Villonodular synovitis (VS), also known as tenosynovial giant cell tumor (TGCT), is a rare, non-cancerous growth. It develops in the synovium, the thin tissue lining joints and tendon sheaths. This condition involves an overgrowth of the synovial tissue. While the tumor is benign and does not spread, this progressive disease can lead to pain, swelling, and joint damage over time, interfering with normal joint movement and function.
Causes and Symptoms
The precise cause of villonodular synovitis is not fully understood, but research points to a genetic mutation. Many cases involve a translocation of chromosome 1p13, leading to the overexpression of the colony-stimulating factor 1 (CSF1) gene. This overexpression results in increased production of the CSF1 protein, which attracts inflammatory cells to the joint, causing the synovial tissue to proliferate abnormally.
Symptoms often appear gradually and can be mistaken for other joint conditions, such as arthritis. Common indicators include persistent joint swelling, pain, and stiffness. Individuals may also experience a catching or locking sensation within the joint, or a limited range of motion. The condition can also cause hemarthrosis, where blood collects in the joint space. These symptoms may fluctuate, appearing for periods and then subsiding, only to return later.
Villonodular synovitis presents in two main forms: localized (nodular) VS, where the tumor is contained to a specific area or affects only the tendons, and diffuse VS, which involves the entire joint lining. Diffuse VS tends to be more aggressive and challenging to manage. The knee is the most frequently affected joint, accounting for about 80% of cases, but VS can also occur in the hip, ankle, shoulder, and, less commonly, the elbow, wrist, or jaw.
The Diagnostic Process
Diagnosing villonodular synovitis begins with a physical examination and a review of the patient’s medical history. A doctor assesses the affected joint for swelling, tenderness, and range of motion limitations. Since symptoms can mimic other joint problems, additional tests are often required to confirm VS.
Imaging tests play a significant role in identifying the condition and determining its extent. While X-rays may not show the tumor in early stages, they can reveal bone erosion in more advanced cases or help rule out other conditions. Magnetic resonance imaging (MRI) is considered the most informative imaging tool for VS. It provides detailed views of soft tissues, including the synovium, and can clearly show synovial thickening, abnormal masses, and bone or cartilage damage.
A characteristic MRI finding for VS is the presence of hemosiderin deposits, which are iron-containing pigments from old bleeding within the joint. These deposits appear as areas of low signal intensity on MRI scans. A definitive diagnosis of villonodular synovitis requires a biopsy. This procedure involves taking a small tissue sample from the affected synovium for microscopic examination, which confirms the specific cellular changes.
Treatment Approaches
The primary treatment for villonodular synovitis is surgical removal of the abnormal tissue, known as a synovectomy. This procedure aims to excise the tumor and the affected synovial lining. The choice of surgical technique depends on the type and extent of the disease.
For localized cases, arthroscopic surgery, a minimally invasive approach, is often used to remove the contained tumor. This technique offers advantages such as smaller scars and quicker recovery. For diffuse or more complex cases where the tumor has spread throughout the joint, open surgery may be necessary to ensure comprehensive removal.
When surgery alone is not sufficient, or in cases of recurrent or inoperable disease, other treatments may be considered. Radiation therapy can be used as an adjuvant treatment after surgery to improve local disease control or as a primary treatment for diffuse forms. This therapy targets and destroys remaining abnormal cells.
Targeted drug therapies represent a newer approach, particularly for diffuse or recurrent VS that cannot be adequately treated by surgery. These medications focus on specific molecular pathways involved in the tumor’s growth. Colony-stimulating factor 1 receptor (CSF1R) inhibitors, such as pexidartinib, block the activity of the CSF1 protein, which drives tumor cell proliferation. These inhibitors have shown promise in reducing tumor size and improving symptoms when surgery is not a suitable option or has been ineffective.
Recurrence and Long-Term Outlook
Villonodular synovitis, particularly the diffuse type, has a tendency to recur even after surgical removal. Recurrence rates can be high, with some studies reporting rates up to 50% after initial treatment, especially for the diffuse form. The complex nature of the diffuse disease makes complete removal challenging, contributing to the likelihood of the tumor growing back.
Due to this recurrence potential, long-term follow-up is a regular component of care for individuals with VS. This typically involves periodic clinical evaluations and imaging studies, such as MRIs, to monitor the joint for any signs of tumor regrowth. These regular checks allow for early detection and intervention if recurrence occurs.
Over time, chronic inflammation and damage caused by the tumor, or from repeated surgical interventions, can lead to the development of osteoarthritis in the affected joint. This degenerative joint disease can cause persistent pain and further limit joint function. While VS is generally not life-threatening, its progressive nature and high recurrence rates can significantly affect a patient’s quality of life and joint function over many years.