Previously known as pigmented villonodular synovitis (PVNS) and giant cell tumor of the tendon sheath (GCT-TS)
TGCT is a type of rare, locally aggressive, non-life threatening, tumor of the joint, tendon sheath, or bursae. TGCT leads to stiffness, pain, swelling, and limited range of motion in the affected joint (1). In 2013, The World Health Organization reclassified giant cell tumor of the tendon sheath (GCT-TS), nodular tenosynovitis, pigmented villonodular synovitis (PVNS), and diffuse-type giant cell tumor as a single disease entity known as Tenosynovial Giant Cell Tumor (TGCT) with two subtypes. There are two subtypes of TGCT, localized, sometimes called nodular, and diffuse (2). Localized/Nodular TGCTencompasses previously named nodular tenosynovitis and GCT-TS, while Diffuse TGCT includes diffuse-type giant cell tumor and PVNS. The subtype of TGCT often influences recurrence risk and treatment options. Learn more about the subtypes at Types of TGCT.
TGCT varies in clinical presentation and can occur at all ages (3). According to NORD, the disease commonly presents in people 25-50 years of age, while diffuse TGCT tends to occur in those < 40 years old (4). TGCTs are rare and researchers don’t know exactly how many people are diagnosed with TGCT each year. However, a study done in the Netherlands was used to calculate the worldwide incidence. Globally, it is estimated that 43 people out of every million are newly diagnosed with TGCT, localized and diffuse subtypes, each year (5). However, a Danish study found that 44 per 100,000 people are currently living with localized TGCT and 12 per 100,000 people are living with diffuse TGCT (6). More people are living with the disease than those who are newly diagnosed, this is because the prevalence includes those newly diagnosed and those who have had it long-term.
Surgery may be curative for many people with TGCT, but for others, TGCT may recur after surgery. Recurrence rates depend on the subtype of TGCT (6). Different types of doctors are likely to be involved in the care of patients with TGCT. For hard-to-treat cases, care teams should include sarcoma specialists. These doctors have experience treating difficult tumors similar to TGCT.
The World Health Organization classifies these tumors as "intermediate tumors". This means that these tumors do not spread to other areas of the body and are locally aggressive (7). These tumors are benign but may share some features to soft tissue cancers, also referred to as sarcoma. It is important to note that these tumors are not cancerous. For example, TGCT may put stress on local bones, tissue, and joints but does not spread; whereas, sarcomas can spread to healthy tissue in distant locations such as the lungs. There is no such thing as a good tumor; however, TGCT is rarely life- threatening, unlike sarcoma. TGCT and sarcoma share some characteristics, such as, both can lead to severe functional impairment when left untreated. Joint deterioration can drastically impact quality of life in patients with TGCT. TGCT, especially the diffuse type, can lack a distinct boundary making complete surgical resection difficult. Diffuse TGCT has high recurrence rates and the surgical difficulties may contribute to the high recurrence rates. Additionally, these tumors may be treated with drugs that are targeted to the tumor, such as pexidartinib (Turalio) and vimseltinib (Romvimza). The best treatment modality is highly debated and should be based on an individualized approach that fits the needs of each patient. Additional treatments are being investigated and research is bridging the knowledge gaps to improve the understanding of which patients would benefit from which specific treatments. To learn more about treatments, go to Treatment.
What makes up tGCT tumors?
There are hundreds of different types of cells in the body. All of these different cells serve a specific and diverse function. The cells within a TGCT are just as diverse. Tumors can begin in almost any type of cells in the body.
The type of cell defines the biology of the tumor and the location can influences the treatment plan. The types of cells in these tumors include fibroblasts, monocytes, macrophages, and giant cells. Fibroblasts: Fibroblasts are a type of cell that make up connective tissue, often in ligaments and tendons (8). They are found throughout the body as structural support for our organs. Monocytes & Macrophages: Monocyte are a type of white blood cell that can function as a macrophage. A macrophage is a specialized white blood cell involved in the inflammatory response. These white blood cells remove dead cells, kill microorganisms (eg. like infections), and recruit other cells. A portion of the TGCT is made up of tumor cells while the rest of the tumor is made up of monocytes and macrophages that become part of the tumor.
