells. Our results indicate a high proportion of chondroblastomas, GCTs, and aneurysmal bone cysts express RANKL while reactivity in fibrous dysplasia is dependent on the presence of osteoclast-type giant cells. On the basis of the success of denosumab therapy for GCTs, our results indicate that it may be a potential therapeutic option in other primary osseous tumors.

Author List

Suster DI, Kurzawa P, Neyaz A, Jarzembowski JA, Lozano-Calderon S, Raskin K, Schwab J, Choy E, Chebib I, Deshpande V


Jason A. Jarzembowski MD, PhD Sr Associate Dean, CEO CSG, Professor in the Pathology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Antineoplastic Agents
Biomarkers, Tumor
Bone Neoplasms
In Situ Hybridization
Middle Aged
Molecular Targeted Therapy
RANK Ligand
Young Adult