Tenosynovial giant cell tumour (TGCT)
TGCT is a benign but destructive tumour of the joint lining 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.
Overview
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.
State of the art today
- 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.
Where it starts and where it drains
Bone sarcomas favour the fast-growing ends of long bones (osteosarcoma) or the shaft (Ewing), soft tissue sarcomas the deep muscle compartments; spread is through the blood to the lungs, rarely via lymph nodes.
- Metaphysis, near the growth plate (osteosarcoma)
- Shaft (Ewing sarcoma)Localised (nodular) TGCT
- Deep soft tissue compartmentLocalised (nodular) TGCT · Diffuse TGCT (pigmented villonodular synovitis) · Malignant TGCT (very rare)
- Skeletal muscle (rhabdomyosarcoma)
- Neurovascular bundle (limb salvage decision)
Lymph node spread is rare (except epithelioid, synovial, clear cell and rhabdomyosarcoma); sarcomas go through the blood to the lungs.
Same organ: Sarcomas (soft tissue, bone, GIST), Osteosarcoma, Ewing sarcoma, Rhabdomyosarcoma, Chordoma, Desmoid tumour, Epithelioid sarcoma, Vascular tumours (angiosarcoma, epithelioid haemangioendothelioma, kaposiform haemangioendothelioma)
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.
- AI in radiologyEstablished
- cfDNA fragmentomicsEstablished
- Colorectal cancer screening (colonoscopy, FIT, stool DNA, blood)Standard of care
- DNA methylation profilingEstablished
- HCC surveillance in cirrhosis (ultrasound + AFP)Standard of care
- High-risk pancreatic surveillance (CAPS / PRECEDE)Established
- A 28-day national pathway for people with a positive multi-cancer blood test
- A breath test to rule out cancer in people with vague symptoms
- A cancer blood test for older people arriving at A&E with unexplained symptoms
- A legislated, publicly reported 28-day standard from urgent referral to diagnosis
- A live national dashboard of stage at diagnosis as the scorecard for early detection
- A single 'cancer check at 60' appointment bundling all screening tests
Background: Alpha-fetoprotein (AFP), Barrett's oesophagus, CA 19-9, Early detection, Faecal immunochemical test (FIT). Also on OnCo: Symptoms and red flags · Early detection roadmap.
Where the cases are
No country-level case numbers. This cancer is not mapped to a GLOBOCAN site.
Marginal excision; recurrence is uncommon and re-excision is curative in most cases.
Open or arthroscopic synovectomy by a sarcoma orthopaedic team; consider neoadjuvant CSF1R inhibition for large tumours (trial setting).
CSF1R inhibitor: vimseltinib (MOTION) or pexidartinib (ENLIVEN, with REMS hepatic monitoring); imatinib or nilotinib off label where neither is available.
Subtypes & biomarkers
top- Localised (nodular) TGCT
- Diffuse TGCT (pigmented villonodular synovitis)
- Malignant TGCT (very rare)
- 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)
Target prevalence in this cancer
- 1941Jaffe describes pigmented villonodular synovitis
- 2006CSF1 translocation identified
West and colleagues show a CSF1-expressing neoplastic minority recruits the macrophage majority (PNAS).
- 2015Pexidartinib phase 1 responses
Tap and colleagues, NEJM: high response rate in diffuse TGCT.
- 2019ENLIVEN phase 3 and FDA approval of pexidartinib
First systemic therapy approved for TGCT (August 2019), with a boxed hepatotoxicity warning.
- 2020EMA refuses pexidartinib
Hepatotoxicity judged to outweigh benefit for a non-lethal disease.
- 2024MOTION phase 3 positive for vimseltinib
Gelderblom and colleagues, Lancet.
- 2025Vimseltinib approved
FDA approval 14 February 2025 for symptomatic TGCT where surgery would worsen function.
Open problems, and what is being done about each
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.
and how the field plans to fix it →What is being done about thisCost and accessAvailable now- ImatinibApproved
- NilotinibApproved
- HPV & HBV vaccinationStandard of care
- Trastuzumab biosimilarsApproved
In trials- Gefitinib vs gefitinib plus pemetrexed-carboplatin in EGFR-mutant lung cancer (Tata Memorial)Positive
- IARC India HPV vaccine dose study (one, two or three doses)Positive
- IMAGINE (varnimcabtagene autoleucel, Immuneel)Positive
- Low-dose nivolumab plus metronomic chemotherapy (Tata Memorial)Positive
- Low-dose olanzapine for cancer anorexia (Tata Memorial)Positive
- METRO PLUS (Tata Memorial Centre, Varanasi)Positive
Ideas and roadmaps- 90-day reliance approval for cancer drugs cleared by two stringent regulators
- A cheap old tablet to restore appetite
- A combination pricing rule so two-drug regimens are not priced as two monopolies
- A coordinated reserve and shared schedule for the world's medical isotope reactors
- A dedicated global financing window for cancer, modelled on the Global Fund
- A delinked market-entry reward paid by payers when a repurposed generic wins approval
Background: Accelerated approval, Biosimilar, Real-world evidence. Also on OnCo: Financial help and assistance navigator · Coverage by country · HTA decisions.
Trials
topRecruiting now (live from ClinicalTrials.gov)
Country and place are remembered in this browser only. A postcode is sent to OpenStreetMap's Nominatim service to find coordinates when you press the button; nothing else leaves your device.
