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The Bone & Joint Journal
Vol. 105-B, Issue 5 | Pages 559 - 567
1 May 2023
Aoude A Nikomarov D Perera JR Ibe IK Griffin AM Tsoi KM Ferguson PC Wunder JS

Aims. Giant cell tumour of bone (GCTB) is a locally aggressive lesion that is difficult to treat as salvaging the joint can be associated with a high rate of local recurrence (LR). We evaluated the risk factors for tumour relapse after treatment of a GCTB of the limbs. Methods. A total of 354 consecutive patients with a GCTB underwent joint salvage by curettage and reconstruction with bone graft and/or cement or en bloc resection. Patient, tumour, and treatment factors were analyzed for their impact on LR. Patients treated with denosumab were excluded. Results. There were 53 LRs (15%) at a mean 30.5 months (5 to 116). LR was higher after curettage (18.4%) than after resection (4.6%; p = 0.008). Neither pathological fracture (p = 0.240), Campanacci grade (p = 0.734), soft-tissue extension (p = 0.297), or tumour size (p = 0.872) affected the risk of recurrence. Joint salvage was possible in 74% of patients overall (262/354), and 98% after curettage alone (262/267). Of 49 patients with LR after curettage, 44 (90%) underwent repeated curettage and joint salvage. For patients treated by curettage, only age less than 30 years (p = 0.042) and location in the distal radius (p = 0.043) predicted higher LR. The rate of LR did not differ whether cement or bone graft was used (p = 0.753), but may have been reduced by the use of hydrogen peroxide (p = 0.069). Complications occurred in 15.3% of cases (54/354) and did not differ by treatment. Conclusion. Most patients with a GCTB can undergo successful joint salvage by aggressive curettage, even in the presence of a soft-tissue mass, pathological fracture, or a large lesion, with an 18.4% risk of local recurrence. However, 90% of local relapses after curettage can be treated by repeat joint salvage. Maximizing joint salvage is important to optimize long-term function since most patients with a GCTB are young adults. Younger patients and those with distal radius tumours treated with joint-sparing procedures have a higher rate of local relapse and may require more aggressive treatment and closer follow-up. Cite this article: Bone Joint J 2023;105-B(5):559–567


The Bone & Joint Journal
Vol. 96-B, Issue 1 | Pages 127 - 131
1 Jan 2014
Wijsbek AE Vazquez-Garcia BL Grimer RJ Carter SR Abudu AA Tillman RM Jeys L

The purpose of this study was to assess whether the use of a joint-sparing technique such as curettage and grafting was successful in eradicating giant cell tumours of the proximal femur, or whether an alternative strategy was more appropriate. Between 1974 and 2012, 24 patients with a giant cell tumour of the proximal femur were treated primarily at our hospital. Treatment was either joint sparing or joint replacing. Joint-sparing treatment was undertaken in ten patients by curettage with or without adjunctive bone graft. Joint replacement was by total hip replacement in nine patients and endoprosthetic replacement in five. All 11 patients who presented with a pathological fracture were treated by replacement. Local recurrence occurred in five patients (21%): two were treated by hip replacement, three by curettage and none with an endoprosthesis. Of the ten patients treated initially by curettage, six had a successful outcome without local recurrence and required no further surgery. Three eventually needed a hip replacement for local recurrence and one an endoprosthetic replacement for mechanical failure. Thus 18 patients had the affected joint replaced and only six (25%) retained their native joint. Overall, 60% of patients without a pathological fracture who were treated with curettage had a successful outcome. Cite this article: Bone Joint J 2014;96-B:127–31


The Bone & Joint Journal
Vol. 104-B, Issue 12 | Pages 1352 - 1361
1 Dec 2022
Trovarelli G Pala E Angelini A Ruggieri P

Aims. We performed a systematic literature review to define features of patients, treatment, and biological behaviour of multicentric giant cell tumour (GCT) of bone. Methods. The search terms used in combination were “multicentric”, “giant cell tumour”, and “bone”. Exclusion criteria were: reports lacking data, with only an abstract; papers not reporting data on multicentric GCT; and papers on multicentric GCT associated with other diseases. Additionally, we report three patients treated under our care. Results. A total of 52 papers reporting on 104 patients were included in the analysis, with our addition of three patients. Multicentric GCT affected predominantly young people at a mean age of 22 years (10 to 62), manifesting commonly as metachronous tumours. The mean interval between the first and subsequent lesions was seven years (six months to 27 years). Synchronous lesions were observed in one-third of the patients. Surgery was curettage in 63% of cases (163 lesions); resections or amputation were less frequent. Systemic treatments were used in 10% (n = 14) of patients. Local recurrence and distant metastases were common. Conclusion. Multicentric GCT is rare, biologically aggressive, and its course is unpredictable. Patients with GCT should be followed indefinitely, and referred promptly if new symptoms, particularly pain, emerge. Denosumab can have an important role in the treatment. Cite this article: Bone Joint J 2022;104-B(12):1352–1361


