➢ Tenosynovial giant-cell tumor (TGCT) is the common term used to describe a group of soft-tissue tumors that share a common etiological link. Historically, the multiplicity of terms used to describe these tumors, in addition to contention regarding etiology, has led to confusion regarding their diagnosis and treatment.
➢ An overexpression of colony-stimulating factor-1 (CSF-1) caused by a specific chromosomal translocation t(1;2) has been identified in both localized and diffuse tumors and has led to an interest in pharmacological therapies targeting the CSF-1/CSF-1R (CSF-1 receptor) axis.
➢ Operative treatment remains the mainstay of treatment for TGCT of the foot and ankle; however, given the rarity of these tumors, treatment recommendations have not been verified on the basis of large cohort studies or high-level evidence.
➢ A multidisciplinary approach is important in TGCT treatment. Open surgical excision or synovectomy is considered to be the first-line treatment. While the roles of arthroscopic excision, radiation therapy, and targeted pharmacological therapies have not been validated, these therapies may be of use for selected patients, particularly those with recurrent or unresectable lesions.
➢ A clear definition of tumor recurrence based on radiographic evidence of progression and/or return of symptoms is required to quantify the outcomes of treatment, to reduce heterogeneity between studies, and to avoid morbidity associated with repeated surgical excisions.
Classification and Terminology
Tenosynovial giant-cell tumor (TGCT) is the term used to describe a family of usually benign, soft-tissue tumors that can arise from the synovial lining of the joint, tendon, or bursa1. Historically, the histological, clinical, and radiographic definition of these lesions has been inconsistent, while the multiple classification systems and ambiguous nomenclature have resulted in controversies in the literature2-4. Chassaignac, in 1852, was the first to describe the lesion5; however, Jaffe et al. coined the term pigmented villonodular synovitis (PVNS) to describe a group of lesions existing as localized or diffuse entities, with similar histopathological features, that were thought to share a common inflammatory etiology2.
The previous World Health Organization (WHO) system for the classification of soft-tissue tumors, published in 2002, differentiated giant cell-containing tumors on the basis of their clinical behavior and tissue origin (bone, soft tissue, synovial tissue, or tendon sheath)4. As a result of the often distinct clinical course of these lesions, the 2002 WHO classification system replaced the general term PVNS with 2 separate terms, diffuse-type giant-cell tumor (Dt-GCT) and giant-cell tumor of tendon sheath (GCT-TS), establishing a distinction of these 2 tumor types as separate pathological entities.
Subsequently, and as a result of increasing evidence supporting a previously unrecognized neoplastic origin common to GCT-TS and PVNS/Dt-GCT6, the updated 2013 WHO system for the classification of soft-tissue tumors adopted the umbrella term tenosynovial giant-cell tumor (TGCT) to describe a family of lesions that exist as either localized-type (l-TGCT) or diffuse-type (d-TGCT) according to the extent of synovial involvement1 (Table I).
With this system, locally invasive lesions associated with extensive synovial involvement are classified as d-TGCT, whereas well-circumscribed lesions affecting only part of the synovial tissue are classified as l-TGCT. Both forms can arise intra-articularly or extra-articularly, although the exact tissue origin of diffuse lesions is not always clear as the synovial tissue of many soft-tissue structures may be concurrently involved.
A clear system for the classification of these tumors is pertinent for several reasons. First, the multiplicity of terms used in the literature adds heterogeneity to study cohorts and, in turn, to the evidence regarding optimal treatment. Second, given the specific genetic abnormality common to TGCT and the emergence of evidence supporting targeted immunological therapies7-13, a clear understanding of the pathogenesis and etiology of these tumors is increasingly relevant. While sharing a common neoplastic origin, the clinical course and treatment of l-TGCT and d-TGCT are often very distinct.
Macroscopically, tumors range in color from dark red-brown to light brown or yellow1,4. Diffuse tumors exhibit synovial changes characterized by a tangled mat of red-brown folds, multiple projections, and nodules. Localized tumors are well circumscribed, with cells growing as a solid, often pedunculated nodule attached to the synovial tissue (Fig. 1).
Microscopically, tumors have a range of appearances, variably showing mononuclear cells with a polyhedral and epithelioid appearance, multinucleated giant cells, foam cells, and areas of hemosiderin deposition, arranged in a lobular to diffuse architecture14 (Fig. 2). This appearance led Jaffe et al. and others to believe that an inflammatory etiology was likely2,3.
