Pigmented Villonodular Synovitis (PVNS)

What it is. Pigmented villonodular synovitis is the older name for tenosynovial giant cell tumour (TGCT), a usually benign but potentially locally aggressive synovial neoplasm. It comes in localised and diffuse forms, which differ in extent, morbidity and recurrence burden, but behaviour also varies by joint, treatment and follow-up. Management should preserve function rather than apply one recurrence percentage to every patient.

Who. Young adults, with a peak incidence at 20-40 years and a slight female predominance of 1.5-2:1. There is no racial predilection and no hereditary pattern, and no clear environmental or genetic risk factors have been identified. The hallmark is chronic monoarticular synovitis with recurrent haemarthrosis, and the disease is usually monoarticular (95%).

Where. The knee dominates:

• Knee - 80% of cases, the most common site
• Hip - 10-15%, and a more challenging diagnosis and treatment
• Ankle, shoulder and elbow - rare, each under 5%
• Temporomandibular joint - case reports

Why it matters. Untreated or progressive diffuse disease can erode cartilage and bone, and the disease brings disability through chronic pain, swelling and mechanical symptoms. Recurrence and progression are time-dependent and greater with diffuse or residual disease, and joint replacement may be required in young patients.

A neoplasm, not an inflammatory arthritis. Despite the name "synovitis", PVNS is a clonal neoplastic proliferation. The driver is a translocation involving the CSF1 gene, in some cases a t(1;2) fusion with COL6A3, and the result is overexpression of colony stimulating factor 1 (CSF1).

The landscape effect. The neoplastic cells are the CSF1-expressing mononuclear stromal cells, and they are a minority of the tumour. The CSF1 they secrete binds CSF1R on macrophages and recruits an inflammatory infiltrate of macrophages, foam cells and giant cells, and it is this recruited, non-neoplastic population that creates the mass. It explains the tissue seen at arthroscopy and why blocking CSF1R works.

Bleeding and destruction. The friable, vascular tissue bleeds into the joint repeatedly, and the iron it leaves behind as haemosiderin gives the rust-brown pigment in the specimen and the blooming artefact on MRI. Macrophages release metalloproteases (MMPs), and cartilage degradation and bone erosion follow from that enzymatic damage together with the mechanical effect of the mass.

Histology. The components to name:

• Mononuclear stromal cells - the neoplastic component, expressing CSF1
• Multinucleated giant cells - the histological hallmark, but reactive rather than neoplastic
• Haemosiderin-laden macrophages - from recurrent haemorrhage
• Foam cells - lipid-laden macrophages
• A villous or nodular synovial architecture

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Gross appearance. Orange-brown villous synovium with nodular projections.

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The key pathological distinction is localised (nodular) versus diffuse (villonodular) disease, because the two forms have different prognosis and recurrence risk, and that difference guides treatment intensity and counselling. Localised PVNS behaves like a benign tumour: it is amenable to complete excision, after which recurrence is low. Diffuse PVNS behaves as a locally aggressive tumour, with high recurrence despite aggressive synovectomy.

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History. Chronic joint swelling over months to years, with recurrent bloody effusions that are not traumatic. The pain is a dull ache, worse with activity, and range of motion is progressively lost. Locking and catching are features of the localised form.

Examination. The effusion is chronic and often tense, and motion is reduced, especially terminal flexion. A discrete nodule may be palpable in localised disease, whereas diffuse disease gives a boggy, thickened synovium. Instability is usually absent, in contrast to inflammatory arthritis.

Amyloid arthropathy can also cause a similar MRI appearance. The critical distinction is benign (PVNS, chondromatosis) versus malignant (synovial sarcoma), and biopsy if there is any doubt.

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The principle. Treatment balances resectability, expected morbidity, joint damage, symptoms and recurrence. For diffuse disease a specialist MDT weighs arthroscopic, open and combined surgery against observation, systemic CSF1R inhibition and selected radiotherapy.

Localised disease. Excision is reasonable for symptomatic, growing or mechanically relevant lesions when morbidity is acceptable. Arthroscopic or open access is chosen from the compartment, size, stalk and adjacent structures, and from the ability to remove the lesion without unnecessary sacrifice of normal synovium; no validated 2-3 mm synovial margin is required. Observation can be appropriate for small, minimally symptomatic disease, and adjuvant therapy is not routine after uncomplicated localised excision.

