Pigmented Villonodular Synovitis

Background

Pigmented villonodular synovitis (PVS) is a rare aggressive lesion occurring primarily within joint spaces, usually the knee. However, other sites including the hip, temporalmandibular joint and bursa have been described. Pain, joint swelling or a tumuor, and repeated joint effusions. A combination of surgery and radiotherapy may be helpful in difficult cases.

OUTLINE

Pathogenesis

Laboratory/Radiologic/Other Diagnostic Testing

Gross Appearance and Clinical Variants

Histopathological Features and Variants

Special Stains/Immunohistochemistry/Electron Microscopy

Differential Diagnosis

Prognosis

Treatment

Commonly Used Terms

Internet Links

PATHOGENESIS CHARACTERIZATION

GENERAL

Localized pigmented villonodular synovitis of the knee joint: neoplasm or reactive granuloma? A review of 18 cases.

Perka C, Labs K, Zippel H, Buttgereit F.

Department of Orthopaedics and. Department of Rheumatology and Clinical Immunology, Charite University Hospital, Humboldt University, Schumannstrasse 20/21, 10117 Berlin, Germany.

Rheumatology (Oxford) 2000 Feb;39(2):172-8 Abstract quote
OBJECTIVE: The localized form of pigmented villonodular synovitis of the knee joint is a rare disease with limited alteration of the synovial membrane, the pathogenesis of which is the subject of controversial discussion.

METHODS: Eighteen cases have been documented in our hospital since 1976. All of the patients had additional cartilage or meniscus damage. Treatment consisted of excision of the lesion and the adjacent synovial membrane, as well as therapy of the additional damage.

RESULTS: The patients who had received such therapy were followed for 3-9 yr, without any clinical, sonographic or magnetic resonance tomographic signs of recurrence. In addition to the lack of a tendency towards recurrence, none of the cases displayed any further characteristics of the diffuse form of villonodular synovitis, such as invasiveness or malignant transformation.

CONCLUSIONS: We therefore suggest that pigmented villonodular synovitis of the knee joint should be classified more strictly than before into a potentially neoplastic (diffuse) form and a reactive granulomatous (local) form. From the cases observed, we conclude that degenerative joint lesions may be the cause of the reactive granulomatous form.

CHROMOSOMAL ALTERATIONS

Analysis of 35 cases of localized and diffuse tenosynovial giant cell tumor: a report from the Chromosomes and Morphology (CHAMP) study group.

Sciot R, Rosai J, Dal Cin P, de Wever I, Fletcher CD, Mandahl N, Mertens F, Mitelman F, Rydholm A, Tallini G, van den Berghe H, Vanni R, Willen H.

Department of Pathology, University of Leuven, Belgium.
Mod Pathol 1999 Jun;12(6):576-9 Abstrac tuqote
The karyotypes of 44 specimens from 35 patients with localized (n = 19) or diffuse (n = 16) tenosynovial giant cell tumors were studied. The majority of cases in both categories (11 of 19 localized; 12 of 16 diffuse) displayed clonal chromosomal aberrations, with a complex karyotype in three cases and a simple chromosomal aberration in the others.

No difference in the distribution of karyotypic abnormalities was found between the localized and diffuse form except for trisomies (usually of chromosomes 5 and/or 7), which were more frequent in the diffuse type. The short arm of chromosome 1 (1p11-13) was most frequently rearranged, with 7 of 11 localized and 7 of 12 diffuse lesions affected.

These findings indicate that the localized and diffuse forms of tenosynovial giant cell tumor might represent two morphologic manifestations of the same entity. The high frequency of clonal chromosomal abnormalities, with a clustering of structural rearrangements to 1p11-13, suggests that this disease is most likely neoplastic in nature and paves the way to search for gene(s) that might be involved in its development.

LABORATORY/RADIOLOGIC/
OTHER TESTS
CHARACTERIZATION

RADIOLOGIC

Localized pigmented villonodular synovitis of the knee with bone involvement mimicking a benign bone tumor: CT and MR findings.

Farrokh D, Annaert JM, Fabeck L, Theunis A, Delince P.

Department of Radiology, University Hospital Saint-Pierre, Brussel, Belgium.

JBR-BTR 2001;84(6):253-5 Abstract quote
The localized form of pigmented villonodular synovitis is characterized by a limited involvement of synovium. Although the knee is the joint that is commonly affected, bone changes in this location are not usual.

We report the case of a histologically proven localized form of this entity in the knee, which mimicked a benign bone tumor on the basis of an MR pattern, CT findings, and scintigraphic results. Bone changes which may cause a pitfall in the diagnosis of the disorder are discussed.

GROSS APPEARANCE/
CLINICAL VARIANTS CHARACTERIZATION

GENERAL

Pigmented villonodular synovitis. Review of 20 cases.

Durr HR, Stabler A, Maier M, Refior HJ.

Department of Orthopedics and Orthopedic Surgery, Ludwig Maximilians University, Munich, Germany.
J Rheumatol 2001 Jul;28(7):1620-30 Abstract quote
OBJECTIVE: Pigmented villonodular synovitis (PVS) is a rare aggressive lesion. Inclusion of this disease in the differential diagnosis of rheumatoid arthritis can lead to early diagnosis and treatment. In this retrospective study we evaluated diagnostic procedures, therapies, and outcomes of PVS.

METHODS: Twenty surgically treated cases of PVS were evaluated: joint, 16; tenosynovial, 3; and bursa, one. The 20 patients had undergone the following surgeries: 4 total synovectomies, 2 subtotal synovectomies, eight arthroscopically assisted resections, 4 resections of extraarticular lesions, and 2 arthroplasties. The mean followup was 17.5 mo (1-54).

RESULTS: At diagnosis, pain was present in 19 of 20 cases. Joint swelling or a tumor was found in 11 cases, and 12 patients complained of repeated joint effusions. The mean duration of symptoms was 23.8 mo (range 1-144). Half the cases had a nodular pattern and the other half a diffuse pattern. The most common location of PVS was the knee (14 patients). Surgical treatment before admission did not always lead to an accurate diagnosis. For example, in 2 patients, arthroscopy did not reveal PVS. In 2 patients a soft tissue sarcoma was suggested. In 3 patients, the diagnosis was made incidentally with arthroscopy or arthroplasty. On radiographs, bone lesions were seen in 8 cases; in 13 of 17 cases the diagnosis was by magnetic resonance imaging (MRI). After surgery 17 patients stayed free of recurrence, 14 without symptoms. One patient who had an incidental diagnosis of PVS has a synovectomy planned as a second procedure. One patient awaits a second dorsal procedure after a ventral knee synovectomy. One patient shows recurrent disease 33 mo after resection of a nodular knee lesion.

CONCLUSION: PVS should be included in the differential diagnosis of any arthritis. MRI is the most effective diagnostic tool in identifying PVS. The treatment of PVS consists of surgical excision in sound tissue. A total synovectomy should be the treatment of choice in diffuse disease. From the literature, nonsurgical therapies, such as steroid injections, 90Y synoviorthesis, or external beam radiation, seem to be of benefit in selected patients.

VARIANTS

FOOT

Pigmented villonodular synovitis of the foot and ankle: a report of eight cases.

Rochwerger A, Groulier P, Curvale G, Launay F.

Department of Orthopaedic Surgery, Hopital de la Conception, Marseille, France.

Foot Ankle Int 1999 Sep;20(9):587-90 Abstract quote
Eight cases of pigmented villonodular synovitis of the foot and ankle are reported. The purpose of this study was to analyze the manifestation of pigmented villonodular synovitis in the foot and to evaluate treatment options. There were four cases in the ankle and hindfoot, one in the first tarsometatarsal joint, and three in the toes. In seven of eight cases, diagnosis was confirmed by magnetic resonance imaging (MRI) scans. The tenosynovial form was found in the toes and the articular form in the hindfoot and ankle.

Surgical treatment was performed in all cases: one arthroscopically assisted synovectomy in the ankle joint, two talocrural arthrodeses, one subtalar arthrodesis, one tarsometatarsal arthrodesis, and tumor removal on the toes with arthrodesis of the distal interphalangeal (DIP) joint in two cases. Average follow-up was 4 years. Recurrence occurred in one toe and led to partial amputation. Malunion in one ankle arthrodesis was operated on again with no sign of recurrence.

