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Synovitis, Pigmented Villonodular

para>Uncommon in elderly patients � �
Pediatric Considerations

Uncommon in children

� �

ETIOLOGY AND PATHOPHYSIOLOGY


  • Exact cause is unknown.
  • History of trauma is noted in ~50% of patients with DPVNS of the knee.
  • DPVNS is thought to be either an inflammatory synovial reaction or a benign neoplastic process.
  • Histologically, LPVNS and DPVNS are similar.
  • Characterized by mononuclear stromal cells infiltrating synovial membrane
  • Hemosiderin-loaded macrophages give the typical brown color ( "pigmented " �).
  • Multinucleated giant cells and foam cells are also involved.
  • DPVNS and LPVNS differ in their disease course.
    • DPVNS (more common than LPVNS)
      • Characterized by involvement of most or all of the joint synovium
      • More rapidly destructive, with poorer prognosis
      • Can encroach on neurovascular structures
      • Continued inflammation and joint erosions lead to articular cartilage destruction and subsequent osteoarthritis.
    • LPVNS
      • Characterized by focal, pedunculated lesions
      • Favorable prognosis due to localized nature
      • Low recurrence rate after surgery

Genetics
  • Translocation of collagen 6A3 gene (2q35) and macrophage colony-stimulating factor gene (1p13) in a fraction of tumor cells
  • Cytogenetic aberrations are seen in most cases.
  • Overexpression of colony-stimulating factor 1

DIAGNOSIS


HISTORY


  • Typically, monarticular involving large joints
    • Knee/hip are most commonly involved joints.
    • Ankle, shoulder, elbow, and spine are less common.
    • Onset of symptoms can be insidious or acute and episodic.
    • Pain, swelling, and stiffness are common in DPVNS.
    • History of locking, catching, or instability is common with LPVNS.
    • Patients occasionally report periods of excessive pain, which may correspond to hemorrhage into the joint space.
    • Symptoms often intermittent and poorly localized

PHYSICAL EXAM


  • May be completely normal
  • May have tenderness to palpation of involved joint such as on patellofemoral area in knee DPVNS
  • May have moderate-to-large joint effusion
  • May have stiffness with decreased active and passive range of motion of involved joint

DIFFERENTIAL DIAGNOSIS


  • Rheumatoid arthritis; osteoarthritis; psoriatic arthritis
  • Septic arthritis
  • Inflammatory arthritis
  • Synovial sarcoma
  • Avascular necrosis
  • Systemic lupus erythematosus (SLE)
  • Gout
  • Other benign/malignant bone tumor

DIAGNOSTIC TESTS & INTERPRETATION


Initial Tests (lab, imaging)
  • Erythrocyte sedimentation rate (ESR)
  • C-reactive protein (CRP)
  • Antinuclear antibody (ANA)
  • Rheumatoid factor (RF)
  • CBC
  • Uric acid
  • Joint fluid analysis
  • Plain radiographs (1,2)
    • Most cases have normal radiographs.
    • Findings seen more commonly in hip joint than in knee joint because the knee capsule can stretch and hold the proliferating hyperplastic synovium.
    • Findings include bony erosions with thin rim of sclerotic margins.
    • Joint space narrowing is a late finding.
  • CT scan (1,2)
    • Underlying bone erosions/cysts with decreased signal
  • MRI (1,2)
    • Modality of choice for diagnosis, determining the extent of the disease and differentiating DPVNS from LPVNS
    • DPVNS
      • Poorly localized synovial thickening with varying degrees of periarticular bony erosions
    • LPVNS
      • Periarticular/synovial nodular mass with varying degree of bony erosion
    • DPVNS and LPVNS
      • Prominent low-signal intensity seen on T1- and T2-weighted images secondary to high hemosiderin content

Diagnostic Procedures/Other
Synovial fluid aspiration/arthrocentesis (2): � �
  • May demonstrate blood-tinged synovial fluid
  • Not pathognomonic sign of PVNS; lacks sensitivity and specificity

Test Interpretation
See " Etiology and Pathophysiology. " � � �

TREATMENT


GENERAL MEASURES


  • Treatment of PVNS is often surgical (2)[A].
  • Synovectomy removes abnormal synovium and is the treatment of choice for, reducing the risk of joint destruction and recurrence.
  • Use of adjuvant treatments along with surgery is recommended, particularly for diffuse PVNS, to prevent recurrence (3)[C].

