Surgical management of 144 diffuse-type TGCT patients in a single institution: A 20-year cohort study.

BACKGROUND AND OBJECTIVES: Surgery is the mainstay of treatment for tenosynovial giant cell tumors (TGCTs). However, achieving a cure through surgery alone remains challenging, especially for the diffuse-type (D-TGCT). METHODS: Our goal was to describe the surgical management of patients with D-TGCT related to large joints, treated between 2000 and 2020. We analyzed the effect of (in)complete resections and the presence of postoperative tumor (POT) on magnetic resonance imaging (MRI) on radiological and clinical outcomes. RESULTS: A total of 144 patients underwent open surgery for D-TGCT, of which 58 (40%) had treatment before. The median follow-up was 65 months. One hundred twenty-five patients underwent isolated open surgeries, in which 25 (20%) patients' D-TGCT was intentionally removed incompletely. POT presence on the first postoperative MRI was observed in 64%. Both incomplete resections and POT presence were associated with higher rates of radiological progression (73% vs. 44%; Kaplan-Meier [KM] analysis p = 0.021) and 59% versus 7%; KM analysis p < 0.001), respectively. Furthermore, patients with POT presence clinically worsened more often than patients without having POT (49% vs. 24%; KM analysis p = 0.003). CONCLUSIONS: D-TGCT is often resected incompletely and tumor presence is commonly observed on the first postoperative MRI, resulting in worse radiological and clinical outcomes. Therefore, surgeons should try to remove D-TGCT in toto and consider other multimodal therapeutic strategies.

Surgical outcomes of patients with diffuse-type tenosynovial giant-cell tumours: an international, retrospective, cohort study.

BACKGROUND: Diffuse-type tenosynovial giant-cell tumour is a rare, locally aggressive, and difficult-to-treat soft tissue tumour. Clinical and surgical outcomes depend on multiple factors, including preoperative diagnostic assessment, the localisation and extent of disease, and possibly the choice of treatment modalities by orthopaedic surgeons. We did a retrospective cohort study to characterise global surgical treatment protocols, and assess surgical outcomes, complications, and functional results in patients with diffuse-type tenosynovial giant-cell tumours. METHODS: In this international, multicentre, retrospective cohort study, we included consecutive patients treated in 31 sarcoma reference centres between Jan 1, 1990, and Dec 31, 2017. Eligible patients were of any age and had histologically proven diffuse-type tenosynovial giant-cell tumour of large joints. Patient data were retrieved from the local databases of participating centres. Patients with localised-type tenosynovial giant-cell tumour were excluded. In the analysis, we only included patients with complete core criteria data regarding admission status, date of treatment, type of treatment at participating centre, and first local recurrence after treatment. We used a non-parametric method to estimate recurrence-free survival at 3, 5, and 10 years after initial surgical resection in a tertiary centre. We used a multivariate Cox regression model to estimate the effect of risk factors. We also present subgroup analyses of disease status at presentation (primary vs recurrent disease) and recurrence-free survival by surgery type (open surgery vs arthroscopic synovectomy), and prespecified risk factors were tested in a univariate and multivariable analyses, with an endpoint of first local recurrence after treatment in a tertiary centre. FINDINGS: Data collection for these analyses occurred between January, 2016, and May, 2018. We received the records of 1192 patients, of which 966 (81%) were surgically treated and had complete information on core criteria. 445 patients were admitted with therapy-naive disease of the knee and were primarily treated in a tertiary centre. Since patients with wait and see treatment do not have a starting date of treatment, these patients were excluded in the calculation of median follow-up time for all patients. For this calculation we used time of surgery as a starting date. 758 (64%) of 1192 patients had knee involvement and 628 (54%) of 1163 patients with complete data on type of surgery had one-staged open synovectomy. At a median follow-up of 54 months (IQR 27-97), recurrent disease developed in 425 (44%) of all 966 surgically treated cases, and recurrence-free survival was 62% (95% CI 59-65) at 3 years, 55% (51-58) at 5 years, and 40% (35-45) at 10 years. Surgical complications were reported in 105 (12%) of 906 patients who had complete data on surgical complications. Pain improved after surgical treatment in 255 (59%) of 434 patients and swelling improved in 328 (72%) of 453 patients who had complete data. INTERPRETATION: This study of patients with diffuse-type tenosynovial giant-cell tumour provides a comprehensive and up-to-date disease overview, assessing the clinical profile and management of the disease in multiple specialised referral centres. Surgical treatment of diffuse-type tenosynovial giant cell tumours is not a definitive treatment for every patient because it involves a high risk for local recurrent disease and a relatively high risk for postoperative complications. After surgical treatment in treatment-naive patients, risk factors for recurrent disease in individual patients were not identified in what we believe is the largest cohort to date. FUNDING: Daiichi Sankyo.