In the toes, the lesion had a tumoral feature; the bone was infiltrated by soft tissue, and the surgical procedure was local removal of the tumor. In the hind-foot, the lesions were intra-articular and required synovectomy, usually with an arthrodesis. In the midfoot, there was a large extraosseous tumor surrounding tendons with destructive articular lesions.

HIP

Pigmented villonodular synovitis of the hip: 2- to 23-year followup study.

Gonzalez Della Valle A, Piccaluga F, Potter HG, Salvati EA, Pusso R.

Instituto de Orthopedia y Traumatologia, Carlos E. Ottolenghi Hospital Italiano de Buenos Aires, Argentina.

Clin Orthop 2001 Jul;(388):187-99 Abstract quote
Pigmented villonodular synovitis affecting the hip is rare. Seven new patients are presented and 117 cases from the literature are reviewed. Among the new patients, two refused treatment; in one patient, severe bone loss was observed after a radiographic followup of 21 years; the second patient showed no radiographic changes 2 years after diagnosis.

One patient underwent a synovectomy and had a recurrence 9 years later, requiring a total hip replacement. The remaining four patients underwent synovectomy and primary total hip replacement with no recurrences detected after an average followup of 13 years (range, 2-23 years). Among 117 cases published, 62 patients (53%) did not have enough information for analysis. A metaanalysis using the remaining 55 patients was done. In nine patients (16%; nine of 55) the diagnosis was made with a preoperative biopsy. Treatment consisted of synovectomy in 26 patients (47%; 26 of 55), arthroplasty in 24 (43%; 24 of 55), arthrodesis in two (4%; two of 55), and hindquarter amputation in a patient misdiagnosed as having synovial sarcoma (2%; one of 55). Two patients (4%; two of 55) were not treated.

Ten patients had a recurrence (19%; 10 of 53); nine in the synovectomy group (35 %; nine of 26) and one in the joint replacement group (4%; one of 24).

Synovectomy is recommended for patients with preserved articular cartilage and total hip replacement is recommended for patients with secondary osteoarthritis. Removal of all macroscopic tumors including careful curetting of the osteolytic lesions should be done as they may constitute a source of recurrence.

LOCALIZED

Localized pigmented villonodular synovitis: arthroscopic diagnosis and management of an "invisible" lesion.

Parikh SN, Chen AL, Ergas E.

Department of Orthopaedics, Hospital for Joint Diseases, New York, New York 10003, USA.
Arthroscopy 2002 Jul-Aug;18(6):E31 Abstract quote
Pigmented villonodular synovitis (PVNS) is a rare disorder that may involve the synovium of joints, bursa, or tendon sheaths. Monoarticular involvement is typical, with the knee most commonly affected.

Localized pigmented villonodular synovitis (LPVNS) involves a discrete region of the synovium. Detection and diagnosis of this entity is clinically challenging, and plain radiographs are usually unremarkable. Magnetic resonance imaging (MRI) has been reported to be sensitive for the detection of synovial abnormalities and is the imaging modality of choice in suspected cases of LPVNS. When the diagnosis remains in doubt, arthroscopy may be used for direct visualization of synovial pathology, as well as to obtain tissue for histologic analysis.

Definitive treatment may also be performed at the time of arthroscopy. We present a case of LPVNS in which a large (4 cm) lesion was not apparent on preoperative radiographs or MRI and was also missed on initial diagnostic arthroscopy.

SHOULDER

Pigmented villonodular synovitis of the shoulder: review and case report.

Muller LP, Bitzer M, Degreif J, Rommens PM.

Klinik fur Unfallchirurgie, Johannes-Gutenberg-Universitat Mainz, Germany.

Knee Surg Sports Traumatol Arthrosc 1999;7(4):249-56 Abstract quote
Pigmented villonodular synovitis (PVNS) as reviewed in detail elsewhere most frequently involves the knee and finger synovial structures; shoulder involvement is rare: A search through the English literature yielded 18 publications describing 25 cases of PVNS affecting the shoulder joint.

Analyzing these reports we found the clinical and radiological findings generally to be nonspecific, often mimicking a malignancy, as in the case presented here of a 16-year-old boy with painful swelling in the area of the left proximal humerus. Magnetic resonance imaging showed a suspected malignant soft tissue mass involving the shoulder capsule and measuring 7.5 x 6 x 4 cm. Preoperatively the patient could recall no trauma; however, postoperatively he did report a distortion trauma of the affected shoulder following a bicycle accident. Intraoperatively, two tumors were found infiltrating the axillary vessels and nerve and tendon structures originating in the capsule of the shoulder joint. Rapid sections of the tissue revealed no signs of malignancy; further pathohistological examination revealed localized PVNS.

Preoperatively, the shoulder joint was not suspected as the primary site of origin of the tumor because the patient had no complaints or functional deficits of the shoulder. The clinical presentation of such a PVNS lesion over the proximal humerus is unusual and to date has only twice been described in the literature.

SPINE

Pigment villonodular synovitis of the spine. Case report and review of the literature.

Dimeco F, Rizzo P, Li KW, Ciceri E, Casali C, Pollo B, Lasio G.

Department of Neurosurgery, Istituto Nazionale Neurologico C. Besta, Milan, Italy
J Neurosurg Sci 2001 Dec;45(4):216-9; discussion 219 Abstract quote
Pigmented villonodular synovitis (PVNS) is a disease of the joints which uncommonly involves the spine. We present a 70-year-old woman with radicular symptoms who was found to have a mass arising from a lumbar zygapophyseal joint with extension into the spinal canal.

Following gross-total excision of the mass, histology revealed PVNS. One month after surgery, the patient had no symptoms and there was no evidence of residual or recurrent disease.

TEMOPOROMANDIBULAR JOINT

Pigmented villonodular synovitis of the temporomandibular joint.

Rickert RR, Shapiro MJ.
Otolaryngol Head Neck Surg 1982 Sep-Oct;90(5):668-70 Abstract quote
A 39-year-old woman had a large asymptomatic left parotid mass that she had apparently not noticed. The clinical appearance suggested a parotid tumor. Aspirated tissue revealed numerous giant cells, histiocytes, and hemosiderin pigment.

At surgical exploration a tumor was found deep to the facial nerve involving the temporomandibular joint, which had a brown-stained roughened synovial membrane. The resected specimen histologically was a proliferative lesion composed of epithelioid histiocytes, spindle cells, and multinucleated giant cells. The appearance was typical of the family of lesions that includes pigmented villonodular synovitis, bursitis, and tenosynovitis (giant cell "tumor" of tendon sheath).

In view of the origin from the temporomandibular joint, reinforced by a characteristic radiologic appearance, we interpret this as a case of pigmented villonodular synovitis. This is the fifth case reported from this site.

HISTOLOGICAL TYPES CHARACTERIZATION

GENERAL

CYTOLOGY

Cytologic appearance of pigmented villonodular synovitis. A case report.

Gupta S, Mishra RS.

Department of Pathology, Cancer Hospital and Research Institute, Gwalior, M.R., India
Acta Cytol 2002 Jul-Aug;46(4):728-30 Abstract quote
BACKGROUND: Pigmented villonodular synovitis (PVNS) is a benign neoplasm of large joints. It may follow a locally aggressive course. The cytologic features of this neoplasm have not been characterized fully.

CASE: A 70-year-old male presented with a lump in the left ankle joint. The histopathologic diagnosis was pigmented villonodular synovitis. Review of the cytologic smears revealed clusters of round and ovoid, bland-looking cells along with siderophages and binucleated and multinucleated giant cells.

CONCLUSION: When interpreted in the clinical context, fine needle aspiration cytology may render a correct preoperative diagnosis of pigmented villonodular synovitis.

VARIANTS

LYMPHADENOPATHY

Extensive pigmented villonodular synovitis with markedly pigmented lymphadenopathy and its implication for differential diagnosis with malignant melanoma.

Wang S, Stewart JM, Ross MI, Prieto VG.

Departments of Pathology and Surgery, The University of Texas M. D. Anderson Cancer Center, Houston, TX.
Ann Diagn Pathol 2003 Apr;7(2):95-9 Abstract quote
A 51-year-old male presented with a 5 cm left knee mass. Fine needle aspiration revealed large epithelioid cells with prominent nucleoli and abundant cytoplasmic pigment, consistent with malignant melanoma. Left inguinal lymphadenopathy was present, which was suspicious for metastatic disease by ultrasound examination.

