Pigmented villonodular synovitis (PVNS) is a rare benign disease of the synovium of joints and tendon sheaths, which may be locally aggressive. We present 18 patients with diffuse-type PVNS of the foot and ankle followed for a mean of 5.1 years (2 to 11.8). There were seven men and 11 women, with a mean age of 42 years (18 to 73). A total of 13 patients underwent open or arthroscopic synovectomy, without post-operative radiotherapy. One had surgery at the referring unit before presentation with residual tibiotalar PVNS. The four patients who were managed non-operatively remain symptomatically controlled and under clinical and radiological surveillance. At final follow-up the mean Musculoskeletal Tumour Society score was 93.8% (95% confidence interval (CI) 85 to 100), the mean Toronto Extremity Salvage Score was 92 (95% CI 82 to 100) and the mean American Academy of Orthopaedic Surgeons foot and ankle score was 89 (95% CI 79 to 100). The lesion in the patient with residual PVNS resolved radiologically without further intervention six years after surgery. Targeted synovectomy without adjuvant radiotherapy can result in excellent outcomes, without recurrence. Asymptomatic patients can be successfully managed non-operatively. This is the first series to report clinical outcome scores for patients with diffuse-type PVNS of the foot and ankle.
Cite this article: Bone Joint J 2013;95-B:384–90.
Pigmented villonodular synovitis (PVNS) is a rare, benign locally aggressive disorder of the synovium of joints, bursae and tendon sheaths.1 First described by Chassignac in 1852,2 it was Jaffe et al1 who introduced the term PVNS. Granowicz and Mankin3 classified PVNS into localised and diffuse forms, which are thought to represent a spectrum of the same pathological process.1,4 The localised form manifests as a pedunculated nodule within the joint, and the diffuse type insidiously infiltrates the synovial lining, leading to osseous erosion. Together they are the most commonly encountered soft-tissue tumours of the foot and ankle.5 Giant-cell tumours of tendon sheaths (GCTTS) are considered to be the extra-articular equivalent of localised PVNS, most commonly observed in the fingers, but also along the tendon sheaths of the foot and ankle.6 The World Health Organization classifies diffuse PVNS as ‘diffuse-type giant cell tumour’ (Dt-GCT) ICD-O code 9251/0, differentiating it from localised PVNS and GCTTS (Table I), and this classification will be used in this paper. In previous surgical literature it is known as Dt-PVNS.7
|Giant cell tumour of tendon sheath||Extra-articular; intra-articular||A family of lesions arising from the synovium of joints, bursae and tendon sheaths. These tumours are usually divided according to their site (intra- and extra-articular, which differ in clinical features and behaviour||9252/0||Extra-articular: tenosynovial giant cell tumour, nodular tenosynovitis. Intra-articular: localised PVNS|
|Diffuse-type giant cell tumour||Destructive proliferation of synovial-like mononuclear cells, mixed with multinucleate giant cells, foam cells, siderophages and inflammatory cells||9251/0||PVNS, pigmented villonodular tenosynovitis, Dt-PVNS|
A 1980 literature review revealed that of 1301 lesions, 69% were GCTTS, 8% localised PVNS and 29% Dt-GCT8; 66% of lesions were found in the knee, 16% in the hip, 7% in the ankle, and 2% affected joints in the foot, with infrequent cases involving the wrist, shoulder or elbow. Dt-GCT commonly involves more than one joint and/or tendon sheath.9,10
The estimated incidence of Dt-GCT is 1.8 new cases annually per million people, indicating its rarity.8 Socioeconomic influences have not shown any influence, although there is conflicting evidence for the gender ratio.8,9,11 Typically patients are between the age of 20 and 50 years, although many examples have been reported involving infants, children and adolescents.12-14 Symptoms range from swelling to diffusely painful, swollen and stiff joints. The swelling may be clearly demonstrated in subcutaneous joints such as those of the foot and the ankle. Some may complain of constant aching with Dt-GCT, or intermittent painful locking with localised nodules.3,11
