High aberrant expression of CSF1 has been implicated in the development of TGCT and recent studies have shown promising activity of several CSF1R inhibitors against benign diffuse-type TGCT; however, little is known about their effects in malignant TGCT.
We recently demonstrated that CSF1, the ligand of the tyrosine kinase receptor, CSF1R, can be translocated in pigmented villonodular synovitis (PVNS) and tenosynovial giant cell tumor (TGCT).
In cases of TGCT and PVNS carrying this translocation, it is present in a minority of the intratumoral cells, leading to CSF1 expression only in these cells, whereas the majority of cells express CSF1R but not CSF1, suggesting a tumor-landscaping effect with aberrant CSF1 expression in the neoplastic cells, leading to the abnormal accumulation of nonneoplastic cells that form a tumorous mass.