The Bone & Joint Journal
Vol. 103-B, Issue 4 | Pages 788 - 794
1 Apr 2021
Spierenburg G Lancaster ST van der Heijden L Mastboom MJL Gelderblom H Pratap S van de Sande MAJ Gibbons CLMH

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


Bone & Joint Research
Vol. 13, Issue 2 | Pages 83 - 90
19 Feb 2024
Amri R Chelly A Ayedi M Rebaii MA Aifa S Masmoudi S Keskes H

Aims. The present study investigated receptor activator of nuclear factor kappa-Β ligand (RANKL), osteoprotegerin (OPG), and Runt-related transcription factor 2 (RUNX2) gene expressions in giant cell tumour of bone (GCTB) patients in relationship with tumour recurrence. We also aimed to investigate the influence of CpG methylation on the transcriptional levels of RANKL and OPG. Methods. A total of 32 GCTB tissue samples were analyzed, and the expression of RANKL, OPG, and RUNX2 was evaluated by quantitative polymerase chain reaction (qPCR). The methylation status of RANKL and OPG was also evaluated by quantitative methylation-specific polymerase chain reaction (qMSP). Results. We found that RANKL and RUNX2 gene expression was upregulated more in recurrent than in non-recurrent GCTB tissues, while OPG gene expression was downregulated more in recurrent than in non-recurrent GCTB tissues. Additionally, we proved that changes in DNA methylation contribute to upregulating the expression of RANKL and downregulating the expression of OPG, which are critical for bone homeostasis and GCTB development. Conclusion. Our results suggest that the overexpression of RANKL/RUNX2 and the lower expression of OPG are associated with recurrence in GCTB patients. Cite this article: Bone Joint Res 2024;13(2):84–91


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_3 | Pages 55 - 55
23 Feb 2023
Boyle R Kim R Maher A Stalley P Bhadri V
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PVNS or TGCT (Pigmented Villonodular Synovitis, or Tenosynovial Giant Cell tumour) is a benign tumour affecting the synovial lining of joints and tendon sheaths, historically treated with surgical excision or debridement. We have shown previously this management is fraught with high recurrence rates, especially in its diffuse form. We present the encouraging early results of medical management for this condition with use of a CSF1 inhibitor, in comparison to a cohort of 137 cases previously treated at our institution


Bone & Joint Open
Vol. 3, Issue 7 | Pages 515 - 528
1 Jul 2022
van der Heijden L Bindt S Scorianz M Ng C Gibbons MCLH van de Sande MAJ Campanacci DA

Aims. Giant cell tumour of bone (GCTB) treatment changed since the introduction of denosumab from purely surgical towards a multidisciplinary approach, with recent concerns of higher recurrence rates after denosumab. We evaluated oncological, surgical, and functional outcomes for distal radius GCTB, with a critically appraised systematic literature review. Methods. We included 76 patients with distal radius GCTB in three sarcoma centres (1990 to 2019). Median follow-up was 8.8 years (2 to 23). Seven patients underwent curettage, 38 curettage with adjuvants, and 31 resection; 20 had denosumab. Results. Recurrence rate was 71% (5/7) after curettage, 32% (12/38) after curettage with adjuvants, and 6% (2/31) after resection. Median time to recurrence was 17 months (4 to 77). Recurrences were treated with curettage with adjuvants (11), resection (six), or curettage (two). Overall, 84% (38/45) was cured after one to thee intralesional procedures. Seven patients had 12 months neoadjuvant denosumab (5 to 15) and sixmonths adjuvant denosumab; two recurred (29%). Twelve patients had six months neoadjuvant denosumab (4 to 10); five recurred (42%). Two had pulmonary metastases (2.6%), both stable after denosumab. Complication rate was 18% (14/76, with 11 requiring surgery). At follow-up, median MusculoSkeletal Tumour Society score was 28 (18 to 30), median Short Form-36 Health Survey was 86 (41 to 95), and median Disability of Arm, Shoulder, and Hand was 7.8 (0 to 58). Conclusion. Distal radius GCTB treatment might deviate from general GCTB treatment because of complexity of wrist anatomy and function. Novel insights on surgical treatment are presented in this multicentre study and systematic review. Intralesional surgery resulted in high recurrence-rate for distal radius GCTB, also with additional denosumab. The large majority of patients however, were cured after repeated curettage. Cite this article: Bone Jt Open 2022;3(7):515–528


The Bone & Joint Journal
Vol. 103-B, Issue 1 | Pages 184 - 191
1 Jan 2021
Perrin DL Visgauss JD Wilson DA Griffin AM Abdul Razak AR Ferguson PC Wunder JS

