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9 slides generated from the cancer page, with a quiz from the open benchmark and speaker notes that cite the sources. Arrow keys move between slides; Print gives one slide per page.
TGCT is a benign but destructive tumour of the joint lining, classed with soft-tissue sarcomas, in which a few cells carrying a CSF1 gene fusion recruit a crowd of normal immune cells that eat away at the joint. Surgery cures most localised cases, and for diffuse or recurrent disease two pills that block the CSF1 receptor, pexidartinib and vimseltinib, shrink tumours and restore joint function.
TGCT is a locally aggressive neoplasm of synovium, bursa and tendon sheath. Its biology is a landscape effect: a minority of neoplastic cells carry a translocation placing CSF1 under the COL6A3 promoter, overproducing colony-stimulating factor 1, which recruits CSF1R-expressing macrophages and osteoclast-like giant cells that make up most of the mass and cause pain, swelling, haemarthrosis and cartilage destruction. Localised (nodular) disease is cured by excision; diffuse disease (formerly pigmented villonodular synovitis) recurs after synovectomy in a large fraction of cases and can lead to joint replacement in young adults.
Because the tumour depends on CSF1 signalling, CSF1R inhibition is mechanistically exact. Pexidartinib (ENLIVEN, Lancet 2019) was the first FDA-approved systemic therapy for TGCT (August 2019), with objective responses and improved range of motion; it carries a boxed warning and REMS programme for serious and occasionally fatal cholestatic hepatotoxicity, which limited uptake and blocked EU approval. Vimseltinib, a switch-control CSF1R inhibitor, showed improved response and function versus placebo in MOTION (Lancet 2024) without the hepatotoxicity signal and was approved by the FDA in February 2025. Emactuzumab (anti-CSF1R antibody) is in the phase 3 TANGENT trial.
| Setting | Approach | Guideline |
|---|---|---|
| Localised TGCT | Marginal excision; recurrence is uncommon and re-excision is curative in most cases. | not mapped |
| Diffuse TGCT, resectable | Open or arthroscopic synovectomy by a sarcoma orthopaedic team; consider neoadjuvant CSF1R inhibition for large tumours (trial setting). | not mapped |
| Diffuse TGCT where surgery would cause severe morbidity or after recurrence | CSF1R inhibitor: vimseltinib (MOTION) or pexidartinib (ENLIVEN, with REMS hepatic monitoring); imatinib or nilotinib off label where neither is available. | NCCN Category 2A |