A dark perianal skin lesion was also identified, therefore raising the possibility of a primary melanoma. The knee and perianal lesions were resected and inguinal sentinel node biopsy was performed. In the specimen from the knee, there were clusters and fascicles of spindle and epithelioid cells with prominent nucleoli. Many of the cells displayed abundant, granular, brown, cytoplasmic pigment. The lymph node showed clusters of similar cells located in the subcapsular sinus.

Immunohistochemical study showed that the cells expressed CD68, but failed to express S-100, MART-1, and gp100. The cytoplasmic pigment was positive for iron staining. The final diagnosis was pigmented villonodular synovitis.

This case illustrates that pigmented villonodular synovitis may present with lymphadenopathy, mimicking a malignant process, including melanoma. Immunohistochemical studies may be essential for establishing the correct diagnosis.

MALIGNANT

Malignant giant cell tumor of synovium (malignant pigmented villonodular synovitis).

Layfield LJ, Meloni-Ehrig A, Liu K, Shepard R, Harrelson JM.

Department of Pathology, University of Utah Health Sciences Center, Salt Lake City 84132, USA.

Arch Pathol Lab Med 2000 Nov;124(11):1636-41 Abstract quote
CONTEXT: Pigmented villonodular synovitis (PVNS) is a well-recognized entity that has the potential for extensive local destruction, even though it rarely metastasizes. Rare reports of malignant forms are recorded in the literature. We observed 2 patients in whom examples of PVNS followed an aggressive course with multiple recurrences, metastasis, or degeneration to an appearance resembling malignant fibrous histiocytoma.

OBJECTIVE: We studied the occurrence and persistence of aneuploidy for chromosomes 5 and 7 in 2 patients with clinically aggressive PVNS.

DESIGN: Fluorescence in situ hybridization was performed for the detection of chromosomes 5 and 7 in the primary lesions, recurrences, and metastases in 2 examples of PVNS.

RESULTS: Fluorescence in situ hybridization demonstrated small but significant numbers of cells with trisomies for chromosomes 7 and/or 5 in both the primary and recurrent lesions of both patients.

CONCLUSIONS: The presence of consistent chromosomal trisomies (5 and 7) in both patients' examples of PVNS suggests a neoplastic nature for this lesion. The persistence of these trisomies in the primary lesions, recurrences, and metastases supports a molecular link between the primaries, recurrences, and metastases despite changes in morphologic features. The presence of persistent trisomies in the recurrent and metastatic lesions supports the concept of malignant PVNS.

SPECIAL STAINS/IMMUNOPEROXIDASE/
OTHER CHARACTERIZATION

SPECIAL STAINS

IMMUNOPEROXIDASE

Giant cell tumor of tendon sheath and pigmented villonodular synovitis: immunophenotype suggests a synovial cell origin.

O'Connell JX, Fanburg JC, Rosenberg AE.

Department of Pathology, Vancouver Hospital and Health Sciences Center, British Columbia.

Hum Pathol 1995 Jul;26(7):771-5 Abstract quote
Giant cell tumor of tendon sheath (GCTS) and pigmented villonodular synovitis (PVNS) are common synovial "tumors."

Their immunohistochemical profile, however, has not been well characterized, and uncertainty exists regarding their histogenesis and relationship to fibroma of tendon sheath. In an effort to clarify these uncertainties and to better define the immunohistochemical profile of GCTS/PVNS, we examined formalin fixed tissue from 35 specimens of GCTS, 12 specimens of PVNS, and three cases of reactive synovitis using avidin biotin complex (ABC) and streptavidin immunohistochemical methods.

Antibodies to vimentin, CD68, HAM56, cytokeratins, EMA, S100, HMB45, leukocyte common antigen, CD34, desmin, and smooth muscle actin were used in the study. The proliferating mononuclear cells and surface synovial cells in GCTS/PVNS and reactive synovitis stained positively for CD68, HAM56, and vimentin only. Multinucleated cells stained for CD68, vimentin, and leukocyte common antigen. All other stains were negative.

Our results suggest that GCTS/PVNS are tumors of synovial cell origin, and do not support an association between GCTS and fibroma of tendon sheath.

DESMIN

Tenosynovial giant cell tumors: evidence for a desmin-positive dendritic cell subpopulation.

Folpe AL, Weiss SW, Fletcher CD, Gown AM.

University of Washington, Seattle, USA.
Mod Pathol 1998 Oct;11(10):939-44 Abstract quote
Diffuse tenosynovial giant cell tumor (DGCT) could present as a large intra-articular mass (pigmented villonodular synovitis, or PVNS) or as an extraarticular mass, which might be confused with a sarcoma, particularly when growth is destructive and giant cells are few.

Prompted by a DGCT in which a subpopulation of cells was desmin positive and in which an erroneous diagnosis of myosarcoma was made, we analyzed the frequency of desmin, myogenin, MyoD1, and muscle-specific actin immunoreactivity in 45 well-characterized GCTs.

We also analyzed a subset of these cases with antibodies to smooth muscle actin, as well as macrophage, follicular dendritic cell, extrafollicular dendritic cell, and dermal dendrocyte-associated antigens. Sections from 45 cases of formalin-fixed GCTs (22 DGCTs, 13 cases of PVNS, and 10 localized GCTs) were immunostained for desmin, myogenin, MyoD1, and muscle-specific actin. The eight cases that showed the largest number of desmin-positive cells were immunostained for smooth muscle actin, CD45, CD68, CD21, CD35, cytokeratin 8, and Factor XIIIa. Desmin-positive cells were seen in 20 (43%) of 45 cases: 10 (43%) of 22 DGCTs, 5 (38%) of 13 cases of PVNS, and 5 (50%) of 10 localized GCTs. In contrast, none were positive for any of the other muscle-associated proteins.

In almost all of the cases, the desmin-positive cells were large and dendriform, with long processes that interdigitated between adjacent round cells. Desmin immunoreactivity was found in almost 50% of all GCTs, in the absence of positivity for other muscle markers.

Desmin immunoreactivity in GCT seemed to be confined to a variably sized subpopulation of large dendritic cells whose exact identity remains uncertain.

DIFFERENTIAL DIAGNOSIS KEY DIFFERENTIATING FEATURES

GENERAL

Giant cell tumor of tendon sheath, tenosynovial giant cell tumor, and pigmented villonodular synovitis: defining the presentation, surgical therapy and recurrence.

Martin RC 2nd, Osborne DL, Edwards MJ, Wrightson W, McMasters KM.

Division of Surgical Oncology, Department of Surgery, University of Louisville School of Medicine and the James Graham Brown Cancer Center, Louisville, KY 40202, USA.

Oncol Rep 2000 Mar-Apr;7(2):413-9 Abstract quote
Giant cell tumor of the tendon sheath (GCTTS), tenosynovial giant cell tumor (TGCT), and pigmented villo-nodular synovitis (PVNS) are the common names for a group of rare proliferative disorders that involve synovial joints and tendon sheaths. Considerable confusion exists about the surgical treatment and diagnosis of these disorders. This review evaluates the presentation, surgical therapy and recurrence of these three proliferative disorders.

We retrospectively reviewed the clinical data from all cases of GCTTS, TGCT, and PVNS from 1985 to 1997. A total of 35 patients were identified: GCTTS (n=8), TGCT (n=1), and PVNS (n=26), there were 18 men and 17 women. The median age was 48 years (range 6-84 years). The most common site of involvement was the knee (15), followed by wrist (7), elbow (4), and hip (4). Seven patients had extra-articular involvement, and 19 were found incidentally at operations for other reasons. Among the 4 patients who developed recurrent disease, 2 had extra-articular disease at the time of their original diagnosis. None died, and none required major amputation. One patient was treated with adjuvant radiotherapy following resection of a recurrence.

It is important to distinguish between focal and diffuse forms of synovial involvement. If focal, simple surgical excision is appropriate. If diffuse, complete synovectomy is indicated for disease confined to the joint, and resection of all gross disease is indicated for extra-articular disease. Radical resection with negative margins is not necessary in most instances. In rare aggressive cases, local recurrence may necessitate more extensive resection and radiation therapy.