Aims. Local recurrence remains a challenging and common problem following curettage and joint-sparing surgery for giant cell tumour of bone (GCTB). We previously reported a 15% local recurrence rate at a median follow-up of 30 months in 20 patients with high-risk GCTB treated with neoadjuvant Denosumab. The aim of this study was to determine if this initial favourable outcome following the use of Denosumab was maintained with longer follow-up. Methods. Patients with GCTB of the limb considered high-risk for unsuccessful joint salvage, due to minimal periarticular and subchondral bone, large soft tissue mass, or pathological fracture, were treated with Denosumab followed by extended intralesional curettage with the goal of preserving the joint surface. Patients were followed for local recurrence, metastasis, and secondary sarcoma. Results. A total of 25 patients with a mean age of 33.8 years (18 to 67) with high-risk GCTB received median six cycles of Denosumab before surgery. Tumours occurred most commonly around the knee (17/25, 68%). The median follow-up was 57 months (interquartile range (IQR) 13 to 88). The joint was salvaged in 23 patients (92%). Two required knee arthroplasty due to intra-articular fracture and arthritis. Local recurrence developed in 11 patients (44%) at a mean of 32.5 months (3 to 75) following surgery, of whom four underwent repeat curettage and joint salvage. One patient developed secondary osteosarcoma and another benign GCT lung metastases. Conclusion. The use of Denosumab for joint salvage was associated with a higher than expected rate of local recurrence at 44%. Neoadjuvant Denosumab for joint-sparing procedures should be considered with caution in light of these results. Cite this article: Bone Joint J 2021;103-B(1):184–191


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_12 | Pages 12 - 12
10 Jun 2024
Barnett J Rudran B Patel S Aston W Welck M Cullen N
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Background. Tenosynovial giant cell tumour (TGCT) is a benign proliferative disease affecting synovial membranes. There are two forms, localised and diffuse, which although histologically similar are managed differently. It is locally invasive and is treated in most cases by operative excision. The aim of this study was to assess outcomes from the largest single-centre experience to date in patients with this condition. Methods. A retrospective analysis of 123 cases was performed in patients treated between 2003 and 2019 with TGCT of the foot and/or ankle. Data was collected on age at presentation, radiological pattern of disease, location of disease, treatment provided and recurrence rates. The minimum follow-up was 2 years with a mean of 7.7 years. Results. 47 male and 76 female patients with a mean age at diagnosis of 39 (range, 11–76) years were identified. 85 (69.1%) cases were categorised as localised and 38 (30.9%) were diffuse. Half of the cases presented in the ankle (62/123, 50.4%). 89% (110) of patients underwent open operative excision of the lesion. Radiotherapy was used in 2 cases for recurrent disease. Pain was the most common postoperative symptom which developed in 20% (22/110) of cases). 13 cases were managed nonoperatively where symptoms were minimal, with one case requiring surgery at a later date. Disease recurrence was 3.5% (3/85) in localised disease and 36.8% (14/38) in diffuse disease giving an overall recurrence rate of 13.8% (17/123). Conclusion. The outcomes of TGCT management are dependent on the type of disease, the extent of preoperative erosive changes and the presence of pre-operative pain. We present a summary of recommended management based on the experience from this single tertiary centre


Bone & Joint Open
Vol. 4, Issue 11 | Pages 846 - 852
8 Nov 2023
Kim RG Maher AW Karunaratne S Stalley PD Boyle RA

Aims. Tenosynovial giant cell tumour (TGCT) is a rare benign tumour of the musculoskeletal system. Surgical management is fraught with challenges due to high recurrence rates. The aim of this study was to describe surgical treatment and evaluate surgical outcomes of TGCT at an Australian tertiary referral centre for musculoskeletal tumours and to identify factors affecting recurrence rates. Methods. A prospective database of all patients with TGCT surgically managed by two orthopaedic oncology surgeons was reviewed. All cases irrespective of previous treatment were included and patients without follow-up were excluded. Pertinent tumour characteristics and surgical outcomes were collected for analysis. Results. There were 111 total cases included in the study; 71 (64%) were female, the mean age was 36 years (SD 13.6), and the knee (n = 64; 57.7%) was the most commonly affected joint. In all, 60 patients (54.1%) had diffuse-type (D-TGCT) disease, and 94 patients (84.7%) presented therapy-naïve as "primary cases" (PC). The overall recurrence rate was 46.8% for TGCT. There was a statistically significant difference in recurrence rates between D-TGCT and localized disease (75.0% vs 13.7%, relative risk (RR) 3.40, 95% confidence interval (CI) 2.17 to 5.34; p < 0.001), and for those who were referred in the ”revision cases” (RC) group compared to the PC group (82.4% vs 48.9%, RR 1.68, 95% CI 1.24 to 2.28; p = 0.011). Age, sex, tumour volume, and mean duration of symptoms were not associated with recurrence (p > 0.05). Conclusion. Recurrence rates remain high even at a tertiary referral hospital. Highest rates are seen in D-TGCT and “revision cases”. Due to the risks of recurrence, the complexity of surgery, and the need for adjuvant therapy, this paper further supports the management of TGCT in a tertiary referral multi-disciplinary orthopaedic oncology service. Cite this article: Bone Jt Open 2023;4(11):846–852


