PIGMENTED VILLONODULAR SYNOVITIS — (PVNS) is a rare but well recognized proliferative lesion of synovial tissue. It is characterized by hypervascular proliferative synovium containing multinucleated giant cells, macrophages and hemosiderin. The multinucleated cells express features of osteoclasts. Progressive nodular disease near or in the joints limits function and may destroy adjacent bone. Although most believe PVNS to be an inflammatory process, others consider it a benign neoplasm.

PVNS occurs in two forms: a diffuse form that involves the entire synovium and accounts for in the majority of cases, and a localized form that involves a discrete section of the synovium. PVNS almost always involves a single joint; the knee, hip and finger synovial structures are most commonly affected, while involvement of the shoulder, foot, and ankle is rare.

Plain radiographs may reveal well circumscribed areas of bone erosion. MRI shows a characteristic lack of signal on both T1 and T2 images which has been attributed to the presence of large amounts of hemosiderin in the synovium. This MRI signature is an important key to correct diagnosisThe principal treatment modality is resection. Although marginal excision represents the optimal treatment for localized PVNS, diffuse PVNS is more difficult to eradicate and is optimally treated with total or near total synovectomy.

The local recurrence rate among patients with localized PVNS is low, but patients with diffuse disease can have multiple recurrences and bulky disease that results in significant bone destruction. In this setting, radiation therapy to a dose of 35 to 50 Gy has been effective. In a preliminary report of the largest series of 41 patients, 40 of whom had microscopic or gross residual disease prior to radiation, 40 maintained local control at an average 77 months follow-up. These data have been corroborated by published experience from at least two other centers

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External Beam Radiation Therapy Enhances Local Control in Pigmented Villonodular Synovitis , 11 February 2009
Melissa Horoschak, Phuoc T. Tran, Pavan Bachireddy, Robert B. West, David Mohler, Christopher F. Beaulieu, Daniel S. Kapp, Sarah S. Donaldson
International Journal of Radiation Oncology * Biology * Physics  1 September 2009 (Vol. 75, Issue 1, Pages 183-187)
 

 

Pigmented villonodular synovitis (PVNS) is a rare proliferative process of the synovium. It was initially thought to be an inflammatory reactive process; however, recent observations have shown that this disease may actually be a “benign neoplastic” process, meaning that it has the predilection for local recurrence, but not metastatic potential  We have demonstrated that a significant subset of PVNS cases contain a translocation resulting in the fusion of CSF1 and COL6A3. The resulting translocation in these neoplastic cells leads to an increase in the functionally active CSF1 protein, which then recruits macrophages and multinucleated giant cells to form the bulk of the tumor mass. PVNS occurs in two forms: focal lesions, usually called tenosynovial giant cell tumors (TGCT), and a diffuse form. Both are morphologically and biologically similar, but diffuse PVNS is clinically more aggressive . The lesions are composed of a mixture of giant cells, mononuclear cells, and inflammatory cells, are usually monoarticular, and often arise in joints, although it may be found in a tendon or bursa. The lesions are best visualized using magnetic resonance imaging (MRI), which reveal characteristic low signal intensity because of hemosiderin deposition

PVNS can have a variable course leading to local destruction and severe symptoms, including joint pain, swelling, hemorrhagic effusion, erythema, and limitation in range of motion. The primary treatment is surgical removal. However, complete resection may be difficult given the nature of diffuse PVNS, with relapse rates for surgery alone ranging from 8% to 56% depending on the resection status. External beam radiation has been advocated to help prevent recurrence and improve local control .However, given the rarity of PVNS, the literature using external beam radiation for this disorder consists of case reports and small series. We reviewed our experience with external beam radiation in the treatment of 17 patients with 18 sites of diffuse PVNS (n = 16) or TGCT (n = 2), all of whom had known or suspected residual disease.

Seventeen patients with 18 sites of PVNS were treated with radiation between 1993 and 2007. Cases were retrospectively reviewed for patient information, treatment parameters, complications, and outcome. Seven sites were primary presentations and 11 were recurrent with an average of 2.5 prior surgical interventions. The most common location was the knee joint (67%). Cytoreductive surgery was performed before radiation therapy in 16/18 sites with all having proven or suspected residual disease. Radiation was delivered using 4–15 MV photons with an average total dose 34 Gy (range, 20–36 Gy). Seventeen of 18 sites (94%) had postradiotherapy imaging.

Results

With average follow-up of 46 months (range, 8–181 months), initial local control was achieved in 75% (12/16) of the sites with prior cytoreductive surgery (mean time to recurrence, 38 months). Ultimate local control was 100% after repeat resection (mean follow-up, 61 months). Two additional sites without prior cytoreductive surgery showed growth after radiotherapy (mean time to documented growth, 10.5 months). Seventeen of the 18 involved joints (94%) were scored as excellent or good PVNS-related function, one site (5%) as fair function, and no site with poor function. No patient required amputation; and there were no Grade 3/4 treatment-related complications.