Does CSF1 overexpression or rearrangement influence biological behaviour in tenosynovial giant cell tumours of the knee?

AIMS: Localised- and diffuse-type tenosynovial giant cell tumours (TGCT) are regarded as different clinical and radiological TGCT types. However, genetically and histopathologically they seem indistinguishable. We aimed to correlate CSF1 expression and CSF1 rearrangement with the biological behaviour of different TGCT-types with clinical outcome (recurrence). METHODS AND RESULTS: Along a continuum of extremes, therapy-naive knee TGCT patients with >3-year follow-up, mean age 43 (range = 6-71) years and 56% females were selected. Nine localised (two recurrences), 16 diffuse-type (nine recurrences) and four synovitis as control were included. Rearrangement of the CSF1 locus was evaluated with split-apart fluorescence in-situ hybridisation (FISH) probes. Regions were selected to score after identifying CSF1-expressing regions, using mRNA ISH with the help of digital correlative microscopy. CSF1 rearrangement was considered positive in samples containing >2 split signals/100 nuclei. Irrespective of TGCT-subtype, all cases showed CSF1 expression and in 76% CSF1 rearrangement was detected. Quantification of CSF1-expressing cells was not informative, due to the extensive intratumour heterogeneity. Of the four synovitis cases, two also showed CSF1 expression without CSF1 rearrangement. No correlation between CSF1 expression or rearrangement with clinical subtype and local recurrence was detected. Both localised and diffuse TGCT cases showed a scattered distribution in the tissue of CSF1-expressing cells. CONCLUSION: In diagnosing TGCT, CSF1 mRNA-ISH, in combination with CSF1 split-apart FISH using digital correlative microscopy, is an auxiliary diagnostic tool to identify rarely occurring neoplastic cells. This combined approach allowed us to detect CSF1 rearrangement in 76% of the TGCT cases. Neither CSF1 expression nor presence of CSF1 rearrangement could be associated with the difference in biological behaviour of TGCT.

Tenosynovial Giant Cell Tumors in Children: A Similar Entity Compared With Adults.

BACKGROUND: Tenosynovial giant cell tumor (TGCT) is a rare, benign, monoarticular entity. Many case-series in adults are described, whereas TGCT is only incidentally reported in children. Therefore, its incidence rate and natural history in children are unknown. QUESTIONS/PURPOSES: (1) How many cases have been reported of this condition, and what were their characteristics? (2) What is the standardized pediatric incidence rate for TGCT? (3) Is there a clinical difference in TGCT between children and adults? (4) What is the risk of recurrence after open resection in children compared with adults? METHODS: Data were derived from three sources: (1) a systematic review on TGCT in children, seeking sources published between 1990 and 2016, included 17 heterogeneous, small case-series; (2) the nationwide TGCT incidence study: the Dutch pediatric incidence rate was extracted from this nationwide study by including patients younger than 18 years of age. This registry-based study, in which eligible patients with TGCT were clinically verified, calculated Dutch incidence rates for localized and diffuse-type TGCT in a 5-year timeframe. Standardized pediatric incidence rates were obtained by using the direct method; (3) from our nationwide bone and soft tissue tumor data registry, a clinical data set was derived. Fifty-seven children with histologically proven TGCT of large joints, diagnosed and treated between 1995 and 2015, in all four tertiary sarcoma centers in The Netherlands, were included. These clinically collected data were compared with a retrospective database of 423 adults with TGCT. Chi-square test and independent t-test were used to compare children and adults for TGCT type, sex, localization, symptoms before diagnosis, first treatment, recurrent disease, followup status, duration of symptoms, and time to followup. The Kaplan-Meier method was used to evaluate recurrence-free survival at 2.5 years. RESULTS: TGCT is seldom reported because only 76 pediatric patients (39 female), 29 localized, 38 diffuse, and nine unknown type, were identified from our systematic review. The standardized pediatric TGCT incidence rate of large joints was 2.42 and 1.09 per million person-years in localized and diffuse types, respectively. From our clinical data set, symptoms both in children and adults were swelling, pain, and limited ROM with a median time before diagnosis of 12 months (range, 1-72 months). With the numbers available, we did not observe differences in presentation between children and adults in terms of sex, symptoms before diagnosis, first treatment, recurrent disease, followup status, or median time to followup. The 2.5-year recurrence-free TGCT survival rate after open resection was not different with the numbers available between children and adults: 85% (95% confidence interval [CI], 67%-100%) versus 89% (95% CI, 83%-96%) in localized, respectively (p = 0.527) and 53% (95% CI, 35%-79%) versus 56% (95% CI, 49%-64%) in diffuse type, respectively (p = 0.691). CONCLUSIONS: Although the incidence of pediatric TGCT is low, it should be considered in the differential diagnosis in children with chronic monoarticular joint effusions. Recurrent disease after surgical treatment of this orphan disease seems comparable between children and adults. With targeted therapies being developed, future research should define the most effective treatment strategies for this heterogeneous disease. LEVEL OF EVIDENCE: Level III, therapeutic study.

