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1.  Surgical outcomes of 26 patients with pigmented villonodular synovitis (PVNS) of the knee at a mean follow-up of 4 years: introducing a novel technique 
Background: Pigmented villonodular synovitis (PVNS) is characterized by the presence of inflammation and hemosiderin deposition in the synovium. Two forms of PVNS distinguished in the literature are diffused and localized involvements. There are controversies in the literature about the surgical management of PVNS. We report our experience in the management of knee PVNS at a mean follow-up of 4 years. We also introduce our preferred method of treatment for these patients.
Methods: A number of 26 patients (26 knees) with histologically proven PVNS of the knee in the pathology department at Shafa Yahyaeyan hospital were identified between January 1996 and February 2012. Annual clinical follow-up was conducted in all patients and a follow-up MRI scans was ordered for symptomatic cases. All patients were examined according to the Knee Society Score (KSS) in which the knees were graded from excellent to poor.
Results: Mean age of the patients was 28.08±12.5. A number of 15 patients (58%) had diffused involvement of the knee joint and 11 (42%) had a localized form of involvement. Mean follow up was 4 years. The mean duration of symptoms prior to presentation was 44.40±38.69 months. In five cases (23%) subtotal synovectomy and in 21 cases (77%) total synovectomy was performed. Two cases (7.7%) had recurrence. In a comparison between new methods vs. routine methods, after adjusting the pre-operation KSS scores, there was a significant difference between both methods in their post-op results. There were no complications in the form of knee instability, infection or neurovascular injury.
Conclusion: The PVNS of knee joint; especially the diffused form should be carefully observed and managed using appropriate investigations. Staged open total synovectomy with a posterior and then an anterior approach seems to be a superior method for surgical treatment of diffused forms.
PMCID: PMC4313448
Knee joint; Pigmented Villonodular Synovitis; Synovectomy; Recurrence
2.  MRI Diagnosis of Recurrent Pigmented Villonodular Synovitis Following Total Joint Arthroplasty 
HSS Journal  2012;9(1):100-105.
Pigmented villonodular synovitis (PVNS) can recur after complete synovectomy and even after total joint replacement. In the authors’ experience, there is a misconception that MRI may not be useful to diagnose PVNS in the setting of a total joint replacement due to dephasing artifact from metal. While there are case reports of PVNS in patients with total joint replacement diagnosed surgically, to our knowledge, diagnosis of recurrent PVNS by MRI following total joint replacement has not been reported. This report illustrates the utility of MRI in the diagnosis of recurrent PVNS following total joint replacement by reviewing two cases of pathologically correlated PVNS recurrence following arthroplasty, and two cases in which PVNS recurrence is strongly suspected, though pathological correlation is not available.
PMCID: PMC3640717  PMID: 24426852
MRI; total knee replacement; total hip arthroplasty; recurrent pigmented villonodular synovitis; recurrent PVNS
3.  Unusual cases of pigmented villonodular synovitis after arthroplasty 
Pigmented Villonodular Synovitis (PVNS) is a relatively rare, benign proliferation lesion of the synovium of large joints. The etiology is varied and unclear. We had report a 79-year-old woman had PVNS after 14 years right hip arthroplasty with metal prosthesis. Here we report another 4 patients had PVNS after arthroplasty. The second one had PVNS in the 2th year after hip arthroplasty with bone cement prosthesis. The specimen was brown and like usual PVNS in tissue. The third case had PVNS in the 8th after arthroplasty with human bone prosthesis because of the recurrence of PVNS. The proliferated synovium became black from brown. There was brown and many groups black pigment in the tissue. The fourth one had PVNS in the 4th year after knee arthroplasty with polyethylene prosthesis. The specimen was yellow. There was no pigment in the tissue but multinucleated giant cells with unstained foreign body. The fifth patient had PVNS in the 10th month after the left hip arthroplasty with metal prosthesis. The macroscopy was yellow. There were hemosiderin particles in the tissue but black metal particles. This indicates that arthroplasty with prosthesis could cause some new disease or PVNS had new etiology with different pathological show.
PMCID: PMC4057877  PMID: 24955198
Pigmented villonodular synovitis; arthroplasty; etiology
4.  Does Combined Open and Arthroscopic Synovectomy for Diffuse PVNS of the Knee Improve Recurrence Rates? 
Diffuse-type pigmented villonodular synovitis (PVNS) has a high local recurrence rate and as such can lead to erosive destruction of the involved joint. Multiple surgical modalities exist, but it is unknown which technique best minimizes local recurrence and surgical morbidity.