While a majority of cells within the tumor mass are not neoplastic, a minority possess a common chromosomal abnormality leading to an overexpression of colony-stimulating factor-1 (CSF-1)15,16. Most commonly, overexpression of CSF-1 results from a t(1;2) translocation, which fuses the CSF-1 gene on chromosome 1 and collagen type-VI promoter gene on chromosome 215-17. The resultant CSF-1 overexpression stimulates the proliferation and attraction of swarms of non-neoplastic inflammatory cells through autocrine and paracrine mechanisms6. Osseous involvement and joint degeneration are common in patients with TGCT of the foot and ankle (Fig. 3)18-20. The formation of multinucleated giant cells possessing an osteoclast-like phenotype capable of lacunar bone resorption has been found to be associated with erosions of bone and cartilage in both variants of TGCT21-24. Although pathological processes are analogous in TGCTs affecting all regions, clinical behavior can vary. Substantially higher rates of bone erosions have been reported in the ankle and hip as compared with the knee, which has been suggested to be secondary to the smaller joint space and subsequent pressure effect25. A catabolic cytokine profile, including joint-destructive matrix metalloproteinases (MMPs), is consistently present in cases of TGCT and has been associated with more aggressive disease26,27; however, the inflammatory changes are less pronounced than those observed in association with true inflammatory arthropathies25. Increased CSF-1 and RANKL (receptor activator of nuclear factor kappa-B ligand) staining have been significantly associated with osteochondral involvement in the knee (p = 0.02) but have not been confirmed in the ankle28. There have been rare reports of malignant transformation and even metastasis in patients with d-TGCT, although the mechanism responsible for these findings has not been established29-32.
TGCTs can occur at any age; however, localized disease is most common in the 30 to 50-year-old age group, with a female predominance. Diffuse disease generally affects younger patients in the 20 to 29-year-old age group, with no sex predominance1. The age at onset in the foot and ankle is comparable with the age at onset in other regions.
In the study by Chou et al., l-TGCT and d-TGCT together represented the most common soft-tissue tumors of the foot and ankle33. Furthermore, compared with all anatomical regions, the foot and ankle region represents the second-most-common site of l-TGCT after the flexor tendons of the hand34,35. However, the rarity and evolving classification make the exact incidence of foot and ankle involvement difficult to establish35-39. Localized foot and ankle disease can be found within the joints; more commonly, however, it is extra-articular. The tibiotalar joint is the most common articular location for l-TGCT of the foot or ankle34,35,40,41. Extra-articular l-TGCTs are commonly found around the dorsal part of the forefoot or adjacent to the interphalangeal joints (particularly around the first and second toes)37,42. Rarely, the tendons crossing the ankle joint are involved, with the lesion presenting as solitary nodules arising from the tenosynovium37,42-47 or as d-TGCT with or without joint involvement19,48. Multiple other tumor locations have been reported, including the sinus tarsi, plantar fascia, and midfoot joints, but the literature on such lesions has been mostly limited to case reports49-55. When reviewing the incidence of d-TGCT, the ankle is among the top 3 most commonly affected large joints56-58. In the largest published series (294 patients), knee lesions comprised 60% of TGCT cases, ankle lesions comprised 16%, and hip lesions comprised 11%58. The subtalar joint is commonly involved, often in association with the ankle joint. As with l-TGCT, diffuse lesions can arise from any region of the foot and ankle.
The diagnosis of TGCT can be challenging59. Radiographs may show bone erosions or cysts, although these are often late signs. Computed tomography (CT) can provide additional information regarding the extent of osseous involvement; however, magnetic resonance imaging (MRI) is the modality of choice for the evaluation of TGCT as it provides information relevant to diagnosis, treatment, and recurrence. MRI findings include synovial proliferation with low to intermediate signal intensity on T1-weighted images and low signal intensity on T2-weighted images (due to a shortening of T2-relaxation time caused by hemosiderin). This effect is particularly pronounced on gradient-echo images, which demonstrate an enlargement of the low-signal-intensity regions (“blooming”). This “blooming artifact” is almost pathognomonic of TGCT and appears as spotty areas of hypointense signal within the tumor mass8,60 (Fig. 4). Enhancement of TGCT is often seen after the administration of gadolinium, although the extent of enhancement can vary. MRI also may show joint effusion or osteochondral erosion.
When classic MRI findings are seen, additional diagnostic testing may not be necessary; however, if MRI findings are equivocal, then additional investigation may be required to rule out malignant pathological processes, particularly synovial sarcoma.
