Modern Interpretation of Giant Cell Tumor of Bone: Predominantly Osteoclastogenic Stromal Tumor

Department of Orthopaedic Surgery, Columbia University Medical Center, Columbia University, New York, NY 10032, USA.
Clinics in orthopedic surgery 06/2012; 4(2):107-16. DOI: 10.4055/cios.2012.4.2.107
Source: PubMed


Owing to striking features of numerous multinucleated cells and bone destruction, giant cell tumor (GCT) of bone, often called as osteoclastoma, has drawn major attractions from orthopaedic surgeons, pathologists, and radiologists. The name GCT or osteoclastoma gives a false impression of a tumor comprising of proliferating osteoclasts or osteoclast precursors. The underlying mechanisms for excessive osteoclastogenesis are intriguing and GCT has served as an exciting disease model representing a paradigm of osteoclastogenesis for bone biologists. The modern interpretation of GCT is predominantly osteoclastogenic stromal cell tumors of mesenchymal origin. A diverse array of inflammatory cytokines and chemokines disrupts osteoblastic differentiation and promotes the formation of excessive multi-nucleated osteoclastic cells. Pro-osteoclastogenic cytokines such as receptor activator of nuclear factor kappa-B ligand (RANKL), interleukin (IL)-6, and tumor necrosis factor (TNF) as well as monocyte-recruiting chemokines such as stromal cell-derived factor-1 (SDF-1) and monocyte chemoattractant protein (MCP)-1 participate in unfavorable osteoclastogenesis and bone destruction. This model represents a self-sufficient osteoclastogenic paracrine loop in a localized area. Consistent with this paradigm, a recombinant RANK-Fc protein and bisphosphonates are currently being tried for GCT treatment in addition to surgical excision and conventional topical adjuvant therapies.

Download full-text


Available from: Yuhree Kim, Mar 23, 2015
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Giant cell tumour of bone is aggressive lesion, although benign. The involvement of the metacarpal bone is rare. Herein, we present a case of a 41-year-old male complaining of painless swelling of the posterior surface of the fourth right metacarpal bone. The radiological examination showed a large expansile lesion with cortical destruction involving the entire fourth metacarpal. Two stages treatment was performed: the first stage included total resection of the metacarpal bone together with partial excision of the surrounding muscles and reconstruction with fibular autograft and carpo-metacarpal arthrodesis; in the second stage a metacarpo-phalangeal cement-free endoprosthesis was done. We also discuss clinical, radiological, and therapeutical characteristics of this pathology.
    Full-text · Article · Jan 2012
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Giant cell tumour of bone is aggressive lesion, although benign. Foot and ankle bone involvement is rare. Herein, we present a case of a 26-year-old woman complaining of increasing pain and swelling along the antero-lateral aspect of the left ankle. Limitation of motion in the joint also occurred. Imaging and biopsy confirmed the diagnosis of giant cell tumour of bone. The lesion was treated with segmental en-bloc resection and ankle arthrodesis with good functional outcome. We also discuss clinical, radiological, and therapeutical characteristics of this pathology.
    Full-text · Article · Jan 2013
  • [Show abstract] [Hide abstract]
    ABSTRACT: Giant cell tumors of bone (GCTBs) exhibit aggressive bone lytic behavior. Studies have shown that interleukin 17A (IL-17A) is involved pathological bone resorption in various skeletal disorders. Thus, we have investigated the role of IL-17A in GCTBs. We evaluated the progression of GCTBs using Campanacci grading and Enneking staging systems in 74 GCTB patients. The expression of IL-17A and the IL-17A receptor A (IL-17RA) was assessed in GCTB tissues and in both multinucleated giant cells (MNGCs) and stromal cells (SCs) cultured in vitro using immunostaining and RT-PCR. The effects of IL-17A on the osteolytic activity of the MNGCs and the proliferation of the SCs were investigated using the "pit" formation and MTT assays, respectively. The effects of IL-17A on the expression of pro-osteolytic factors were examined in primary cultured MNGCs and SCs using RT-PCR, Western blotting, and gene expression microarrays. In GCTBs, we detected abundant levels of IL-17A, which were associated with tumor extension and grade. IL-17A is predominantly produced by MNGCs, whereas IL-17RA is expressed by both MNGCs and SCs in GCTBs. In the MNGCs, the IL-17A increased the mRNA expression of IL-17A and pro-osteolytic enzymes, also enhanced osteolytic ability. In the SCs, the IL-17A stimulated cellular proliferation and the expression of pro-osteolytic factors, including RANKL through myc and STAT3, respectively. In addition, IL-17A stimulated in vivo tumor growth and the extent of angiogenesis in GCTBs. IL-17A stimulates the progression of GCTBs and might represent a useful candidate marker for progression and as a therapeutic target for GCTBs.
    No preview · Article · Jul 2013 · Clinical Cancer Research
Show more