Incidence and demographics of giant cell tumor of bone in The Netherlands: First nationwide Pathology Registry Study.

Background and purpose - Giant cell tumors of bone (GCT-B) are rare, locally aggressive tumors characterized by an abundance of giant cells. Incidence studies for GCT-B are rare. This is the first study using a fully automated 100% covering pathology database, the nationwide Dutch Pathology Registry (17 million inhabitants), PALGA, to calculate incidence rates for GCT-B. Patients and methods - From PALGA, all pathology excerpts were retrieved for patients diagnosed with GCT-B, giant cell tumors of tenosynovium, and giant cell tumors of soft tissue between January 1, 2009 and December 31, 2013. The incidence of GCT-B was calculated. Results - In total, 8,156 excerpts of 5,922 patients were retrieved; these included 138 first GCT-B diagnosis. For GCT-B the incidence was 1.7 per million inhabitants per year with a male to female ratio of 1:1.38 and a median age of 35 years (9-77). Most common localization was the femur (35%), followed by the tibia (18%). No differences in localization according to age and sex were found. The incidence rate of local recurrence was 0.40 per million inhabitants per year. Interpretation - This is the first nationwide study reporting the incidence of GCT-B, based on a nationwide pathology database with 100% coverage of pathology departments. Current incidence calculations are based only on doctor-driven registries. We confirmed that GCT-B is a rare disease with an incidence that is slightly higher than previously published. The relatively young median age of patients and the high incidence of recurrence stresses the importance of developing more effective treatments for this disease.

Higher incidence rates than previously known in tenosynovial giant cell tumors.

Background and purpose - Tenosynovial giant cell tumors (TGCT) are rare, benign tumors, arising in synovial lining of joints, tendon sheaths, or bursae. 2 types are distinguished: localized, either digits or extremity, and diffuse lesions. Current TGCT incidence is based on 1 single US-county study in 1980, with an incidence of 9 and 2 per million person-years in localized (including digits) and diffuse TGCT, respectively. We aim to determine nationwide and worldwide incidence rates (IR) in TGCT affecting digits, localized-extremity TGCT and diffuse-type TGCT. Material and methods - Over a 5-year period, the Dutch Pathology Registry (PALGA) identified 4,503 pathology reports on TGCT. Reports affecting digits were solely used for IR calculations. Reports affecting extremities were clinically evaluated. Dutch IRs were converted to world population IRs. Results - 2,815 (68%) digits, 933 (23%) localized-extremity and 390 (9%) diffuse-type TGCT were identified. Dutch IR in digits, localized-extremity, and diffuse-type TGCT was 34, 11 and 5 per million person-years, respectively. All 3 groups showed a female predilection and highest number of new cases in age category 40-59 years. The knee joint was most often affected: localized-extremity (46%) and diffuse-type (64%) TGCT, mostly treated with open resection: localized (65%) and diffuse (49%). Reoperation rate due to local recurrence for localized-extremity was 9%, and diffuse TGCT 23%. Interpretation - This first nationwide study and detailed analyses of IRs in TGCT estimated a worldwide IR in digits, localized-extremity and diffuse TGCT of 29, 10, and 4 per million person-years, respectively. Recurrence rate in diffuse type is 2.6 times higher, compared with localized extremity. TGCT is still considered a rare disease; however, it is more common than previously understood.

