Summary Pigmented Villonodular Synovitis is a locally aggressive neoplastic synovial disease (not a true neoplasm) characterized by joint effusions, expansion of the synovium, and bony erosions. The condition usually presents in patients between 30 and 40 years old with recurrent atraumatic knee hemarthrosis. Diagnosis is multifaceted with clinical assessment for joint effusion (most commonly the knee), MRI studies showing synovial expansion, arthrocentesis revealing a brown fluid, and biopsy revealing hemosiderin-stained multinucleated giant cells. Treatment generally consists of partial or total surgical synovectomy depending on presence of localized or diffuse PVNS. Epidemiology Incidence rare 9.2 per million per year in the United States Demographics most commonly in adults age 30-40 but can occur at any age equal incidence in men and women Anatomic location may occur locally (within a joint) or diffusely localized (intra-articular or classic form) anterior knee is the most common site of involvement (80%) most commonly affects the patellofemoral compartment at the infrapatellar fat pad knee > hip > ankle > shoulder > elbow diffuse (extra-articular extension) behaves differently from localized Etiology Pathophysiology pathobiology caused by an overexpression of CSF1 gene overexpression leads to clusters of aberrant cells creating focal areas of soft tissue hyperplasia in the synovial cells lining joints a locally aggressive neoplastic synovial disease (not a true neoplasm) Genetics mutations locations of chromosome 1p13 in majority of cases 5q33 chromosomal rearrangement Associated conditions Giant Cell Tumor of Tendon Sheath also known as pigmented villonodular tumor of the tendon sheath (PVNTS) Classification Localized versus Diffuse PVNS Characteristic Localized PVNS Diffuse PVNS Location Knee > hip > ankle Knee (75%) Age 30-50y <40y Gender Male = Female Female =/> Male Presentation Painless, swollen joint, longstanding Painful, swollen, tender, limited mobility Radiograph Osseous erosion from localized pressure Degenerative changes on both sides of the joint MRI Well circumscribed soft tissue mass Ill-defined (poorly circumscribed) soft tissue mass Recurrence 8% after synovectomy 30% after synovectomy Presentation History 50% of patients will have a prior history of trauma to the area Symptoms common symptoms insidious onsent of pain in affected joint stiffness in the affected joint swelling in the affected joint recurrent atraumatic hemarthrosis is hallmark of disorder Physical exam inspection joint effusion erythema palpation tenderness along joint line motion limited motion of affected joint Imaging Radiographs recommended views AP and lateral of affected joint findings soft tissue swelling may show cystic erosion with sclerotic margins on both sides of the joint CT indications to evaluate for extent of cystic bone loss findings may show cystic erosions on both sides of the joint similar to radiographs MRI indications most sensitive imaging study provides excellent delineation of both intra-articular and extra-articular disease findings reveals joint effusion, hemosiderin deposits, expansion of the synovium, and bony erosion low signal intensity on T1 due to hemosiderin deposits presence of fat signal (T1) within the lesion low signal intensity on T2 "blooming artifact" signal loss on gradient-echo sequences because of iron in hemosiderin extra-articular extension commonly see posterior extension outside of the knee joint of an intra-articular process Studies Labs CRP and ESR often normal despite signs of soft tissue swelling Arthrocentesis indication recurrent hemarthrosis findings grossly bloody effusion Diagnostic arthroscopy indications gold standard for diagnosis synovial biopsy should be performed findings brownish or reddish inflamed synovium is typical of PVNS frond-like pattern of papillary projections Histology gross histology shows a proliferative mass extending from the synovium low power mononuclear stromal cells infiltrating the synovium highly vascular villi lined with plump hyperplastic synovial cells high power hemosiderin stained multinucleated giant cells pigmented foam cells (lipid-laden histiocytes) mitotic figures common Differential Synovial chondromatosis Hemophilia/hemarthrosis Rheumatoid arthritis Septic joints Other neoplasia Treatment Nonoperative observation indications asymptomatic disease only CSF-1 receptor antagonist (pexidartinib) indications approved in 2019 for use in patients with extensive disease who are not likely to benefit from surgical intervention Operative partial synovectomy indications local form of PVNS technique if lesion is accessible from anterior knee, this is can be done arthroscopically posterior or extra-articular lesions should be performed open total synovectomy +/- external beam radiation indications in grossly symptomatic and painful disease technique total synovectomy is classified as marginal excision techniques range from arthroscopic to fully open total synovectomy depending on extent and location of disease outcomes improved functional and range of motion outcomes with arthroscopic technique frequent recurrence is common mostly due to incomplete synovectomy external beam irradiation technique 30-35Gy in 15 fractions, or 50Gy in 25 fractions outcomes when combined with total synovectomy, reduces rate of recurrence to 10-20% total synovectomy and total joint arthroplasty indications advanced disease with severe degenerative joint changes i knee, hip, and shoulder associated with higher rates of post-operative stiffness and infection compared to standard OA indications total synovectomy and arthrodesis indications severe disease of the ankle Techniques CSF-1 receptor antagonist (pexidartinib) technique oral medication taken once daily for 24 weeks showed significant improvement of PVNS disease burden in ~40% of patients. complications cholestatic hepatotoxicity was a noted side-effect of the drug Arthroscopic synovectomy of knee for PVNS approach routine arthroscopic portals for knee, ankle, and shoulder technique perform as thorough resection of synovium as possible through portals can be challenging to access the posterior portions of the joint or extra-articular disease Open posterior synovectomy of knee for PVNS approach posterior approach to the knee via transverse or S-shape incision across popliteal fossa approach between medial and lateral heads of gastrocnemius retract neurovascular bundle to access posterior joint capsule technique disease is often seen posterior and extra-articular to the knee complete posterior synovectomy and resection of extra-articular disease complications posterior approach to the knee places popliteal neurovascular bundle at risk Complications Recurrence incidence recurrence is the most frequent complication for both intra-articular and extra-articular disease 30%-50% recurrence rate despite complete synovectomy same rates for complete open vs open+arthroscopic rates can be reduced with addition of external beam radiation Joint destruction moderate to severe joint deformity treatment may lead to the need for arthrodesis or amputation Skin necrosis, radiation induced sarcoma risk factors radiation therapy Prognosis PVNS is associated with a high rate of recurrence and accelerated degenerative changes of the knee ultimately requiring arthroplasty TKA in patients with PVNS is associated with complication rates