The aetiology of Dt-GCT has been linked to trauma and recurrent haemarthrosis6 and histologically homogeneous inflammatory arthropathies,8 but neither theory has been well supported in the literature.15,16 The presence of chromosomal abnormalities,4 the capacity for autonomous growth,7 the invasion of bone6,17 and the identification of rare malignant transformation18,19 suggest a neoplastic cause. The translocation of the colony-stimulating factor (CSF1) gene in chromosome 1p13, and its over-expression, have been implicated in the pathogenesis of Dt-GCT.20 Imatinib (a tyrosine-kinase inhibitor) infusions, which block CSF receptor activation, may have a therapeutic role in refractory Dt-GCT lesions,21,22 although toxicity has been reported in up to 22% of patients.23
Early radiological appearances may include synovial swelling without calcification, effusion and a preserved joint space, progressing to juxta-articular and subchondral erosions and cysts.8,17 Smaller-capacity joints are more likely to have extrinsic bone erosions, which are present in up to 56% of lesions involving the ankle.24 MRI is the investigation of choice,9 revealing heterogeneous low to intermediate signal nodular synovial lesions on both T1- and T2-weighted images.6,11 In Dt-GCT lesions ferromagnetic haemosiderin deposition causes the pathognomonic sign of larger (‘blooming’) lesions on gradient echo sequences.23,25 MRI enables the extent of the lesion and the associated erosion and invasion to be characterised, features crucial to planning surgical treatment. The presence of erosive changes and extensive soft-tissue infiltration may also lead to the suspicion of soft-tissue sarcoma or haemophiliac arthropathy.26 Consequently, biopsies are routinely taken to confirm the diagnosis before surgery.
Macroscopically lesions are usually large (> 5 cm), firm or sponge-like, with pale multicoloured tissue ranging from tan to golden brown.7,27 The synovial hyperplasia consists of irregular villous projections and larger nodular protrusions. Histological appearances include proliferative synovial-like mononuclear cells, compacted fibrous stromal cells, foam and haemosiderin-laden cells, mixed round cell infiltration, mononuclear polyhedral cells of fibrohistiocytic origin, and multinucleated giant cells.1,9,17 Dt-GCT lesions have greater vascularity and haemosiderin deposition8 and a typically villous pattern, which is absent in GCTTS.7
Total synovectomy is the recommended treatment for Dt-GCT lesions. The aim is to achieve complete excision with the minimum of soft-tissue disruption in order to prevent joint erosions and degenerative changes. Combined medial and lateral approaches to the ankle and subtalar joint may be required. Rates of recurrence of up to 40% have been reported following excision of Dt-GCT lesions of the foot and ankle.25 Repeat excision combined with radiotherapy has been recommended for recurrent cases.28 Degenerative changes may necessitate subsequent arthroplasty,29 arthrodesis10 or amputation.30
The aim of this study was to describe the presentation, surgical intervention, complications, local recurrences and functional outcomes in patients who presented to our tertiary orthopaedic oncology unit during the preceding 12 years with Dt-GCT lesions involving the foot and ankle.
Patients and Methods
In a prospective study between 2000 and 2012 a total of 25 patients with radiologically and histologically confirmed PVNS were followed. Of these, seven with localised disease were excluded, leaving 18 patients with Dt-GCT.
The clinical features including age, gender, site of pain, type of surgery, complications and recurrence were recorded for each patient together with the histopathological and radiological features (Table II). MRI was used to localise the lesion before biopsy, and post-operatively to assess for recurrence in selected cases. All imaging was reported by dedicated musculoskeletal consultant radiologists. Haematoxylin and eosin-stained slides were reviewed after biopsy and surgery by a consultant histopathologist specialised in soft-tissue tumours (DCM). All cases were discussed before and after biopsy, and post-operatively at a dedicated multidisciplinary team meeting. All patients were reviewed at least annually during the follow-up period.