We compared recurrence rates, arthritis progression, and complications between arthroscopic and open modalities for diffuse PVNS of the knee.
We retrospectively identified 103 patients with PVNS treated between 1993 and 2011. Of these, 48 had diffuse-type PVNS of the knee treated by all-arthroscopic, open posterior with arthroscopic anterior, or open anterior and open posterior synovectomy. We recorded patient demographics, treatment profiles, recurrence rates, and arthritic progression. Minimum followup was 3 months (median, 40 months; range, 3–187 months).
Recurrence rates were lower in the open/arthroscopic group compared with the arthroscopic or open/open groups: 9% versus 62% versus 64%, respectively. Arthritic progression occurred in 17% of the total study group with 8% going onto total knee arthroplasty within the followup period. We detected no difference between groups with regard to arthritic progression or progression to arthroplasty. The most common complication was hemarthrosis, which we drained in three patients (6% of the total study group), but there were no detectable differences between groups.
Open posterior with arthroscopic anterior synovectomy is a viable, comprehensive approach to diffuse PVNS of the knee and provides both low recurrence rates and a low postoperative complication profile. Greater numbers of recurrences may be partially explained in the arthroscopic group by technical challenges associated with posterior arthroscopic synovectomy and in the open/open group by selection bias toward more aggressive disease.
Level of Evidence
Level III, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.
PMCID: PMC3563816  PMID: 22996360
5.  Unusual presentation of giant cell tumor originating from a facet joint of the thoracic spine in a child: a case report and review of the literature 
Giant cell tumor of the synovium is a common benign lesion that frequently occurs at the tendon sheaths in the hand; it is usually found in adults over 30 years old. It is related to pigmented villonodular synovitis. Giant cell tumor of the synovium or pigmented villonodular synovitis has been described rarely in the axial skeleton especially in the thoracic vertebrae of a child.
Case presentation
A previously healthy 7-year-old Thai girl presented with back pain and progressive paraparesis and was unable to walk for 1 month. She had weakness and hyperreflexia of both lower extremities. Magnetic resonance imaging showed a well-defined homogeneously and intensely enhanced extradural mass with cord compression at T4 to T7 levels. The patient underwent laminectomy at T4 through to T7 and total tumor removal. Permanent histopathologic sections and immunostains revealed a giant cell tumor of the synovium. Postoperative neurological status recovered to grade V. Magnetic resonance imaging at the 1-year follow-up showed no recurrence and there was no clinical recurrence at the 2-year follow-up.
We report an extremely rare case of giant cell tumor in the epidural space that extended from a thoracic facet joint. The tumor was removed successfully through laminectomies. Although giant cell tumor of a facet joint of the thoracic spine is very rare, it must be considered in the differential diagnosis for masses occurring in the epidural space in a child. Total tumor removal is the best treatment. Careful monitoring of recurrence can achieve a good clinical outcome.
PMCID: PMC3711725  PMID: 23830026
Giant cell tumor; Spine; Synovium
6.  Pigmented villonodular synovitis: a retrospective study of seventy five cases (eighty one joints) 
International Orthopaedics  2013;37(6):1165-1170.
Pigmented villonodular synovitis (PVNS) is a relatively rare, benign proliferation lesion of the synovium of large joints, but there is not much information available about the disease’s aetiology, clinical history, differential diagnosis, treatment, and long-term effects. We conducted a study to analyse these aspects of PVNS.
We reviewed all clinical data for 75 patients with PVNS (81 joints) who were treated either by synovectomy alone or synovectomy plus arthroplasty.
In all cases, the diagnosis of PVNS was confirmed by pathological examination. The ratio of males to females was 27:48, and the average age of patients was 46 years (range, 15–80 years). Lesions were located in the knee, hip, or ankle, and pain and swelling were the main symptoms. Of 75 patients, 42 had a history of trauma to the involved joint. Forty-one patients (43 joints) underwent synovectomy alone, and 34 patients (38 joints) underwent synovectomy and arthroplasty together. Of the 75 patients, 61 had full follow-up data. Twelve patients had recurrent legions detected by pathological examinations; four patients had more than two recurrences. Moreover, five patients developed PVNS after arthroplasty.
