Pigmented Villonodular Synovitis (PVNS)

Definition

Epidemiology & Incidence

• Rare condition with an estimated incidence of ~1.8 per million per year
• Most patients are young adults in the 3rd and 4th decades of life, though it can present in childhood
• No strong sex predilection; some series show a slight female predominance
• Knee is the most commonly affected joint (~75-80%), followed by the hip (~15%), and less commonly the ankle, shoulder, wrist, and elbow

Classification / Forms

Pathogenesis / Aetiology

1. Inflammatory/reactive theory - recurrent hemarthrosis causing reactive synovial hyperplasia
2. Neoplastic theory - now favored; chromosomal translocations (especially t(1;2)) lead to overexpression of colony-stimulating factor 1 (CSF1), driving monocyte/macrophage proliferation of the synovium. This forms the basis of targeted CSF1R inhibitor therapy.

Clinical Features

• Monoarticular involvement (almost always a single joint)
• Chronic, insidious onset of pain and swelling of the affected joint
• Serosanguineous or blood-tinged joint aspirate - this is characteristic and an important clinical clue
• Mechanical symptoms (locking, clicking) when intraarticular loose bodies are present
• A palpable soft-tissue mass may be present
• Long diagnostic delay is common due to the nonspecific nature of symptoms
• In long-standing cases: destruction of cartilage and secondary degenerative change with joint space narrowing

Investigations

1. Joint Aspiration

• Aspirate is characteristically serosanguineous or frankly haemorrhagic (Group IV hemorrhagic fluid on classification)
• Not diagnostic on its own; cytology can rule in/out PVNS

2. Plain Radiographs

• Often normal early in the disease
• May show: joint effusion / soft-tissue swelling
• Bone erosion on both sides of the joint (on a background of preserved joint space and normal bone density)
• Importantly, calcification is rare (helps distinguish from synovial chondromatosis)
• In the hip: erosion can produce an "apple core" appearance (narrowing of femoral neck), with subchondral cysts having sclerotic rims (Fig 30.14A & B)
• In large joints (knee): erosions are less frequent because the capsule has greater capacity

3. MRI - Investigation of Choice

• Provides the best diagnostic clue due to hemosiderin deposition in hypertrophied synovium
• Classic finding: low signal intensity on BOTH T1 and T2 weighted images (dark on both) - this is due to hemosiderin from recurrent hemorrhage
• T2 (gradient-echo) sequences* show characteristic blooming artifact due to hemosiderin - most sensitive
• Bone erosions, subchondral "cysts," and synovial tissue extent clearly delineated
• Joint effusion also well seen
• Post-contrast: synovial proliferation enhances

4. CT

• Non-enhanced CT shows high attenuation within the mass (due to hemosiderin)
• Synovial proliferation enhances with contrast
• Useful for bony detail

Histopathology

• Bland polyhedral (synoviocyte-like) cells in sheets or papillary projections
• Multinucleated giant cells (osteoclast-type)
• Hemosiderin deposits (golden-brown pigment in macrophages)
• Foamy (lipid-laden) macrophages
• Collagenous stroma with chronic inflammatory infiltrate
• No cytological atypia or high mitotic activity (benign)

Differential Diagnosis

Treatment

Localized Form

• Arthroscopic or open marginal excision - treatment of choice
• Recurrence rate: 0-8% after arthroscopic excision
• Excellent prognosis

Diffuse Form

• Total synovectomy - either open, arthroscopic, or combined
• Can be done arthroscopically (e.g., posterior trans-septal portal technique for the knee)
• Higher recurrence rates (up to ~45% with incomplete synovectomy)
• If secondary degenerative changes are present: arthroplasty should be strongly considered
• Radiotherapy (adjuvant radiation synovectomy) may be justified in the diffuse form if surgery fails to control the disease
• CSF1R inhibitors (e.g., pexidartinib): clinical trials underway and showing promise - targets the CSF1/CSF1R pathway that drives synovial proliferation; FDA-approved for TGCT not amenable to surgery

