Pigmented Villonodular Synovitis (Tenosynovial Giant Cell Tumor)
What is Pigmented Villonodular Synovitis (Tenosynovial Giant Cell Tumor)?
Pigmented villonodular synovitis (PVNS), also known as tenosynovial giant cell tumor (TGCT), is a rare, benign (non-cancerous), but locally aggressive joint disease. It occurs when the synovium—the thin layer of tissue that lines the joints and tendons—thickens and overgrows, forming a mass or tumor. This overgrowth leads to the production of excess joint fluid, causing swelling, pain, and potential joint damage over time.
The condition is divided into two main types:
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Localized: Affects only a small, specific area of the joint space or tendon sheath.
-
Diffuse: Widespread involvement throughout the entire joint capsule. This type is more aggressive and harder to treat.
The knee is by far the most commonly affected joint (accounting for up to 80% of cases), though it can also occur in the hip, ankle, shoulder and elbow.
Synonyms
- Tenosynovial Giant Cell Tumor
- Diffuse-type giant cell tumor
- Giant cell tumor of the tendon sheath
Pigmented villonodular synovitis (PVNS), also known as tenosynovial giant cell tumor (TGCT), is a rare, benign (non-cancerous), but locally aggressive joint disease. It occurs when the synovium—the thin layer of tissue that lines the joints and tendons—thickens and overgrows, forming a mass or tumor. This overgrowth leads to the production of excess joint fluid, causing swelling, pain, and potential joint damage over time.
The condition is divided into two main types:
-
Localized: Affects only a small, specific area of the joint space or tendon sheath.
-
Diffuse: Widespread involvement throughout the entire joint capsule. This type is more aggressive and harder to treat.
The knee is by far the most commonly affected joint (accounting for up to 80% of cases), though it can also occur in the hip, ankle, shoulder and elbow.
PVNS is an extremely rare condition, occurring in approximately 1.8 cases per million people. It typically strikes young to middle-aged adults between the ages of 20-50 and has a slightly higher incidence in women. The knees are most commonly affected, accounting for 66-80% of cases.
| Name | Abbreviation |
|---|---|
| Tenosynovial Giant Cell Tumor | TGCT |
| Diffuse-type giant cell tumor | Dt-GCT |
| Giant cell tumor of the tendon sheath | GCTTS |
PVNS is not caused by trauma, diet or lifestyle. It is considered a tumor-like process driven by a specific genetic mutation rather than a purely inflammatory condition. A chromosomal rearrangement involving the short arm of chromosome 1p11-13 (see RareShare guide on chromosomal nomenclature) is associated with the excessive production of macrophage colony- stimulating factor 1 (CSF-1), which in turn, attracts a large number of macrophage white cells to a joint resulting in a characteristic thickened mass. Pigment from broken-down red blood cells becomes deposited in the tissue, giving a yellow, brown or rust-colored appearance.
Symptoms often develop gradually and can mimic other common joint issues like arthritis or a meniscus tear, resulting in delayed diagnosis. They include:
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Unexplained recurrent or chronic joint swelling
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Dull, aching joint pain that worsens with activity
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A feeling of stiffness or reduced range of motion
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Catching, popping, or locking of the joint
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Warmth over the affected joint
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Episodes of sudden, painful swelling caused by bleeding into the joint (hemarthrosis)
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In advanced cases, joint destruction and secondary osteoarthritis
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Diffuse PVNS tends to be more aggressive and symptomatic than localized disease
Because it mimics other conditions, PVNS is often diagnosed months or even years after symptoms begin. Diagnosis typically involves:
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Physical Exam: Checking for swelling, limited movement, and joint stability.
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X-rays: Often normal in the early stages, but later stages may show bone cysts or joint damage.
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MRI (Magnetic Resonance Imaging): The modality of choice for PVNS diagnosis, showing the thickened synovium and characteristic dark spots from red cell-derived iron deposits.
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Joint Aspiration: Fluid from the joint is often bloody or dark brown.