TGCT promotes the growth and recruitment of these cells to become part of the tumor.
Multi-nucleated Giant Cells: These cells formed by the joining of monocytes and macrophages to become a single cell. These cells are often associated with the soft tissue and bone damage. These cells are large and mediate tissue repair and remodeling. However in TGCT patients, only 2-16% of the tenosynovial giant cells have a genetic abnormality that provokes tumor growth (9).
Myth: TGCT is caused or worsened by high-impact activity. Fact: High-impact activity or injury can impact the overall health of the joint. However, there are many drivers of joint health and there is no known relationship between activity and TGCT formation or growth.
Myth: Hormones impact TGCT. Fact: Sex-based hormones (e.g., testosterone, estrogen, progesterone) are not identified to impact TGCT growth or development. Although some studies have identified higher prevalence of TGCT in females, it occurs frequently in both sexes. Unlike forms of breast cancer which are driven by estrogen, TGCT has not been shown to be driven by any sex-based hormone. There is also no link to other hormone events such as pregnancy or menstruation.
Myth: The worsening of TGCT symptoms means the TGCT is growing. Fact: There does not appear to be a clear correlation between TGCT growth and the presence of symptoms. Symptoms tend to come and go with intermittent flares and symptoms may change without changes in the disease. TGCT may also grow and change without impact to symptoms.
Myth: TGCT can spread. Fact: TGCT occurs in a single joint and will not spread to any other part of the body. However, TGCT can worsen which can cause damage to surrounding regions of the joint. Additionally, when one joint is impacted, patients often compensate, for example by limping, thus putting more stress on other joints, causing pain. Unfortunately, misdiagnosis is common in TGCT. Approximately 50% of patients are misdiagnosed prior to receiving their accurate diagnosis. This may be due to the lack of familiarity with the condition. Similarly, patients may be misdiagnosed with TGCT in multiple locations. It is important to note that TGCT occurs in a single joint and is not likely to spread. Patients may have multiple conditions at the same time. Patients may also experience pain in other areas of their body due to overcompensation. Consider seeking out an expert from the TGCT Support specialists list to ensure you are receiving multidisciplinary care.
Myth: TGCT and PVNS are different diseases. Fact: PVNS is an old name for the same disease, TGCT. In 2013, The World Health Organization reclassified giant cell tumor of the tendon sheath (GCT-TS), nodular tenosynovitis, pigmented villonodular synovitis (PVNS), and diffuse-type giant cell tumor as a single disease entity known as Tenosynovial Giant Cell Tumor (TGCT) with two subtypes. This change was in response to the fragmented care and lack of biological relevance of old naming. For instance, TGCT is not responsive to corticosteroids like a synovitis may be. The discovery of the genetic abnormality also changed the understanding that inflammation was secondary to the tumor growth and the disease was better treated under oncology.
Myth: TGCT always require treatment. Fact: In 2022, a global group of TGCT experts came together and created a consensus document of the treatments for localized and diffuse TGCT. The consensus found that patients should be treated based on symptoms, not radiographic appearance, and the preferred treatment for asymptomatic TGCT is active monitoring. Surgical removal remains the most common treatment approach when a patient is symptomatic. There is no current consensus on the type of surgery or the technique that is best suited for TGCT patients. Each patient’s disease should be evaluated on an individual basis with their healthcare provider. Additionally, when a patient has a high risk of surgical complications, lack of prospective benefit from surgery and a high chance of recurrence or has had prior recurrences, the patient may benefit from a medication. There is no rush! It is important to note that while there is no standard treatment pathway for TGCT, surgery can be curative. Particularly, localized TGCT can be cured when complete removal of the tumor (complete resection) is possible. However, complete removal of tumor(s) in diffuse TGCT remains difficult and other treatment options, such as medications, may be considered. This is because diffuse TGCT can be aggressive and infiltrate the surrounding tissue inside and outside the affected joint, thus, it can be more difficult to treat. Treatment should be patient-centric and determined based on consultation with your healthcare team.
