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.
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.
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.
PVN; synovitis; radiosynovectomy; synovectomy
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.
magnetic resonance imaging; thallium-201 scintigraphy; pigmented villonodular synovitis; localized type; elbow joint; soft tissue tumor
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.
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).
Pigmented villonodular synovitis is a proliferative disease involving joints, bursas and tendon sheaths with typical histological changes in the synovial tissue. A local and diffuse form are described. Aetiology is uncertain, MRI is helpful to establish the diagnosis, which is confirmed with by biopsy. Treatment is based on the principles of tumor resection: arthroscopically in the local form, or by a open synovectomy in the diffuse form, often followed by adjuvant radiotherapy. The rate of recurrence is high, but differs in consideration of the treatment chosen. We report a 35 year old soccer player with diffuse pigmented villonodular synovitis with a history of chronic swelling knee. The patient underwent a one step open synovectomy without adjuvant therapy, with the conservation of the heads of gastrocnemius muscle. At five years of follow-up, the patient had no sign of recurrence of the condition. One step open synovectomy in this patient showed an excellent outcome with the return to his previous sport. The short follow-up and the neoplastic characteristic of the disease cannot exclude the risk of recurrence.
Diffuse pigmented villonodular synovitis; Open sinovectomy; Soccer
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.
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.
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.
Pigmented villonodular synovitis (PVNS) is characterized by hyperplasia of the synovial tissue in joints, of tendon sheaths, and of the mucous membranes, or fibrous tissue adjacent to the tendons. Its etiology is unknown. We report a case of diffuse intra-articular PVNS of the right knee in a 38-year-old man. Ultrasound and magnetic resonance imaging (MRI) features of the disease are described.
Pigmented villonodular synovitis; Knee; Ultrasound examination; MRI
Malignant pigmented villonodular synovitis (PVNS) (or malignant giant cell tumor of tendon sheath (GCTTS) is an extremely rare condition defined as a malignant lesion occurring with concomitant or previously documented PVNS at the same site. To date, only less than 20 cases have been reported in English literatures. We report a case of malignant PVNS in the knee in a 56-year-old woman with unpredictable rapid progression. This case raised a caution that when atypical components in specimens of recurrent benign PVNS are detected, even if low-grade or tiny, both pathologists and surgeons should consider the risk of malignant PVNS, which could display aggressive clinical progression.
Soft tissue tumor; malignant pigmented villonodular synovitis; malignant giant cell tumor of tendon sheath.
The diffuse form of pigmented villonodular synovitis of eight knee joints of eight patients was treated by intra-articular injection of 185 MBq yttrium-90 silicate (90Y). Six patients had a recurrence of disease after one or two surgical synovectomies. After treatment with 90Y once or twice four knees showed clinical improvement with an accompanying decrease of the inflammatory activity as measured by the technetium-99m pertechnetate (99mTcO4-) uptake ratio and the severity of the diseased synovial tissue. Arthroscopy was performed before and six months after each 90Y treatment. The ratio of 99mTcO4- uptake in the inflamed compared with the normal knee joint correlated well with the macroscopical grading of pigmented villonodular synovitis. In all cases areas of persistent synovitis were found after the 90Y injection and this was confirmed both by histological examination and 99mTcO4- uptake measurements. Biopsy specimens taken from the diseased synovial areas showed histologically mostly less prominent and less numerous villi. The cartilage damage was slightly increased in only two cases. No radiological deterioration was found during follow up (mean 24 months, range 12-41). No complications of the radiosynoviortheses were noted.
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.
Pigmented villonodular synovitis; Knee; Children
We followed up seven patients with histologically confirmed diffuse pigmented villonodular synovitis in a prospective study between 1992 and 2001. The mean age at diagnosis was 30.7 years. The patients underwent synovectomy, followed by radiotherapy with a total dose of 35 Gy in 20 fractions. In all cases, the excision was considered incomplete when examined histologically. At an average follow up of 24 (18–36) months, six patients reported better function and reduced levels of pain. One patient remained symptomatic but did not have a recurrence. We conclude that a combined approach to a primary pigmented villonodular synovitis of the foot and ankle may reduce the risk of recurrence without functional impairment.
Case report: A patient presented with severe treatment resistant PVNS of the right knee joint. Several conventional treatment regimens, including open surgical synovectomy and intra-articular injections of yttrium-90 (90Y) failed to control the disease. After finding marked tumour necrosis factor α (TNFα) expression in arthroscopic synovial tissue samples, treatment with an anti-TNFα monoclonal antibody (infliximab) at a dose of 5 mg/kg was started. Additional courses with the same dose given 2, 6, 14, and 20 weeks later, and bimonthly thereafter up to 54 weeks, controlled the signs and symptoms. Immunohistological analysis at follow up identified a marked reduction in macrophage numbers and TNFα expression in the synovium.
Discussion: This is probably the first case which describes treatment with TNFα blockade of PVNS in a patient who is refractory to conventional treatment. It provides the rationale for larger controlled studies to elucidate further the efficacy of TNFα blockade treatment in refractory PVNS.
