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What Affects the Recurrence and Clinical Outcome of Pigmented Villonodular Synovitis?

Chiari, Catharina*; Pirich, Christian; Brannath, Werner§; Kotz, Rainer*; Trieb, Klemens*

Author Information
Clinical Orthopaedics and Related Research: September 2006 - Volume 450 - Issue - p 172-178
doi: 10.1097/01.blo.0000224051.01873.fb


Pigmented villonodular synovitis (PVNS) is a rare proliferative synovial tumor mainly affecting the joints, tendon sheaths, and bursae. When Jaffe et al first described the lesion in 1941,14 its origin was considered inflammatory or neoplastic. Its neoplastic character still is accepted.28,32 Clinically, there are two types of growth patterns: the localized or nodular type, which is a solitary nodule, and the diffuse type, which is a villous, pigmented process involving the synovial tissue.9,12,15,24,28 Histologically, both types have similar morphologic features, with diffuse or nodular isomorphic proliferations of mononuclear synovial cells having a scant, nonfoamy cytoplasm and bland nuclei, scattered osteoclast-like giant cells, and a lymphocytic infiltrate with focal accumulations of lipid-loaded macrophages and deposits of iron pigment. Studies analyzing expression patterns of cell cycle-regulating gene products showed increased proliferation rates of synovial cells, but predictive markers for a possible tumor recurrence could not be determined.29,34 Pigmented villonodular synovitis is benign despite the high risk of recurrence.25,28

Metastasis is extremely rare, although some authors have reported small series of malignant tenosynovial giant cell tumors (GCT) developing metastatic and atypical sarcomatous histologic features.1,32 Areas of predilection are the digits of the hand for nodular PVNS and the knee for diffuse PVNS.32 Pigmented villonodular synovitis occurs in the hip,11,33 ankle, elbow, shoulder, toes, and occasionally the cervical spine.8,20,30 Clinical symptoms include asymptomatic conditions, diffuse swelling, joint locking, pain, bony erosions, and joint destruction.3,22 Diagnosis often is delayed because of the nonspecific symptoms, which may result in a long course of disease associated with multiple operations.30 Generally, PVNS is treated operatively but surgery can be combined with adjuvant treatments such as external beam radiation2,17 or radiation synovectomy, especially in patients with extensive or recurrent disease.18,27 However, there is the risk of adverse effects such as skin damage, infection, or leakage.18,27,31

The type of surgery depends on location and lesion type. It is known that eradication of PVNS is more difficult in large joints than in digits and in patients with diffuse disease rather than single nodules.9,16,26,28 However, previous studies were restricted to certain locations or types of PVNS,7,16,26 and did not provide adequate documentation of followup to perform a Kaplan-Meier analysis of disease-free survival.3,7,9,28

Therefore we wanted to confirm previous findings by a thorough followup of all patients with the diagnosis of PVNS treated at our instution by addressing the following questions: What were the recurrence rates especially when considering location and type of PVNS (diffuse or nodular)?; What was the long-term clinical outcome?; and Was magnetic resonance imaging (MRI) essential for the correct diagnosis?


We retrospectively reviewed 67 patients identified in the Vienna Bone Tumor Registry who had a histologic diagnosis of PVNS or GCT of the tendon sheath from 1972-2002. Fourteen patients had their initial surgery at other centers and were referred to our institution for recurrent disease; these patients were excluded as their recurrences might bias the sample. Of the remaining 53 patients, four had died and seven could not be located, leaving 42 patients available for followup at an average of 80 months (range, 26-294 months) after the initial procedure. The patients were divided into nodular (19 patients) and diffuse (23 patients) groups. Twenty-seven of the 42 patients (64%) were females. The average age of the patients at symptom onset was 40 years (range, 6-76 years) and 44.5 years (range, 13-78 years) at the initial surgery. The average duration of preoperative symptoms was 49 months (range, 0.5-361 months). Pigmented villonodular synovitis was located in 18 hands, 12 knees, five feet, three ankles, three hips, and one shoulder (Table 1).

Clinical Data

Clinical information was retrieved from patients' records and during followups. Thirty-one patients had clinical followups performed by one physician (CC) who was not involved in their care. Eleven patients were interviewed by telephone and had current radiographs sent to us for review. Preoperative MRI scans were available for 23 patients (10 hands, nine knees, two ankles, and two feet). Six patients had preoperative biopsies. Intraoperative frozen sections were obtained in 20 patients, which provided the correct diagnosis of PVNS in all but one patient. In this patient, the diagnosis of posttraumatic synovial alteration was suggested.

The surgeries performed at our institution consisted of 28 tumor excisions, 12 synovectomies, and two total joint arthroplasties (Table 2).

