Pigmented Villonodular Synovitis (PVNS) / Tenosynovial Giant Cell Tumor (TGCT)

Pigmented villonodular synovitis (PVNS) and tenosynovial giant cell tumour (TGCT) are now recognised as the same entity — a locally aggressive neoplasm of synovial origin characterised by clonal proliferation of histiocyte-like mononuclear cells accompanied by multinucleated giant cells, haemosiderin deposition, and lipid-laden foam cells. The WHO 2020 classification unifies them under the term tenosynovial giant cell tumour, replacing the older descriptive terminology.

• Diffuse type (formerly diffuse PVNS): involves the entire synovium of a joint or tendon sheath; aggressive, locally destructive; high recurrence rate; primarily affects the knee; the main clinical challenge
• Localised type (formerly localised nodular PVNS, giant cell tumour of tendon sheath): discrete nodular lesion in a joint or more commonly in a tendon sheath (especially fingers); less aggressive; excellent prognosis after excision
• Incidence: approximately 1.8–9 per million population; young adults (3rd–4th decade); no significant gender predominance for the diffuse type; slight female predominance for localised tendon sheath type
• Molecular basis: most cases driven by translocation involving the CSF1 gene (colony-stimulating factor 1) — overexpression of CSF1 recruits non-neoplastic inflammatory cells (macrophages, giant cells) that compose the majority of the tumour mass; this CSF1 pathway is the therapeutic target for systemic treatment

• Diffuse PVNS/TGCT: insidious onset of joint pain and swelling; recurrent haemarthroses (blood-stained joint aspirate); restricted range of motion; knee most commonly affected (80%), followed by hip (15%), shoulder, ankle
• Recurrent bloody (chocolate-coloured) joint aspirate in a young adult is the classic presentation — haemosiderin-stained synovial fluid from repeated micro-haemorrhages within the tumour; should always prompt MRI to exclude PVNS/TGCT before attributing to trauma
• Localised TGCT (tendon sheath): slow-growing painless firm nodule on the flexor tendons of the fingers; most common benign tumour of the hand; second most common hand tumour after ganglion cyst; 2nd–4th decades; may cause triggering or limited finger flexion
• Duration before diagnosis: typically 1–5 years for diffuse type — diagnostic delay is common; often misdiagnosed as inflammatory arthritis or haemophilic arthropathy

• Plain radiographs: early disease often normal; in advanced disease — soft tissue mass, periarticular osteoporosis, erosions of bone on both sides of the joint (hallmark of diffuse PVNS), joint space preservation until late; extrinsic pressure erosions on both the femur and tibia/fibula simultaneously ("kissing lesions") — pathognomonic of diffuse PVNS in the knee
• MRI: investigation of choice — low signal on both T1 and T2 sequences due to haemosiderin deposition (magnetic susceptibility effect); "blooming" on gradient echo (T2*) sequences — this low signal on T2 distinguishes PVNS from other causes of synovitis (TB, RA, septic) which are T2 bright; may also show high T1 signal (lipid-laden foam cells) and intermediate T2 signal (cellular areas)
• Joint aspiration: bloody or xanthochromic (yellow-brown) fluid; haemosiderin-laden macrophages on cytology; sent for culture to exclude TB and infection
• Synovial biopsy: definitive diagnosis — histology shows mononuclear cells, multinucleated giant cells, haemosiderin deposits, foam cells (lipid-laden macrophages), and fibrous stroma; immunohistochemistry (CD68 positive macrophages); CSF1 FISH for translocation in uncertain cases
• CT: assesses bony erosions; pre-surgical planning; detects osseous involvement

• Localised intra-articular TGCT (knee): arthroscopic excision with adequate margin around the nodule pedicle; excellent results; recurrence rate <10%; simple nodule resection without extensive synovectomy
• Localised TGCT of tendon sheath (finger): marginal excision under tourniquet; careful identification of involvement with adjacent neurovascular bundles and flexor tendon; recurrence 10–20%; higher recurrence if incomplete excision or if joint involvement; no adjuvant therapy required for localised type
• Recurrence after excision of localised type: re-excision is the treatment of choice; usually achievable

Diffuse TGCT is the major management challenge — high recurrence rates after surgery alone have driven the development of adjuvant and systemic therapies.

