TGCT is a locally aggressive tumor, meaning it is not cancerous, but can be aggressive and cause unpredictable symptoms. Importantly, only a subset of the TGCT cells are abnormal and there are no known abnormalities in the rest of the body. TGCT growth occurs when TGCT cells 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, producing this protein in excess (1). TGCT relies on the over production of CSF1 to recruit tumor-promoting cells to the tumor (2). The over production of this protein, CSF1, by the tumor cells is the driving force for other tumor-promoting cells to incorporate into 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). CSF1 is also involved in the clearance and repair of damaged cells.
In TGCT, a chromosomal abnormality occurs in which a segment of one chromosome breaks off and attaches to another, a process known as a translocation (4). This is depicted in part B of the schematic. In the schematic (Part B), a fragment of chromosome 1 attaches to chromosome 2, leading to overproduction of the CSF1 protein. This excess CSF1 drives the recruitment of immune cells and contributes to the inflammation and swelling commonly seen in TGCT. This over production of CSF1 may also contribute to the inflammation and swelling seen in some cases (4). It is believed that treatment that blocks CSF1 at the cell source, such as pexidartinib (Turalio), vimseltinib (Romvimza) and imatinib, target the immune cells being recruited and not the tumor cells themselves (5).
To learn about the medications available, go to Medication.
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 5. David G.P.van IJzendoorn, MagdalenaMatusiak, et al. Interactions in CSF1-driven Tenosynovial Giant Cell Tumors. BioRxiv. 2022. Doi: 10.1101/2022.06.01.494428