PVNS occurs most often in middle-aged women and most frequently involves the knee, followed by the hip and ankle. The disease’s etiology is varied and unclear. Surgical excision alone or with arthroplasty is an effective treatment, but there is a high rate of recurrence.
PMCID: PMC3664172  PMID: 23503697
7.  Pigmented Villonodular Synovitis of the Thoracic Vertebra Presenting with Progressive Spastic Paraparesis 
Case Reports in Orthopedics  2013;2013:870324.
Pigmented villonodular synovitis (PVNS) is a proliferative benign lesion originating from the synovium and commonly affects large joints of the extremities. PVNS can arise from any synovium in the whole body and rarely affects the zygapophyseal joints of the spine. Spinal PVNS is diagnosed mostly after resection of the mass. In our case we present a 22-year-old male patient showing progressive spastic paraparesis with insidious onset of back pain and difficulty of walking in a relatively short period of 1 month. After gross excision of the mass, diagnosis was established through histopathology. Two years of follow-up period reveals complete resolution of the patient's complaints and no recurrence on radiologic images.
PMCID: PMC3789316  PMID: 24159395
8.  A rare case of extensive diffuse nonpigmented villonodular synovitis as a cause of total knee arthroplasty failure 
Nonpigmented villonodular synovitis (non-PVNS) is a benign proliferative disease involving the synovium. It is a rare condition that is little recognized. Non-PVNS has been reported as a cause of total knee replacement failure.
We report a case of extensive diffuse non-PVNS in a patient with tibial component loosening after total knee replacement and review the related literature.
It is reported that pigmented villonodular synovitis (PVNS) occurs less frequently than non-PVNS after knee replacement. However, there are many more case reports of PVNS than non-PVNS after knee arthroplasty in the English-language literature.
Previously, there were no reported cases of extensive diffuse non-PVNS after total knee arthroplasty (TKA). This case study highlights an unusual case of non-PVNS as a cause of TKA failure. We propose that non-PVNS should be considered as a differential diagnosis in patients after TKA who present with recurrent pain and effusion/hemarthrosis of the knee, and that it is one of the causes of implant loosening after TKA.
PMCID: PMC4064475  PMID: 24892248
Nonpigmented villonodular synovitis; Component loosening; Revision knee arthroplasty; Total synovectomy
9.  Pigmented Villonodular Synovitis on Lumbar Spine : A Case Report and Literature Review 
Pigmented villonodular synovitis (PVNS) is a benign proliferative joint disease with an uncertain etiology that uncommonly involves the spine. We present a case of PVNS involving the lumbar spine. A 38-year-old male developed back pain and pain in both legs caused by a mass in the L4 region of the right lamina. After gross total tumor removal, the symptoms improved. The pathological finding was synovial hyperplasia with accumulation of hemosiderin-laden macrophages. He was diagnosed with PVNS and experienced no recurrence for up to 2 years after surgery. In this report, we review the previous literature and discuss etiology, clinical manifestations, diagnosis, and treatment.
PMCID: PMC4217069  PMID: 25368775
Pigmented villonodular synovitis; Lumbar spine; Giant cell tumor
10.  Low-dose external beam radiotherapy as a postoperative treatment for patients with diffuse pigmented villonodular synovitis of the knee 
Acta Orthopaedica  2012;83(3):256-260.
Background and purpose
Pigmented villonodular synovitis (PVNS) is a rare proliferative disorder involving synovial membranes, and patients with PVNS have a variable prognosis. We retrospectively analyzed clinical outcomes after synovectomy plus low-dose external beam radiotherapy for diffuse PVNS of the knee.
We reviewed the medical records of 23 patients who underwent postoperative radiotherapy between 1998 and 2007. 19 patients had primary disease and 4 had recurrent disease with an average of 2.5 prior surgeries. After synovectomy (17 arthroscopic surgeries; 6 open), all 23 patients received 4-MV or 6-MV external beam radiotherapy with a median dose of 20 (12–34) Gy in 10 fractions.
At a median follow-up of 9 (0.8–12) years, 4 patients had recurrent disease, with a median disease-free interval of 5 years. Of these 4 patients, 3 received salvage synovectomy and regained local control. Univariate analysis showed that age, sex, history of trauma, and total dose of radiation were not predictive of local control. 22 patients reported excellent or good joint function, and 1 who refused salvage synovectomy had poor joint function. None of the patients experienced grade 3 or higher radiation-related toxicity or radiation-induced secondary malignancies.
