Pigmented Villonodular Synovitis
Dr. KS Dhillon
Introduction
Pigmented Villonodular Synovitis (PVNS) is a locally aggressive neoplastic synovial disease (not a true neoplasm) that affects joints, bursae, and tendon sheaths. It is characterized by synovial thickening, joint effusions, and bony erosions. Pigmented villonodular synovitis usually affects a single joint. Polyarticular cases are rare. Polyarticular involvement is more likely to occur in children.
Patients between the ages of 30 and 40 are usually affected. It can occur anytime between the 1st and 7th decade and equally affects men and women.
Pigmented villonodular synovitis is rare. It accounts for less than 5% of all primary soft tissue tumors. Localized lesions are more common than diffuse lesions.
Large joints are predominantly affected by diffuse PVNS, with the knee being the most common (66-80%). The hip, ankle, shoulder, and elbow are affected in descending frequency.
The intra-articular form of PVNS occurs almost exclusively in the knee. The tendon sheaths of the hand and wrist are affected more frequently. The volar aspect of the index and long fingers are the most common sites of disease.
Occasionally pigmented villonodular tenosynovitis can coexist with other synovial conditions such as synovial chondromatosis. Microscopically, PVNS synovitis has fibrohistiocytic origin.
Pigmented villonodular synovitis is usually benign. There are however a few cases of malignant transformation that have been reported. It may cause significant morbidity.
Types of Pigmented Villonodular Synovitis
Pigmented villonodular synovitis can be classified as extraarticular and intraarticular.
Intraarticular
Diffuse – Diffuse involvement of joint synovium
Localized – Polypoid or nodular joint synovial lesion within the joint
Extraarticular
Diffuse – Diffuse multifocal involvement of extraarticular synovial membrane
Nodular or Localized – Localized extraarticular nodular lesion, also referred to as giant-cell tumor of the tendon sheath
Both the localized intraarticular forms and diffuse forms predominantly involve the major weight-bearing joints of the lower extremities. The knee is the most common joint involved followed by the hip, ankle, foot, elbow, and shoulder. The nodular extraarticular variant typically involves the acral (limbs and fingers) soft tissues and is mainly found in the fingers and metacarpal/carpal areas. The forearm tendons are rarely involved.
When all types are taken into consideration, the fingers are involved in about 60% of the cases, the knee is involved in approximately 30% of cases and the toes are involved in about 10% of the cases.
Causes
The causes of PVNS include:
Overexpression of CSF1 gene.
This leads to clusters of aberrant cells creating focal areas of soft tissue hyperplasia
Mutations
Chromosome 1p13 in the majority of cases
5q33 chromosomal rearrangement
The Giant Cell Tumor of the tendon sheath is an associated condition.
Presentation of Pigmented Villonodular Synovitis
The symptoms are usually intermittent or steadily progressive. The knee is the most commonly affected large joint. Finger joints can present with localized swelling on the palmar aspect.
The patient usually presents with longstanding pain of insidious onset in the joints that are affected. In about 50% of the patients, there is a prior history of trauma to the area.
Other symptoms include:
Swelling in the affected joint
Stiffness in the affected joint
Recurrent atraumatic hemarthrosis ( Hallmark of the disorder)
Examination would show joint effusion. The overlying skin may be erythematous. There would be joint line tenderness and movements of the joint would be limited. Fluid aspiration usually yields hemorrhagic fluid.
Laboratory Investigations
Bloodwork is usually normal. In patients with recurrent haemarthrosis, arthrocentesis will grossly show bloody effusion.
Diagnostic arthroscopy will show brownish or reddish inflamed synovium which is typical of PVNS. The frond-like pattern of papillary projections is the gold standard for diagnosis. During arthroscopy, synovial biopsy is obtained.
The biopsy will show that the synovium is covered with tan to brown, irregular papillary projections and larger nodular protrusions. Microscopic findings include fibrohistiocytic proliferations and mononuclear stromal cells infiltration into the synovium. It will also show hemosiderin stained multinucleated giant cells, pigmented foam cells (lipid-laden histiocytes), and mitotic figures.