PROGNOSIS CHARACTERIZATION

GENERAL

Diffuse and localized pigmented villonodular synovitis: evaluation of treatment of 38 patients.

de Visser E, Veth RP, Pruszczynski M, Wobbes T, Van de Putte LB.

Department of Orthopaedic Surgery, Nijmegen University Hospital, The Netherlands.

Arch Orthop Trauma Surg 1999;119(7-8):401-4 Abstract quote
We performed a retrospective study of 38 patients with pigmented villonodular synovitis (PVNS) to evaluate the treatment and functional results. The mean age of the patients was 32 (range 12-72) years at the time of treatment.

Three types of PVNS have been identified: localized nodules in 9 patients, diffuse PVNS of the entire synovial membrane in 26, a combination of a diffuse involvement of the synovial membrane and an extra-articular presentation in 1, and extra-articular lesions in 2. The location of the lesions was knee (n = 31), hip (n = 3), ankle (n = 2), femoral triangle (n = 1), and gluteal region (n = 1). The procedures performed were surgery alone, surgery combined with radiosynovectomy and radiosynovectomy only. A follow-up was done after a mean of 4 (range 1-19) years in 34 patients.

A functional evaluation according to the Musculoskeletal Tumor Society was performed in 31 patients. The mean functional evaluation score of 34 patients was 24 (range 15-30). Most of the ratings were excellent or good, in 6 cases fair, and in 2 cases poor.

This study demonstrates that the functional results are good despite residual or recurrent disease; in addition, we showed that functional evaluation after treatment gives an optimal view of the impact and results of the operation.

EXTRA-ARTICULAR

Extraarticular pigmented villonodular synovitis: a cause for failed knee arthroscopy.

Chin KR, Brick GW.

Department of Orthopaedics, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.

Clin Orthop 2002 Nov;(404):330-8 Abstract quote
Arthroscopic treatment of diffuse pigmented villonodular synovitis of the knee is reported to have low recurrence rates and morbidity.

The purpose of the current study was to evaluate demographic information, clinical symptoms, treatment parameters, and functional outcome in a group of 38 consecutive patients referred to the authors' hospital with persistent extraarticular diffuse pigmented villonodular synovitis of the knee after arthroscopic synovectomy. There were 23 males and 15 females with an average age of 31.7 years (range, 11-65 years) at the time of arthroscopy. All had an average of 1.7 (range, 1-5) arthroscopies. Thirty-four of 38 (89.5%) patients had some improvements of their symptoms after arthroscopic synovectomy, but all had worse symptoms and function at the latest followup of 3.63 years (range, 0.25-19.5 years).

Although arthroscopic synovectomy offered some short-term relief, a critical review of prior reports and the data in the current study suggest poor outcomes in patients who have extraarticular diffuse pigmented villonodular synovitis of the knee after arthroscopic synovectomy. Magnetic resonance imaging is recommended for accurate staging of the disease and for long-term followup after arthroscopic treatment.

RECURRENCE

Recurrent and non-recurrent pigmented villonodular synovitis 1.

Adem C, Sebo TJ, Riehle DL, Lohse CM, Nascimento AG.

Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.

Ann Pathol 2002 Dec;22(6):448-52 Abstract quote
Pigmented villonodular synovitis (PVNS) is a benign intra-articular lesion. Patients are at risk for local recurrence. Factors that predict recurrence are not established. Two groups of patients were retrieved from our files. One consisted of 25 patients who had one or more recurrences within 5 years after primary surgery. The second group contained 18 historical controls free of recurrence for at least 5 years after primary surgery. Patient medical records and surgical notes were reviewed.

We compared proliferative activity and DNA ploidy using digital image analysis, and other clinicopathologic features between the 2 groups of patients. The location of PVNS was significantly different between the two groups (p=0.03). In the recurrence group, there were 7 (28%) cases with disease in the knee. However, none of the controls had disease in the knee. Among recurrent cases, tumors in the knee were, on average, larger than tumors in the small joints. The size of all recurrent tumors was not significantly different than non-recurrent tumors (median of 1.8 cm versus 1.3 cm, respectively; p=0.06).

There were no significant differences in age, sex, completeness of surgical removal, MIB-I index, DNA ploidy, or the percent of tumor nuclei in the diploid, S-phase, tetraploid, or hypertetraploid DNA histogram categories between the two groups.

Our results indicate that recurrent PVNS tumors were more likely to be located in the knee, which may be related to larger tumor size. Patient age, sex, completeness of surgical removal, DNA ploidy, and MIB-I proliferation were not significantly different between recurrent and non-recurrent lesions.

TREATMENT CHARACTERIZATION

GENERAL

RADIOSYNOVECTOMY

Radiosynovectomy in pigmented villonodular synovitis.

Kat S, Kutz R, Elbracht T, Weseloh G, Kuwert T.

Clinic of Nuclear Medicine, Friedrich-Alexander University Erlangen-Nurnberg, Germany.
Nuklearmedizin 2000 Nov;39(7):209-13 Abstract quote
BACKGROUND: Pigmented villonodular synovitis (PVS) is a very rare disorder characterized by a slowly progressive benign proliferation of synovial tissue. As yet, the mainstay of its treatment has been surgical or athroscopic synovectomy. However, the relapse rates reported are relatively high, ranging between 8% and 46%. The aim of this study was to evaluate the efficacy of a combined treatment with radiosynovectomy (RS) and surgical synovectomy.

METHOD: We studied the effect of thirteen radiosynovectomies performed in eleven pigmented villonodular synovitis patients with Y-90 citrate or Re-186 sulfide. All patients had undergone intraarticular radiation therapy within 6 months after surgical synovectomy. Eight patients suffered from pigmented villonodular synovitis in the knee, the remaining three from pigmented villonodular synovitis in the hip. Two of eleven patients had to be treated twice, due to a relapse of symptoms occurring four months after the first treatment. Therapy responses were evaluated one year after the initial radiosynovectomy. Clinical response was assessed on three-point rating scales evaluating the degree of hydrops, rubor, and motility as well as the degree of pain, these four parameters were then averaged to an overall clinical score (CS). We also quantified the relative uptake of Tc-99m-diphosphonate in the joint involved on the blood pool (BUR) and delayed images (DUR).

RESULTS: Clinical score decreased from 5.45 +/- 1.04 to 1.18 +/- 1.16 at one year after treatment (p < 0.005), and the blood pool from 0.51 +/- 0.36 to 0.08 +/- 0.44 (p < 0.005). Delayed images were not significantly changed: 0.66 +/- 0.71 versus 0.66 +/- 0.73 (p = 0.3).

CONCLUSION: A combination of surgical synovectomy with radiosynovectomy is highly efficacious in treating clinical symptoms of pigmented villonodular synovitis. It also improves bone scintigraphic signs of inflammation, but has no influence on late diphosphonate uptake.

SURGERY

Treatment of advanced primary and recurrent diffuse pigmented villonodular synovitis of the knee.

Chin KR, Barr SJ, Winalski C, Zurakowski D, Brick GW.

Department of Orthopaedic Surgery, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
J Bone Joint Surg Am 2002 Dec;84-A(12):2192-202 Abstract quote
BACKGROUND: Diffuse pigmented villonodular synovitis of the knee is a difficult tumor to eradicate. We report our experience with a combined open posterior and anterior synovectomy with and without adjuvant postoperative radiation therapy in patients with advanced extracapsular disease.

METHODS: A single surgeon operated on forty patients, with an average age of thirty-five years (range, fourteen to sixty-eight years), who had diffuse pigmented villonodular synovitis of the knee. All patients had been referred to us after having initially undergone arthroscopic or open surgical procedures without eradication of the disease. Patients were retrospectively placed into one of three groups: Group I received surgery alone (five patients), Group II had surgery and intra-articular radiation synovectomy with use of dysprosium-165 (thirty patients), and Group III had surgery and external beam radiation (five patients). Adjuvant radiation was performed three months postoperatively. Magnetic resonance imaging was used for all patients for preoperative staging and postoperative follow-up.

RESULTS: The average Knee Society score for the entire series improved from 61 points preoperatively to 92 points at the time of follow-up, at an average of five years (range, 1.5 to eight years) (p < 0.001). There was also a significant (p < 0.001) increase in the average range of motion of the knees across all groups. On the basis of the Knee Society scores, thirty-seven patients (93%) had a good or excellent result, two patients had a fair result, and one patient had a poor result. Complications included stiffness requiring manipulation in three knees, one case of reflex sympathetic dystrophy, advanced osteoarthritis leading to a total knee replacement in four patients, and seven recurrences (a prevalence of 18%) after operative treatment and radiation therapy.