Postoperative external beam radiotherapy is an effective and acceptable modality to prevent local recurrence and preserve joint function in patients with diffuse PVNS of the knee. Low-dose (20 Gy) radiotherapy appears to be as effective as moderate-dose treatment (around 35 Gy).
PMCID: PMC3369151  PMID: 22489888
11.  Pigmented villonodular synovitis of the temporomandibular joint - computed tomography and magnetic resonance findings: a case report 
Pigmented villonodular synovitis (PVNS) is a benign but locally aggressive and destructive disease originating in the synovial membranes. It is a proliferative disorder of unknown etiology. Involvement of the temporomandibular joint (TMJ) is very rare. Computed tomography clearly reveals areas of lytic bone erosion and sclerosis, and also clearly defines the extent of the tumor which is the focal areas of hyperdensity within the soft-tissue mass. Magnetic resonance images invariably show profound hypointensity on both T1- and T2-weighted sequences due to hemosiderin pigmentation. Additionally, high signal intensity on T2-weighted images may indicate cystic loculation of the joint fluid. This case study describes a rare case of PVNS of the TMJ with bone destruction of the mandibular condyle. Complete surgical excision of the lesion was performed through a preauricular approach with temporal extension. During the 10-year follow-up, two more operations were performed due to local recurrence and the fracture of the reconstruction plate. Total joint reconstruction with Biomet was finally performed, and the absence of disease was confirmed with a biopsy report showing fibrosis with hyalinization and mild inflammation of the excised soft tissue from the old lesion.
PMCID: PMC4095812  PMID: 25045642
Temporomandibular joint; Pigmented villonodular synovitis; Mandibular reconstruction
12.  Adult multifocal pigmented villonodular synovitis—clinical review 
International Orthopaedics  2013;37(4):729-733.
Pigmented villonodular synovitis (PVNS) is a rare, benign proliferative disease of the synovial tissue that affects a single joint or a tendon sheath. Data from the literature present only a few cases of multifocal PVNS. This paper presents multifocal PVNS in the adult. This disease can affect bilateral shoulders, hips and knees. The diagnosis may be delayed by the slow evolution of the disease (up to ten years); some patients may be seen with late-stage degenerative joints, serious complications, painful and functionally uncompensated, with significant locomotion deficit. PVNS requires a radical treatment with prosthetic arthroplasty associated with synovectomy. Complex imaging (X-Rays, magnetic resonance imaging (MRI), ultrasound) and macroscopic appearance of the lesions during surgery confirms the clinical diagnosis of multifocal PVNS with secondary bone lesions. Histology marks the final diagnosis of multifocal PVNS. The postoperative results are good, with recovery in functional parameters of the joints with endoprosthesis.
PMCID: PMC3609970  PMID: 23361936
13.  Pigmented Villonodular Synovitis Causing Osteonecrosis of the Femoral Head: A Case Report 
Case Reports in Orthopedics  2013;2013:756954.
We report a case of a 27-year-old man with pigmented villonodular synovitis of the hip joint with coincident osteonecrosis of the femoral head. According to our review of the English-language literature, no detailed report of osteonecrosis of the femoral head complicated with pigmented villonodular synovitis has been published. Preoperative X-ray images showed joint narrowing and severe multiple bone erosions at the acetabulum and femoral neck. Magnetic resonance imaging revealed a low-intensity band attributable to osteonecrosis of the femoral head and massive diffuse pigmented villonodular synovitis lesions. Comparison of a three-dimensional computed tomographic image of this patient with an angiographic image of a normal individual demonstrated proximity of the pigmented villonodular synovitis-induced bone erosions to the medial and lateral femoral circumflex arteries and retinacular arteries, suggesting likely the compromise of the latter by the former. We propose that the massive pigmented villonodular synovitis may have contributed to the pathogenesis of osteonecrosis of the femoral head in this patient. We performed open synovectomy and total hip arthroplasty. No operative complications occurred, and no recurrence of the pigmented villonodular synovitis was detected for 3 years after the operation.