|Patient/Gender/ Age (yrs)||Follow-up (mths)||Tumour site*||Adjacent synovial involvement||Biopsy type†||Surgical approach||Recurrence‡|
|1 / F / 40||72||Calcaneocuboid||-||Percutaneous needle||-||n/a|
|2 / F / 73||54||Tibiotalar||-||US-guided||-||n/a|
|3 / F / 18||29||Tibiotalar||-||US-guided||-||n/a|
|4 / M / 33||28||Tibiotalar||Subtalar||Percutaneous needle||-||n/a|
|5 / F / 46||101||Tibiotalar||Tibialis posterior, flexor digitorum longus||Excisional biopsy (referring centre)||Posteromedial||Yes|
|6 / M / 60||144||Tibiotalar||-||US-guided||Dorsolateral||Nil|
|7 / F / 27||107||MTPJ||-||Percutaneous needle||Dorsal||Nil|
|8 / M / 39||86||Tibiotalar||Subtalar, peronei||Percutaneous needle||Lateral to subtalar and tibiotalar||Nil|
|9 / F / 52||69||Tibiotalar||-||Percutaneous needle||2 incisions: medial and lateral||Nil|
|10 / F / 46||66||Subtalar||-||US-guided||Lateral to subtalar||Nil|
|11 / F / 28||65||Tibiotalar||-||Percutaneous needle||Arthroscopic||Nil|
|12 / F / 42||62||Subtalar||Flexor hallucis longus||US-guided||Medial||Nil|
|13 / F / 19||46||PIPJ||-||Percutaneous needle||Dorsal||Nil|
|14 / M / 43||44||MTPJ||Flexor digitorum longus||Percutaneous needle||2 dorsal incisions||Nil|
|15 / M / 31||38||Tibiotalar||-||US-guided||Arthroscopic||Nil|
|16 / F / 65||35||Tibiotalar||Subtalar, tibialis posterior||US-guided||3 incisions: lateral, medial, posteromedial||Nil|
|17 / M / 51||32||Tibiotalar||Subtalar||US-guided||2 incisions – medial and lateral||Nil|
|18 / M / 51||24||Subtalar||-||US-guided||Posterolateral approach||Nil|
* MTPJ, metatarsophalangeal joint; PIPJ, proximal interphalangeal joint † US, ultrasound ‡ n/a, recurrence not applicable as the patients declined surgery
Functional status was assessed at the time of the last follow-up using the Musculoskeletal Tumour Society (MSTS) score,31 which is based on three general factors (pain, function, emotional acceptance) and three factors specific to the lower limb (use of supports, ability to walk and gait). A numerical score and percentage of the expected normal function for the patient were calculated.31
After local ethical approval, questionnaires including the Toronto Extremity Salvage Score (TESS)32 and the American Academy of Orthopaedic Surgeons (AAOS) foot and ankle score33 were posted to all patients, with a response rate of 100%. The TESS score assesses routine daily activities after musculoskeletal tumour surgery and includes 30 questions regarding activities such as dressing, work and mobility.32 The total score is calculated as a percentage of the greatest possible score out of 100. The AAOS foot and ankle score also has a maximum score of 100 and is a validated tool for assessing the clinical outcome in patients following surgery of the foot and ankle.33 It was converted to a normative score, where 50 represents the average score for the normal population.
This was performed using R software (University of Vienna, Vienna, Austria).34 A p-value < 0.05 was considered to indicate statistical significance. Correlation between scores was analysed using Pearson’s method.
There were 11 women and seven men with a mean age at presentation of 42 years (18 to 73) and a mean follow-up of 5.1 years (2 to 11.8). The mean duration of symptoms before presentation was 28 months (3 to 72). All patients presented with swelling, seven had pain, and four had limitation of movement, three of the tibiotalar joint and one of the subtalar joint. The tibiotalar (n = 11), subtalar (n = 3), calcaneocuboid (n = 1), metatarsophalangeal (n = 2) and proximal interphalangeal joints (n = 1) were affected. There was erosion of the joint in five patients, all involving the tibiotalar joint. In seven patients adjacent joints or tendon sheaths were involved (39%) (Table II). These included the subtalar joint in two, both the subtalar joint and tendon sheaths in two and tendon sheaths alone in three. Adjacent tendon sheaths involved comprised one case each of the tibialis posterior, tibialis posterior and flexor digitorum longus, flexor hallucis longus, flexor digitorum longus, and the peronei.