The Journal of Bone & Joint Surgery British Volume
Vol. 88-B, Issue 3 | Pages 396 - 399
1 Mar 2006
Leichtle CI Leichtle UG Gärtner V Schimmel H Hartmann JT Rudert M

A giant cell tumour is a primary lesion of bone of intermediate severity. Its histogenesis is unclear. In a few cases pulmonary metastases have been described. Multiple skeletal metastases in the absence of sarcomatous change have been observed. We present a case report of a 25-year-old woman with a recurrent giant cell tumour of the distal fibula. After a second recurrence and six years after the initial diagnosis, she rapidly developed multiple bony metastases. The outcome was fatal


The Bone & Joint Journal
Vol. 104-B, Issue 2 | Pages 297 - 301
1 Feb 2022
Jamshidi K Bagherifard A Mohaghegh MR Mirzaei A

Aims. Giant cell tumours (GCTs) of the proximal femur are rare, and there is no consensus about the best method of filling the defect left by curettage. In this study, we compared the outcome of using a fibular strut allograft and bone cement to reconstruct the bone defect after extended curettage of a GCT of the proximal femur. Methods. In a retrospective study, we reviewed 26 patients with a GCT of the proximal femur in whom the bone defect had been filled with either a fibular strut allograft (n = 12) or bone cement (n = 14). Their demographic details and oncological and nononcological complications were retrieved from their medical records. Limb function was assessed using the Musculoskeletal Tumor Society (MSTS) score. Results. Mean follow-up was 116 months (SD 59.2; 48 to 240) for the fibular strut allograft group and 113 months (SD 43.7; 60 to 192) for the bone cement group (p = 0.391). The rate of recurrence was not significantly different between the two groups (25% vs 21.4%). The rate of nononcological complications was 16.7% in the strut allograft group and 42.8% in the bone cement group. Degenerative joint disease was the most frequent nononcological complication in the cement group. The mean MSTS score of the patients was 92.4% (SD 11.5%; 73.3% to 100.0%) in the fibular strut allograft group and 74.2% (SD 10.5%; 66.7% to 96.7%) in the bone cement group (p < 0.001). Conclusion. Given the similar rate of recurrence and a lower rate of nononcological complications, fibular strut grafting could be recommended as a method of reconstructing the bone defect left by curettage of a GCT of the proximal femur. Cite this article: Bone Joint J 2022;104-B(2):297–301


Orthopaedic Proceedings
Vol. 93-B, Issue SUPP_II | Pages 198 - 198
1 May 2011
Lehner B Dimitrakopoulou-Strauss A Witte D
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Introduction: Following intralesional resection of giant cell tumour local recurrence happens in up to 40% depending on type of treatment. Common plain radiography or Magnetic resonance tomography (MRI) often has the problem not to discriminate between scar and recurrent tumour. Materials and Methods: In 19 patients with giant cell tumour dynamic PET using F18-Fluordeoxyglucose (FDG) for estimation of FDG turnover was carried out. PET was performed before surgery and as follow up. In case of evidence in x-ray or MRI of recurrent giant cell tumour PET was performed again. results of histologic evaluation after reoperation then were compared to results of PET. Results: All giant cell tumours showed a specific PET pattern with a very high standard uptake value (SUV) of 4.8 in median. In one case pulmonary metastases could be found. In follow up after surgery this value dropped to 0.3. Recurrence was suspected in the follow up in 5 patients by MRI or plain radiography. In all these patients PET could show an elevated SUV above 4.0. In these 5 patients surgery was performed and recurrence could be proven by histology. In one patient MRI was negative but PET showed a SUV of 5.2 indicating re-recurrent tumour which could be demonstrated by histology. Conclusion: We conclude that PET is a very helpful tool not only in the first line diagnosis of giant cell tumour but also in diagnosis of metastatic disease and especially for detection of recurrent tumour


The Bone & Joint Journal
Vol. 96-B, Issue 8 | Pages 1106 - 1110
1 Aug 2014
Malhotra R Kiran Kumar GN K. Digge V Kumar V

