Clin Orthop Surg.  2012 Jun;4(2):107-116. 10.4055/cios.2012.4.2.107.

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

• Kim Y
• Nizami S
• Goto H
• Lee FY

• KMID: 1383871
• DOI: http://doi.org/10.4055/cios.2012.4.2.107

Abstract

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.

Keyword

Bone tumor; Giant cell tumor; Osteoclast

MeSH Terms

Bone Neoplasms/diagnosis/*pathology/therapy
Giant Cell Tumor of Bone/diagnosis/*pathology/therapy
Humans

Figure

• 

  Fig. 1 Osteoclastogenesis by giant-cell tumor is constituted of stromal cells (GCTSCs). A diagram representing pathophysiology of osteoclast-rich giant-cell tumor (GCT). A neoplastic component of GCT is mainly dysfunctional stromal cells. Mesenchymal stromal cell markers such as STRO-1 and SDF-1α are positive. Stromal cells produce sufficient chemokines and cytokines which recruit CXCR4 (+) osteoclast precursors from blood vessels and promote osteoclastogenesis. SDF: stromal cell-derived factor, MCP: monocyte chemoattractant protein, TNF: tumor necrosis factor, IL: interleukin, RANKL: receptor activator of nuclear factor kappa-B ligand, RANK: receptor activator of nuclear factor kappa, M-CSF: macrophage colony-stimulating factor.

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