Landmark trials in OnCo
Expert centres
topCentres linked to this cancer in OnCo
- Seoul St. Mary's HospitalSeoul, KRvia Imatinib, Nilotinib
- Central Drugs Standard Control OrganizationNew Delhi, INvia Imatinib
- GIMEMARome, ITvia Imatinib
- via Imatinib
Questions to ask
topQuestions to ask your oncologist about Tenosynovial giant cell tumour
Newly diagnosed
- What is my exact diagnosis, stage, and grade, and which tests established them?Why: Everything else follows from an accurate stage and subtype.
- Which biomarkers have been tested on my tumour (for example CSF1 rearrangementin neoplastic cells, CSF1R-positive macrophage-rich infiltrate, MRI pattern, Liver function tests before and during pexidartinib), and what were the results?Why: These results decide eligibility for targeted therapy, immunotherapy, and trials.
- Which subtype is my cancer, and does that change the recommended treatment?Why: Recognised subtypes for this cancer include LocalisedTGCT, Diffuse TGCT, Malignant TGCT.
- Is germline (inherited) genetic testing recommended for me or my family?Why: Inherited variants can change treatment and matter for relatives.
Localised TGCT
- For my situation (localised tgct), which of the standard options do you recommend and why?Why: Guideline options include: Marginal excision; recurrence is uncommon and re-excision is curative in most cases.
Diffuse TGCT, resectable
- For my situation (diffuse tgct, resectable), which of the standard options do you recommend and why?Why: Guideline options include: Open or arthroscopic synovectomy by a sarcoma orthopaedic team; consider neoadjuvant CSF1R inhibition for large tumours (trial setting).
Diffuse TGCT where surgery would cause severe morbidity or after recurrence
- For my situation (diffuse tgct where surgery would cause severe morbidity or after recurrence), which of the standard options do you recommend and why?Why: Guideline options include: CSF1R inhibitor: vimseltinib (MOTION) or pexidartinib (ENLIVEN, with REMS hepatic monitoring); imatinib or nilotinib off label where neither is available.
- Am I a candidate for Vimseltinib, Pexidartinib, Imatinib or related drugs, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
- How do the results of MOTION apply to someone like me?Why: Trial populations differ from individual patients; ask how closely you match.
Any stage
- Are there clinical trials I could join, for example of Vimseltinib, MOTION?Why: Trials are how the next standard of care is set; asking early keeps options open.
- Would a second opinion at a high-volume centre change anything, and can you help arrange it?Why: Rare or high-stakes decisions benefit from a centre that treats many similar patients.
- What supportive care (symptom control, nutrition, exercise, mental health, financial help) is available from the start?Why: Supportive care improves quality of life and helps patients complete treatment.
- I read that “Duration of CSF1R therapy and rebound after stopping: extension cohorts and intermittent schedules are being studied”. How does that affect my plan?Why: Open problems are where trials and second opinions matter most.
- I read that “Hepatotoxicity of pexidartinib: newer agents (vimseltinib, emactuzumab) are designed to avoid it”. How does that affect my plan?Why: Open problems are where trials and second opinions matter most.
Print this page for your appointment (your browser's print command). These prompts are for discussion; your clinical team knows your case.
Direct links plus the targets, companies, and technologies of this cancer's products.
technologies
4targets
3drugs
4companies
4pathways
1terms
1trials
1bottlenecks
2Latest papers
topQuery for this cancer: (TITLE:"Tenosynovial giant cell tumour" OR ABSTRACT:"Tenosynovial giant cell tumour" OR TITLE:"TGCT" OR ABSTRACT:"TGCT" OR TITLE:"Pigmented villonodular synovitis" OR ABSTRACT:"Pigmented villonodular synovitis" OR TITLE:"PVNS" OR ABSTRACT:"PVNS" OR TITLE:"Giant cell tumour of the tendon sheath" OR ABSTRACT:"Giant cell tumour of the tendon sheath") AND (treatment OR therapy OR trial OR survival OR diagnosis). Results are unfiltered search hits about Tenosynovial giant cell tumour (TGCT), not a curated reading list.
Pages like this
not linked directly; found by shared links- CancerDesmoid tumour
Shares Limb-salvage surgery and endoprosthetic reconstruction, Rare cancers, MRI, Rare and paediatric cancers without markets and the tags nci-coverage, rare, sarcoma.
- CancerEpithelioid sarcoma
Shares Limb-salvage surgery and endoprosthetic reconstruction, Rare cancers, Rare and paediatric cancers without markets and the tags nci-coverage, rare, sarcoma.
- CancerChordoma
Shares Rare cancers, Imatinib, Rare and paediatric cancers without markets, Sarcomas (soft tissue, bone, GIST) and the tags nci-coverage, rare, sarcoma.
- CancerUterine sarcoma
Shares Rare cancers, MRI, Imatinib, Rare and paediatric cancers without markets and the tags nci-coverage, rare, sarcoma.
- CancerInflammatory myofibroblastic tumour (IMT)
Shares Limb-salvage surgery and endoprosthetic reconstruction, Rare cancers, Imatinib, Rare and paediatric cancers without markets and the tags nci-coverage, rare, sarcoma.
- CancerVascular tumours (angiosarcoma, epithelioid haemangioendothelioma, kaposiform haemangioendothelioma)
Shares Rare cancers, Rare and paediatric cancers without markets, Sarcomas (soft tissue, bone, GIST) and the tags nci-coverage, rare, sarcoma.
- CancerParathyroid carcinoma
Shares Rare cancers, Rare and paediatric cancers without markets and the tags nci-coverage, rare.
- CancerSystemic mastocytosis
Shares Imatinib, Rare and paediatric cancers without markets, Toxicity and quality of life are undervalued, Small-molecule kinase inhibitors and the tags nci-coverage, rare.