PMCID: PMC3876680  PMID: 24416606
14.  Magnetic resonance imaging and thallium-201 scintigraphy for the diagnosis of localized pigmented villonodular synovitis arising from the elbow: A case report and review of the literature 
Pigmented villonodular synovitis (PVNS) arising from the elbow joint is extremely rare; only 24 cases have been reported. It is extremely difficult to differentiate PVNS from other soft tissue tumors on the basis of imaging findings alone. Therefore, a biopsy is required for definitive diagnosis. A 20-year-old female reported a mass on her right elbow. Physical examination revealed a tumor measuring 3.0x3.0 cm. Magnetic resonance imaging (MRI) revealed that the signal intensity of the tumor was isointense to muscle on T1-weighted images; however, it was hyper- or isointense to muscle on T2-weighted images. In images obtained by gadolinium-enhanced MRI, the margin of the tumor was well-contrasted. Thallium (Tl)-201 scintigrams revealed an abnormal accumulation in the area of the mass in the early and delayed phases. On the basis of clinical findings, imaging characteristics and incision biopsy results, localized PVNS was diagnosed and marginal excision was performed. We thus identified an extremely rare case of PVNS arising from the elbow joint. When interpreting Tl-201 images for the assessment of bone and soft tissue lesions, it is important to recognize PVNS as a condition that simulates malignant tumors. Furthermore, PVNS should be considered in the differential diagnosis when increased Tl-201 activity is closely related to the joint. MRI aids in the differentiation by demonstrating features of hemosiderin degradation products. These findings are likely to be extremely helpful in the differential diagnosis of bone and soft tissue tumors.
PMCID: PMC3671781  PMID: 23737864
magnetic resonance imaging; thallium-201 scintigraphy; pigmented villonodular synovitis; localized type; elbow joint; soft tissue tumor
15.  Simultaneous Anterior and Posterior Synovectomies for Treating Diffuse Pigmented Villonodular Synovitis 
The current treatment methods for diffuse intraarticular or extraarticular type pigmented villonodular synovitis (PVNS) include arthroscopic synovectomy or staged anterior and posterior open synovectomies. However, it is unclear whether simultaneous anterior and posterior synovectomies achieve local control and recovery of function.
We therefore determined the recurrence rate and function in patients with diffuse PVNS treated with anterior and posterior synovectomies and adjuvant radiotherapy.
We retrospectively reviewed all 19 patients with diffuse PVNS involving the knee treated with anterior and posterior synovectomies and adjuvant radiotherapy between January 2001 and November 2007. From the records, we determined local recurrence and Tegner-Lysholm scores. The minimum followup was 42 months (median, 98 months; range, 42–143 months).
Postoperative MRI revealed residual tumor in five of the 19 patients, although three had no disease progression during followup and had knee scores of 86 to 90. Two patients had recurrences at 6 and 9 months with knee scores of 88 at 42 months and 90 at 68 months. The mean Tegner-Lysholm knee score improved from 59 to 93 points. Mean maximum extension and flexion angles improved from 11° to 2° and from 76° to 127°, respectively.
Compared with the literature, simultaneous anterior and posterior synovectomies associated with postoperative radiotherapy provided rates of residual or recurrent tumor and knee function recovery comparable to that with staged synovectomies reported in the literature.
Level of Evidence
Level IV, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.
PMCID: PMC3348323  PMID: 22359272
16.  Treatment of Diffuse Pigmented Villonodular Synovitis of the Knee with Combined Surgical and Radiosynovectomy 
HSS Journal  2008;5(1):19-23.
Treatment of extensive diffuse pigmented villonodular synovitis (PVNS) of large joints by isolated surgical resection is unsatisfactory, with high rates of local recurrence. Post-synovectomy adjuvant treatment with external beam radiation therapy or intra-articular injection of radioactive material as yttrium-90 (90Y) yielded better results. Between January 2005 and January 2007, 12 patients (eight men and four women aged 19–49 years) with extensive diffuse PVNS of the knee were treated. All patients had an adjuvant post-operative external beam radiation therapy (2,600–3,000 cGy) conventionally fractionated 200 cGy/fraction, five fractions/week, 6–8 weeks after surgery. Mean follow-up time was 27 months (range from 20 to 36 months). All patients were followed up using clinical assessment, magnetic resonance imaging, and plain X-ray. In all patients, neither evidence of disease recurrence nor progression of bone or articular destruction was noted. No complications were noticed after surgery or after post-operative external beam radiation therapy. A combination of debulking surgery using anterior and posterior approach with adjuvant post-operative external beam radiation therapy for extensive diffuse PVNS of the knee joint is a reliable treatment method, with good results in regard to the incidence of local recurrence and functional outcome.