CONCLUSIONS: This surgical technique allows excellent visualization and removal of intra-articular and extra-articular diffuse pigmented villonodular tissue and yields excellent functional results and a low prevalence of knee stiffness. However, the rate of recurrence detected by magnetic resonance imaging was 18%. Adjuvant intra-articular radiation therapy may be beneficial for eradication of small foci of residual disease, but complete resection of all pigmented villonodular tissue appears to be the key to preventing recurrence. Magnetic resonance imaging was essential for accurate preoperative staging of the tumor and for follow-up since the presence of residual disease did not reliably correlate with the clinical findings. Patients with minimal degenerative arthritis and primary or recurrent extra-articular disease will benefit most from this approach.

The use of surgery and yttrium 90 in the management of extensive and diffuse pigmented villonodular synovitis of large joints.

Shabat S, Kollender Y, Merimsky O, Isakov J, Flusser G, Nyska M, Meller I.

The National Unit of Orthopaedic Oncology, Sapir Medical Center, Kfar-Saba, Israel.

Rheumatology (Oxford) 2002 Oct;41(10):1113-8 Abstract quote
OBJECTIVE: The surgical treatment of extensive diffuse pigmented villonodular synovitis (PVNS) of large joints alone is unsatisfactory, with high rates of local recurrence. Post-synovectomy adjuvant treatment with external beam radiation therapy or intra-articular injection of yttrium 90 (90Y) yielded better results. We report our experience with 10 cases treated with debulking surgery followed by intra-articular injection of 90Y.

PATIENTS AND METHODS: Between January 1989 and June 1998, 10 patients (eight males and two females aged 15-49 yr) with extensive diffuse PVNS were treated. In six patients the knee joint, in three patients the ankle joint, and in one patient the hip joint were involved. The 10 patients underwent 15 operations, one patient had three surgical procedures, and three patients underwent two surgeries (the intervals between re-operations for local recurrence were 2-4 yr). All patients had an intra-articular injection of 15-25 mCi (555-925 MBq) 90Y, 6-8 weeks after the last surgery.

RESULTS: Mean follow-up time was 6 yr (range 2.5-12 yr). All patients were followed using repeated computerized tomography (CT) scans, magnetic resonance imaging (MRI), plain X-ray films and bone scans semi-annually. In nine patients, neither evidence of disease nor progression of bone or articular destruction were noted. In one patient, stabilization of disease was achieved with no further evidence of bony or articular damage. No complications were noticed after surgery or after the intra-articular 90Y injection.

CONCLUSION: A combination of debulking surgery with intra-articular injection of 90Y for extensive diffuse PVNS of major joints is a reliable treatment method, with good results.

Henry JB. Clinical Diagnosis and Management by Laboratory Methods. Twentieth Edition. WB Saunders. 2001.
Rosai J. Ackerman's Surgical Pathology. Eight Edition. Mosby 1996.
Sternberg S. Diagnostic Surgical Pathology. Third Edition. Lipincott Williams and Wilkins 1999.
Robbins Pathologic Basis of Disease. Sixth Edition. WB Saunders 1999.
DeMay RM. The Art and Science of Cytopathology. Volume 1 and 2. ASCP Press. 1996.
Weedon D. Weedon's Skin Pathology Second Edition. Churchill Livingstone. 2002
Fitzpatrick's Dermatology in General Medicine. 5th Edition. McGraw-Hill. 1999.
Weiss SW and Goldblum JR. Enzinger and Weiss's Soft Tissue Tumors. Fourth Edition. Mosby 2001.