Types of Surgery

The patients were evaluated for pain, swelling, and range of motion (ROM). An Enneking score10 also was calculated. This system assigns numerical values (range, 0-5) for each of six categories: pain, function, and emotional acceptance in upper and lower extremities; supports, walking ability and gait for the lower limb; and hand positioning, dexterity, and lifting ability for the upper limbs. The results are reported numerically as percentages of normal, which is determined by dividing the maximum score into the total score. Knees were evaluated using the Lysholm and Gillquist score,19 hips were evaluated using the Harris hip score,13 and shoulders were evaluated using the Constant and Murley score.5 Twenty-nine patients had MRI scans performed at followup. Nine patients (six with fingers involved and three with toes involved) declined MRI as they had no complaints. Plain radiographs were available for the patients who had total joint replacements (two hips and two knees).

We analyzed the following factors for their influence on relapse time: age, preoperative MRI, preoperative duration of symptoms, gender, preoperative suspicion of PVNS, performance of an intraoperative frozen section, radical surgery, upper versus lower extremities, digits (hands and feet) versus large joints (ankles, knees, hips, shoulders), and nodular versus diffuse PVNS. We analyzed the influences of age and preoperative symptom duration by univariate Cox regression analyses. All other factors were investigated by univariate log-rank tests and Kaplan-Meyer plots. Factors with a significant influence on relapse time also were applied to the subgroup of patients with diffuse PVNS (19 patients with eight events) to determine if these factors had an influence beyond the PVNS type. There were insufficient numbers of recurrences (23 patients, two recurrences) in the patients with nodular PVNS to justify additional analysis. Probability values ≤ 0.05 were considered significant.


Ten of the 42 patients (two hands, three hips, three ankles, one knee, and one shoulder) had recurrences. Recurrences were more frequent (p = 0.011) in patients with diffuse PVNS than in patients with nodular PVNS and more frequent (p = 0.025) in large joints than in digits. The 1-year recurrence-free survival rate for the diffuse PVNS group was 80% (95% confidence interval [CI], 0.58-1) in large joints and 100% in digits, whereas the 5-year survival rate decreased to 27% (95% CI, 0.04-0.97) in large joints and 89% (95% CI, 0.67-1) in digits (Fig 1). For patients with nodular PVNS, the 1-year recurrence-free survival was 100% in large joints and 93% (95% CI, 0.82-1) in digits. Their 5-year recurrence-free survival rate was 88% (95% CI, 0.6-1) in large joints and 93% (95% CI, 0.82-1) in digits. Recurrence of diffuse PVNS occurred more often in large joints (p = 0.034). Recurrence was confirmed histologically in seven patients, as they already had reoperations by the time of the followup. Magnetic resonance imaging at followup revealed recurrent PVNS in three patients. The average time from surgery until recurrence was 26 months (range, 0.6-60 months).

Fig 1
Fig 1:
A Kaplan-Meier recurrence-free survival analysis shows a comparison of PVNS types and disease location. Recurrences were more frequent (p = 0.011) for diffuse compared with nodular PVNS, and were more frequent (p = 0.025) in large joints than in digits. The 1-year recurrence-free survival for diffuse PVNS was 80% in large joints and 100% in digits, whereas 5-year recurrence-free survival decreased to 27% in large joints and 89% in digits. For nodular PVNS, the 1-year recurrence-free survival was 100% in large joints and 93% in digits, and the 5-year recurrence-free survival was 88% in large joints and 93% in digits.
Fig 2
Fig 2:
Recurrent nodular PVNS in the popliteal region presents with low signal intensity in a T2-weighted MRI because of hemosiderin deposits.

The average Enneking score of 91.7% (range, 60-100 points) showed a favorable clinical outcome (Table 3). The patients with PVNS of the knee had an average Lysholm and Gillquist score of 95.2 (range, 79-100 points). Pain, swelling, and restricted ROM improved postoperatively (Table 4). Perioperative complications included delayed wound healing (one patient) and local paresthesia of the scar (two patients). In one patient, paresthesias occurred after partial resection of the radial nerve of the fourth finger. The other patient had a hypesthetic area of the skin after an open dorsal synovectomy of the knee.

Enneking Scores at Followup

Eighteen of the 23 patients with preoperative MRI had imaging results that corresponded to the histologic diagnoses and intraoperative findings regarding the location and extent of the disease. There were five incorrect diagnoses based on imaging. A foreign body granuloma, described as a hypovascularized, fibrotic lesion, was suspected in one patient after an injury with a piece of broken glass at the hypothenar eminence 4 years before. The patient since then felt a slowly growing mass. A lesion in the Hoffa fat pad was misdiagnosed as an unspecific synovitis, with a hypodense region on T1-weighted images, but areas of hyperdensity on T2-weighted images. One nodular lesion at the distal phalanx of the index finger was misinterpreted as a ganglion. Two fibromas were diagnosed: one at the thenar eminence, which was hyperintense on T1- and T2-weighted images and did not show contrast media enhancement and one in the popliteal region, described as a fibrotic lesion with moderate contrast media enhancement. The followup MRI revealed three cases of previously undiagnosed recurrences (two ankles with diffuse PVNS and one knee with nodular PVNS).