PMCID: PMC2642543  PMID: 19096892
PVN; synovitis; radiosynovectomy; synovectomy
17.  Cytokine and matrix metalloproteinase expression in pigmented villonodular synovitis may mediate bone and cartilage destruction. 
BACKGROUND: Pigmented villonodular synovitis (PVNS) is characterized by hypervascular proliferative synovium containing multinucleated giant cells, macrophages, and hemosiderin. The destruction of articular cartilage and erosion of periarticular bone is thought to be mediated by matrix metalloproteinases (MMPs). Expression of MMPs in some tumors appears to be stimulated through local production of cytokines, and several specific cytokines (TNF alpha, IL-1, and IL-6) play an important role in the stimulation of osteoclastic bone resorption. The role of cytokine secretion and regulation of MMP production in PVNS has not been investigated. DESIGN: In the present study, ten specimens from eight patients (ages 19 to 80) were evaluated histologically according to a modified Mirra classification and immunohistochemically (IHC) for the expression of MMP-9 (92 kDa gelatinase B), tumor necrosis factor alpha (TNF alpha), interleukin 1-beta (IL-1 beta), and interleukin 6 (IL-6). Localization of IL-6 and TNF alpha production was confirmed by in situ hybridization (ISH) for mRNA. RESULTS: All specimens, regardless of location (six knees, one ankle, one subtalar joint), showed diffuse and intense immunoreactivity for cytokines in the giant cells and synovial cells, and less intense and diffuse staining in the activated macrophages. Staining in the fibroblastic elements was minimal. In situ hybridization for TNF alpha and IL-6 mRNA mirrored the immunohistochemistry results, although the IL-6 staining was weaker than that for TNF alpha. Immunoreactivity for MMP-9 was diffuse and strong in giant cells, diffuse and moderate in synovial cells, and focal and moderate to strong in macrophages. In contrast, normal synovium demonstrated focal, moderate immunoreactivity for IL-1 beta, IL-6, TNF alpha and MMP-9 localized in the synovial lining cells. CONCLUSION: These findings suggest that periarticular bone resorption and cartilage destruction which characterize PVNS may be related to the expression of inflammatory cytokines, which in turn stimulate MMP production.
PMCID: PMC2378164  PMID: 9807705
18.  Increased expression of humanin peptide in diffuse-type pigmented villonodular synovitis: implication of its mitochondrial abnormality 
Annals of the Rheumatic Diseases  2004;64(6):816-823.
Objectives: To define the pathogenesis of pigmented villonodular synovitis (PVNS), by searching for highly expressed genes in primary synovial cells from patients with PVNS.
Methods: A combination of subtraction cloning and Southern colony hybridisation was used to detect highly expressed genes in PVNS in comparison with rheumatoid synovial cells. Northern hybridisation was performed to confirm the differential expression of the humanin gene in PVNS. Expression of the humanin peptide was analysed by western blotting and immunohistochemistry. Electron microscopic immunohistochemistry was performed to investigate the distribution of this peptide within the cell.
Results: 68 highly expressed genes were identified in PVNS. Humanin genes were strongly expressed in diffuse-type PVNS, but were barely detected in nodular-type PVNS, rheumatoid arthritis, or osteoarthritis. Humanin peptide was identified in synovium from diffuse-type PVNS, and most of the positive cells were distributed in the deep layer of the synovial tissue. Double staining with anti-humanin and anti-heat shock protein 60 showed that humanin was expressed mainly in mitochondria. Electron microscopy disclosed immunolocalisation of this peptide, predominantly around dense iron deposits within the siderosome.
Conclusions: Increased expression of the humanin peptide in mitochondria and siderosomes is characteristic of synovial cells from diffuse-type PVNS. Humanin is an anti-apoptotic peptide which is encoded in the mitochondrial genome. Present findings suggest that mitochondrial dysfunction may be the principal factor in pathogenesis of diffuse-type PVNS and that humanin peptide may play a part in the neoplastic process in this form of PVNS.
PMCID: PMC1755539  PMID: 15567815
19.  Pigmented villonodular synovitis of the knee in skeletally immature patients 
Pigmented villonodular synovitis (PVNS) is a benign idiopathic proliferative disorder that results in villous or nodular formation in the joints, tendons sheaths, and bursae. As PVNS is a rare pathology in children, diagnosis is often delayed. In this study, we analyze the therapeutic methods used and results obtained in the treatment of this pathology.
