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Neoplastic lesions
TGCT is a reactive, inflammatory neoplasm, although originally it was regarded as a nontumoral process.1,3,4
Molecular pathogenesis
As explained above, pathogenesis of TGCT is believed to start when a small number of neoplastic cells that arise from the lining of the synovium overexpress a growth factor called CSF-1. In most patients, CSF-1 overexpression is reported as a result of a genetic translocation.1,2
Tumor landscape
Typically, TGCT tumors are composed of a small number of these neoplastic cells (2% to 16%) and a high number of CSF-1R–expressing myeloid-lineage cells, including monocytes and macrophages, recruited through CSF-1 signaling.1,3
CSF-1 and TGCT formation and progression
Autocrine stimulation
CSF-1 may activate CSF-1R in cells within
the tumor, resulting in the proliferation of neoplastic cells.1
Paracrine effect
CSF-1 may recruit CSF-1R–expressing myeloid-lineage cells that comprise
the majority of the tumor mass.1
TGCT morbidity
CSF-1 overexpression may also contribute
to the inflammation and osteochondral destruction seen in some cases of tenosynovial giant cell tumor (TGCT)
within the affected joint.2,5
References
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- West RB, Rubin BP, Miller MA, et al. A landscape effect in tenosynovial giant-cell tumor from activation of CSF1 expression by a translocation in a minority of tumor cells. Proc Natl Acad Sci U S A. 2006;103(3):690-695. doi:10.1073/pnas.0507321103
- Cupp JS, Miller MA, Montgomery KD, et al. Translocation and expression of CSF1 in pigmented villonodular synovitis, tenosynovial giant cell tumor, rheumatoid arthritis and other reactive synovitides. Am J Surg Pathol. 2007;31(6):970-976. doi:10.1097/PAS.0b013e31802b86f8
- So-called fibrohistiocytic tumours. In: Fletcher CDM, Bridge JA, Hogendoorn PCW, Mertens F, eds. WHO Classification of Tumours of Soft Tissue and Bone. 4th ed. International Agency for Research on Cancer; 2013:99-108. Bosman FT, Jaffe ES, Lakhani SR, Ohgaki H, eds. World Health Organization Classification of Tumours; vol 5.
- Gouin F, Noailles T. Localized and diffuse forms of tenosynovial giant cell tumor (formerly giant cell tumor of the tendon sheath and pigmented villonodular synovitis). Orthop Traumatol Surg Res. 2017;103(1S):S91-S97. http://dx.doi.org/10.1016/j.otsr.2016.11.002
- Ota T, Urakawa H, Kozawa E, et al. Expression of colony-stimulating factor 1 is associated with occurrence of osteochondral change in pigmented villonodular synovitis. Tumor Biol. 2015;36(7):5361-5367. doi:10.1007/s13277-015-3197-5
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