# Tenosynovial giant cell tumour (TGCT)

Source: https://onco.cc/cancers/tenosynovial-giant-cell-tumour/  
OnCo record `tenosynovial-giant-cell-tumour` (Cancer). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Summary

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.

Open questions are treatment duration and rebound after stopping, the role of neoadjuvant CSF1R inhibition before surgery, and how to handle the many patients with disease that is symptomatic but not surgically threatening.

## Fields

- Kind: Cancer
- Last checked: 2026-09-10
- Also known as: TGCT; Pigmented villonodular synovitis; PVNS; Giant cell tumour of the tendon sheath
- Tags: nci-coverage; rare; sarcoma
- Group: sarcoma
- Burden: Localised disease is relatively common (tens of cases per million per year); the diffuse form that needs drugs is rare, at a few cases per million, mostly in adults aged 20 to 50.
- Subtypes: Localised (nodular) TGCT; Diffuse TGCT (pigmented villonodular synovitis); Malignant TGCT (very rare)
- Biomarkers: CSF1 rearrangement (COL6A3-CSF1) in neoplastic cells; CSF1R-positive macrophage-rich infiltrate; MRI pattern (haemosiderin blooming on gradient echo); Liver function tests before and during pexidartinib (REMS)

## Sections of this record

The page is a hub with ten sections in reading order; large sections have their own page. The same plan as JSON: https://onco.cc/api/v1/cancers/tenosynovial-giant-cell-tumour/sections.json

- Overview (on the hub): The TL;DR, the family this cancer belongs to, the organ, who gets it and what the state of the art is. https://onco.cc/cancers/tenosynovial-giant-cell-tumour/#overview [4 state-of-the-art points]
- What it is (on the hub): Anatomy, the subtypes and how they differ, how it is staged, and where advanced disease spreads. https://onco.cc/cancers/tenosynovial-giant-cell-tumour/#what-it-is [3 subtypes]
- Finding it (on the hub): How it shows itself, how it is confirmed, what screening exists, and the biomarkers clinicians test for. https://onco.cc/cancers/tenosynovial-giant-cell-tumour/#finding-it [4 biomarkers]
- Treating it (on the hub): The standard of care by setting, the medicines, surgery and radiotherapy named in it, and the regimens behind them. https://onco.cc/cancers/tenosynovial-giant-cell-tumour/#treating-it [3 settings, 1 decision with options]
- Evidence (on the hub): Trials recruiting now, the landmark trials, the key papers and what they mean, the latest literature, and the milestones year by year. https://onco.cc/cancers/tenosynovial-giant-cell-tumour/#evidence [7 trials, 2 key papers, 7 milestones]
- The science (on the hub): The molecular landscape: the targets and how often each appears, the pathways, the mechanics stages and the preclinical models. https://onco.cc/cancers/tenosynovial-giant-cell-tumour/#science [4 targets, 1 pathway]
- Where you are (own page): Cases by country, the UK and NHS pathway and other country lenses, and the expert centres with trials on record. https://onco.cc/cancers/tenosynovial-giant-cell-tumour/where-you-are/
- Living with it (on the hub): The decisions you may face, the aids that walk through them, the warnings on record, the first sixty days and the questions to ask. https://onco.cc/cancers/tenosynovial-giant-cell-tumour/#living-with-it [14 questions, 6 red cards]
- What is coming (own page): Everything in development, the open problems and what is being done about them, the roadmaps, and what changed on this record. https://onco.cc/cancers/tenosynovial-giant-cell-tumour/coming/ [6 medicines, 7 trials, 4 open problems]
- Data (own page): Every connected record, the notes, the JSON, Markdown and RDF twins, and where the record came from and when it was checked. https://onco.cc/cancers/tenosynovial-giant-cell-tumour/data/ [33 connected records]

## Standard of care

- Localised TGCT: Marginal excision; recurrence is uncommon and re-excision is curative in most cases. ([Limb-salvage surgery and endoprosthetic reconstruction](https://onco.cc/technologies/limb-salvage-surgery/))
- Diffuse TGCT, resectable: Open or arthroscopic synovectomy by a sarcoma orthopaedic team; consider neoadjuvant CSF1R inhibition for large tumours (trial setting). ([Limb-salvage surgery and endoprosthetic reconstruction](https://onco.cc/technologies/limb-salvage-surgery/))
- 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. ([Vimseltinib](https://onco.cc/drugs/vimseltinib/), [Pexidartinib](https://onco.cc/drugs/pexidartinib/), [MOTION](https://onco.cc/trials/motion/), [Imatinib](https://onco.cc/drugs/imatinib/), [Nilotinib](https://onco.cc/drugs/nilotinib/))

## State of the art

- TGCT is a textbook case of targeting the signal rather than the neoplastic cell: blocking CSF1R removes the recruited macrophage mass that causes symptoms.
- Vimseltinib (MOTION, 2024; FDA 2025) delivers the class benefit without the cholestatic liver injury that has restricted pexidartinib to a REMS programme in the US and kept it off the EU market.
- Patient-reported function and stiffness were co-primary or key secondary endpoints in both phase 3 trials, an unusual and appropriate design for a non-lethal tumour.
- Surgery remains curative for localised disease; the medical advance is for the diffuse minority.