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Biopsy: Microscopic examination of a tissue sample can help confirm the diagnosis with the appearance of multi-nucleated giant cells, macrophages and hemosiderin iron storage complexes, and rule out other types of tumors.
Genetic testing: Specifically look for the CSF1 gene rearrangement using techniques such as fluorescence in-situ hybridization (FISH) or polymerase chain reaction (PCR).
Treatment aims to remove the tumor, relieve pain, and preserve joint function.
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Surgery (Synovectomy): The primary treatment, where the surgeon removes the affected synovial lining. This can be done arthroscopically (using small incisions and a camera) or via open surgery, depending on how diffuse the tumor is.
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Targeted Systemic Therapy: For patients with severe, diffuse PVNS that cannot be surgically removed, or for tumors that continually return, medications called CSF1R inhibitors such as Pexidartinib (Turalio) can be used while monitoring for liver toxicity.
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Radiation Therapy: Sometimes used after surgery for the diffuse type to kill remaining abnormal cells and reduce the risk of recurrence.
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Joint Replacement: In advanced cases where the cartilage and bone have been severely destroyed, a total joint replacement (like a knee or hip replacement) may be performed.
The prognosis depends on the disease type (localized vs. diffuse), completeness of the synovectomy and the joint involved. Localized PVNS has an excellent prognosis since once the localized mass is surgically removed, it rarely returns. For diffuse PVNS, the prognosis is more guarded as recurrence rates after surgery can range from 10-50%. PVNS is benign and generally does not metastasize to other organs or cause death.
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Tap WD, Wainberg ZA, Anthony SP, Ibrahim PN, Zhang C, Healey JH, Chmielowski B, Staddon AP, Cohn AL, Shapiro GI, Keedy VL, Singh AS, Puzanov I, Kwak EL, Wagner AJ, Von Hoff DD, Weiss GJ, Ramanathan RK, Zhang J, Habets G, Zhang Y, Burton EA, Visor G, Sanftner L, Severson P, Nguyen H, Kim MJ, Marimuthu A, Tsang G, Shellooe R, Gee C, West BL, Hirth P, Nolop K, van de Rijn M, Hsu HH, Peterfy C, Lin PS, Tong-Starksen S, Bollag G. 2015. “Structure-Guided Blockade of CSF1R Kinase in Tenosynovial Giant-Cell Tumor.” N Engl J Med. 373(5):428-37. doi: 10.1056/NEJMoa1411366. PMID: 26222558.
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Bernard CD, Rooker JL, Morey TD, Long RE, Sweeney KR, Powers BC, Vopat BG. 2024. “Pigmented Villonodular Synovitis: A Critical Review.” Kans J Med. 17(5):113-118. doi: 10.17161/kjm.vol17.21831. PMID: 39758547; PMCID: PMC11698232.
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National Organization for Rare Disorders (NORD): Tenosynovial giant cell tumor.
Last updated 1 May 2020, 08:34 PM
Last updated 17 Aug 2009, 07:29 PM
17 Aug 2009, 07:29 PM
After 20 yrs of tenderness and pain in both knees that have both stumped sports doctors and severely limited my activities, I am now diagnosed with synovitis and scheduled for surgery. The pain has always been a burning and stinging sensation just below the kneecaps. Has anyone else with synovitis had similar symptoms? I was also wondering what sort of improvement I might expect following arthoscopic surgery. It would be wonderful to ride a bike again. Thanks for the help. Frank Lawler
Last updated 15 May 2009, 05:19 PM
15 May 2009, 05:19 PM
Update on me: I had arthroscopic surgery yesterday. The surgeon thought she was going to go in and remove the Hoffa Fat Pad, as she did not think it was PVNS, but it turned out it was. She said she has good results usually, as she cauterizes as she removes it. She said it was a fairly large amount, and was on the end of two separate stalks....so does that mean diffuse? Hopefully, this will take care of it, but from what I have read...it may not. Since this site is not very active, I also found a site on facebook. My PCP is a very intelligent and current kind of guy, so when he hadn't heard of this, I knew it was pretty rare. So, the more support between those of us who have it is important to me....so, hopefully, I have been "cured"...good luck to those of you who have this, or think you may....
