Treatment of tenosynovial giant cell tumor and pigmented villonodular synovitis
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Vinod Ravi1, Wei-Lien Wang, Valerae O Lewis
1Department of Sarcoma Medical Oncology, UT MD Anderson Cancer Center, Houston, Texas 77030, USA. vravi@mdanderson.org
Purpose Of Review:
To review recent developments in the molecular pathogenesis of tenosynovial giant cell tumor (TGCT) or pigmented villonodular synovitis (PVNS) and its therapeutic implications.
Recent Findings:
TGCT or PVNS is a benign clonal neoplastic proliferation arising from the synovium characterized by a minor population of intratumoral cells that harbor a recurrent translocation. These cells overexpress CSF1, resulting in recruitment of CSF1R-bearing macrophages that are polyclonal and make up the bulk of the tumor. Inhibition of CSF1R using small molecule inhibitors such as imatinib, nilotinib or sunitinib can result in clinical, radiological and functional improvement in the affected joint.
Summary:
Currently, surgery remains the treatment of choice for patients with TGCT/PVNS. Localized TGCT/PVNS is managed by marginal excision. Recurrences occur in 8-20% of patients and are easily managed by re-excision. Diffuse TGCT/PVNS tends to recur more often (33-50%) and has a much more aggressive clinical course. Patients are often symptomatic and require multiple surgical procedures during their lifetime. For patients with unresectable disease or multiple recurrences, systemic therapy using CSF1R inhibitors may help delay or avoid surgical procedures and improve functional outcomes.
Insights
Tenosynovial giant cell tumor (TGCT), or pigmented villonodular synovitis (PVNS), is a neoplastic proliferation driven by CSF1. Targeting CSF1R with inhibitors offers a promising therapeutic option for unresectable or recurrent cases.
Area of Science:
- Oncology
- Molecular Biology
- Pathology
Background:
- Tenosynovial giant cell tumor (TGCT), also known as pigmented villonodular synovitis (PVNS), is a rare benign neoplastic proliferation.
- It originates from the synovium and is characterized by a specific genetic translocation in a subset of tumor cells.
Purpose of the Study:
- To review recent advancements in understanding the molecular pathogenesis of TGCT/PVNS.
- To explore the therapeutic implications of these molecular discoveries.
Main Methods:
- Review of recent scientific literature on TGCT/PVNS molecular pathogenesis.
- Analysis of therapeutic strategies based on molecular findings, particularly CSF1R inhibition.
Main Results:
- TGCT/PVNS arises from clonal neoplastic cells overexpressing CSF1, attracting CSF1R-bearing macrophages.
- Inhibition of CSF1R with small molecule inhibitors has shown clinical, radiological, and functional improvements.
Conclusions:
- Surgery is the primary treatment for TGCT/PVNS, with varying recurrence rates for localized versus diffuse forms.
- For unresectable or recurrent disease, CSF1R inhibitors represent a potential systemic therapy to manage symptoms and improve outcomes, potentially avoiding surgery.
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