## Open problems

- Duration of CSF1R therapy and rebound after stopping: extension cohorts and intermittent schedules are being studied.
- Hepatotoxicity of pexidartinib: newer agents (vimseltinib, emactuzumab) are designed to avoid it.
- Neoadjuvant use to make surgery smaller or unnecessary: phase 2 studies under way.
- Access and cost for a benign disease in health systems that price by survival gain.

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Giant-cell_tumor_of_the_tendon_sheath
- NCI PDQ: soft tissue sarcoma: https://www.cancer.gov/types/soft-tissue-sarcoma
- MOTION (Lancet 2024): https://doi.org/10.1016/S0140-6736(24)00885-7
- ENLIVEN (Lancet 2019): https://doi.org/10.1016/S0140-6736(19)30764-0
- FDA approval of vimseltinib: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-vimseltinib-symptomatic-tenosynovial-giant-cell-tumor

## Connected records

- cancers: [Dermatofibrosarcoma protuberans](https://onco.cc/cancers/dermatofibrosarcoma-protuberans/), [Desmoid tumour](https://onco.cc/cancers/desmoid-tumour/), [Inflammatory myofibroblastic tumour (IMT)](https://onco.cc/cancers/inflammatory-myofibroblastic-tumour/), [Perivascular epithelioid cell tumour (PEComa)](https://onco.cc/cancers/pecoma/), [Sarcomas (soft tissue, bone, GIST)](https://onco.cc/cancers/sarcoma/)
- technologies: [Limb-salvage surgery and endoprosthetic reconstruction](https://onco.cc/technologies/limb-salvage-surgery/), [Monoclonal antibodies](https://onco.cc/technologies/monoclonal-antibody/), [MRI](https://onco.cc/technologies/mri/), [Small-molecule kinase inhibitors](https://onco.cc/technologies/kinase-inhibitors/)
- targets: [CSF1](https://onco.cc/targets/csf1/), [CSF1R](https://onco.cc/targets/csf1r/)
- drugs: [Emactuzumab](https://onco.cc/drugs/emactuzumab/), [Imatinib](https://onco.cc/drugs/imatinib/), [Nilotinib](https://onco.cc/drugs/nilotinib/), [Pexidartinib](https://onco.cc/drugs/pexidartinib/), [Pimicotinib](https://onco.cc/drugs/pimicotinib/), [Vimseltinib](https://onco.cc/drugs/vimseltinib/)
- companies: [Abbisko Therapeutics](https://onco.cc/companies/abbisko/), [Daiichi Sankyo](https://onco.cc/companies/daiichi-sankyo/), [Deciphera Pharmaceuticals (Ono)](https://onco.cc/companies/deciphera/)
- pathways: [Tumour microenvironment (TME)](https://onco.cc/pathways/tumor-microenvironment/)
- terms: [Rare cancers](https://onco.cc/terms/rare-cancers/)
- trials: [A Study of the Efficacy and Safety of Pexidartinib in Adult Subjects With TGCT](https://onco.cc/trials/nct04488822/), [ENLIVEN](https://onco.cc/trials/enliven/), [MOTION](https://onco.cc/trials/motion/), [Study of Emactuzumab for Tenosynovial Giant Cell Tumor (TGCT)](https://onco.cc/trials/nct05417789/), [Study of Pimicotinib (ABSK021) for Tenosynovial Giant Cell Tumor (MANEUVER)](https://onco.cc/trials/nct05804045/), [Study of Pimicotinib in Japanese Participants With Tenosynovial Giant Cell Tumor (TGCT) (J-MANEUVER)](https://onco.cc/trials/nct07499362/), [Study of Vimseltinib (DCC-3014) in Patients With Advanced Tumors and Tenosynovial Giant Cell Tumor](https://onco.cc/trials/nct03069469/)
- bottlenecks: [Rare and paediatric cancers without markets](https://onco.cc/bottlenecks/b-rare-cancers/), [Toxicity and quality of life are undervalued](https://onco.cc/bottlenecks/b-toxicity-qol/)
- key papers: [Pexidartinib versus placebo for advanced tenosynovial giant cell tumour (ENLIVEN): a randomised phase 3 trial](https://onco.cc/key-papers/paper-tap-lancet/), [Vimseltinib versus placebo for tenosynovial giant cell tumour (MOTION): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial](https://onco.cc/key-papers/paper-gelderblom-lancet/)

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JSON: https://onco.cc/api/v1/entities/tenosynovial-giant-cell-tumour.json