Myth: Surgery is the only option for treatment. Fact: Surgery is often the first-line treatment for TGCT that is symptomatic and where the entire disease may be removed. However, Active Surveillance (also known as active monitoring) is the preferred approach for patients managing their symptoms or those asymptomatic. Research suggests that only a minority of patients who do not treat their disease for 1 year after diagnosis develop arthritis meaning it is safe to monitor TGCT when you are asymptomatic. Systemic therapies (medications) were designed for patients with symptoms related to TGCT, and when surgery is unlikely to provide benefit or control disease. These medications may be used for patients with diffuse and recurrent TGCT.
Myth: TGCT always leads to joint degeneration. Fact: Joint degeneration is based on many factors such as exercise, weight, genetics, and health history. TGCT may not increase joint degeneration for all patients. However, there are no known strategies which prevent degeneration. Many healthcare providers and patients note reducing high-impact activities such as running and jumping to reduce stress on the joint.
Myth: I can control my TGCT with diet alone. Fact: No specific diet or lifestyle modifications have been identified as helpful for TGCT. However, patients modify activities based on their symptoms. Many patients with TGCT change components of their diet and/or take supplements to improve overall health, well-being, and systemic inflammation. While anti-inflammatory diets and supplements can be used to aid in overall health, it is important to note that these changes may not impact the disease itself or symptoms associated with TGCT. Patients with TGCT may struggle to remain active. Modifying movements to make them achievable may keep you active. Patients often find physical therapy helpful to find modifications that work for their unique situation.
Check out more Frequently Asked Questions using our Comprehensive FAQ!
REFERENCES
1. Gelhorn HL, Tong S, McQuarrie K, et al. Patient-reported Symptoms of Tenosynovial Giant Cell Tumors. Clin Ther. 2016. doi:10.1016/j.clinthera.2016.03.008 2. Righi A, Gambarotti M, Sbaraglia M, et al. Metastasizing tenosynovial giant cell tumour, diffuse type/pigmented villonodular synovitis. Clin Sarcoma Res. 2015. doi:10.1186/s13569-015-0030-2 3. Healey JH, Bernthal NM, van de Sande M. Management of Tenosynovial Giant Cell Tumor: A Neoplastic and Inflammatory Disease. J Am Acad Orthop Surg Glob Res Rev. 2020. doi:10.5435/JAAOSGlobal-D-20-00028 4. National Organization for Rare Disorders. Tenosynovial Giant Cell Tumor. NORD. 2017. https://rarediseases.org/rare-diseases/tenosynovial-giant-cell-tumor/. 5. Mastboom MJL, Verspoor FGM, Verschoor AJ, et al. Higher incidence rates than previously known in tenosynovial giant cell tumors. Acta Orthop. 2017. 6. Ehrenstein V, Andersen SL, Qazi I, et al. Tenosynovial Giant Cell Tumor: Incidence, Prevalence, Patient Characteristics, and Recurrence. A Registry-based Cohort Study in Denmark. J Rheum. 2017. https://www.jrheum.org/content/44/10/1476.long 7. Levin A. Tenosynovial Giant Cell Tumor: A New Name and a New Treatment Option for PVNS and GCTTS. Am Acad Orthop Surg. 2021. https://www.aaos.org/aaosnow/2021/jan/research/research01/. 8. Al Saanna G, Bovée J, Hornick J, Alexander Lazar A. A Review of the WHO Classification of Tumours of Soft Tissue and Bone. ESUN B Rev. 2013. http://sarcomahelp.org/reviews/who-classification-sarcomas.html. 9. Hügel H. Fibrohistiocytic skin tumors. JDDG - J Ger Soc Dermatology. 2006. doi:10.1111/j.1610-0387.2006.06021.x 10. Gouin F, Noailles T. Localized and diffuse forms of tenosynovial giant cell tumor (formerly giant cell tumor of the tendon sheath and pigmented villonodular synovitis). Orthopaedic and Traumatology: Surgery & Research. 2017. doi: 10.1016/j.otsr.2016.11.002