ADDITIONAL THERAPIES


Pharmacotherapy (4,5)[C] � �
  • TNF-α (tumor necrosis factor-α) blockade: after surgical excision of abnormal synovium
  • Infliximab, sunitinib, and imatinib may inhibit CSF1R activation (5)[C],(6).
  • May also induce complete response and be used as an option for nonsurgical treatment; must balance symptom alleviation with drug toxicities (4)[C]
  • Bisphosphonates may inhibit periarticular bone destruction carried out by osteoclasts in PVNS.

SURGERY/OTHER PROCEDURES


  • Surgical resection (2,5)[C]
    • Mainstay of treatment
    • Complete synovectomy by open surgical procedure for active diffuse PVNS.
    • Arthroscopic partial synovectomy for local PVNS
    • Patients with large popliteal masses or extra-articular involvement are generally not candidates for arthroscopic surgery.
    • Arthroscopic treatment of DPVNS is associated with higher recurrence rate, unlike rare recurrence after limited local treatment in LPVNS.
    • Joint replacement is indicated in patients with significant joint destruction.
  • Radiation therapy (1),(3)[C]
    • Recommended as an adjuvant to surgery
    • Useful in challenging cases with extensive extra-articular involvement, recurrent disease, or involvement of critical anatomic structures
    • Serious complications include skin reactions, poor wound healing, and sarcomatous transformation.
    • Contraindicated in children and in those with prosthetic joints

INPATIENT CONSIDERATIONS


Primarily treated as outpatient with surgery � �

ONGOING CARE


FOLLOW-UP RECOMMENDATIONS


Close follow-up for recurrence and progression of disease � �

DIET


No restrictions � �

PROGNOSIS


  • Patients with recurrent disease have more extensive involvement and less chance for successful treatment.
  • DPVNS is more rapidly destructive and has a poorer prognosis.
  • Recurrence rates after synovectomy range from 8% to 20%.
    • Rates are higher with DPVNS.
    • Rates increase with extra-articular involvement.
  • Articular cartilage destruction and the development of osteoarthritis may hasten joint replacement surgery.
  • Malignant transformation is rare.

COMPLICATIONS


  • Surrounding cortical erosion and tissue damage resulting in limited ambulation and debilitating pain
  • Extensive joint involvement and extra-articular spread may result after failed arthroscopic management.
  • Recurrence may lead to joint replacement.
  • Postoperative stiffness occurs in ~25% of patients after open procedure.

REFERENCES


11 Murphey � �MD, Rhee � �JH, Lewis � �RB, et al. Pigmented villonodular synovitis: radiologic-pathologic correlation. Radiographics.  2008;28(5):1493 " �1518.22 Tyler � �WK, Vidal � �AF, Williams � �RJ, et al. Pigmented villonodular synovitis. J Am Acad Orthop Surg.  2006;14(6):376 " �385.33 Bruns � �J, Ewerbeck � �V, Dominkus � �M, et al. Pigmented villo-nodular synovitis and giant-cell tumor of tendon sheaths: a binational retrospective study. Arch Orthop Trauma Surg.  2013;133(8):1047 " �1053.44 Blay � �JY, El Sayadi � �H, Thiesse � �P, et al. Complete response to imatinib in relapsing pigmented villonodular synovitis/tenosynovial giant cell tumor (PVNS/TGCT). Ann Oncol.  2008;19(4):821 " �822.55 Ravi � �V, Wang � �WL, Lewis � �VO. Treatment of tenosynovial giant cell tumor and pigmented villonodular synovitis. Curr Opin Oncol.  2011;23(4):361 " �366.66 Cassier � �PA, Gelderblom � �H, Stacchiotti � �S, et al. Efficacy of imatinib mesylate for the treatment of locally advanced and/or metastatic tenosynovial giant cell tumor/pigmented villonodular synovitis. Cancer.  2012;118(6):1649 " �1655.