Materials and methods
All patients with PVNS of the knee seen between January 1988 and June 2006 were evaluated. We assessed the form of presentation, time to diagnosis, previous diagnosis, type of treatment, relapse, and the need for subsequent treatment.
Nine patients with age range 2–15 years and a mean follow-up of 8.5 years were evaluated. Four patients had the diffuse form and four had the localized or nodular form; all of them were intra-articular. In only three cases were preoperative radiographic findings observed. The mean delay in diagnosis was 18 months. Open resection was performed in five patients and arthroscopic resection in four. Joint function was satisfactory in 78% of the patients at the last follow-up and there were no postoperative recurrences.
Magnetic resonance imaging (MRI) is a useful diagnostic tool and the way to detect relapse, and allows accurate determination of the tumor extent. Surgery is the treatment of choice. Worse results are directly related to delay in diagnosis.
PMCID: PMC2839859  PMID: 21455469
Pigmented villonodular synovitis; Knee; Children
20.  Outcomes after Excision of Pigmented Villonodular Synovitis of the Knee 
Pigmented villonodular synovitis (PVNS) has a high but variable recurrence rate. Prior studies do not compare recurrence-free survival (RFS) for various surgical approaches or salvage surgery for relapse. We therefore determined: (1) RFS after excision; (2) RFS after salvage surgery for relapse; (3) factors associated with relapse. We retrospectively reviewed the medical records of 49 patients with previously untreated PVNS of the knee (12 localized, 37 diffuse) who were treated with synovectomy from 1991 to 2008; there were 22 males and 27 females, with mean age of 35.2 years (range, 10–73). Minimum followup was 1 year (mean, 6.2 years; range, 1–13). Twenty-one patients had a relapse. The RFS for index surgery was 75% and 53%; and for salvage surgery was 71% and 52% at 2 and 5 years respectively. The RFS was 95% for open versus 62% for arthroscopic synovectomy at 2 years, 71% and 41% at 5 years. The RFS was 91% for localized and 70% for diffuse PVNS at 2 years, 73% and 48% at 5 years. Diffuse disease (RR = 4.49) and arthroscopic synovectomy (RR = 3.30) were associated with relapse. Recurrence was frequent after synovectomy. Reexcision can salvage relapses as successfully as excision for primary disease; however, morbidity was associated with additional surgeries.
Level of Evidence: Level IV, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.
PMCID: PMC2758986  PMID: 19543865
21.  Localized Pigmented Villonodular Synovitis of the Proximal Tibiofibular Joint 
Knee Surgery & Related Research  2014;26(4):249-252.
Pigmented villonodular synovitis (PVNS) is a rare disease. It is a benign neoplastic process typically affecting young to middle-aged adults and most commonly involving the knee, hip, and shoulder joints. The symptoms include diffuse pain and swelling with discomfort. We report a rare case of localized PVNS originating at the proximal tibiofibular joint in a 39-year-old female patient with radiologic changes for short duration of time. The clinical history, plain radiographs, magnetic resonance imaging, and pathologic findings of the reported patient were reviewed. Complete surgical excision was performed and there was no evidence of recurrence after one-year follow-up.
PMCID: PMC4258493  PMID: 25505708
Pigmented villonodular synovitis; Tibiofibular joint
22.  Giant Cell Tumor of the Pes Anserine Bursa (Extra-Articular Pigmented Villonodular Bursitis): A Case Report and Review of the Literature 
Case Reports in Medicine  2011;2011:491470.
Pigmented villonodular synovitis (PVNS) is a rare, benign, proliferating disease affecting the synovium of joints, bursae, and tendon sheaths. Involvement of bursa (PVNB, pigmented villonodular bursitis) is the least common, and only few cases of exclusively extra-articular PVNB of the pes anserinus bursa have been reported so far. We report a case of extra-articular pes anserine PVNB along with a review of the literature. The lesion presented as a painful soft tissue mass in the medial part of the proximal leg. A magnetic resonance imaging showed areas of low to intermediate signals in all sequences and the lesion enhanced heterogeneously with contrast. Diagnosis was confirmed by an incisional biopsy, and an intralesional resection was performed. The postoperative course was uneventful, and the patient is free of disease with no functional deficit at 2 years followup. As with other rare lesions, clinical and radiographic findings in addition to histological examination are essential for correct diagnosis.