Core-needle biopsy or fine-needle aspiration can be used to diagnose TGCT; however, their application is limited by the small size of the tissue sample that is obtained. Differential diagnoses, including hemosiderotic synovitis and other benign and malignant lesions, can be considered in cases of small tissue samples14. Diagnosis is therefore often confirmed histologically after surgical excision of the tumor, rather than on the basis of a preoperative tissue sample.
Inflammatory markers, including the erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) level, and white blood-cell count (WBC), have been studied as potential serum markers of TGCT. The majority of studies have demonstrated normal serum levels in patients with TGCT61-64. Xie et al. found an elevated ESR in 46% (66) of 144 cases of TGCT and an elevated CRP in 38% (53) of 138 cases; however, they noted that these serum markers are not specific or sensitive for diagnosing or predicting the recurrence of TGCT64.
There are some clear differences in the behavior and clinical features of diffuse and localized TGCT of the foot and ankle. Diffuse-type tumors are more likely to occur in the ankle and subtalar joints, with intra-articular involvement and synovial infiltration regularly demonstrated20,48,65-67. Pain is the most common presenting complaint, followed by swelling1,4. Hemarthrosis can occur in association with TGCT of the ankle, although it is more commonly associated with TGCT of the knee1,14.
Localized TGCT commonly present as a slow-growing, painless, firm mass or nodule that has progressed over months to years. Pain associated with weight-bearing may be reported, depending on tumor location37,48. Limitation of joint motion and impingement with or without pain also can occur. Neurological symptoms have been reported to be associated with TGCT; however, this finding is uncommon67.
TGCT of the ankle and subtalar joints also has a tendency to recur after surgical excision, with a pooled analysis of case series showing a 20% to 23% rate of recurrence in the ankle and subtalar joints (Table II). The recurrence rate of d-TGCT is higher than that of l-TGCT (Table III), likely due to the technical difficulty of complete excision of a diffuse-type lesion involving vast areas of synovial tissue.
The relationship of TGCT with previous trauma involving the affected joint is still unclear. Some studies have demonstrated preceding trauma in association with up to 53% of cases62, whereas in a recent cohort study of 237 patients with d-TGCT of various joints, the reported rate of preceding trauma was only 17% (40 of 237 cases)64. In the foot and ankle, aside from 1 study in which in which 90% (9) of 10 patients with TGCT had had previous lateral ankle sprains19, most authors have noted no association with preceding trauma20,48.
Osseous or osteochondral destruction has been noted in up to 90% of cases of d-TGCT involving the foot and ankle65; the exact rates associated with l-TGCT are unclear but have been reported to range from 0% to 24%37,42,67, which are consistent with the rates in other anatomical regions36,38. The clinical progression of osteoarthritis in patients with TGCT of the foot and ankle is not clear; however, in cases of severe osteochondral damage, salvage procedures such as ankle arthrodesis have been described18.
Due to the rarity of TGCT, factors associated with recurrence are often indeterminate. Two recently published large-cohort studies involving 237 and 294 patients with TGCT involving all anatomical regions (not solely the foot and ankle) demonstrated recurrence rates of 20% and 28%, respectively, although the majority of cases were d-TGCT58,64. In the earlier study, Palmerini et al. found that tumor size (>20 mm), macroscopically incomplete resection, male sex, and previous recurrence were prognostic for local failure postoperatively; however, subsequent multivariate analysis revealed that previous recurrence was the only independent risk factor for recurrence58.
Incomplete excision, tumor cellularity and mitotic activity, and osseous erosions have been associated with recurrence65-67. Bruns et al., in a multicenter study of upper and lower-limb TGCT, found that centers treating >20 patients had lower recurrence rates56. Because of a dearth of large series, establishing risk factors for recurrence in the foot and ankle is difficult. Overall, the rate of recurrence is generally higher in cases of ankle and subtalar TGCT, likely as a result of tumor behavior and the difficulty of achieving complete surgical excision42,68,69. Bruns et al. found that the foot had the lowest recurrence rate of TGCT in comparison with other large joints (4%; 7 of 173), followed by the ankle and subtalar joints (9%; 16 of 173)56; however, this finding has not been verified in recent large-cohort studies58.
Recurrence rates are often equated with treatment success rates; however, the clinical heterogeneity between and within studies means there are substantial limitations in interpreting the clinical importance of recurrence rates. Radiographic evidence of recurrence is often reported; however, the association with clinical outcomes or progression of degenerative joint disease is not clear.