Imaging
X-rays
In the early stages, the X-rays may appear normal. AP and lateral view X-rays of the affected joint are usually done. The X-rays may show an ill-defined soft tissue mass around the joint. Often degenerative joint diseases are seen along with multiple subchondral cysts in the bones on both sides of the affected joint.
Pressure erosion of the joints may occur leading to saucerization of the joint. Narrowing of joint space and osteophyte formation may be seen.
Sometimes, the effusion may be seen as a dense shadow which signifies the presence of hemosiderin.
CT Scan
A CT scan can reveal the extent of involvement and the extent of cystic lesion loss and bone erosions. A CT scan is also useful for guiding needle biopsy.
MRI
MRI is the imaging choice for PVNS. MRI can provide excellent demarcation of both intra and extra-articular disease. MRI will show joint effusion, hemosiderin deposits, synovial expansion, and bony erosions.
Nuclear Imaging
Bone and/or PET scans are not very useful in diagnosing pigmented villonodular synovitis.
Differential Diagnoses
The differential diagnosis includes:
Rheumatoid arthritis
Synovial hemangiomatosis
Tuberculosis
Gout
Hemochromatosis
Low-grade infectious arthritis
Synovial Osteochondromatosis
Synovial Sarcoma
Hemophilia/hemarthrosis
Treatment of Pigmented Villonodular Synovitis
Excision of the affected synovium is the treatment of choice. In clinically aggressive cases, low-dose radiotherapy can be used to control the disease process. It is beneficial in preventing further destruction of the joint and in reducing the risk of recurrences.
In sporadic cases, transformation to a spindle-cell malignancy with metastases to the contralateral thigh has been reported.
Although it is a benign condition, PVNS can result in significant morbidity if left untreated.
The primary treatment options include surgical resection or radiation therapy.
Nonoperative Treatment
Observation can be carried out in asymptomatic patients.
CSF-1 receptor antagonist (pexidartinib) can be used in patients with extensive disease who are unlikely to benefit from the operative treatment.
Perxidartinib taken once daily for 24 weeks has significantly improved the disease burden in approximately 40% of patients. A major side effect is liver toxicity.
Radiotherapy
Radiotherapy is indicated in advanced disease. Radiotherapy reduces the rate of recurrence to less than 20%.
Operative Treatment
Partial synovectomy
For local form of PVNS that is accessible arthroscopic partial removal of synovium can be done. Otherwise, open surgery can be carried out.
Total synovectomy
Total synovectomy is done in patients with overtly symptomatic and painful disease. It can be done by arthroscopy or open surgery. Synovectomy improves the symptoms and function. Recurrence is common. It is often due to incomplete removal of the synovium.
Total synovectomy and total joint arthroplasty
It is done in patients with advanced disease with severe degenerative joint changes in the hip, knee, and shoulder.
Total synovectomy and arthrodesis
It is done in patients with severe disease of the ankle.
Amputation
In patients with a long course of the disease and numerous recurrences, an amputation may be required.
Complications of PVNS
Recurrence
Recurrence is the most common complication. Despite complete synovectomy, it occurs in about 50% of the patients. The rates are similar for both arthroscopic and open surgery. It can be reduced with addition of external beam radiation.
Joint destruction
PVNS can produce joint destruction which can result in moderate to severe joint deformity. It may lead to a need for arthrodesis or amputation. Skin necrosis can occur. Exposure to radiation can produce radiation-induced sarcoma
Prognosis
PVNS is associated with a high recurrence rate and accelerated degeneration of the knee. Often ultimately knee arthroplasty is required.
TKA in patients with PVNS is often associated with complications.
Conclusion
Pigmented Villonodular Synovitis is a locally aggressive synovial disease characterized by joint effusions, expansion of the synovium, and bony erosions. It usually presents in patients who are between 30 and 40 years of age, with recurrent atraumatic knee hemarthrosis.
The diagnosis is multifaceted, involving clinical assessment and MRI studies. Arthrocentesis reveals a brown fluid, and biopsy reveals hemosiderin-stained multinucleated giant cells.
Treatment generally consists of partial or total surgical synovectomy depending on the presence of localized or diffuse PVNS.