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Last Updated 5/9/2003

GROSS APPEARANCE/ CLINICAL VARIANTS	CHARACTERIZATION
GENERAL
Pigmented villonodular synovitis. Review of 20 cases. Durr HR, Stabler A, Maier M, Refior HJ. Department of Orthopedics and Orthopedic Surgery, Ludwig Maximilians University, Munich, Germany.	J Rheumatol 2001 Jul;28(7):1620-30 Abstract quote OBJECTIVE: Pigmented villonodular synovitis (PVS) is a rare aggressive lesion. Inclusion of this disease in the differential diagnosis of rheumatoid arthritis can lead to early diagnosis and treatment. In this retrospective study we evaluated diagnostic procedures, therapies, and outcomes of PVS. METHODS: Twenty surgically treated cases of PVS were evaluated: joint, 16; tenosynovial, 3; and bursa, one. The 20 patients had undergone the following surgeries: 4 total synovectomies, 2 subtotal synovectomies, eight arthroscopically assisted resections, 4 resections of extraarticular lesions, and 2 arthroplasties. The mean followup was 17.5 mo (1-54). RESULTS: At diagnosis, pain was present in 19 of 20 cases. Joint swelling or a tumor was found in 11 cases, and 12 patients complained of repeated joint effusions. The mean duration of symptoms was 23.8 mo (range 1-144). Half the cases had a nodular pattern and the other half a diffuse pattern. The most common location of PVS was the knee (14 patients). Surgical treatment before admission did not always lead to an accurate diagnosis. For example, in 2 patients, arthroscopy did not reveal PVS. In 2 patients a soft tissue sarcoma was suggested. In 3 patients, the diagnosis was made incidentally with arthroscopy or arthroplasty. On radiographs, bone lesions were seen in 8 cases; in 13 of 17 cases the diagnosis was by magnetic resonance imaging (MRI). After surgery 17 patients stayed free of recurrence, 14 without symptoms. One patient who had an incidental diagnosis of PVS has a synovectomy planned as a second procedure. One patient awaits a second dorsal procedure after a ventral knee synovectomy. One patient shows recurrent disease 33 mo after resection of a nodular knee lesion. CONCLUSION: PVS should be included in the differential diagnosis of any arthritis. MRI is the most effective diagnostic tool in identifying PVS. The treatment of PVS consists of surgical excision in sound tissue. A total synovectomy should be the treatment of choice in diffuse disease. From the literature, nonsurgical therapies, such as steroid injections, 90Y synoviorthesis, or external beam radiation, seem to be of benefit in selected patients.
VARIANTS
FOOT
Pigmented villonodular synovitis of the foot and ankle: a report of eight cases. Rochwerger A, Groulier P, Curvale G, Launay F. Department of Orthopaedic Surgery, Hopital de la Conception, Marseille, France.	Foot Ankle Int 1999 Sep;20(9):587-90 Abstract quote Eight cases of pigmented villonodular synovitis of the foot and ankle are reported. The purpose of this study was to analyze the manifestation of pigmented villonodular synovitis in the foot and to evaluate treatment options. There were four cases in the ankle and hindfoot, one in the first tarsometatarsal joint, and three in the toes. In seven of eight cases, diagnosis was confirmed by magnetic resonance imaging (MRI) scans. The tenosynovial form was found in the toes and the articular form in the hindfoot and ankle. Surgical treatment was performed in all cases: one arthroscopically assisted synovectomy in the ankle joint, two talocrural arthrodeses, one subtalar arthrodesis, one tarsometatarsal arthrodesis, and tumor removal on the toes with arthrodesis of the distal interphalangeal (DIP) joint in two cases. Average follow-up was 4 years. Recurrence occurred in one toe and led to partial amputation. Malunion in one ankle arthrodesis was operated on again with no sign of recurrence. In the toes, the lesion had a tumoral feature; the bone was infiltrated by soft tissue, and the surgical procedure was local removal of the tumor. In the hind-foot, the lesions were intra-articular and required synovectomy, usually with an arthrodesis. In the midfoot, there was a large extraosseous tumor surrounding tendons with destructive articular lesions.
HIP
Pigmented villonodular synovitis of the hip: 2- to 23-year followup study. Gonzalez Della Valle A, Piccaluga F, Potter HG, Salvati EA, Pusso R. Instituto de Orthopedia y Traumatologia, Carlos E. Ottolenghi Hospital Italiano de Buenos Aires, Argentina.	Clin Orthop 2001 Jul;(388):187-99 Abstract quote Pigmented villonodular synovitis affecting the hip is rare. Seven new patients are presented and 117 cases from the literature are reviewed. Among the new patients, two refused treatment; in one patient, severe bone loss was observed after a radiographic followup of 21 years; the second patient showed no radiographic changes 2 years after diagnosis. One patient underwent a synovectomy and had a recurrence 9 years later, requiring a total hip replacement. The remaining four patients underwent synovectomy and primary total hip replacement with no recurrences detected after an average followup of 13 years (range, 2-23 years). Among 117 cases published, 62 patients (53%) did not have enough information for analysis. A metaanalysis using the remaining 55 patients was done. In nine patients (16%; nine of 55) the diagnosis was made with a preoperative biopsy. Treatment consisted of synovectomy in 26 patients (47%; 26 of 55), arthroplasty in 24 (43%; 24 of 55), arthrodesis in two (4%; two of 55), and hindquarter amputation in a patient misdiagnosed as having synovial sarcoma (2%; one of 55). Two patients (4%; two of 55) were not treated. Ten patients had a recurrence (19%; 10 of 53); nine in the synovectomy group (35 %; nine of 26) and one in the joint replacement group (4%; one of 24). Synovectomy is recommended for patients with preserved articular cartilage and total hip replacement is recommended for patients with secondary osteoarthritis. Removal of all macroscopic tumors including careful curetting of the osteolytic lesions should be done as they may constitute a source of recurrence.
LOCALIZED
Localized pigmented villonodular synovitis: arthroscopic diagnosis and management of an "invisible" lesion. Parikh SN, Chen AL, Ergas E. Department of Orthopaedics, Hospital for Joint Diseases, New York, New York 10003, USA.	Arthroscopy 2002 Jul-Aug;18(6):E31 Abstract quote Pigmented villonodular synovitis (PVNS) is a rare disorder that may involve the synovium of joints, bursa, or tendon sheaths. Monoarticular involvement is typical, with the knee most commonly affected. Localized pigmented villonodular synovitis (LPVNS) involves a discrete region of the synovium. Detection and diagnosis of this entity is clinically challenging, and plain radiographs are usually unremarkable. Magnetic resonance imaging (MRI) has been reported to be sensitive for the detection of synovial abnormalities and is the imaging modality of choice in suspected cases of LPVNS. When the diagnosis remains in doubt, arthroscopy may be used for direct visualization of synovial pathology, as well as to obtain tissue for histologic analysis. Definitive treatment may also be performed at the time of arthroscopy. We present a case of LPVNS in which a large (4 cm) lesion was not apparent on preoperative radiographs or MRI and was also missed on initial diagnostic arthroscopy.
SHOULDER
Pigmented villonodular synovitis of the shoulder: review and case report. Muller LP, Bitzer M, Degreif J, Rommens PM. Klinik fur Unfallchirurgie, Johannes-Gutenberg-Universitat Mainz, Germany.	Knee Surg Sports Traumatol Arthrosc 1999;7(4):249-56 Abstract quote Pigmented villonodular synovitis (PVNS) as reviewed in detail elsewhere most frequently involves the knee and finger synovial structures; shoulder involvement is rare: A search through the English literature yielded 18 publications describing 25 cases of PVNS affecting the shoulder joint. Analyzing these reports we found the clinical and radiological findings generally to be nonspecific, often mimicking a malignancy, as in the case presented here of a 16-year-old boy with painful swelling in the area of the left proximal humerus. Magnetic resonance imaging showed a suspected malignant soft tissue mass involving the shoulder capsule and measuring 7.5 x 6 x 4 cm. Preoperatively the patient could recall no trauma; however, postoperatively he did report a distortion trauma of the affected shoulder following a bicycle accident. Intraoperatively, two tumors were found infiltrating the axillary vessels and nerve and tendon structures originating in the capsule of the shoulder joint. Rapid sections of the tissue revealed no signs of malignancy; further pathohistological examination revealed localized PVNS. Preoperatively, the shoulder joint was not suspected as the primary site of origin of the tumor because the patient had no complaints or functional deficits of the shoulder. The clinical presentation of such a PVNS lesion over the proximal humerus is unusual and to date has only twice been described in the literature.
SPINE
Pigment villonodular synovitis of the spine. Case report and review of the literature. Dimeco F, Rizzo P, Li KW, Ciceri E, Casali C, Pollo B, Lasio G. Department of Neurosurgery, Istituto Nazionale Neurologico C. Besta, Milan, Italy	J Neurosurg Sci 2001 Dec;45(4):216-9; discussion 219 Abstract quote Pigmented villonodular synovitis (PVNS) is a disease of the joints which uncommonly involves the spine. We present a 70-year-old woman with radicular symptoms who was found to have a mass arising from a lumbar zygapophyseal joint with extension into the spinal canal. Following gross-total excision of the mass, histology revealed PVNS. One month after surgery, the patient had no symptoms and there was no evidence of residual or recurrent disease.
TEMOPOROMANDIBULAR JOINT
Pigmented villonodular synovitis of the temporomandibular joint. Rickert RR, Shapiro MJ.	Otolaryngol Head Neck Surg 1982 Sep-Oct;90(5):668-70 Abstract quote A 39-year-old woman had a large asymptomatic left parotid mass that she had apparently not noticed. The clinical appearance suggested a parotid tumor. Aspirated tissue revealed numerous giant cells, histiocytes, and hemosiderin pigment. At surgical exploration a tumor was found deep to the facial nerve involving the temporomandibular joint, which had a brown-stained roughened synovial membrane. The resected specimen histologically was a proliferative lesion composed of epithelioid histiocytes, spindle cells, and multinucleated giant cells. The appearance was typical of the family of lesions that includes pigmented villonodular synovitis, bursitis, and tenosynovitis (giant cell "tumor" of tendon sheath). In view of the origin from the temporomandibular joint, reinforced by a characteristic radiologic appearance, we interpret this as a case of pigmented villonodular synovitis. This is the fifth case reported from this site.

SPECIAL STAINS/IMMUNOPEROXIDASE/ OTHER	CHARACTERIZATION
SPECIAL STAINS
IMMUNOPEROXIDASE
Giant cell tumor of tendon sheath and pigmented villonodular synovitis: immunophenotype suggests a synovial cell origin. O'Connell JX, Fanburg JC, Rosenberg AE. Department of Pathology, Vancouver Hospital and Health Sciences Center, British Columbia.	Hum Pathol 1995 Jul;26(7):771-5 Abstract quote Giant cell tumor of tendon sheath (GCTS) and pigmented villonodular synovitis (PVNS) are common synovial "tumors." Their immunohistochemical profile, however, has not been well characterized, and uncertainty exists regarding their histogenesis and relationship to fibroma of tendon sheath. In an effort to clarify these uncertainties and to better define the immunohistochemical profile of GCTS/PVNS, we examined formalin fixed tissue from 35 specimens of GCTS, 12 specimens of PVNS, and three cases of reactive synovitis using avidin biotin complex (ABC) and streptavidin immunohistochemical methods. Antibodies to vimentin, CD68, HAM56, cytokeratins, EMA, S100, HMB45, leukocyte common antigen, CD34, desmin, and smooth muscle actin were used in the study. The proliferating mononuclear cells and surface synovial cells in GCTS/PVNS and reactive synovitis stained positively for CD68, HAM56, and vimentin only. Multinucleated cells stained for CD68, vimentin, and leukocyte common antigen. All other stains were negative. Our results suggest that GCTS/PVNS are tumors of synovial cell origin, and do not support an association between GCTS and fibroma of tendon sheath.
DESMIN
Tenosynovial giant cell tumors: evidence for a desmin-positive dendritic cell subpopulation. Folpe AL, Weiss SW, Fletcher CD, Gown AM. University of Washington, Seattle, USA.	Mod Pathol 1998 Oct;11(10):939-44 Abstract quote Diffuse tenosynovial giant cell tumor (DGCT) could present as a large intra-articular mass (pigmented villonodular synovitis, or PVNS) or as an extraarticular mass, which might be confused with a sarcoma, particularly when growth is destructive and giant cells are few. Prompted by a DGCT in which a subpopulation of cells was desmin positive and in which an erroneous diagnosis of myosarcoma was made, we analyzed the frequency of desmin, myogenin, MyoD1, and muscle-specific actin immunoreactivity in 45 well-characterized GCTs. We also analyzed a subset of these cases with antibodies to smooth muscle actin, as well as macrophage, follicular dendritic cell, extrafollicular dendritic cell, and dermal dendrocyte-associated antigens. Sections from 45 cases of formalin-fixed GCTs (22 DGCTs, 13 cases of PVNS, and 10 localized GCTs) were immunostained for desmin, myogenin, MyoD1, and muscle-specific actin. The eight cases that showed the largest number of desmin-positive cells were immunostained for smooth muscle actin, CD45, CD68, CD21, CD35, cytokeratin 8, and Factor XIIIa. Desmin-positive cells were seen in 20 (43%) of 45 cases: 10 (43%) of 22 DGCTs, 5 (38%) of 13 cases of PVNS, and 5 (50%) of 10 localized GCTs. In contrast, none were positive for any of the other muscle-associated proteins. In almost all of the cases, the desmin-positive cells were large and dendriform, with long processes that interdigitated between adjacent round cells. Desmin immunoreactivity was found in almost 50% of all GCTs, in the absence of positivity for other muscle markers. Desmin immunoreactivity in GCT seemed to be confined to a variably sized subpopulation of large dendritic cells whose exact identity remains uncertain.

