Chondroblastoma Expresses RANKL by RNA In Situ Hybridization and May Respond to Denosumab Therapy. Am J Surg Pathol 2020 Dec;44(12):1581-1590
Date
08/23/2020Pubmed ID
32826531DOI
10.1097/PAS.0000000000001568Scopus ID
2-s2.0-85091274697 (requires institutional sign-in at Scopus site) 11 CitationsAbstract
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-κB 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 VAuthor
Jason A. Jarzembowski MD, PhD Sr Associate Dean, CEO CSG, Professor in the Pathology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AdolescentAdult
Aged
Antineoplastic Agents
Biomarkers, Tumor
Bone Neoplasms
Chondroblastoma
Denosumab
Female
Humans
In Situ Hybridization
Male
Middle Aged
Molecular Targeted Therapy
RANK Ligand
Young Adult
