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Tenosynovial giant cell tumor (TGCT)

Tenosynovial giant cell tumor (TGCT), previously known as PVNS, are relatively rare neoplasms that arise from the synovial lining of joints, bursae, and tendon sheaths

Prevalence

2-5/100,000

6,620-16,550

US Estimated

9,000-22,500

Europe Estimated

Age of Onset

ICD-10

D48.1

Rare View

The most common form of rare synovial tumors, TGCT is caused by overexpression of the CSF1 gene, leading to abnormal macrophage-like cell accumulation within joint tissue. Patients typically present with chronic joint pain, recurrent effusions, and limited range of motion — most often affecting the knee in the diffuse form, or fingers and wrist in the localized form. The presence of hemosiderin deposits on MRI and high recurrence rates in diffuse-type TGCT distinguish it from other benign joint lesions.

5 Facts you should know

FACT

1

TGCT, previously known as pigmented villonodular synovitis (PVNS) or giant cell tumor of the tendon sheath (GCT-TS), is a locally aggressive neoplasm associated with overexpression of the CSF1 gene. It presents in two forms: localized/nodular TGCT and diffuse TGCT, the latter carrying a substantially higher risk of recurrence

FACT

2

TGCT typically presents in young to middle adulthood, with a median age of approximately 33 years, and an estimated annual incidence of 11 to 50 cases per million people. Recurrence following surgical resection is particularly common in diffuse-type TGCT, where rates approaching 70% have been reported

FACT

3

In an international, prospective patient registry, over 90% of individuals with TGCT reported pain and 85% reported limited range of motion, underscoring the substantial impact of this disease on physical function and quality of life

FACT

4

When inadequately managed, diffuse TGCT can cause progressive cartilage destruction, bone erosion, and joint degeneration, with severe cases ultimately requiring joint replacement or amputation

FACT

5

Surgical resection is the standard of care for TGCT but is not always curative, and repeated resections can lead to increased morbidity. For patients in whom surgery may result in severe morbidity or worsening functional limitation, CSF1R-targeted tyrosine kinase inhibitors represent an FDA-approved systemic treatment option

Tenosynovial giant cell tumor is also known as...

Tenosynovial giant cell tumor is also known as:

  • Pigmented Villonodular Synovitis (PVNS) — diffuse form
  • Giant Cell Tumor of Tendon Sheath (GCT-TS) — localized form
  • Diffuse-type Giant Cell Tumor
  • Extra-articular TGCT

What’s your Rare IQ?

Which molecular pathway is most directly implicated in the pathogenesis of TGCT and represents the therapeutic target of FDA-approved systemic treatment?

Common signs & symptoms

Joint pain — often the earliest and most consistent complaint

Joint swelling and effusion — may be significant in diffuse

TGCT Limited range of motion — stiffness and restricted movement

Locking or catching sensation — particularly with knee involvement

Palpable soft tissue mass — more common in localized form (fingers, wrist)

Joint tenderness on palpation

Joint warmth

Bone erosion — seen in advanced diffuse TGCT on imaging

Current treatments

Surgical Synovectomy

The primary treatment for both forms. Arthroscopic or open synovectomy aims for complete removal of affected synovium. Complete resection is often achievable in localized TGCT; diffuse TGCT recurs in up to 50% of cases after surgery alone due to the extent of synovial involvement.

Vimseltinib (Romvimza)

FDA-approved February 2025 for adult patients with symptomatic TGCT not amenable to improvement with surgery. Vimseltinib is a selective CSF1R inhibitor taken orally twice weekly. Approval was based on the Phase 3 MOTION trial, which demonstrated a 40% overall response rate versus 0% in the placebo arm, with meaningful improvements in tumor volume, pain, and physical function. Notably, vimseltinib showed no treatment-related serious hepatotoxicity in clinical trials — a significant differentiator from earlier systemic options — making it a preferred choice for eligible patients requiring systemic therapy.

Pexidartinib (Turalio)

FDA-approved 2019 as the first systemic therapy for symptomatic TGCT not amenable to surgery. A CSF1R inhibitor with demonstrated efficacy; carries a boxed warning for serious and potentially fatal hepatotoxicity and requires enrollment in a REMS program.

Active surveillance

Appropriate for small, asymptomatic localized TGCT with no functional impairment. Regular monitoring with MRI is recommended.