A case is presented of pigmented villonodular synovitis involving three joints in a 7-year-old girl. The diagnosis was confirmed at surgery and by histology. The patient also exhibited a haemangioma of the upper lip and a congenital pulmonary stenosis of mild degree. Subtotal synovectomy of the right knee and of both ankles was performed. The lesion recurred in both ankles after 6 months. Review of the literature failed to reveal any previous report of multiple joint involvement by pigmented villonodular synovitis in childhood and it appears that simultaneous involvement of three joints has not previously been described. Scintiscanning with 99mTc stannous pyrophosphate showed increased vascularity of the involved joints immediately after injection, but no increased osteoblastic activity was seen on the delayed scan. This radionuclide scanning technique is therefore helpful in distinguishing pigmented villonodular synovitis from other arthropathies.
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.
Pigmented villonodular synovitis; PVNS; Imatinib; Targeted therapy
Pigmented villonodular synovitis is a disease which affects the synovial joints and tendon sheaths. Although the exact aetiological factors are not known, we believe that recurrent haemarthrosis has a role in the aetiology of this condition.
A 62-year-old Caucasian man presented with gradually worsening pain and stiffness in his right knee. The patient was on anticoagulation therapy and had been treated for recurrent episodes of spontaneous haemarthrosis of the knee. The International Normalized Ratio on each occasion suggested poor control of the anticoagulation therapy. A diagnosis of pigmented villonodular synovitis was made based on intra-operative findings and was further confirmed by a histopathological examination.
This report is presented to highlight the unusual association of haemarthrosis and pigmented villonodular synovitis.
Pigmented villonodular synovitis is a rare, benign, but potentially locally aggressive disease that should be considered in younger patients who present with monoarticular joint symptoms and pathology. We present the case of a 33-year-old woman with a mass arising from her right hip joint that was examined using a multimodal radiological approach. Because her clinical presentation mimicked that of synovial osteochondromatosis of the hip, surgical dislocation was performed. Histopathological examination of the resected specimen confirmed the diagnosis of localized pigmented villonodular synovitis, with the mass consisting of proliferation of fibrohistiocytic cells, abundant hemosiderin, foamy histiocytes, and occasional giant cells. Because of the presence of tumor necrosis, we hypothesize that torsion of the tumor pedicle was the cause of acute presentation.
Pigmented villonodular synovitis (PVS) is an uncommon, usually monoarticular disorder encountered mainly in adults. A boy and a girl, both 7 years old, were referred because of recurrent knee effusions. Both were medically treated for other rheumatic disorders for five years. PVS was diagnosed by arthroscopy and synovectomy was curative in both cases.
We report a case of pigmented villonodular synovitis (PVNS) in an adolescent with monarticular involvement of the ankle and without congenital anomalies or sibling involvement.
Pigmented villonodular synovitis is a rare disease of unknown etiology mostly affecting the knee and foot. Until now an association with autoimmune diseases has not been reported.
The diagnosis of systemic lupus erythematosus was made in a 15-year-old Caucasian girl based on otherwise unexplained fatigue, arthralgia, tenosynovitis, leukopenia, low platelets and the presence of antinuclear and deoxyribonucleic antibodies. At the age of 20 a renal biopsy revealed lupus nephritis class IV and she went into complete remission with mycophenolate mofetil and steroids. She was kept on mycophenolate mofetil for maintenance therapy. At the age of 24 she experienced a flare-up of lupus nephritis with nephrotic syndrome and new onset of pain in her right hip. Magnetic resonance imaging, arthroscopy and subtotal synovectomy identified pigmented villonodular synovitis as the underlying diagnosis. Although her systemic lupus erythematosus went into remission with another course of steroids and higher doses of mycophenolate mofetil, the pigmented villonodular synovitis persisted and she had to undergo open synovectomy to control her symptoms.
Systemic lupus erythematosus is associated with many different musculoskeletal manifestations including synovitis and arthritis. Pigmented villonodular synovitis has not previously been reported in association with systemic lupus erythematosus, but as its etiology is still unknown, the present case raises the question about a causal relationship between systemic lupus erythematosus and pigmented villonodular synovitis.
We report six children with pigmented villonodular synovitis. they ranged in age from seven to fifteen years. In four patients, the knee was involved. One patient had involvement of the ankle, and one had diffuse involvement along a metacarpal. In five cases, the diagnosis was not suspected clinically or radiographically, and the delay in making the correct diagnosis was as long as two years. clinical diagnosis in these five patients was usually bacterial synovitis or juvenile rheumatoid arthritis. We feel that the diagnoses of pigmented villonodular synovitis should be considered in any child with chronic joint effusion.
Pigmented villonodular synovitis is a benign proliferative disease involving the synovium. Pigmented villonodular synovitis is rare after replacement arthroplasty and has not been recognised and reported as a cause of failure of unicompartmental knee replacement in the literature.