TGCT occurs when cells in the joint lining produce too much of a specific protein, called colony stimulative factor 1 (CSF1). It is estimated that 2-16% of the tumor cells are abnormal(1). TGCT relies on the over production of CSF1 to recruit tumor-promoting cells to the central tumor(2). The over production of this protein, CSF1, by the tumor cells is the driving force for the recruitment of other tumor-promoting cells as part of the tumor, leading to tumor development and growth (A).
In normal healthy cells, CSF1 is used to help white blood cells grow and develop into their designated function(3).
In TGCT, a chromosome abnormality occurs leading to a break in a chromosome and that broken portion attaches to a different chromosome within the tumor(4). This biological event is called a translocation, depicted in part B of the schematic. In B, chromosome 1 (Chr 1) and chromosome 2 (Chr 2) swap portions of their chromosome, leading to over production of the CSF1 protein in TGCT. This over production of CSF1 may also contribute to the inflammation and swelling seen in some cases(4).
References
1. Mastboom M. tenosynovial giant cell tumours. Leiden Univ. 2018. 2. West R.B., Rubin R.P., Miller M.A., 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 3. Stanley ER, Berg KL, Einstein DB, et al. Biology and action of colony-stimulating factor-1. Mol Reprod Dev. 1997. doi:10.1002/(SICI)1098-2795(199701)46:1<4::AID-MRD2>3.0.CO;2-V 4. 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. doi:10.1097/PAS.0b013e31802b86f8
