Pigmented villonodular synovitis (PVNS)

Tumor biology and incidence

Condition of synovial membrane
Characterized by presence of inflammation and hemosiderin deposition in synovium
Controversy: Is PVNS a neoplastic or an inflammatory process?
- Traditionally described as neoplastic process due to unrelenting growth pattern, capacity to erode surrounding boneand joint tissue, and high recurrence rate after resection
- Newer reports consider PVNS to be an inflammatory process
Two disease entities: localized form and diffuse form
- Virtually identical histologically
- Vary significantly in clinical presentation, prognosis, and response to treatment
- Probably co-exist along a continuum of a single disease process
Usually monoarticular
Estimated incidence of PVNS is 1.8 cases/million; diffuse form is more common
Etiology unknown
- Inflammatory versus neoplastic origin
  - Histologic samples have tested positive for markers of chronic inflammation, while excess iron has been seen to transform synoviocytes and fibroblasts into cells with macrophage-like characteristics
  - Reports have linked PVNS to trisomy 7 and have identified presence of clonal DNA
  - Literature describes potential malignant transformations and metastasis
- Mechanical versus metabolic sources of trauma
  - Mechanical trauma causing recurrent local hemorrhage into joint seen in hemophiliacs
  - Suffer from progressive erosive arthropathies, with similar lobular synovitis and hemosiderin deposition
  - Hemophiliacs, however, lack lipid-laden histiocytes and giant cells considered classic indications of PVNS
  - Trauma associated with in less than one-third of cases of PVNS
  - Altered local metabolic environment creates insults to the synovium leading to chronic inflammation.

Age

Often appears in third and fourth decades of life

Gender

M:F = 1:1

Presentation/physical findings

Slow, insidious onset of pain, swelling, and stiffness in involved joint
If knee joint involved, local form commonly has symptoms that mimic meniscal pathology
Diffuse form presents with global joint problems; poorly localized pain with a greater intensity and associated swelling
- Can also manifest extra-articular extensions that encroach on major neurovascular structures, creating a mass effect.

Plain films

Plain radiographs nonspecific and insensitive as a diagnostic tool; 30% or fewer patients present with radiographic findings
If findings are present on plain radiographs, generally appear as periarticular erosions, with a thin rim of reactive bone
Reciprocal bony lesions on opposite sides of the joint, despite articular preservation, highly suggestive of PVNS, but can be seen in other conditions
Late finding of joint space narrowing on plain radiograph indicates articular cartilage loss; can be difficult to distinguish from primary osteoarthritis

Site

Combined, the two forms of PVNS most often affect the knee (approximately 80%); the hip, ankle, and shoulder are less commonly affected
- Local form targets knee's anterior compartment at meniscocapsular junction (anterior horn of the medial meniscus)
- Diffuse form, while affecting knee's entire synovial surface, primarily affects posterior compartment
Considered separately, the localized form occurs most frequently in fingers -- especially volar aspect of first 3 fingers
- Most common soft tissue tumor of the hand

Size

Variable

Soft tissue mass

Localized form pedunculated and lobular; localized to one area of synovium
Diffuse form involves most, if not all, of the joint's synovium

Bone scan

Increased uptake of TI-201, although bone scan not commonly used in PVNS

CT scan

Lesions have high attenuation and appear hyperdense secondary to presence of intracellular and extracellular hemosiderin
Affected synovium hypervascular and generally enhances following administration of radiographic contrast

MRI

Preferred imaging modality; can be highly sensitive and specific
Useful in determining extent of disease involvement and in distinguishing diffuse PVNS from local PVNS
Typical MRI findings for local PVNS:
- Periarticular or synovial nodular mass with varying degrees of bone erosion
- Sporadic or extensive low signal on T1 and T2 (secondary to high hemosiderin content)
- Joint effusion
- "Dark on dark" on T1- and T2-weighted images, but early inflammatory lesions with less hemosiderin may have large amounts of high signal on T2 sequences
- High signal on fat-suppressed images (hemosiderin cannot be seen)
- Hemosiderin seen on fast field echo sequences
- Lesions enhance with contrast

Differential diagnosis

Synovial osteochondromatosis
Synovial hemangioma
Hemochromatosis
Hemophiliac arthropathy
Secondary osteoarthritis
Amyloid arthropathy
Gout
Tuberculosis

Natural history

Continued chronic pain in localized form, possibly resulting in significant disability
Local form has more favorable prognosis with lower recurrence rate following treatment
In diffuse from, progressive destructive changes continue to attack joint and affect articular surface, leading to degenerative joint disease (necessitating total joint arthroplasty or arthrodesis)
- 8% recurrence rate following surgical excision in diffuse form

Pathology

Histological sections characterized by lipid-laden macrophages, multinucleated giant cells, hemosiderin deposition, and stromal and fibroblast cell proliferation

Diagnosis and treatment

Diagnosis made on combination of clinical exam and radiologic/imaging findings
Synovial fluid aspiration commonly used for early diagnosis; brownish-stained bloody fluid indicative of PVNS
- Method lacks specificity and sensitivity
Treatment goal: Eradicate all abnormal synovial tissue, removing source of pain and reducing risk of joint destruction and recurrence
Treatment modalities
- Arthroscopic synovectomy with external beam radiation
  - No significant advantage compared with surgical synovectomy alone
  - Significant complications have been reported: skin reactions, poor wound healing, joint stiffness, sarcomatous transformation
  - Local recurrence rate of 14%, comparable to rate for open total synovectomy
  - Modality can be highly useful in managing refractory cases of PVNS or in those with extensive extra-articular involvement
- Surgical synovectomy with intra-articular radiation
  - Mixed results in the literature
  - Series of 30 patients treated with adjuvant intra-articular radiation at a standard dose after combined open anterior and posterior synovectomy: recurrence rate 17%, compared to 0% for open synovectomy alone
  - Other studies demonstrated eradication of residual disease following intra-articular radiation and MRI follow-up
- Arthroscopic synovectomy
  - Associated with better functional results and lower rates of postoperative stiffness than open techniques
  - Improper application of technology, however, associated with unacceptable recurrence rates in some instances (ie, surgeon inexperience or attempts to debride extensive, diffuse PVNS lesions)
  - No clinical trials compare open with arthroscopic synovectomy for treatment of localized PVNS
  - Extensive joint involvement and extra-articular spread may result after failed arthroscopic management
  - Currently recommended for local disease only
- Open synovectomy (anterior and combined anterior/posterior)
  - May be required to access difficult areas affected by diffuse form of disease
  - Main drawback: significant postoperative stiffness, up to 24% of the patients.
- Combination open/arthroscopic synovectomy
  - Uses combination of open posterior approach and arthroscopic anterior debridement
  - No additional benefits shown in literature

Complications

Osteoarthritis secondary to articular cartilaginous erosions, necessitating total joint arthroplasty (few reports on long-term outcomes in those with total joint arthroplasty and concomitant PVNS)