Prognosis

• Benign, locally aggressive; no metastatic potential
• Localized form has excellent prognosis with low recurrence
• Diffuse form has significant recurrence rates (varies 10-50% depending on completeness of synovectomy)
• Long-standing disease causes progressive cartilage and bone destruction, resulting in secondary osteoarthritis
• Malignant transformation is extremely rare

Key Points Summary

1. PVNS = benign synovial proliferation; now called tenosynovial giant cell tumor
2. Young adults; knee most common joint (~75%)
3. Monoarticular; blood-tinged aspirate is characteristic
4. MRI hallmark: dark on both T1 and T2 due to hemosiderin; blooming on T2* GRE
5. Histology: polyhedral cells + multinucleated giant cells + hemosiderin
6. Two forms: localized (marginal excision) vs. diffuse (total synovectomy)
7. No calcification (distinguishes from synovial chondromatosis)
8. Hip involvement causes "apple-core" erosion of femoral neck
9. CSF1R overexpression is the underlying molecular driver
10. Adjuvant radiotherapy and CSF1R inhibitors available for refractory cases

Paget's Disease of Bone (Osteitis Deformans)

Definition

Aetiology & Pathogenesis

• Genetic: Mutations in SQSTM1 (sequestosome-1, encoding p62 protein) found in ~50% familial and ~10% sporadic cases, leading to increased NF-κB activity and osteoclast hyperactivity. Mutations in RANK (TNFRSF11A) and OPG (TNFRSF11B) account for juvenile Paget's. Positive family history in 15-25% of patients.
• Viral: Paramyxovirus-like inclusions (measles, RSV, canine distemper virus) found in osteoclast nuclei. Viral mRNA detected in pagetic osteoclasts. The declining incidence of Paget's disease coincides with measles vaccination - supporting this theory, though a live virus has never been cultured.

Phases of Disease (Three Sequential Stages)

Epidemiology

• Age: Usually >40 years; prevalence increases with age (~3% at autopsy in those >40)
• Sex: Slight male predominance
• Geography: Common in Western Europe (UK, France, Germany), rare in Asia, Africa, Scandinavia
• Distribution: Monostotic in ~15%; polyostotic in ~85%
• Most commonly affected bones: pelvis, vertebrae, skull, femur, tibia
• Often asymptomatic - discovered incidentally on X-ray or elevated ALP

Clinical Features

• Bone pain (most common) - from lytic expansion, microfractures, hypervascularization
• Bowing of tibia and femur - the classic orthopaedic deformity
• Gait abnormality and secondary osteoarthritis of hip/knee
• Back pain; spinal stenosis from vertebral overgrowth
• Leontiasis ossea (lion face) from skull/facial bone enlargement
• Skull enlargement → increased head size, kyphosis
• Platybasia (invagination of skull base) causing posterior fossa compression
• Deafness from temporal bone involvement (cochlear or ossicular compression)
• Chalk-stick (banana) fractures in long bones - horizontal transverse fractures (not oblique/spiral), typically in the lateral cortex of femur/tibia

• Warm skin overlying pagetic bone (increased local blood flow)
• High-output cardiac failure in severe polyostotic disease (arteriovenous shunt effect)

Investigations

Complications

1. Pathological fractures - chalk-stick / banana fractures; fractures heal normally
2. Secondary osteoarthritis - from bony deformity distorting joint mechanics
3. Nerve compression - deafness (VIII nerve), spinal stenosis, cranial nerve palsies
4. High-output cardiac failure - in severe polyostotic disease
5. Malignant transformation to osteosarcoma - <1% overall, but 5-10% in severe polyostotic disease; rapidly fatal; suspect if sudden increase in pain or ALP

Treatment

• Fracture fixation (intramedullary nailing preferred)
• Osteotomy for severe deformity
• Joint replacement for secondary OA
• Pre-operative bisphosphonate to reduce hypervascularization before elective surgery on pagetic bone