PMCID: PMC3114461  PMID: 21687595
23.  Arthroscopic synovectomy in pigmented villonodular synovitis of the knee: clinical series and outcome 
International Orthopaedics  2013;37(12):2363-2369.
The aim of this study was to evaluate the long-term results of arthroscopic excision of pigmented villonodular synovitis (PVNS) of the knee joint.
We retrospectively assessed the results of arthroscopic excision of PVNS done in 40 patients from 1987 to 2012 by the senior author (JVS). No radiotherapy was given to any patient. All patients were followed for a mean of seven years. At follow-up functional assessment was done using the Lysholm score. Recurrence-free survival and recurrence-free survival probability were calculated.
No recurrence was noted in the localised variety. In the diffuse variety the five year recurrence-free survival probability was 57 %. Twelve patients developed recurrences between three months and two years. No recurrence was noted after two years. The mean recurrence interval was 6.25 months.
We concluded from this series that arthroscopic excision is an effective treatment for localised as well as diffuse PVNS. Recurrences can also be successfully dealt with by arthroscopic excision with excellent functional outcome.
PMCID: PMC3843212  PMID: 23860791
24.  Response to imatinib in villonodular pigmented synovitis (PVNS) resistant to nilotinib 
Pigmented villonodular synovitis (PVNS) is a rare locally aggressive tumor. PVNS is characterized in most cases by a specific t(1;2) translocation, which fuses the colony stimulating factor-1 (CSF1) gene to the collagen type VIa3 (COL6A3) promoter thus leading through a paracrine effect to the attraction of non-neoplastic inflammatory cells expressing CSF1-receptor. Imatinib is a tirosin-kinase inhibitors (TKI) active against CSF1-receptor whose activity in naïve PVNS was already described. We report on two PVNS patients who responded to imatinib after failure to nilotinib, another CSF1-receptor inhibitor.
Since August 2012, 2 patients with progressive, locally advanced PVNS resistant to nilotinib (Patient 1: man, 34 years; Patient 2: woman, 24 years) have been treated with second-line imatinib 400 mg/day. Both patients are evaluable for response.
Both patients are still on treatment (7 and 4 months). Patient 1 had a dimensional response by MRI after 2 months from starting imatinib, together with symptomatic improvement. In Patient 2 a metabolic response was detected by [18F]fluorodeoxyglucose–positron emission tomography (PET) at 6 weeks coupled with tumor shrinkage by MRI, and symptomatic improvement.
Imatinib showed antitumor activity in 2 patients with nilotinib-resistant PVNS. This observation strengthen the idea that targeted agent with similar profile can give a different clinical result, as already described for gastrointestinal stromal tumor (GIST) patients treated with the same agents. Molecular studies are needed to clarify the biologic mechanism(s) underlying the response.
PMCID: PMC3661378  PMID: 23668619
Pigmented villonodular synovitis; PVNS; Imatinib; Targeted therapy
25.  Pigmented villous nodular synovitis mimicking metastatic melanoma on PET-CT 
Positron Emission Tomography – Computed Tomography (PET-CT) is routinely utilized in the management of melanoma, either as a part of staging workup or during surveillance. Since melanomas have a high metastatic potential, any FDG avid lesion is considered suspicious for recurrence. We report a case of a FDG avid lesion, diagnosed during melanoma surveillance, its management and review of literature.
A 58 year-old-male underwent wide local excision for melanoma of the left cheek, and one year post-operatively a PET-CT that revealed a hypermetabolic focus in his right subscapularis muscle, which upon resection was diagnosed as Pigmented Villonodular Synovitis (PVNS).
PVNS is a rare benign giant cell tumor that requires no additional treatment in asymptomatic individuals. PET-CT is used for staging and surveillance of numerous malignancies, including melanoma. A hypermetabolic lesion on a PET-CT scan in the setting of malignancy is always suspicious for recurrence.
The surgeon is reminded of a uncommon benign FDG avid lesion. Typical location, nonspecific symptoms and characteristic imaging findings help cue in the diagnosis of PVNS and a tissue diagnosis will establish the diagnosis, thus avoiding unnecessarily aggressive surgical management.
PMCID: PMC4008855  PMID: 24705190
Metastatic melanoma; Pigmented villous nodular synovitis

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