Inflammatory markers were normal with C-reactive protein (CRP) < 19 g/dl and erythrocyte sedimentation rate (ESR) < 15 mm/h in 16 patients (89%).
All patients except one had biopsy and surgery performed in our unit; ultrasound-guided biopsies (n = 9) and percutaneous needle biopsies (n = 8) were used. The final patient had exploration and partial synovectomy of the tibiotalar joint at the referring hospital. The low- and high-power photomicroscopic appearances are shown in Figure 1. MRI at presentation (Fig. 2a) revealed residual lesions involving the medial tibiotalar joint and the tendon sheaths of tibialis posterior and flexor digitorum longus, though symptoms were minimal. She was managed non-operatively and underwent annual MRI scans. The lesions became smaller and had disappeared six years post-operatively (Fig. 2b), although minor symptoms remained.
Figs. 2a - 2b
Figs. 1a - 1b
Four patients with lesions of the tibiotalar (n = 2), tibiotalar and subtalar (n = 1) and calcaneocuboid (n = 1) joints chose to be treated non-operatively. They have undergone routine annual review.
Synovectomy was performed in 13 patients, via a single incision in eight, using multiple incisions in three and arthroscopically in two. Peri-articular erosions and cysts were curetted where appropriate, but no bone graft was required. Drains were used in two extensive cases. Immediate weight-bearing was permitted. No patients received radiotherapy, and none has required amputation or arthroplasty.
One patient had a superficial infection requiring antibiotic treatment, besides which all wounds healed unremarkably. One patient had paraesthesiae involving the distribution of the superficial peroneal nerve, suggesting injury from the lateral ankle arthroscopy portal. Another with tibiotalar, subtalar and tibialis posterior tendon sheath involvement required manipulation under anaesthesia, arthroscopy and inpatient physiotherapy six months after three approaches to the joint.
None of the 13 patients who underwent synovectomy had clinical or radiological evidence of recurrence. The two patients who underwent arthroscopic debridement have had recurrence excluded with MRI at 38 and 65 months’ follow-up, respectively.
Eight years post-operatively the patient referred with residual Dt-GCT achieved MSTS, TESS and AAOS scores of 93, 87 and 83, respectively.
Of the four patients who elected not to have surgery, three had maximum MSTS, TESS and AAOS scores of 100 each, and all remain asymptomatic at a mean follow-up of three years (2.3 to 6). The fourth patient has no clinical or radiological evidence of deterioration in the tibiotalar joint with MSTS, TESS and AAOS scores of 80, 78 and 83, respectively, at follow-up of 4.5 years.
The mean MSTS, TESS and AAOS scores at final follow-up for those treated surgically were 93.5 (83 to 100), 92 (48 to 100) and 88 (43 to 100), respectively.
Overall, for the 18 patients at final follow-up the mean MSTS score was 93.8 (95% CI 85.1 to 100), mean TESS score was 92.0 (95% CI 81.1 to 100) and mean AAOS score was 89.5 (95% CI 79.5 to 99.8) (Fig. 3). In 11 patients (61%) the AAOS normative scores were greater than the average for the general population,33 and this included three of the non-operatively managed patients. The remaining seven patients (39%) recorded normative scores lower than those for the average population; four of these had evidence of joint degeneration at presentation, one required further surgery for stiffness, and another had a stroke resulting in ipsilateral hemiparesis. Correlation between the TESS and AAOS scores was broadly consistent. Pearson’s correlation between the two scores for all patients was 0.62 (95% CI 0.23 to 0.85, p = 0.005) (Fig. 4). The outlier demonstrated in Figure 4 is the one with hemiparesis; his low TESS score of 48 and high AAOS score of 79 reflect this disability.
This is the largest published series of patients with Dt-GCT affecting the foot and ankle, with a mean follow-up of 5.1 years. The mean age of the patients was 42 years, in keeping with other series.9,10,25-27 All patients presented with swelling, combined with pain in seven cases. The disease involved adjacent synovial structures in seven (39%) patients, and five (29%) had radiological evidence of erosions or cysts at presentation.