Management of tenosynovial giant cell tumour of the foot and ankle.

AIMS: Tenosynovial giant cell tumour (TGCT) is one of the most common soft-tissue tumours of the foot and ankle and can behave in a locally aggressive manner. Tumour control can be difficult, despite the various methods of treatment available. Since treatment guidelines are lacking, the aim of this study was to review the multidisciplinary management by presenting the largest series of TGCT of the foot and ankle to date from two specialized sarcoma centres. METHODS: The Oxford Tumour Registry and the Leiden University Medical Centre Sarcoma Registry were retrospectively reviewed for patients with histologically proven foot and ankle TGCT diagnosed between January 2002 and August 2019. RESULTS: A total of 84 patients were included. There were 39 men and 45 women with a mean age at primary treatment of 38.3 years (9 to 72). The median follow-up was 46.5 months (interquartile range (IQR) 21.3 to 82.3). Localized-type TGCT (n = 15) predominantly affected forefoot, whereas diffuse-type TGCT (Dt-TGCT) (n = 9) tended to panarticular involvement. TGCT was not included in the radiological differential diagnosis in 20% (n = 15/75). Most patients had open rather than arthroscopic surgery (76 vs 17). The highest recurrence rates were seen with Dt-TGCT (61%; n = 23/38), panarticular involvement (83%; n = 5/8), and after arthroscopy (47%; n = 8/17). Three (4%) fusions were carried out for osteochondral destruction by Dt-TGCT. There were 14 (16%) patients with Dt-TGCT who underwent systemic treatment, mostly in refractory cases (79%; n = 11). TGCT initially decreased or stabilized in 12 patients (86%), but progressed in five (36%) during follow-up; all five underwent subsequent surgery. Side effects were reported in 12 patients (86%). CONCLUSION: We recommend open surgical excision as the primary treatment for TGCT of the foot and ankle, particularly in patients with Dt-TGCT with extra-articular involvement. Severe osteochondral destruction may justify salvage procedures, although these are not often undertaken. Systemic treatment is indicated for unresectable or refractory cases. However, side effects are commonly experienced, and relapses may occur once treatment has ceased. Cite this article: Bone Joint J 2021;103-B(4):788-794.

Outcome after 52 Salto Ankle Prostheses Implanted by a Single Surgeon.

While ankle arthrodesis was traditionally the gold standard method of treatment for disabling end-stage ankle arthritis, total ankle replacement (TAR) has been an acceptable alternative. The satisfaction rate of patients with TAR however differs. The purpose of our study is to investigate whether implant survival and results with special emphasis on the satisfaction rate of patients treated with a TAR implanted by a single surgeon were comparable to the literature. This was a retrospective cohort study in a teaching hospital. Data was collected from 52 patients who received a total ankle replacement (TAR) between 05/2002 and 06/2014. The mean follow-up time was 4.2 years (95% CI 3.3 - 5.0). Results showed a high satisfaction rate of 94% and 94% survival of the TAR after 5 years. We conclude that TAR with the Salto prosthesis is, in our hands, a reliable solution for end-stage ankle arthritis, with results comparable to the literature.

Limb Amputation after Multiple Treatments of Tenosynovial Giant Cell Tumour: Series of 4 Dutch Cases.

In Tenosynovial Giant Cell Tumours (TGCT), previously named Pigmented Villonodular Synovitis (PVNS), a distinction is made between a single nodule (localized-type) and multiple nodules (diffuse-type). Diffuse-type is considered locally aggressive. Onset and extermination of this orphan disease remain unclear. Surgical resection is the most commonly performed treatment. Unfortunately, recurrences often occur (up to 92%), necessitating reoperations and adjuvant treatments. Once all treatments fail or if severe complications occur, limb amputation may become unavoidable. We describe four cases of above-knee amputation after TGCT diagnosis.