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FranceIn short
Giant cell tumour of tendon sheath is a noncancerous growth that forms in the protective sleeve surrounding tendons, most commonly in the hands and feet. While these tumours are always benign and cannot spread like cancer, they can grow quickly, cause joint problems, and return after treatment if not completely removed.
When someone develops a giant cell tumour of tendon sheath, the main goals of treatment are to completely remove the tumour, restore normal movement to the affected joint, reduce pain and swelling, and prevent the tumour from coming back. The approach to treatment depends on several factors, including where the tumour is located in the body, how large it has grown, whether it involves nearby joints or bone, and the overall health of the patient. These tumours, also known as tenosynovial giant cell tumours or by their older name pigmented villonodular synovitis, are the second most common type of tumour found in the hand, appearing less frequently only than simple ganglion cysts.
Treatment options have evolved significantly in recent years. While surgery remains the cornerstone of treatment for most patients, new drug therapies have become available for cases where surgery is not possible or when tumours keep returning. Medical societies and clinical guidelines generally recommend complete surgical removal as the first-line treatment for localized tumours, but each patient's situation is unique and requires careful consideration by their medical team.
There are two main forms of this condition that affect treatment planning. The localized form is more common and typically affects small joints like those in the fingers. These tumours grow slowly and are usually confined to a specific area, making them easier to remove completely. The diffuse form is less common but more challenging to treat because it grows quickly and can spread beyond the initial area to involve surrounding tissues, including the joint capsule, nearby ligaments, and even bone.
Surgery to remove the tumour, called marginal excision, is the standard treatment that doctors recommend for most patients with giant cell tumour of tendon sheath. During this procedure, the surgeon carefully removes the entire tumour along with a small amount of surrounding normal tissue to ensure no tumour cells are left behind. The surgery is typically performed under local or regional anesthesia, though general anesthesia may be used depending on the location and size of the tumour.
The surgical approach requires wide exposure of the affected area and very careful dissection. Surgeons often use magnifying loupes or even operating microscopes to see tiny details during the operation. This magnification is crucial because these tumours can have small satellite nodules – tiny separate pieces of tumour tissue near the main mass – that must be identified and removed to prevent recurrence. Studies have shown that using magnification during surgery helps surgeons identify and remove these satellite nodules, which significantly reduces the chance of the tumour coming back.
Before surgery, doctors typically obtain tissue for examination through a procedure called fine needle aspiration cytology, which involves inserting a thin needle into the tumour to collect cells. This test helps confirm the diagnosis before proceeding with surgery. However, in about one in six cases, this test may not provide clear results, and the diagnosis must be confirmed through other imaging studies and eventually through examination of the removed tumour tissue.
The duration of surgery varies depending on the tumour's location and complexity, but most procedures take between one and three hours. Recovery time also varies, but patients typically need several weeks for the surgical wound to heal. Physical therapy is often recommended after surgery to help restore full movement and strength to the affected area. This rehabilitation phase is important because the surgery may temporarily affect how well the joint moves, and guided exercises help patients regain function more quickly.
One of the main challenges with surgical treatment is the risk of recurrence – the tumour growing back after it has been removed. Studies have found widely varying recurrence rates, ranging from as low as 4% to as high as 44%, depending on several factors. Tumours near the distal interphalangeal joints (the joints at the tips of the fingers), those with evidence of bone erosion on X-rays, and those classified as diffuse type are more likely to return after surgery. The single most important factor in preventing recurrence is achieving complete removal of all tumour tissue, including any satellite nodules, during the initial surgery.
Complications from surgery can include infection, bleeding, damage to nearby nerves or blood vessels, joint stiffness, and in rare cases, loss of finger or toe function. However, when performed by experienced surgeons using proper techniques including magnification, serious complications are uncommon. Poor health of the patient or the presence of life-threatening illnesses are considered reasons not to perform surgery, as these conditions increase surgical risks.
