Synonyms

• Diffuse TGCT
• pigmented villonodular synovitis (PVNS)

Category

Soft tissue

Behaviour

Intermediate

Gender

Female

Tissue of Origin

Synovial/tenosynovial tissue

Epidemiology

• Less common than localised TGCT
• Peak incidence in 3rd–5th decades
• Intra-articular (PVNS) or extra-articular forms

Clinical Features

• Joint swelling, pain, and stiffness - chronic recurrent course
• Haemarthrosis - bloody aspirate
• Progressive joint destruction if untreated
• Restricted range of motion

Location

• Knee (most common intra-articular)
• Hip, ankle, shoulder
• Temporomandibular joint
• Extra-articular: soft tissue around major joints

Imaging

• MRI: diffuse synovial thickening with hemosiderin (Low signal on T2) - 'blooming' on gradient echo
• Joint effusion and erosions on X-ray
• CT: synovial masses with dense areas (haemosiderin)
• Bone erosions characteristic with intact joint space (early)

Pathology

• Diffuse villonodular proliferation of synovial-type cells with giant cells, foam cells, and haemosiderin
• CSF1 overexpression by neoplastic cells
• More locally aggressive than localised form
• Rare Malignant transformation to Malignant TGCT

Genetics

• CSF1 translocation or overexpression in neoplastic cells
• Same molecular drivers as localised TGCT
• Malignant TGCT: additional genomic complexity

Treatment

• Total synovectomy (arthroscopic or open) - High recurrence rate
• Pexidartinib (CSF1R inhibitor): FDA-approved, significant response rates
• External beam radiotherapy or intra-articular radiocolloid (yttrium-90) for recurrent disease
• Total joint replacement for severe joint destruction

Prognosis

• Locally aggressive with High recurrence rate (20–50% after synovectomy)
• Progressive joint destruction without treatment
• Distant metastasis extremely rare (Malignant TGCT)
• Pexidartinib achieves 40% objective response rate

Key Points

• Formerly called PVNS - now classified as diffuse TGCT per WHO 2020
• Haemosiderin deposition causes characteristic Low signal on T2 MRI - 'blooming' on GRE is pathognomonic
• Pexidartinib is FDA-approved and can achieve durable disease control

Workup - Blood Tests

No routine blood tests required

Workup - Local Imaging

• MRI primary joint with gadolinium - diffuse synovial thickening with haemosiderin (Low signal T2, 'blooming' on GRE); characteristic
• Plain radiograph - Bone erosions
• CT - characterises erosion pattern

Workup - Biopsy

• Core needle or synovial biopsy - confirm diagnosis
• Histology: diffuse villonodular synovial proliferation with giant cells, haemosiderin
• CSF1 overexpression - diagnostic molecular feature

Workup - Staging

No metastatic staging required (metastases extremely rare)

Follow-up Summary

• Intermediate soft tissue tumour (PVNS/diffuse TGCT) - long-term surveillance for local recurrence
• Post-op visit at 6 weeks; MRI primary joint at 3 months post-synovectomy as new baseline
• Year 1–2: 6-monthly clinical review + MRI primary joint (recurrence rate 20–50%)
• Years 3–5: Annual clinical review + MRI joint
• Pexidartinib therapy: monthly LFTs for first 6 months (hepatotoxicity risk); then 3-monthly; imaging response at 3–6 months
• Yttrium-90 synovectomy: post-procedure review at 3 months with MRI
• Years 6–10: Annual clinical review; MRI if symptomatic
• Discharge at 10 years with documented self-monitoring advice