The pathogenesis of tenosynovial giant cell tumor (TGCT) is driven by dysregulation of the CSF1 gene, leading to overexpression of the CSF1 ligand.1,2
CSF1R signaling regulates the production and differentiation of macrophages. CSF1R is expressed
in multiple tissue types and cell subsets, such as hematopoietic stem cells, monocytes,
macrophages, microglia and osteoclasts3
CSF1 overexpression promotes tumor growth via local proliferation of CSF1R-dependent inflammatory cells, such as macrophages.2,4
Overexpression of CSF1 promotes cell proliferation and accumulation in the synovium2
Binding of CSF1R leads to activation of signaling pathways that modulate differentiation, proliferation and chemotaxis toward the source of CSF12
Inflammatory cells, including macrophages, are recruited to the joint cavity1
Research indicates that CSF1-expressing neoplastic cells make up 2–16% of the tumor; the remaining cells in these tumors are non-neoplastic cells recruited by the local overexpression of CSF15
CSF1R belongs to the platelet-derived growth factor family, and plays a key role in neoplastic and inflammatory diseases2
In TGCT, the CSF1-driven inflammatory response is characterized by macrophage accumulation and synovial proliferation, leading to swelling, pain, joint stiffness, limited range of motion and fatigue.6
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