We report a series of 17 consecutive patients with 18 irradiated sites of localized or diffuse PVNS. The ultimate local control is 100% in sites that underwent cytoreductive surgery before radiation treatment, with good quality of life outcome noted. Ninety-four percent of sites are considered to have excellent or good function with reduced symptoms in the affected site when compared with preradiotherapy status. Our results are consistent with previously published reports, which have also shown a significant benefit from postresection radiation in the treatment of PVNS. Postresection radiation can improve local control as complete resection may be difficult given the nature of diffuse PVNS, with local control rates for surgery alone ranging from 44–92% depending on the resection status (partial versus complete synovectomy) and the joint involved

In our patient group, the symptoms, location of the disease, and patient age were all consistent with previous reports using radiation therapy for PVNS . There was no difference in the treatment or outcomes of sites with diffuse PVNS when compared to sites with TGCT. Most of our patients had disease involving the synovium of the knee, which is shown to have the highest rates of recurrence . Our cohort differs from some of the other reported series  because of the high percentage (61%) of patients with recurrent disease prior to administration of radiotherapy, suggesting more aggressive disease process. All were symptomatic for at least 1 year before treatment and none were discovered incidentally. Four patients underwent joint replacement after radiotherapy for mechanical symptoms of pain from degenerative joint disease. The clinical symptoms of effusions and mass effect attributed to active PVNS had resolved in all 4 patients after synovectomy and radiotherapy. At the time of joint replacement, only 1 patient had visibly persistent disease at 6 months after his partial surgical resection and radiotherapy. In our cohort, we have considered joint replacement after radiotherapy a surrogate for extensive PVNS and subsequent local destruction, suggesting the importance of initiating early radiation therapy before irreversible joint dysfunction or bone destruction.

Our results support a treatment approach of cytoreduction before radiotherapy. Two sites that were not resected before radiation therapy demonstrated continued disease growth despite irradiation, with an average time to documented growth of 10.5 months. The surgical technique most commonly used was an arthroscopic radical synovectomy to maximize disease removal and minimize surgical complications. However, each site should be approached individually. There has also been a recent case report of complete PVNS remission after imatinib treatment; therefore, cytoreductive treatment with imatinib might be considered in cases of multiple local recurrences or local recurrence after radiotherapy. We recommend thorough imaging after resection (before radiotherapy) and as surveillance after radiotherapy. Our results differ from the report of O'Sullivan  who noted no imaging evidence of recurrent or persisting disease when patients were reassessed beginning 12 months after treatment. However, the type and exact time of the imaging study performed was not indicated. Similarly, Blanco  did not mention any routine imaging, other than ultrasound to confirm recurrences. By contrast, in our series, all sites of disease were imaged by diagnostic MRI and 78% had imaging after the last surgical intervention before beginning radiation therapy. Furthermore, 94% of patients had routine imaging surveillance after radiotherapy. However, the decision to pursue additional treatment should not be based on imaging evidence alone, but should also incorporate clinical assessment. We found considerable discordance between radiographic evidence of recurrence and clinical signs and symptoms of recurrence. Follow-up imaging suggested five sites of recurrence in our cohort, but one of these sites had no clinical evidence of recurrence (a 20% discordance rate), and required no further intervention; these patients currently have excellent or good function. This may be explained by the difficulties in image interpretation in the setting of multiple prior surgeries, radiotherapy, and the effects of the PVNS disease process. Interpretation of images by a musculoskeletal radiologist is essential in assisting the radiation oncologist in determining appropriate treatment fields, and useful in detecting stability after treatment.

It is also unclear as to the appropriate interval after surgery and radiation therapy for additional intervention. O'Sullivan reported that all of their patients with measurable disease had obvious disease for at least 12 months after radiotherapy. However, of the six sites in our series that demonstrated growth after radiation therapy or clinical recurrence, two were apparent within the first 12 months after radiotherapy and were resected soon thereafter. Similarly, the optimal dose and fractionation schedule of radiation for PNVS is unclear. Some have reported using doses as low as 16–20 Gy without recurrence , whereas others have used doses as high as 50 Gy without complications. The three sites that demonstrated recurrence after resection in our series were given 20 Gy, 35.7 Gy, and 36 Gy. Overall, we have had excellent control with radiation doses in the range of 34–36 Gy and recommend 36 Gy with conventional fractionation.

The limitations of our study include those inherent in all retrospective series, including possible selection bias and patient recall bias. In addition, the span of time over that our cohort was collected was more than 14 years and may have introduced confounding effects associated with improvements in diagnosis, surgical treatment, and surveillance.

Using radiotherapy in the treatment of benign disease may raise concerns about the risk of radiation-associated injury. Although the numbers of reported cases of PVNS treated with radiation therapy are modest, to date we know of no case of radiation-induced malignancy. Additionally, at the radiation doses that are used to treat PVNS, we believe joint dysfunction is likely due to the combined effects of the disease process, the cumulative effects of repeated surgeries, and that of previous joint trauma rather than being associated to the radiation therapy.

Conclusion 

Although the preferred treatment of PVNS is surgical resection, local recurrences after surgery are common. Radiation allows acceptable functional preservation without complications, with many patients enjoying significant benefit. Our data support the use of radiation therapy in patients with a diagnosis of either localized or diffuse PVNS. We recommend irradiating patients with suspected or confirmed residual PVNS and found radiotherapy to be an effective and safe modality in enhancing postoperative local control. On this basis, we advocate consideration of radiation therapy not only in patients with recurrent disease after prior resections, but also in those primary cases in which local recurrence appears likely because of extensive disease. We believe radiation should be used early in the management, before irreversible bone and joint destruction, which is an inevitable outcome of this proliferative disorder. Finally, an MRI should be obtained for diagnosis, before initiation of radiation therapy for proper treatment planning, and for follow-up surveillance.

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