Giant cell tumour is the most common aggressive benign tumour of the musculoskeletal system and has a high rate of local recurrence. When it occurs in proximity to the hip, reconstruction of the joint is a challenge. Options for reconstruction after wide resection include the use of a megaprosthesis or an allograft-prosthesis composite. We performed a clinical and radiological study to evaluate the functional results of a proximal femoral allograft-prosthesis composite in the treatment of proximal femoral giant cell tumour after wide resection. This was an observational study, between 2006 and 2012, of 18 patients with a mean age of 32 years (28 to 42) and a mean follow-up of 54 months (18 to 79). We achieved excellent outcomes using Harris Hip Score in 13 patients and a good outcome in five. All allografts united. There were no complications such as infection, failure, fracture or resorption of the graft, or recurrent tumour. Resection and reconstruction of giant cell tumours with proximal femoral allograft–prosthesis composite is a better option than using a prosthesis considering preservation of bone stock and excellent restoration of function. A good result requires demanding bone banking techniques, effective measures to prevent infection and stability at the allograft-host junction. . Cite this article: Bone Joint J 2014; 96-B:1106–10


Orthopaedic Proceedings
Vol. 92-B, Issue SUPP_III | Pages 383 - 383
1 Jul 2010
Sharma H Reid R Reece A
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Introduction: Giant cell tumours are locally highly aggressive and extremely unpredictable bone tumours. Treatment of spinal GCTs remains controversial. We report our experience of 11 Giant cell tumours of the spine identified from the Scottish Bone Tumour Registry. Materials and Methods: Details of 11 cases of histologically confirmed Giant cell tumours of the spine (9 benign and 2 malignant) between 1960 and 2004, were extracted from the Scottish Bone Tumour Registry. The casenotes and radiographs were retrospectively reviewed. Results: There was a slight feminine predominance of 7 cases. Mean age was 34 years (range, 16 to 61 years). The sacrum (5) was most common location, followed by lumbar (3), thoracic (2) and rarely in cervical (1). Operative intervention was carried out in 5 (curettage-1; excision-5). Three also received supplemented bone grafts. Radiotherapy (including some of the operative cases) was administered in 9 patients. There were 5 recurrences (45.4%). There were 7 survivors 2 of whom still had evidence of persistent primary disease. Two died with unrelated illnesses and two from local recurrences. Conclusions: Axial GCTs behave aggressively with a high recurrence rate (45%). Radiotherapy is useful in the management of GCTs of the spine and conservative surgery with local radiotherapy is a viable treatment option in some selected patients


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XVI | Pages 4 - 4
1 Apr 2012
Jalgaonkar A Mani G Rao S
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Giant cell tumours of tendon sheaths have been given multiple denominations due to the uncertain pathologic nature of this lesion. Various contributory factors have been accounted for a wide variation in their recurrence rates. Owing to their high recurrence rates ranging from 9% to 44%, these tumours continue to present with treatment dilemma. There is a lack of consensus regarding how to best manage the balance between extensive dissection and preservation of normal tissues for normal function and recovery versus the risk of recurrence. The authors studied 46 patients with histopathologically confirmed Giant cell tumours over a period of 9 years between 1997 and 2006. The average follow-up in this case series was 35 months. This study aims to analyse the distribution of giant cell tumours of tendon sheaths in hand and our experience with their resection in a District General Hospital with possible predictors associated with recurrence. The referral letters, radiographs, operative and histology records were reviewed. The data was carefully analysed including patients' age and sex at the time of presentation and surgery, presenting symptoms, any associated trauma and the anatomical location of the tumour. A telephonic questionnaire was conducted and the patients with any complications or recurrence were reviewed. Our recurrence rate of 8.6% (4 patients) is lower than previously reported in the literature when the patients did not receive post-operative radiotherapy. Recurrence was seen to be statistically higher in cases where the tumours were excised piecemeal as opposed to removed in one piece and in patients with osseous erosions which were confirmed radiologically and intra-operatively. No atypical mitosis was reported on histology. None of our patients received radiotherapy post-operatively. Other factors including age, size, degenerative joint disease and location within the digit were not confirmed as risk factors in our study. We recommend meticulous surgical technique by an experienced hand surgeon and warning patients of the risk of recurrence if any risk factors were identified


Orthopaedic Proceedings
Vol. 88-B, Issue SUPP_II | Pages 300 - 300
1 May 2006
Trehan R Chan J Marsh G
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Giant cell tumour of tendon sheath is usually benign in nature but their tendency to recur is well known, this cause problems for surgeons and there is always a puzzle in determining the appropriate therapy. This study was done to highlight characteristics, differential diagnosis and current options of treatment for giant cell tumour of tendon sheath. We report two cases treated at our hospital. Both are females, one of 24 years while other was 65 years at the time of diagnosis. First patient had incidental associated benign teratoma of ovary as well. One tumour was of thumb in non dominant hand while in older patient it was at distal interphalangeal joint of ring finger in dominant hand. Both presented with history of slowly growing painful swelling, they were treated with local excision but in both patients there was an aggressive local recurrence. Revision surgery was performed with wider local excision. There was no recurrence this time. Giant cell tumour of tendon sheath is mostly benign condition but need to be differentiated from serious conditions like clear cell sarcoma. Therapy of choice is local excision. Wider excision after surgery should be reconsidered where microscopic examination reveals a lesion with characteristics suggestive of potential aggressive behaviour. A literature review and discussion of salient diagnostic and treatment issues is included