Eight previous studies have included patients with Dt-GCT of the foot and ankle (Table III). Recurrence rates following surgery alone range from 0% to 40%.10,25 Sharma et al25 reviewed all patients with Dt-GCT involving the foot and ankle from the Scottish Bone Tumour registry for the preceding 62 years. Following limited surgical excision, there were two recurrences in five patients; both were successfully treated with further surgery. Ghert et al26 and Brien et al29 reported single recurrences in their series of respectively six and seven patients who were treated without radiotherapy. Saxena et al6 described five sportsmen and women with diffuse articular lesions; two had a recurrence preventing resumption of their sporting activities. Only Rochwerger et al10 have reported recurrence-free follow-up at a mean of four years, without radiotherapy, in four patients with tibiotalar Dt-GCT.
|Author/s||Cases (n)||Mean age (yrs)||Radiotherapy||Mean follow-up (yrs)||Recurrences (n)|
|Rochwerger et al10||4||47||n/a||4||0|
|Ghert et al26||6||37||n/a||1||1|
|Brien et al29||11||35||4/11||3.5||1|
|Bisbinas et al9||2||35||Yes||1.5||0|
|Saxena et al6||5||46||n/a||4.2||2|
|Lee et al27||7||31||Yes||2||0|
|Sharma et al25||5||26||n/a||4.5||2|
|Bickels et al36||7||39||Intra-articular synoviorthesis||3.9||0|
Adjuvant focused external beam radiotherapy has been used with mixed results.11 Bisbinas et al9 reported two patients with Dt-GCT of the tibiotalar joint treated with open synovectomy and radiotherapy, in which multiple symptomatic recurrences developed within three years. Lee et al27 reported seven patients who underwent open synovectomy with post-operative radiotherapy with a total dose of 35 Gy in 20 fractions. There was no recurrence at a mean follow-up of two years. Brien et al29 reported successful treatment of four patients with residual Dt-GCT using further excision and radiotherapy without recurrence at a mean of 3.5 years. They recommend this form of treatment for recurrent lesions. Adjuvant intra-articular injections of radioactive colloid (synoviortheses) have produced low recurrence rates for lesions involving the knee.35 Bickels et al,36 however, reported three serious complications in seven patients with Dt-GCT of the ankle, including full-thickness skin necrosis and deep infection, and the authors discontinued the use of yttrium-90.
In these patients the surgical approach was planned with MRI guidance and we believe this is essential to ensure excision of all diseased tissue. Arthroscopic approaches are justified only when MRI has shown that satisfactory clearance is possible. One patient was referred with residual disease following open excisional biopsy, and after six years of sequential radiological regression the lesion had disappeared. This has not previously been reported. Thus, asymptomatic Dt-GCT lesions may disappear without ever presenting to the orthopaedic surgeon. The four patients managed non-operatively are symptomatically stable, and three remain asymptomatic with maximal clinical outcome scores, suggesting that not all patients require surgery if their symptoms do not warrant it, though we would advocate continued clinical and radiological surveillance.
Limitations of this study include the small numbers of patients, the differing surgical approaches and the limited follow-up. The use of self-reporting scores allows patients to record their opinions without inferences and bias. Patients may, however, under- or overestimate their functional level or symptoms compared with clinician-reported scores.37 The small cohort highlights the rarity of this disorder and its presentation to a regional musculoskeletal oncology centre, and that surgery is tailored to the lesion and the patient.
This study is the largest series of Dt-GCT lesions involving the foot and ankle, comprising 18 patients with a good medium-term follow-up from a tertiary orthopaedic oncological service. It is the first report of objective clinical outcome scores for patients with Dt-GCT lesions affecting the foot and ankle. Asymptomatic patients can be managed non-operatively with surveillance. Dt-GCT may be self-limiting. Targeted synovectomy can result in cure and excellent clinical outcomes without adjuvant radiotherapy.
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No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article.
This article was primary edited by P. Baird and first-proof edited by J. Scott.
Supplementary material. A table showing the outcome scores (Musculoskeletal Tumor Society score, Toronto Extremity Salvage score and American Academy of Orthopaedic Surgeons foot and ankle score) for each patient is available with the electronic version of this article on our website www.bjj.boneandjoint.org.uk