Diffuse disease. Map anterior, posterior, extra-articular, tendon-sheath, bone and neurovascular disease on MRI, then choose arthroscopic, open or combined synovectomy or debulking from access and morbidity. Attempting microscopic completeness can create more disability than residual indolent disease, and systemic CSF1R therapy or selected radiotherapy are considered when surgery is incomplete, recurrent or unacceptably morbid. The rest of the plan:

• Erosions and cartilage - curette and graft erosions, or address cartilage and arthrosis, only when mechanically relevant
• CSF1R inhibition - discuss when symptomatic disease is not amenable to surgery or surgery would cause unacceptable morbidity; agent availability, label and monitoring differ by jurisdiction
• External-beam radiotherapy - only in selected residual or recurrent cases after sarcoma and radiation-oncology review; dose and indication are individual, especially in young joints
• Arthroplasty - a solution for joint destruction, not a recurrence step, and active disease complicates its timing

Systemic therapy. CSF1R inhibitors (pexidartinib, vimseltinib, imatinib) block macrophage recruitment. Pexidartinib and vimseltinib have phase 3 evidence for symptomatic TGCT not amenable to surgery: pexidartinib was FDA-approved for TGCT in 2019, and vimseltinib followed on the phase 3 MOTION trial reported in 2024. They can reduce tumour volume and, importantly, improve range of motion, stiffness, pain and function.

Their limits. Response is incomplete, duration of treatment and cessation remain open questions, and toxicities require agent-specific monitoring. Imatinib is an off-label, lower-evidence option in some settings.

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What it is. Malignant TGCT is a sarcomatous transformation of, or a malignant tumour arising alongside, a diffuse-type giant cell tumour. It is very rare, well under 5% of TGCT, but carries a metastatic potential and mortality quite unlike benign PVNS. It is a genuine exam curveball for a disease otherwise taught as benign, and it is why excluding malignancy appears in every management algorithm.

When to suspect it. Most malignant cases arise in recurrent, previously benign diffuse disease rather than at first presentation. The red flags:

• Older age at onset
• A large or rapidly enlarging mass
• Recurrent disease that becomes more aggressive
• Destructive or atypical imaging, with aggressive bone destruction and soft-tissue extension beyond the usual PVNS pattern

Diagnosis is histological. Alongside the typical mononuclear, haemosiderin and giant-cell background there are overtly malignant features: marked cytological atypia, high mitotic activity, atypical mitoses, spindling into a sarcomatous pattern, necrosis and enlarged mononuclear cells. An atypical, aggressive or unexpectedly recurrent lesion therefore warrants generous biopsy and expert sarcoma pathology, not a diagnosis of "recurrent PVNS", and a benign label must never be applied without adequate sampling.

Management is that of a sarcoma. Wide surgical resection rather than simple synovectomy, with adjuvant radiotherapy/chemotherapy and staging for metastases (lungs, nodes), through a sarcoma MDT. Prognosis is markedly worse than benign disease, with a real risk of metastasis and death.

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What it is. Radiosynovectomy (radiosynoviorthesis) is the intra-articular injection of a beta-emitting radionuclide that is taken up by the synovium and ablates residual diseased synovial lining from within, a "medical synovectomy". It targets the microscopic residual disease that surgery leaves behind, which is the very reason diffuse PVNS recurs.

Isotope by joint size. The agent is matched to the joint by the radionuclide's tissue penetration, and colloid or particulate carriers keep the isotope in the joint:

• Yttrium-90 (⁹⁰Y) - the knee: a large joint, deeper penetration
• Rhenium-186 (¹⁸⁶Re) - medium joints: hip, shoulder, ankle, wrist, elbow
• Erbium-169 (¹⁶⁹Er) - small finger and toe joints

Where it fits. It is used mainly as an adjunct after surgical synovectomy in diffuse disease, to treat residual synovium and reduce recurrence, or for inaccessible or multiply recurrent disease where repeat open surgery is unattractive. Conceptually it resembles adjuvant external-beam radiotherapy, delivered from inside the joint with less exposure to surrounding tissues. It is also long established for haemophilic and inflammatory synovitis.

Cautions. The joint must be sealed, with no leak or fistula, to avoid radionuclide escape and lymphatic or systemic spread, and post-injection rest or immobilisation limits leakage. It is generally avoided in the very young because of theoretical radiation risk, and availability is limited to centres with nuclear-medicine support.

Setup. Standard positioning for knee arthrotomy: supine on a standard operating table, a tourniquet on the proximal thigh, the leg free-draped from the tourniquet distally, and a lateral post at the foot of the table for valgus stress. Secure and pad the contralateral leg, keep the heel free of the bed to prevent pressure injury, and pad the tourniquet adequately. No fluoroscopy is needed, but the preoperative MRI is reviewed in theatre for the extent of disease.

Approach. A 15-20 cm midline anterior incision runs from the proximal pole of the patella to the tibial tubercle and can be extended proximally if needed. A medial parapatellar arthrotomy incises the retinaculum from the quadriceps tendon to the medial border of the tibial tubercle, and the patella is everted laterally to expose the entire joint.

Inspection. The key is complete visualisation of all synovial surfaces, inspected systematically:

• Suprapatellar pouch - a common site of disease
• Medial and lateral gutters
• Intercondylar notch and the cruciate ligaments
• Posterior capsule - often requires a posterior approach

Posterior approach. When MRI shows extensive posterior disease, a posteromedial or posterolateral approach gives access to the posterior capsule and the posterior synovium.