PROGNOSIS	CHARACTERIZATION
GENERAL
Diffuse and localized pigmented villonodular synovitis: evaluation of treatment of 38 patients. de Visser E, Veth RP, Pruszczynski M, Wobbes T, Van de Putte LB. Department of Orthopaedic Surgery, Nijmegen University Hospital, The Netherlands.	Arch Orthop Trauma Surg 1999;119(7-8):401-4 Abstract quote We performed a retrospective study of 38 patients with pigmented villonodular synovitis (PVNS) to evaluate the treatment and functional results. The mean age of the patients was 32 (range 12-72) years at the time of treatment. Three types of PVNS have been identified: localized nodules in 9 patients, diffuse PVNS of the entire synovial membrane in 26, a combination of a diffuse involvement of the synovial membrane and an extra-articular presentation in 1, and extra-articular lesions in 2. The location of the lesions was knee (n = 31), hip (n = 3), ankle (n = 2), femoral triangle (n = 1), and gluteal region (n = 1). The procedures performed were surgery alone, surgery combined with radiosynovectomy and radiosynovectomy only. A follow-up was done after a mean of 4 (range 1-19) years in 34 patients. A functional evaluation according to the Musculoskeletal Tumor Society was performed in 31 patients. The mean functional evaluation score of 34 patients was 24 (range 15-30). Most of the ratings were excellent or good, in 6 cases fair, and in 2 cases poor. This study demonstrates that the functional results are good despite residual or recurrent disease; in addition, we showed that functional evaluation after treatment gives an optimal view of the impact and results of the operation.
EXTRA-ARTICULAR
Extraarticular pigmented villonodular synovitis: a cause for failed knee arthroscopy. Chin KR, Brick GW. Department of Orthopaedics, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.	Clin Orthop 2002 Nov;(404):330-8 Abstract quote Arthroscopic treatment of diffuse pigmented villonodular synovitis of the knee is reported to have low recurrence rates and morbidity. The purpose of the current study was to evaluate demographic information, clinical symptoms, treatment parameters, and functional outcome in a group of 38 consecutive patients referred to the authors' hospital with persistent extraarticular diffuse pigmented villonodular synovitis of the knee after arthroscopic synovectomy. There were 23 males and 15 females with an average age of 31.7 years (range, 11-65 years) at the time of arthroscopy. All had an average of 1.7 (range, 1-5) arthroscopies. Thirty-four of 38 (89.5%) patients had some improvements of their symptoms after arthroscopic synovectomy, but all had worse symptoms and function at the latest followup of 3.63 years (range, 0.25-19.5 years). Although arthroscopic synovectomy offered some short-term relief, a critical review of prior reports and the data in the current study suggest poor outcomes in patients who have extraarticular diffuse pigmented villonodular synovitis of the knee after arthroscopic synovectomy. Magnetic resonance imaging is recommended for accurate staging of the disease and for long-term followup after arthroscopic treatment.
RECURRENCE
Recurrent and non-recurrent pigmented villonodular synovitis 1. Adem C, Sebo TJ, Riehle DL, Lohse CM, Nascimento AG. Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.	Ann Pathol 2002 Dec;22(6):448-52 Abstract quote Pigmented villonodular synovitis (PVNS) is a benign intra-articular lesion. Patients are at risk for local recurrence. Factors that predict recurrence are not established. Two groups of patients were retrieved from our files. One consisted of 25 patients who had one or more recurrences within 5 years after primary surgery. The second group contained 18 historical controls free of recurrence for at least 5 years after primary surgery. Patient medical records and surgical notes were reviewed. We compared proliferative activity and DNA ploidy using digital image analysis, and other clinicopathologic features between the 2 groups of patients. The location of PVNS was significantly different between the two groups (p=0.03). In the recurrence group, there were 7 (28%) cases with disease in the knee. However, none of the controls had disease in the knee. Among recurrent cases, tumors in the knee were, on average, larger than tumors in the small joints. The size of all recurrent tumors was not significantly different than non-recurrent tumors (median of 1.8 cm versus 1.3 cm, respectively; p=0.06). There were no significant differences in age, sex, completeness of surgical removal, MIB-I index, DNA ploidy, or the percent of tumor nuclei in the diploid, S-phase, tetraploid, or hypertetraploid DNA histogram categories between the two groups. Our results indicate that recurrent PVNS tumors were more likely to be located in the knee, which may be related to larger tumor size. Patient age, sex, completeness of surgical removal, DNA ploidy, and MIB-I proliferation were not significantly different between recurrent and non-recurrent lesions.