The Bone & Joint Journal
Vol. 102-B, Issue 10 | Pages 1392 - 1398
3 Oct 2020
Zhao Y Tang X Yan T Ji T Yang R Guo W

Aims. There is a lack of evidence about the risk factors for local recurrence of a giant cell tumour (GCT) of the sacrum treated with nerve-sparing surgery, probably because of the rarity of the disease. This study aimed to answer two questions: first, what is the rate of local recurrence of sacral GCT treated with nerve-sparing surgery and second, what are the risk factors for its local recurrence?. Methods. A total of 114 patients with a sacral GCT who underwent nerve-sparing surgery at our hospital between July 2005 and August 2017 were reviewed. The rate of local recurrence was determined, and Kaplan-Meier survival analysis carried out to evaluate the mean recurrence-free survival. Possible risks factors including demographics, tumour characteristics, adjuvant therapy, operation, and laboratory indices were analyzed using univariate analysis. Variables with p < 0.100 in the univariate analysis were further considered in a multivariate Cox regression analysis to identify the risk factors. Results. The rate of local recurrence of sacral GCT treated with nerve-sparing surgery was 28.95% (33/114). Multivariate Cox regression analysis showed that large tumour size (> 8.80 cm) (hazard ratio (HR) 3.16; 95% confidence interval (CI) 1.27 to 7.87; p = 0.014), high neutrophil-to-lymphocyte ratio (NLR) (> 2.09) (HR 3.13; 95% CI 1.28 to 7.62; p = 0.012), involvement of a sacroiliac joint (HR 3.09; 95% CI 1.06 to 9.04; p = 0.039), and massive intraoperative blood loss (> 1,550 ml) (HR 2.47; 95% CI 1.14 to 5.36; p = 0.022) were independent risk factors for local recurrence. Conclusion. Patients with a sacral GCT who undergo nerve-sparing surgery have a local recurrence rate of 29%. Large tumour size, high NLR, involvement of a sacroiliac joint, and massive intraoperative blood loss are independent risk factors. Cite this article: Bone Joint J 2020;102-B(10):1392–1398


Orthopaedic Proceedings
Vol. 92-B, Issue SUPP_III | Pages 440 - 440
1 Jul 2010
Balke M Neumann A Agelopoulos K Korsching E Hardes J Kersting C Buerger H Gosheger G Hagedorn M
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Because of the lack of a suitable in vivo model for giant cell tumors of bone little is known about their biological behavior and mechanisms of metastasis. No existing cell line contains all tumor components, so that testing of anti tumor agents is hardly possible. We therefore modified the chick chorio-allantoic membrane (CAM) assay for giant cell tumor of bone (GCTB). Out of tumor tissue obtained during surgery of 5 patients a solution was produced. The solute was grafted onto the CAM at day 10 of embryonic development. The growth process was monitored by daily observation and photo documentation using in vivo microscopy. After 5 to 6 days of tumor growth the samples were fixed in formalin and further analyzed using standard histology (hematoxylin and eosin stains). The tissue solute of all 5 patients formed solid tumors when grafted to the CAM. In vivo microscopy and standard histology revealed a rich vascularisation of the tumors. The tumors were composed of the typical components of GCTB including multinuclear giant cells. A reliable protocol for grafting of human giant cell tumors onto the chick chorio-allantoic membrane was established. This model is the first in vivo model for giant cell tumors of bone. Further characterization of the growing tissue is necessary in further experiments


Orthopaedic Proceedings
Vol. 93-B, Issue SUPP_I | Pages 76 - 76
1 Jan 2011
Gibbons CLMH Jones F Taylor R Knowles H Hogendoorn P Wass JAH Balke M Picci P Gebert C Athanasou NA
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Introduction: Giant cell tumour of bone (GCTB) is an expansile osteolytic tumour of bone which contains numerous osteoclast-like giant cells. GCTB is a locally aggressive tumour which can cause extensive bone destruction that can be difficult to control surgically, up to 35% of cases recurring after simple curettage. Bisphosphonates are anti-resorptive agents that have proved effective in the treatment of a number of osteolytic conditions. Methods: This study reports results from four European centres where bisphosphonates are being used to treat problematic GCTBs. Details of treatment with bisphosphonates of 25 cases of primary, recurrent and metastatic GCTBs was assessed clinically and radiologically. Results: Most primary/recurrent tumours did not exhibit progressive enlargement and, in some cases, both primary and metastatic GCTBs showed a degree of radiological improvement following treatment. Some patients also noted relief of pain following treatment. In a few cases, no apparent treatment effect was noted and there was disease progression. Several inoperable large spinal/pelvic GCTBs remained stable in size following treatment. Discussion: Our findings provide preliminary evidence for the use of bisphosphonates to inhibit the progressive osteolysis associated with GCTB. These agents had a beneficial clinical and/or radiological effect in most cases. This study reports results from four European centres and highlights the fact that these centres are all employing different clinical indications and different regimes of bisphosphonate treatment. Bisphosphonates have significant side effects and indications for treatment and standardisation of drug type and dosage regimes (and measurement of agreed outcome measures to determine treatment efficacy) should be established for the use of these agents to control GCTB tumour growth and osteolysis