Synovectomy. Work through the joint in order:

1. Suprapatellar pouch - remove all synovium; this is a common site of recurrence if excision is incomplete
2. Gutters - excise the synovium, extending posteriorly as far as possible
3. Intercondylar notch - carefully strip synovium from the ACL and PCL, preserving the ligaments; synovectomy of the cruciates is delicate, so avoid damaging them
4. Meniscal surfaces - remove synovium from the peripheral meniscal surfaces
5. Posterior capsule - if a posterior approach has been used, remove all posterior synovium, which is critical in diffuse disease; the popliteal neurovascular structures lie posterior
6. Bone erosions - curette mechanically relevant erosions and burr to healthy bleeding bone

Remove disease that can be accessed without unacceptable damage. Microscopic completeness is not worth sacrificing cruciates, capsule, vessels or function.

Closure. Meticulous haemostasis matters because the friable, vascular tissue risks postoperative haemarthrosis. A drain is used selectively according to dead space, bleeding and closure, and is not mandatory; if one is used, it is removed at 24-48 hours when output decreases. The arthrotomy is repaired with absorbable suture (number 1 Vicryl) and the skin with staples or sutures, under a bulky dressing and a knee immobiliser.

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The major complication of PVNS is recurrence, which drives the need for surveillance and adjuvant therapy strategies. The hepatotoxicity of pexidartinib is set out with systemic therapy above.

Days 0-1. Multimodal analgesia (opioids, NSAIDs, ice), DVT prophylaxis with aspirin or LMWH per protocol, and mobilisation from bed to chair, weight-bearing as tolerated. Monitor the output of any drain.

Days 2-7. Watch the wound for bleeding and infection, and mobilise fully weight-bearing with crutches for comfort. Gentle passive range of motion starts now, because early motion is critical to prevent stiffness after extensive synovectomy. Discharge is home with a physiotherapy referral.

Weeks 2-12. The rehabilitation timeline is similar to total knee arthroplasty, given the extent of the synovectomy:

• Weeks 2-4, restore motion and reduce swelling - active and active-assisted ROM exercises, quadriceps and hamstring isometrics, patellar mobilisation to prevent adhesions, gait training without aids
• Weeks 4-8, strength and function - progressive resistance, closed kinetic chain exercises (leg press, squats), cycling and swimming for low-impact cardio, proprioception exercises
• Weeks 8-12, return to activities - sport-specific exercises if applicable; full ROM expected by 12 weeks and unrestricted activities at 3 months

Outcomes depend on localised versus diffuse morphology, joint and compartment, cartilage and bone damage, residual disease, treatment morbidity and duration of follow-up. Recurrence percentages from series are not interchangeable, because definitions and surveillance differ.

Reading the surgical evidence. Surgical approach is confounded by disease severity. The observational data below associate open or combined synovectomy with lower recurrence in diffuse knee disease, but open surgery should not be called intrinsically prognostic without accounting for selection.

Why it recurs. Incomplete synovectomy leaves microscopic disease, and CSF1 overexpression allows regrowth from the residual cells. Diffuse, posterior and extra-articular disease is harder to control, hip disease is harder to access and recurs more, and each recurrence increases the risk of the next.

Surveillance. Establish a postoperative or post-treatment baseline when it will clarify residual disease or improve later interpretation. Review symptoms, swelling, motion and function at intervals matched to subtype, site and prior treatment, and repeat MRI for known residual or diffuse disease, new symptoms or a planned decision. After localised excision, image when symptoms, difficult anatomy or recurrence risk justify it.

No fixed calendar. There is no universal six-month MRI schedule, and no fixed three- or five-year schedule fits every patient. Long-term surveillance is nonetheless essential given the high recurrence risk in diffuse PVNS.

Red flags for recurrence. Four features:

• Recurrent swelling - a new or worsening effusion
• Mechanical symptoms - locking or catching from a new nodule
• Pain - progressive, and not explained by arthritis
• MRI - synovial thickening, with the blooming artefact reappearing

At suspected recurrence. First confirm whether the MRI change represents residual or progressive TGCT, postoperative scar, bleeding synovitis or another diagnosis. Then reassess symptoms, joint damage, compartments, previous morbidity and patient goals, and choose observation, resection, systemic CSF1R therapy, selected radiotherapy or arthroplasty from the current disease, not from whether this is the first or second recurrence. The goal is durable function and symptom control, not automatic escalation.

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WHO classifies PVNS within TGCT. No universal surgical guideline or registry compares complete pathways; management is rare-tumour, sarcoma-network and multidisciplinary practice.

Counselling should distinguish usually benign histology from locally destructive behaviour, malignant red flags, recurrence uncertainty, treatment morbidity and future joint health.