Top Clinical Trials

TitleDescriptionPhasesStatusInterventionsMore Information
A Study of Pexidartinib in Tenosynovial Giant Cell Tumor in JapanThis phase 2, multicenter, two-part, open-label, single-arm study will be conducted in Japan and will evaluate the safety, tolerability, pharmacokinetics (PK), and efficacy of pexidartinib in adult participants with symptomatic tenosynovial giant cell tumor (TGCT) associated with severe morbidity or...Phase 2ActiveDrug: PexidartinibMore Info
Tenosynovial Giant Cell Tumor (TGCT) Real-World Participant Experience With VimseltinibThe goal of this observational study is to better understand real-world use of vimseltinib, treatment patterns, and health-related quality of life in participants treated with vimseltinib for TGCT.

This study will collect data in an observational disease registry involving no intervention to the pa...
RecruitingMore Info
Study of Pimicotinib (ABSK021) for Tenosynovial Giant Cell Tumor (MANEUVER)The goal of this clinical trial is to assess the efficacy and safety of Pimicotinib (ABSK021) in patients with Tenosynovial Giant Cell Tumor (TGCT). The main questions it aims to answer are:

* Whether the Pimicotinib(ABSK021) works well in patients with TGCT.
* Whether the Pimicotinib(ABSK021) is s...
Phase 3ActiveDrug: Pimicotinib(ABSK021)
Drug: Placebo
More Info
Study of Vimseltinib (DCC-3014) in Patients With Advanced Tumors and Tenosynovial Giant Cell TumorThis is a multicenter, open-label Phase 1/2 study of vimseltinib in patients with malignant solid tumors and tenosynovial giant cell tumor (TGCT). There will be 2 distinct parts in this study: Dose Escalation (Phase 1) and Expansion (Phase 2). Phase 1 will enroll both malignant solid tumor and TGCT...Phase 1, Phase 2ActiveDrug: VimseltinibMore Info
Phase I Trial of TURALIO(R) (Pexidartinib, PLX3397) in Children and Young Adults With Refractory Leukemias and Refractory Solid Tumors Including Neurofibromatosis Type 1 (NF1) Associated Plexiform Neurofibromas (PN) and Tenosynovial Giant Cell Tumor ...Background:

\- Some people with cancer have solid tumors. Others have refractory leukemia. This may not go away after treatment. Researchers want to see if a drug called TURALIO(R) can shrink tumors or stop them from growing.

Objectives:

\- To find the highest safe dose and side effects of TURALI...
Phase 1RecruitingDrug: TURALIO(R)More Info
A Study of the Efficacy and Safety of Pexidartinib in Adult Subjects With TGCTThis study will assess pexidartinib in adult participants with symptomatic TGCT that is associated with severe morbidity or functional limitations and not amendable to improvement with surgery.Phase 3ActiveDrug: PexidartinibMore Info
Accuracy of Indocyanine Green (ICG) Fluorescence Imaging in Tenosynovial Giant Cell Tumor SurgeryThis study evaluates the diagnostic accuracy of Indocyanine Green (ICG) fluorescence imaging in visualizing Tenosynovial Giant Cell Tumor (TGCT) lesions during surgery. Patients diagnosed with TGCT will receive an intravenous injection of ICG prior to the operation to label tumor tissues. During the...Phase 4RecruitingDrug: Indocyanine GreenMore Info
Study of Vimseltinib for Tenosynovial Giant Cell TumorThis is a multicenter Phase 3 clinical study, which aims to evaluate the effectiveness of an investigational drug called vimseltinib for the treatment of tenosynovial giant cell tumor (TGCT) in cases where surgical removal of the tumor is not an option.

The study consists of two parts. In Part 1, e...
Phase 3ActiveDrug: Vimseltinib
Drug: Placebo
More Info
Study of Emactuzumab for Tenosynovial Giant Cell Tumor (TGCT)This is a multicenter, Phase 3, randomised, double-blind, placebo-controlled study, which aims to evaluate the efficacy and safety of the investigational drug emactuzumab for the treatment of patients with localized or diffuse TGCT where surgical removal of the tumor is not viewed as an option.

The...
Phase 3ActiveDrug: Emactuzumab
Drug: Placebo
More Info