TGCT in the joints and tendon sheaths negatively impact quality of life.

Not all patients are eligible for surgery due to tumor characteristics and chance of recurrence.

Overexpression of CSF1 leads to accumulation of CSF1R and increased neoplastic TGCT.

Molecular pathways have been identified as potential therapeutic targets for TGCT.

Multiple systemic therapies have been evaluated or are under investigation.

Tenosynovial giant cell tumors (TGCT) are rare, locally aggressive, mesenchymal tumors occurring in the joints and tendon sheaths, which can cause pain, swelling, and have a substantial negative impact on patient quality of life. While surgery is the current standard of care for most cases of TGCT, there are several drawbacks including risk of recurrence and repeated operations. As such, systemic therapies have an important role in the treatment of TGCT. Encompassing both inflammatory and tumorous features, the pathological mechanism of TGCT is relatively complex and the development of effective drugs requires in-depth research and analysis of these mechanisms. Colony stimulating factor 1 (CSF1) is one of several known drivers in TGCT and has been a focus of investigation, among other potential therapeutic targets. Systemic treatments for TGCT have been utilized as part of a multimodal therapeutic strategy for patients who have recurrent or refractory disease, or who are not amenable to surgery. This review summarizes current knowledge of the mechanisms underlying tumorigenesis in TGCT, providing an overview of the key drivers and corresponding therapeutic targets. Further research into the specific mechanisms of TGCT and further development of diagnostics and treatments are warranted.

TGCT

CSF1

Pathophysiology

Therapeutics

Tumorigenesis

Immunology

© 2025 The Authors. Published by Elsevier B.V.