Orthopaedic Proceedings
Vol. 84-B, Issue SUPP_III | Pages 304 - 304
1 Nov 2002
Robinson D Dotan A Nevo Z
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Objectives: Development a giant cell tumor model arising from the mutated mesenchymal cells present in its stroma. This establishes the pathogenic mechanism of giant cell tumor, and allows the evaluation of the possible role of biphosphonates and retinoic acid in medical therapy of giant cell tumor of bone. Introduction: In previous studies our group has shown that mesenchymal stroma contains mesenchymal cells capable of recruiting osteoclasts, and lacking capacity to undergo osteoblastic differentiation. These cells represent the actual neoplastic component of the tumor. In the current study, an attempt was made to establish a giant cell tumor in an animal model by injection of these cells. Methods: 6 Balb/C named mice were used. The mice were kept in a laminar flow hood and injected when they were 4 weeks old. The injection was in an intra-osseous location into the distal femur. The cell inoculum consisted of 1 million stromal cells. The cells were derived from a grade III giant cell tumor occurring in the hip joint of a 30 years old woman. The mice were kept for 2 months and than sacrificed. Results: A lytic lesion similar to that occurring in humans developed. The tumor consisted of stromal cells with interspersed osteoclasts. These were identified as being of host origin by mice-specific monoclonal antibodies. The tumor penetrated the cortex but did not infiltrate the articular cartilage. Metastases were not observed. Discussion: Giant cell tumor of bone is typified by osteolytic bone destruction mediated by osteoclasts. In previous studies, our group has shown that the proliferation rate of the stromal component correlates closely with prognosis and grade of the tumor. The stromal component was shown to consist of pre-osteoblasts that fail to differentiate into osteoblasts, but instead recruit giant cells (osteoclasts), mediating bone destruction. Addition of retinoic acid in culture induces osteoblastogenesis cells by blocking AP-1. The current study confirms in an animal model that indeed the stromal cells are capable of osteoclast recruitment and bone destruction. This animal model might allow development of medical remedies to this tumor


The Journal of Bone & Joint Surgery British Volume
Vol. 93-B, Issue 12 | Pages 1665 - 1669
1 Dec 2011
Gaston CL Bhumbra R Watanuki M Abudu AT Carter SR Jeys LM Tillman RM Grimer RJ

We retrospectively compared the outcome after the treatment of giant cell tumours of bone either with curettage alone or with adjuvant cementation. Between 1975 and 2008, 330 patients with a giant cell tumour were treated primarily by intralesional curettage, with 84 (25%) receiving adjuvant bone cement in the cavity. The local recurrence rate for curettage alone was 29.7% (73 of 246) compared with 14.3% (12 of 84) for curettage and cementation (p = 0.001). On multivariate analysis both the stage of disease and use of cement were independent significant factors associated with local recurrence. The use of cement was associated with a higher risk of the subsequent need for joint replacement. In patients without local recurrence, 18.1% (13 of 72) of those with cement needed a subsequent joint replacement compared to 2.3% (4 of 173) of those without cement (p = 0.001). In patients who developed local recurrence, 75.0% (9 of 12) of those with previous cementation required a joint replacement, compared with 45.2% (33 of 73) of those without cement (p = 0.044)


Orthopaedic Proceedings
Vol. 93-B, Issue SUPP_II | Pages 110 - 110
1 May 2011
Garg B Kotwal P
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Introduction: Giant cell tumor of the tendon sheath is a solitary benign soft tissue tumor of the limb. We present our prospective experience of 106 cases, over a period of 22 years to assess the effectiveness of prophylactic radiotherapy in postoperative period. We also present a classification system to help in selecting patients for postoperative radiotherapy. Material & Methods: Between 1986 and 2008, we treated 106 patients with giant cell tumor of the tendon sheath of the hand. There were 77 females and 29 males with a mean age of 31.2 years. All patients presented with gradually progressive swelling. Pain was present in 3 cases. All patients were investigated preoperatively with plain X-rays. MRI was done in 36 cases. A preoperative diagnosis of giant cell tumour of the tendon sheath was made in 98 patients preoperatively. Rest 8 patients were diagnoses on histo- pathological examination. We developed a classification system to identify the patients for risk of recurrence and consequently selection of patients for postoperative radiotherapy. Group 1(a) and 2(a) were identifies as low risk groups and comprised of 56 patients. Results: None of the patient in this group received postoperative radiotherapy and no patient had recurrence among them. All other patients (50 patients) were considered to be high risk and given postoperative radiotherapy. Among them 4 had recurrence. A total recurrence rate of 3.7% was found in our study, which is favourably comparable to reported incidences of between 25% to 45%. Conclusion: In our series, we gave radiotherapy to only high risk patients and had a recurrence rate of only 3.7%. Even in high risk group alone, to whom postoperative radiotherapy was given, recurrence rate was 8%. This indicate the role of radiotherapy as well as importance of our classification system to identify the patients for high risk of recurrence