In a recent study of postoperative recurrence of d-TGCT of the knee, a rate of 13% (2 of 15) was reported; however, an additional 7 patients (47%) had MRI evidence of residual disease that was asymptomatic and radiographically stable at a mean of 83 months of follow-up70. The authors therefore proposed that recurrence be defined as new symptomatic disease or clinical or radiographic progression of known residual disease following surgery. Similarly, Stevenson et al. noted that although tumors in the foot and ankle were found on MRI after excision in 2 (11%) of 18 cases, the patients were asymptomatic and reduction in tumor size over time was evident in 1 case20. Analogous findings were reported by Korim et al.48 in 1 (12.5%) of 8 cases of d-TGCT. Similarly, Sung and Ko noted that 2 of 4 patients with recurrent disease experienced no pain or limitation of function68.
Furthermore, Palmerini et al. found that 117 (46%) of 253 patients who were reported to have incomplete resection margins had a 5-year progression-free survival58. The authors therefore concluded that complete excision must be balanced with function preservation, given that almost half of the lesions that were thought to have been incompletely excised did not recur.
Moreover, while close follow-up is required in cases of TGCT, the importance of symptomatic and radiographically stable recurrent or residual tumors is equivocal. In foot and ankle-specific cohorts, low numbers of patients have often precluded meaningful statistical conclusions regarding the risk of recurrence68,69,71-75. Nevertheless, on the basis of current evidence, the importance of asymptomatic residual tissue after excision is unclear.
Future research in this area would benefit from a clear definition of recurrence, such as that proposed by Mollon et al.70, as a repeat operation for asymptomatic recurrence may compromise patient outcomes.
Adequate surgical excision remains the gold-standard treatment for TGCT; however, while poor tumor clearance may increase recurrence, extensive surgery can increase surgical morbidity. Adjuncts to operative intervention, including external beam radiation therapy71,72 and isotopic synovectomy73,74, have been used to mitigate this risk; however, their efficacy has not been validated. Furthermore, newer targeted therapies, in particular the tyrosine-kinase inhibitors targeting the CSF-1/CSF-1R (CSF-1 receptor) axis, have shown promising early results for the treatment of these tumors8. Recommendations for the treatment of foot and ankle TGCT based on current evidence are presented in Table IV.
Open Synovectomy or Local Excision
Limitations in the current literature regarding TGCT in the foot and ankle make comparative analysis of treatment outcomes difficult. Reports of recurrence after surgical excision are often unclear and methods of postoperative follow-up are similarly vague. As a result, true recurrence rates are not clearly defined.
Despite this limitation, primary surgical excision of l-TGCT has been shown to result in low recurrence rates and good clinical outcomes35,36,38. Reported rates of recurrence in the foot and ankle have ranged from 0% to 33% after open excision; however, pooled outcomes of the available studies suggest a recurrence rate of <10% overall37,42,48,68,72,76.
Complete synovectomy for d-TGCT can be difficult to achieve in the foot and ankle for anatomical reasons. Neurovascular structures and tendons run in close proximity to the joints, and the minimal soft-tissue coverage can make resection difficult; as a result, local invasion is common20,48,69.
Open synovectomy is commonly performed for the treatment of d-TGCT of the ankle and subtalar joints19,20,48,68,69,72,73,75,76; however, arthroscopic excision has been associated with good results18,20.
Korim et al. reported on a group of 30 patients with l-TGCT (22 patients; 73%) or d-TGCT (8 patients; 27%) of the foot and ankle48. Open synovectomy was employed in all patients, with a recurrence rate of 25% (2 of 8) in the d-TGCT group and with no local recurrences in the l-TGCT group at the time of the latest follow-up; however, recurrence was investigated with yearly MRI in the d-TGCT group, whereas only symptomatic patients were investigated for recurrence in the l-TGCT group.
Stevenson et al.20, in 1 of the largest prospective series involving TGCT of the foot and ankle, reported on 13 patients with d-TGCT involving the ankle (8 patients), subtalar joint (3 patients), or forefoot (2 patients) who underwent open (11 patients) or arthroscopic (2 patients) surgical excision at a tertiary-care oncology hospital. Good clinical outcomes were reported for all patients, with no recurrences after a mean of 62 months of follow-up20. Sung and Ko reported a recurrence rate of 40% (4 of 10) among patients in whom d-TGCT of the ankle or hindfoot had been diagnosed with routine postoperative imaging68. Two (50%) of the 4 patients with recurrence were asymptomatic, with an American Orthopaedic Foot & Ankle Society (AOFAS) score of 100 at the time of follow-up. Recurrence was noted in 3 (33%) of the 9 patients who underwent open synovectomy and in the 1 patient who underwent arthroscopic synovectomy. The authors noted that complete resection was not possible at the time of initial surgery in 1 of the 4 patients with recurrence.