TREATMENT	CHARACTERIZATION
GENERAL
RADIOSYNOVECTOMY
Radiosynovectomy in pigmented villonodular synovitis. Kat S, Kutz R, Elbracht T, Weseloh G, Kuwert T. Clinic of Nuclear Medicine, Friedrich-Alexander University Erlangen-Nurnberg, Germany.	Nuklearmedizin 2000 Nov;39(7):209-13 Abstract quote BACKGROUND: Pigmented villonodular synovitis (PVS) is a very rare disorder characterized by a slowly progressive benign proliferation of synovial tissue. As yet, the mainstay of its treatment has been surgical or athroscopic synovectomy. However, the relapse rates reported are relatively high, ranging between 8% and 46%. The aim of this study was to evaluate the efficacy of a combined treatment with radiosynovectomy (RS) and surgical synovectomy. METHOD: We studied the effect of thirteen radiosynovectomies performed in eleven pigmented villonodular synovitis patients with Y-90 citrate or Re-186 sulfide. All patients had undergone intraarticular radiation therapy within 6 months after surgical synovectomy. Eight patients suffered from pigmented villonodular synovitis in the knee, the remaining three from pigmented villonodular synovitis in the hip. Two of eleven patients had to be treated twice, due to a relapse of symptoms occurring four months after the first treatment. Therapy responses were evaluated one year after the initial radiosynovectomy. Clinical response was assessed on three-point rating scales evaluating the degree of hydrops, rubor, and motility as well as the degree of pain, these four parameters were then averaged to an overall clinical score (CS). We also quantified the relative uptake of Tc-99m-diphosphonate in the joint involved on the blood pool (BUR) and delayed images (DUR). RESULTS: Clinical score decreased from 5.45 +/- 1.04 to 1.18 +/- 1.16 at one year after treatment (p < 0.005), and the blood pool from 0.51 +/- 0.36 to 0.08 +/- 0.44 (p < 0.005). Delayed images were not significantly changed: 0.66 +/- 0.71 versus 0.66 +/- 0.73 (p = 0.3). CONCLUSION: A combination of surgical synovectomy with radiosynovectomy is highly efficacious in treating clinical symptoms of pigmented villonodular synovitis. It also improves bone scintigraphic signs of inflammation, but has no influence on late diphosphonate uptake.
SURGERY
Treatment of advanced primary and recurrent diffuse pigmented villonodular synovitis of the knee. Chin KR, Barr SJ, Winalski C, Zurakowski D, Brick GW. Department of Orthopaedic Surgery, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.	J Bone Joint Surg Am 2002 Dec;84-A(12):2192-202 Abstract quote BACKGROUND: Diffuse pigmented villonodular synovitis of the knee is a difficult tumor to eradicate. We report our experience with a combined open posterior and anterior synovectomy with and without adjuvant postoperative radiation therapy in patients with advanced extracapsular disease. METHODS: A single surgeon operated on forty patients, with an average age of thirty-five years (range, fourteen to sixty-eight years), who had diffuse pigmented villonodular synovitis of the knee. All patients had been referred to us after having initially undergone arthroscopic or open surgical procedures without eradication of the disease. Patients were retrospectively placed into one of three groups: Group I received surgery alone (five patients), Group II had surgery and intra-articular radiation synovectomy with use of dysprosium-165 (thirty patients), and Group III had surgery and external beam radiation (five patients). Adjuvant radiation was performed three months postoperatively. Magnetic resonance imaging was used for all patients for preoperative staging and postoperative follow-up. RESULTS: The average Knee Society score for the entire series improved from 61 points preoperatively to 92 points at the time of follow-up, at an average of five years (range, 1.5 to eight years) (p < 0.001). There was also a significant (p < 0.001) increase in the average range of motion of the knees across all groups. On the basis of the Knee Society scores, thirty-seven patients (93%) had a good or excellent result, two patients had a fair result, and one patient had a poor result. Complications included stiffness requiring manipulation in three knees, one case of reflex sympathetic dystrophy, advanced osteoarthritis leading to a total knee replacement in four patients, and seven recurrences (a prevalence of 18%) after operative treatment and radiation therapy. CONCLUSIONS: This surgical technique allows excellent visualization and removal of intra-articular and extra-articular diffuse pigmented villonodular tissue and yields excellent functional results and a low prevalence of knee stiffness. However, the rate of recurrence detected by magnetic resonance imaging was 18%. Adjuvant intra-articular radiation therapy may be beneficial for eradication of small foci of residual disease, but complete resection of all pigmented villonodular tissue appears to be the key to preventing recurrence. Magnetic resonance imaging was essential for accurate preoperative staging of the tumor and for follow-up since the presence of residual disease did not reliably correlate with the clinical findings. Patients with minimal degenerative arthritis and primary or recurrent extra-articular disease will benefit most from this approach.
The use of surgery and yttrium 90 in the management of extensive and diffuse pigmented villonodular synovitis of large joints. Shabat S, Kollender Y, Merimsky O, Isakov J, Flusser G, Nyska M, Meller I. The National Unit of Orthopaedic Oncology, Sapir Medical Center, Kfar-Saba, Israel.	Rheumatology (Oxford) 2002 Oct;41(10):1113-8 Abstract quote OBJECTIVE: The surgical treatment of extensive diffuse pigmented villonodular synovitis (PVNS) of large joints alone is unsatisfactory, with high rates of local recurrence. Post-synovectomy adjuvant treatment with external beam radiation therapy or intra-articular injection of yttrium 90 (90Y) yielded better results. We report our experience with 10 cases treated with debulking surgery followed by intra-articular injection of 90Y. PATIENTS AND METHODS: Between January 1989 and June 1998, 10 patients (eight males and two females aged 15-49 yr) with extensive diffuse PVNS were treated. In six patients the knee joint, in three patients the ankle joint, and in one patient the hip joint were involved. The 10 patients underwent 15 operations, one patient had three surgical procedures, and three patients underwent two surgeries (the intervals between re-operations for local recurrence were 2-4 yr). All patients had an intra-articular injection of 15-25 mCi (555-925 MBq) 90Y, 6-8 weeks after the last surgery. RESULTS: Mean follow-up time was 6 yr (range 2.5-12 yr). All patients were followed using repeated computerized tomography (CT) scans, magnetic resonance imaging (MRI), plain X-ray films and bone scans semi-annually. In nine patients, neither evidence of disease nor progression of bone or articular destruction were noted. In one patient, stabilization of disease was achieved with no further evidence of bony or articular damage. No complications were noticed after surgery or after the intra-articular 90Y injection. CONCLUSION: A combination of debulking surgery with intra-articular injection of 90Y for extensive diffuse PVNS of major joints is a reliable treatment method, with good results.

Pathogenesis
Laboratory/Radiologic/Other Diagnostic Testing
Gross Appearance and Clinical Variants
Histopathological Features and Variants
Special Stains/Immunohistochemistry/Electron Microscopy
Differential Diagnosis
Prognosis
Treatment
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HISTOLOGICAL TYPES	CHARACTERIZATION
GENERAL
CYTOLOGY
Cytologic appearance of pigmented villonodular synovitis. A case report. Gupta S, Mishra RS. Department of Pathology, Cancer Hospital and Research Institute, Gwalior, M.R., India	Acta Cytol 2002 Jul-Aug;46(4):728-30 Abstract quote BACKGROUND: Pigmented villonodular synovitis (PVNS) is a benign neoplasm of large joints. It may follow a locally aggressive course. The cytologic features of this neoplasm have not been characterized fully. CASE: A 70-year-old male presented with a lump in the left ankle joint. The histopathologic diagnosis was pigmented villonodular synovitis. Review of the cytologic smears revealed clusters of round and ovoid, bland-looking cells along with siderophages and binucleated and multinucleated giant cells. CONCLUSION: When interpreted in the clinical context, fine needle aspiration cytology may render a correct preoperative diagnosis of pigmented villonodular synovitis.
VARIANTS
LYMPHADENOPATHY
Extensive pigmented villonodular synovitis with markedly pigmented lymphadenopathy and its implication for differential diagnosis with malignant melanoma. Wang S, Stewart JM, Ross MI, Prieto VG. Departments of Pathology and Surgery, The University of Texas M. D. Anderson Cancer Center, Houston, TX.	Ann Diagn Pathol 2003 Apr;7(2):95-9 Abstract quote A 51-year-old male presented with a 5 cm left knee mass. Fine needle aspiration revealed large epithelioid cells with prominent nucleoli and abundant cytoplasmic pigment, consistent with malignant melanoma. Left inguinal lymphadenopathy was present, which was suspicious for metastatic disease by ultrasound examination. A dark perianal skin lesion was also identified, therefore raising the possibility of a primary melanoma. The knee and perianal lesions were resected and inguinal sentinel node biopsy was performed. In the specimen from the knee, there were clusters and fascicles of spindle and epithelioid cells with prominent nucleoli. Many of the cells displayed abundant, granular, brown, cytoplasmic pigment. The lymph node showed clusters of similar cells located in the subcapsular sinus. Immunohistochemical study showed that the cells expressed CD68, but failed to express S-100, MART-1, and gp100. The cytoplasmic pigment was positive for iron staining. The final diagnosis was pigmented villonodular synovitis. This case illustrates that pigmented villonodular synovitis may present with lymphadenopathy, mimicking a malignant process, including melanoma. Immunohistochemical studies may be essential for establishing the correct diagnosis.
MALIGNANT
Malignant giant cell tumor of synovium (malignant pigmented villonodular synovitis). Layfield LJ, Meloni-Ehrig A, Liu K, Shepard R, Harrelson JM. Department of Pathology, University of Utah Health Sciences Center, Salt Lake City 84132, USA.	Arch Pathol Lab Med 2000 Nov;124(11):1636-41 Abstract quote CONTEXT: Pigmented villonodular synovitis (PVNS) is a well-recognized entity that has the potential for extensive local destruction, even though it rarely metastasizes. Rare reports of malignant forms are recorded in the literature. We observed 2 patients in whom examples of PVNS followed an aggressive course with multiple recurrences, metastasis, or degeneration to an appearance resembling malignant fibrous histiocytoma. OBJECTIVE: We studied the occurrence and persistence of aneuploidy for chromosomes 5 and 7 in 2 patients with clinically aggressive PVNS. DESIGN: Fluorescence in situ hybridization was performed for the detection of chromosomes 5 and 7 in the primary lesions, recurrences, and metastases in 2 examples of PVNS. RESULTS: Fluorescence in situ hybridization demonstrated small but significant numbers of cells with trisomies for chromosomes 7 and/or 5 in both the primary and recurrent lesions of both patients. CONCLUSIONS: The presence of consistent chromosomal trisomies (5 and 7) in both patients' examples of PVNS suggests a neoplastic nature for this lesion. The persistence of these trisomies in the primary lesions, recurrences, and metastases supports a molecular link between the primaries, recurrences, and metastases despite changes in morphologic features. The presence of persistent trisomies in the recurrent and metastatic lesions supports the concept of malignant PVNS.