For patients who cannot undergo surgery or whose tumours keep returning despite multiple operations, new drug treatments tested in clinical trials have provided hope. The most significant development has been the approval of medications that target specific molecules involved in tumour growth. These treatments represent a shift in thinking about giant cell tumours, as research has shown they are not just inflammatory conditions but have characteristics of true neoplasms – abnormal tissue growths with specific genetic changes.
The first systemic drug approved specifically for tenosynovial giant cell tumour was pexidartinib, which received approval from the U.S. Food and Drug Administration in 2019. This medication works by blocking a protein receptor called colony stimulating factor-1 receptor (CSF1R), which is a type of tyrosine kinase enzyme. The tumour cells depend on signals from this receptor to survive and multiply. By attaching to CSF1R on certain immune cells like monocytes, macrophages, and osteoclasts, pexidartinib prevents the receptor from being activated by its natural triggers, including a molecule called interleukin-34. This blockage stops the production of inflammatory chemicals by these immune cells, which in turn inhibits tumour cell growth.
The approval of pexidartinib was based on results from a Phase III clinical trial called ENLIVEN, which was the first placebo-controlled study of a drug treatment for this condition. In this trial, patients were randomly assigned to receive either pexidartinib or a placebo (inactive treatment) for comparison. The primary measure of success was the overall response rate – the percentage of patients whose tumours shrank significantly. At week 25 of treatment, 38% of patients who received pexidartinib showed a response, compared to 0% of those who received placebo. Among the responders, 15% had complete disappearance of their tumours and 23% had partial shrinkage. The drug's effects were durable, meaning they lasted over time: all patients who were followed for at least 12 months maintained their response throughout that period.
Beyond tumour shrinkage, the ENLIVEN study also found statistically significant improvements in secondary measures that matter to patients' daily lives. These included better range of motion in the affected joint, improved physical function, and reduced stiffness. These improvements mean that patients could more easily perform everyday activities that had become difficult due to their tumour.
However, pexidartinib does have significant side effects that require careful monitoring. The most serious concern is liver toxicity – damage to the liver that can show up in blood tests or, in rare cases, cause serious symptoms. Because of this risk, the FDA requires doctors to monitor liver function with blood tests before starting treatment and regularly throughout treatment. In the original clinical trials, some patients needed to reduce their dose or stop taking the medication because of liver problems. In 2022, the FDA approved a lower dose regimen to reduce the risk of excessive drug levels in the blood that could lead to liver damage and other adverse effects.
These medications are typically reserved for patients with advanced, symptomatic disease where surgical removal would potentially cause severe morbidity or significant functional limitation. This means they are generally used when surgery would require removing important structures like nerves, blood vessels, or large portions of bone or joint, which would severely affect how the hand or foot works. The drugs may also be considered for patients whose tumours have returned multiple times after surgery.
Clinical trials are ongoing to test other drugs that work through similar or different mechanisms. Some studies are evaluating other CSF1R inhibitors with potentially different side effect profiles. Researchers are also studying whether these drugs might be useful before surgery to shrink tumours and make them easier to remove completely, or after surgery to reduce the risk of recurrence. These Phase II trials aim to demonstrate not just that the drugs are safe, but that they effectively reduce tumour size and improve symptoms. The trials are being conducted at medical centers in the United States, Europe, and other regions, with specific eligibility criteria regarding tumour location, size, and previous treatments.
Another treatment approach that has been studied is radiosynoviorthesis with yttrium-90, a form of radiation therapy where radioactive particles are injected directly into the joint. This treatment has been used primarily for patients with diffuse-type tumours affecting the knee. The radiation damages the abnormal tissue lining the joint while minimizing exposure to surrounding normal tissues. Some studies have reported beneficial results with this approach as an adjuvant treatment – meaning it is used in addition to surgery rather than as the sole treatment. However, this technique requires specialized facilities and expertise, and is not widely available.
This guide is here to help you understand the condition. It does not replace a conversation with your doctor, who knows your situation best.
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