6 Mar 2009, 05:11 PM
Hi I have PVNS in my ankle, not knee but the way the pvns works is still the same. The pvns starts growing in the lining of a joint. There are 2 types - nodular which tends to keep an encapsulated "bubble" around the disease and helps to prevent it spreading. This is usually removed surgically and that is the end of it. The other type is diffuse - spreads around the local area and grows in long ribbons and grows through and around tendons and has been known to attack some of the bone (but not in all instances). It affects one in about 1.7 million and usually affects people between 30-40 years but does affect ages either side. This is not classed as cancer, just the immune system causing cells to be different. It is widely thought that with the diffuse type once it is opened up it grows at a much faster rate and there are some of us who cannot have a joint replacement (ankle replacements are not so easy yet) but many people have a few surgeries on their knees before needing a knee replacement. The only drug that seems to have any effect is Sutent and that is very expensive (you would need good insurance cover in the States and here in the UK they will only give it to forms of malignant cancer and even then people have had to fight). I also have ME.CFS & Fibromyalgia and know how difficult it is to keep going with exercise etc. I cannot walk on my right leg at all now but find that swimming really helps me to feel more loose even though it takes a while to get going in a morning first!!! I also take a natural product called Bromelain (extracts from the Pineapple plant). This is supposed to help keep inflammation down and it is thought that inflammation assists the pvns to grow. If you go online to delphiforums and look up pvns you will see many stories about pvns and what people have tried and more importantly what doctors in what countries people have found to be good. Make sure you see a good orthopaedic oncologist (they specialise in tumours (benign and malignant) and will best help you. Good luck.
6 Mar 2009, 01:36 AM
I have not been officially diagnosed yet, but had an MRI that I kind of forced them to do, and the radiologist said the mass in my left knee looks like PVNS. I think it has been in there for quite some time, and I am having a hard time finding anyone who will take this seriously. My PCP has referred me to the orthopedic surgeon who I saw about 2 years ago who thought maybe it was just a little scar tissue. But, now she has an MRI to look at, so maybe she will change her idea. The more research I do, the more I think it is PVNS. For about 4 years my knee has been swelling on and off and getting very warm to touch. There is pain too, but it is hard to figure out where that is coming from as I also have very bad osteoarthritis, my ACL is holding on by a thread, as is the MCL. I had most of the cartiledge removed about 10 years earlier. At that time the surgeon said I had synovitis, so I wonder if it was beginning then?? SO, I think my journey with this is just beginning. I would love to hear anything from anyone about your experience. Since none of my doctors, or the PT I work for has any idea about this disease, I have been doing all the research myself. Is it considered cancer? just not malignant? It looks like the doctors that people go to are oncologists....I am in Vermont...anyone close to here? Have any idea about doctors? I see one in Boston some have recommended at Dana Farber. well, I hope since I have broken the ice...now people will write.....I look forward to meet others with this illness......I also have fibromyalgia and chronic fatigue, and I am on disability because of them. Hope to meet you soon! M
Last updated 14 May 2009, 02:35 AM
14 May 2009, 02:35 AM
Hi. I'm a noobie to this site so please be patient. I've been diagnosed with PVNS a couple of years ago and since then I have had 4 surgeries and am about to undergo radiation therapy. I hear mixed news about the therapy. Wondering if anyone else has done it. Actually, I'd like any other ideas about the disease. Even my docs are noobies at it so I would like some input from people that have been dealing with it. Thx
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See Disorder Resources for news link on FDA approved therapy for Pigmented Villonodular Synovitis.
Created by shannon.ashoori | Last updated 1 May 2020, 08:34 PM
Recent Synovitis Diagnosis
Created by recyclist | Last updated 17 Aug 2009, 07:29 PM
ok I will start
Created by maryla | Last updated 15 May 2009, 05:19 PM
Recurrent Diffuse PVNS in Both Knees
Created by FrankieB | Last updated 14 May 2009, 02:35 AM
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