Rochwerger et al. noted that 7 (88%) of 8 patients had cortical erosions and degenerative joint changes and were managed with arthrodesis or amputation18.
Other case series involving <15 patients who underwent operative treatment alone for d-TGCT have demonstrated recurrence rates ranging from 0% to 100%18,19,75,76. Pooled data reported by Korim et al. demonstrated an average recurrence rate of 12% among patients with d-TGCT who underwent excision48. Surgical excision without adjuvant therapy is generally successful for the treatment of l-TGCT37,42,48,68. Zhang et al.42 reported a recurrence rate of 20% (4 of 20) following the treatment of l-TGCT with local excision, whereas Gibbons et al.37 reported no recurrences in a study of 15 patients. While operative intervention alone is usually successful for the treatment of l-TGCT, a recent literature review by Vargaonkar et al. (including 17 case reports or series) indicated that 5 (29%) of the 17 included studies did not assess recurrence39. Of the remaining 12 reports, 11 (92%) described no recurrences of l-TGCT of the foot and ankle.
To our knowledge, there have been no comparative studies evaluating open versus arthroscopic treatment for TGCT of the foot and ankle. Published reports on both diffuse and localized disease have described the use of arthroscopic excision in selected patients18,20,68. Rochwerger et al. reported that arthroscopic synovectomy was used for 1 (11%) of 9 patients with d-TGCT18, whereas Stevenson et al. reported that arthroscopic treatment was used for 2 (15%) of 13 patients20. Although no recurrences were reported in those patients, all tumors were limited to the ankle joint, with no involvement of adjacent structures. Comparative analysis of open and arthroscopic surgery for the treatment of TGCT of the knee has revealed contrasting results26,70,77-79. The systematic review by Mollon et al. demonstrated that open synovectomy resulted in lower rates of recurrence compared with arthroscopic treatment in patients with d-TGCT, with no such difference being observed in the l-TGCT group70. Aurégan et al. pooled the results from 60 studies (1,019 patients) and found no increase in recurrence rates, and lower complication rates, following arthroscopic treatment of TGCT of the knee26. Palmerini et al. also showed no difference in the rate of recurrence between arthroscopic and open excision of TGCT involving various joints58.
Although arthroscopic excision of TGCT in the ankle and hindfoot is not supported by high-level evidence, this approach may be appropriate for the treatment of localized or less-aggressive lesions. A solely arthroscopic approach is contraindicated for the treatment of TGCT invading adjacent structures or involving vast areas of joint capsule. A combined arthroscopic and open approach can help to mitigate the risks and limitations associated with these techniques when used alone25,70.
Arthrodesis and Amputation
Arthrodesis has been used successfully to treat TGCT of the foot and ankle in patients with extensive osteochondral destruction18. Rochwerger et al., in a series of 8 patients with d-TGCT, reported that 7 patients (88%) had substantial osseous destruction; all 7 patients were successfully managed with arthrodesis of the hindfoot (3 patients), midfoot (1 patient), or forefoot (2 patients), or with amputation of the forefoot (1 patient), with overall good functional outcomes and no recurrence at the time of the latest follow-up18. Definitive recommendations regarding the use of arthrodesis for the treatment of TGCT are unclear; however, arthrodesis in the setting of TGCT should be considered when extensive degenerative joint disease is present or when there is limited joint motion in the midfoot48. Amputation has been described for the treatment of disease around the interphalangeal joints, and good results have been reported76; however, amputation may represent an unacceptable outcome in some patients, particularly as TGCT affects a younger patient population. Increasing evidence for newer medical modalities may result in arthrodesis and amputation being utilized less frequently for the treatment of TGCT in the future.
External Beam Radiation Therapy and Intra-Articular Radioactive Isotope Injection
External beam radiation therapy (EBRT) has been studied most extensively for the treatment of d-TGCT of the knee79. When used as an adjuvant to surgical excision or for the treatment of recurrent or unresectable disease, improved tumor control has been reported79-83.