Pigmented villonodular synovitis is rare. We identified only 42 patients during a period of 30 years. The two morphologic types, nodular and diffuse PVNS, are almost identical in histologic appearance, and on a cellular level, there are no differences in predictive markers for possible tumor recurrence.29,34 However, eradication of PVNS is more difficult in certain locations and for the diffuse type.9,16,26,28 The small number of long-term followup studies evaluating the different locations and types of PVNS3,22,28 prompted us to analyze disease-free survival after surgical eradication of PVNS. We investigated whether location or disease type affected the probability of recurrence.

Our study has some limitations. Given the retrospective nature, some data were missing and some patients were lost to followup. However, almost complete preoperative information based on data from the Vienna Bone Tumor Registry and an 80% clinical and 70% MRI followup rate after an average of 80 months (range, 26-294 months) were available for patients surgically treated at one center. The numbers of affected joints such as the hip, ankle, or shoulder were low, however, we overcame this problem by pooling them into one group of large joints, which were compared against digits therefore providing adequate numbers for each group. The epidemiologic data of our cohort were consistent with those in the literature: PVNS occurs most often in women between the ages of 20 and 50 years.28 The distribution of the lesions was similar to distributions described in previous studies.3,20 The hands and knees were the most common sites, and the feet, ankles, hips and shoulders were less common.

Recurrence is the major concern with PVNS with 9-46% recurrence rates reported for the diffuse-type PVNS.3,30 Nodular PVNS has reported lower recurrence rates of 5-29%.3,20,28 This was confirmed by our study showing a significantly greater recurrence rate in patients with diffuse PVNS. Recurrences were more frequent in large joints than in the digits of hands and feet. This issue has not been adequately addressed in the literature. We are aware of only two long-term followup studies including large joints and digits. Byers et al3 reported a slightly higher recurrence rate for large joints, whereas Rao and Vigorita28 reported more recurrences in the digits (Table 5). However, in both studies detection of patients with recurrent disease might have been incomplete as only clinical symptoms and radiographs were used to detect recurrence. Comparison among studies is problematic as recurrence rates mostly are calculated as percentages from poorly documented followups rather than as a survival analysis. The only other survival study in addition to ours was performed by Schwartz et al30 who reported an 85% probability of recurrence-free survival after 5 years for patients with diffuse PVNS of the knees. Our 5-year recurrence free survivorship was less favorable with only 27% in the group of patients with large joints affected by diffuse PVNS. This discrepancy can be explained by the fact that there was only one knee affected by recurrent disease, whereas recurrences predominantly affected the rare locations such as the hip, ankle, and shoulder, which are less amenable to complete synovectomy.

Long-term Followup Studies

Despite of the benign character of the disease, patients often are severely compromised by the long course of the disease and multiple surgeries, which may lead to bad functional results. Our patients achieved an average of 92% of normal function and had excellent outcomes in the joint-specific scores. Symptoms were reduced notably at the followups. De Visser et al7 also evaluated the functional aspects of treatment of PVNS according to the Enneking score10 and found excellent or good results despite a 55% recurrence rate. These findings indicate that prevention of recurrence does not automatically equate to a successful clinical outcome. A recent study of PVNS of the hip also showed that preventing recurrence does not prevent other complications such as secondary osteoarthritis.33 Some authors have reported that arthroscopic knee procedures optimize functional results by reducing knee stiffness and result in acceptable rates of recurrence, but MRI was not used in any of the studies to detect recurrences.6,26,35 Chin et al4 performed extensive open surgery using a standardized combined posterior and anterior technique for treating patients with advanced primary and recurrent diffuse PVNS of the knee. They had excellent functional results; however, the recurrence rate was 18% as detected by MRI. We can confirm that surgical treatment leads to good clinical results.

Preoperative MRI is an important diagnostic tool.21 MRI shows a typical image of the lesion because of hemosiderin deposition, which leads to low to intermediate signal intensity on T1-weighted and low signal intensity on T2-weighted images.23 Without MRI, PVNS rarely is diagnosed preoperatively.3,7,28 In the current study, 67% of the preoperative MRI findings corresponded to the intraoperative findings and had provided the correct diagnosis before surgery. This is consistent with the findings of Durr et al, who reported that a preoperative diagnosis was possible by MRI in 76% of their series.9 Followup MRI allows detection of recurrent disease, even when clinical symptoms are minimal. Therefore, three cases of recurrent PVNS in patients without clinical symtoms were detected during the followup MRI. Although we did not perform a study on MRI specificity and sensitivity for PVNS, our findings support the consequent use of MRI for diagnosis of PVNS.

There are two factors associated with a greater incidence of recurrence: the diffuse type of PVNS and the location in large joints. However, despite recurrence, surgical treatment of PVNS leads to good functional results. Preoperative MRI is successful in providing the correct preoperative diagnosis. Magnetic resonance imaging also faciltates detection of recurrence especially in patients who are asymptomatic.


We thank Franz Kainberger for help with interpretation of the MRI scans and Joanna Wagner for review of this manuscript.


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