• Surgical synovectomy: total synovectomy (arthroscopic or open) is the primary treatment — arthroscopic synovectomy for anterior compartment; open posterior approach for posterior knee compartment; combined approach for complete excision; recurrence rate 20–50% after synovectomy alone — driven by the difficulty of achieving complete synovial excision
• Radiosynovectomy (yttrium-90, rhenium-186): radioisotope injection into joint destroys synovium; used as adjuvant after surgical synovectomy to reduce recurrence; or primary treatment in high surgical risk patients; reduces recurrence rate when combined with surgery
• External beam radiotherapy: reserved for recurrent, unresectable, or extra-articular diffuse TGCT; risk of radiation-induced sarcoma with high doses
• CSF1R inhibitors (pexidartinib, imatinib): systemic targeted therapy for diffuse TGCT; pexidartinib (Turalio) is a CSF1R tyrosine kinase inhibitor — approved by FDA 2019 for symptomatic TGCT not amenable to surgery; objective response rate approximately 38%; hepatotoxicity is the main serious adverse effect (serious liver injury including fatal cases reported — REMS programme required); reserved for advanced/unresectable diffuse TGCT
• Total joint arthroplasty: for end-stage arthropathy secondary to diffuse PVNS — cartilage and bone destruction by the pannus may require TKA or THA; higher complication rate in PVNS than in OA arthroplasty due to haemosiderin staining and synovial fibrosis

• Diffuse PVNS of the hip: particularly challenging — deep location, dense haemosiderin staining, and proximity to neurovascular structures make complete open synovectomy difficult; arthroscopic hip synovectomy increasingly performed; high recurrence rate; THA required in advanced cases; the combined hip synovectomy + THA approach (simultaneous) has been reported with acceptable outcomes at specialist centres
• Malignant TGCT: rare (<1%); local recurrence with high-grade sarcomatous transformation; treat like a high-grade sarcoma — wide excision + adjuvant therapy; poor prognosis; suspect if rapid growth, pain, or pathological fracture in a known TGCT
• Pexidartinib hepatotoxicity: serious hepatotoxic reactions including fatal cases; liver function tests must be monitored before treatment and weekly for first 8 weeks; avoid in patients with hepatic impairment; not combined with strong CYP3A4 inducers; counsel patients about liver injury risk
• PVNS and advanced arthropathy: haemosiderin deposition in cartilage and subchondral bone causes progressive joint damage; TKA/THA outcomes slightly inferior to primary OA arthroplasty; pigmented tissue at time of arthroplasty indicates active disease — thorough synovectomy at time of arthroplasty reduces recurrence risk; consider concurrent yttrium-90 radiosynovectomy post-arthroplasty

• PVNS = TGCT (WHO 2020 term); CSF1 gene overexpression drives disease; mononuclear + giant cells + haemosiderin + foam cells
• Recurrent bloody joint aspirate in young adult = classic presentation; dark xanthochromic fluid
• MRI: low signal on T1 AND T2 due to haemosiderin; blooming on T2* (gradient echo) — pathognomonic; distinguishes from TB and RA (T2 bright)
• Kissing erosions on plain X-ray (both sides of joint simultaneously): pathognomonic of diffuse PVNS in the knee
• Localised tendon sheath TGCT: most common benign hand tumour after ganglion; marginal excision; 10–20% recurrence
• Diffuse PVNS: 20–50% recurrence after synovectomy alone; combined surgery + radiosynovectomy reduces recurrence
• Pexidartinib: CSF1R inhibitor; FDA approved 2019; objective response 38%; hepatotoxicity — monitor LFTs weekly × 8 weeks; reserved for unresectable diffuse TGCT
• Do not give corticosteroids to treat PVNS — will worsen TB if TB is mistaken for PVNS; biopsy before any immunosuppressive therapy
• Malignant TGCT: rare; rapid growth or fracture in known TGCT = suspect malignant transformation; treat as high-grade sarcoma
• TKA/THA in end-stage PVNS: higher complication rate than OA; synovectomy at time of arthroplasty; consider post-operative radiosynovectomy