Adjuvant EBRT for the treatment of TGCT of the foot and ankle has been reported in a few small series69,71,72. Lee et al. reported no recurrences at 24 months of follow-up in a study of 7 patients with TGCT of the foot (4 patients) or ankle (3 patients) who were managed with surgery and adjuvant EBRT at a dose of 35 Gy in 20 fractions over 4 weeks71, whereas Brien et al. reported no recurrences at 42 months of follow-up in a report on 4 patients with ankle disease who were managed with surgical excision and EBRT at a dose of 36 to 40 Gy in 20 to 35 fractions69. Conversely, Bisbinas et al. reported multiple recurrences in 2 (22%) of 9 patients who were managed with 20 fractions of 35-Gy EBRT and surgery72.
Intra-articular injection of radioactive colloid has produced low recurrence rates in patients with knee lesions84,85. Bickels et al. reported serious complications, including full-thickness skin necrosis, in 3 (43%) of 7 patients who were managed with yttrium-90 (dose, 15 mCi) for the treatment of TGCT of the ankle73. While other studies have demonstrated no serious complications in association with intra-articular colloid injections65,74, on the basis of the findings of Bickels and colleagues, their use cannot be recommended for the treatment of ankle lesions. Furthermore, concerns exist regarding the risk of potentiating complications such as skin reactions, poor wound-healing, joint fibrosis, joint stiffness, and malignant transformation following the use of radiation therapy22. As TGCT is generally benign, such complications may represent an unacceptable risk, particularly if the new targeted pharmacological therapies being developed to treat TGCT prove safe and effective.
Recent progress in the understanding of the pathology and etiology of TGCT has created interest in potential systemic pharmacological therapies8,11,86, particularly agents targeting the CSF-1/CSF-1R axis, which act to block excessive CSF-mediated recruitment of macrophages and monocytes to the tumor site.
Cassier et al. reported that emactuzumab, a recombinant, monoclonal antibody, was associated with an objective response in 24 (86%) of 28 patients with locally advanced TGCT9. These responses correlated with early and sustained symptomatic improvement and no serious adverse events9. PLX3397 is a novel oral CSF-1R inhibitor that was specifically developed to treat TGCT87. This agent similarly showed promising early results in a phase-II trial, with 11 of 14 patients having a ≥50% reduction in tumor volume87. Earlier studies also showed potential benefit in association with the use of the tyrosine-kinase inhibitors imatinib and nilotinib, classically used for the treatment of chronic myeloid leukemia, although the benefits appear to be inferior to those of the aforementioned newer agents10,12,88. It is worth noting that the above therapies have only been investigated in trials involving patients with either locally advanced TGCT or recalcitrant disease. Currently, there are no systemic medical therapies approved for the treatment of TGCT. If these systemic therapies can be shown to be efficacious and safe in phase-III trials, then we likely will see a combined medical and surgical approach being approved for the treatment of recurrent or advanced TGCT in the future. This pharmacological targeted-treatment approach also may prove useful as a neoadjuvant option prior to operative treatment, pending evidence regarding the tolerability and safety of such agents.
Overview and Perspective
TGCTs represent an important treatment challenge. A clear classification of these tumors is important for allowing comparative research to be undertaken with less heterogeneity among studies.
Given the paucity of large-cohort or comparative studies, it is difficult to make recommendations for treatment solely on the basis of the existing literature on the foot and ankle.
Operative intervention remains the primary treatment for both diffuse and local lesions and is consistently supported by low-level evidence. Arthroscopic excision can be successful in producing favorable functional results in some cases. While the literature on the knee supports the selective use of arthroscopy, there is insufficient evidence to make this recommendation for the treatment of lesions involving the ankle.
Furthermore, although complete surgical margins should be the goal of surgery, the clinical importance of residual or asymptomatic tumor tissue is unclear. Therefore, the definition of recurrence needs clarification. Moreover, although MRI remains invaluable for diagnosis, surgical planning, and follow-up, imaging findings need to be considered in the context of patient symptoms and function.
The identification of biological or cytogenetic factors that influence tumor behavior may help to predict tumor prognosis; currently, however, there is no evidence to support the use of any biomarkers for predicting recurrence. In addition, targeted therapies acting on the CSF-1/CSF-1R axis may be effective for treating TGCT; however, their adverse effects and clinical applications need verification.
Investigation performed at the St. Vincent’s Clinic, Darlinghurst, Sydney, Australia
Disclosure: There was no external source of funding. On the Disclosure of Potential Conflicts of Interest forms, which are provided with the online version of the article, one or more of the authors checked “yes” to indicate that the author had a relevant financial relationship in the biomedical arena outside the submitted work.
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