ADDITIONAL READING


  • Al-Nakshabandi � �NA, Ryan � �AG, Choudur � �H, et al. Pigmented villonodular synovitis. Clin Radiol.  2004;59(5):414 " �420.
  • de Carvalho � �LHJr, Soares � �LF, Gon � �alves � �MB, et al. Long-term success in the treatment of diffuse pigmented villonodular synovitis of the knee with subtotal synovectomy and radiotherapy. Arthroscopy.  2012;28(9):1271 " �1274.
  • Frassica � �FJ, Bhimani � �MA, McCarthy � �EF, et al. Pigmented villonodular synovitis of the hip and knee. Am Fam Physician.  1999;60(5):1404 " �1410.
  • Verspoor � �FG, van der Geest � �IC, Vegt � �E, et al. Pigmented villonodular synovitis: current concepts about diagnosis and management. Future Oncol.  2013;9(10):1515 " �1531.

CODES


ICD10


  • M12.20 Villonodular synovitis (pigmented), unspecified site
  • M12.259 Villonodular synovitis (pigmented), unspecified hip
  • M12.269 Villonodular synovitis (pigmented), unspecified knee
  • M12.279 Villonodular synovitis (pigmented), unsp ankle and foot
  • M12.261 Villonodular synovitis (pigmented), right knee
  • M12.252 Villonodular synovitis (pigmented), left hip
  • M12.251 Villonodular synovitis (pigmented), right hip
  • M12.262 Villonodular synovitis (pigmented), left knee
  • M12.271 Villonodular synovitis (pigmented), right ankle and foot
  • M12.29 Villonodular synovitis (pigmented), multiple sites
  • M12.249 Villonodular synovitis (pigmented), unspecified hand
  • M12.28 Villonodular synovitis (pigmented), vertebrae
  • M12.221 Villonodular synovitis (pigmented), right elbow
  • M12.242 Villonodular synovitis (pigmented), left hand
  • M12.211 Villonodular synovitis (pigmented), right shoulder
  • M12.219 Villonodular synovitis (pigmented), unspecified shoulder
  • M12.272 Villonodular synovitis (pigmented), left ankle and foot
  • M12.222 Villonodular synovitis (pigmented), left elbow
  • M12.229 Villonodular synovitis (pigmented), unspecified elbow
  • M12.231 Villonodular synovitis (pigmented), right wrist
  • M12.232 Villonodular synovitis (pigmented), left wrist
  • M12.239 Villonodular synovitis (pigmented), unspecified wrist
  • M12.241 Villonodular synovitis (pigmented), right hand
  • M12.212 Villonodular synovitis (pigmented), left shoulder

ICD9


  • 719.20 Villonodular synovitis, site unspecified
  • 719.25 Villonodular synovitis, pelvic region and thigh
  • 719.26 Villonodular synovitis, lower leg
  • 719.27 Villonodular synovitis, ankle and foot
  • 719.29 Villonodular synovitis, multiple sites
  • 719.28 Villonodular synovitis, other specified sites
  • 719.23 Villonodular synovitis, forearm
  • 719.22 Villonodular synovitis, upper arm
  • 719.21 Villonodular synovitis, shoulder region
  • 719.24 Villonodular synovitis, hand

SNOMED


  • Pigmented villonodular synovitis
  • Pigmented villonodular synovitis of hip joint
  • Pigmented villonodular synovitis of knee joint
  • Villonodular synovitis of the ankle and foot (disorder)
  • Villonodular synovitis of the pelvic region and thigh (disorder)
  • Villonodular synovitis of upper limb (disorder)

CLINICAL PEARLS


  • PVNS is characterized by synovial inflammation and hemosiderin deposition. The etiology is unknown.
  • Most frequent in 3rd and 4th decades of life
  • Typically presents insidiously over time with intermittent episodes of joint pain and swelling. The knee is the most commonly involved joint.
  • MRI is the diagnostic modality of choice for PVNS.
  • Surgery is mainstay of treatment. Pharmacotherapy and radiotherapy can be used as adjuncts.
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