Orthopaedic Proceedings
Vol. 104-B, Issue SUPP_12 | Pages 76 - 76
1 Dec 2022
Eltit F Ng T Gokaslan Z Fisher C Dea N Charest-Morin R
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Giant cell tumors of bone (GCTs) are locally aggressive tumors with recurrence potential that represent up to 10% of primary tumors of the bone. GCTs pathogenesis is driven by neoplastic mononuclear stromal cells that overexpress receptor activator of nuclear factor kappa-B/ligand (RANKL). Treatment with specific anti-RANKL antibody (denosumab) was recently introduced, used either as a neo-adjuvant in resectable tumors or as a stand-alone treatment in unresectable tumors. While denosumab has been increasingly used, a percentage of patients do not improve after treatment. Here, we aim to determine molecular and histological patterns that would help predicting GCTs response to denosumab to improve personalized treatment. Nine pre-treatment biopsies of patients with spinal GCT were collected at 2 centres. In 4 patients denosumab was used as a neo-adjuvant, 3 as a stand-alone and 2 received denosumab as adjuvant treatment. Clinical data was extracted retrospectively. Total mRNA was extracted by using a formalin-fixed paraffin-embedded extraction kit and we determined the transcript profile of 730 immune-oncology related genes by using the Pan Cancer Immune Profiling panel (Nanostring). The gene expression was compared between patients with good and poor response to Denosumab treatment by using the nSolver Analysis Software (Nanostring). Immunohistochemistry was performed in the tissue slides to characterize cell populations and immune response in CGTs. Two out of 9 patients showed poor clinical response with tumor progression and metastasis. Our analysis using unsupervised hierarchical clustering determined differences in gene expression between poor responders and good responders before denosumab treatment. Poor responding lesions are characterized by increased expression of inflammatory cytokines as IL8, IL1, interferon a and g, among a myriad of cytokines and chemokines (CCL25, IL5, IL26, IL25, IL13, CCL20, IL24, IL22, etc.), while good responders are characterized by elevated expression of platelets (CD31 and PECAM), coagulation (CD74, F13A1), and complement classic pathway (C1QB, C1R, C1QBP, C1S, C2) markers, together with extracellular matrix proteins (COL3A1, FN1,. Interestingly the T-cell response is also different between groups. Poor responding lesions have increased Th1 and Th2 component, but good responders have an increased Th17 component. Interestingly, the checkpoint inhibitor of the immune response PD1 (PDCD1) is increased ~10 fold in poor responders. This preliminary study using a novel experimental approach revealed differences in the immune response in GCTs associated with clinical response to denosumab. The increased activity of checkpoint inhibitor PD1 in poor responders to denosumab treatment may have implications for therapy, raising the potential to investigate immunotherapy as is currently used in other neoplasms. Further validation using a larger independent cohort will be required but these results could potentially identify the patients who would most benefit from denosumab therapy


The Journal of Bone & Joint Surgery British Volume
Vol. 88-B, Issue 4 | Pages 531 - 535
1 Apr 2006
von Steyern FV Bauer HCF Trovik C Kivioja A Bergh P Jörgensen PH Foller̊s G Rydholm A

We retrospectively studied local recurrence of giant cell tumour in long bones following treatment with curettage and cementing in 137 patients. The median follow-up time was 60 months (3 to 166). A total of 19 patients (14%) had at least one local recurrence, the first was diagnosed at a median of 17 months (3 to 29) after treatment of the primary tumour. There were 13 patients with a total of 15 local recurrences who were successfully treated by further curettage and cementing. Two patients with a second local recurrence were consequently treated twice. At the last follow-up, at a median of 53 months (3 to 128) after the most recent operation, all patients were free from disease and had good function. We concluded that local recurrence of giant cell tumour after curettage and cementing in long bones can generally be successfully treated with further curettage and cementing, with only a minor risk of increased morbidity. This suggests that more extensive surgery for the primary tumour in an attempt to obtain wide margins is not the method of choice, since it leaves the patient with higher morbidity with no significant gain with respect to cure of the disease


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XXXVIII | Pages 91 - 91
1 Sep 2012
Ben-Lulu OY Rao A Gyomorey S Backstein D
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Purpose. Secondary degenerative changes of the knee are a well recognized complication of Giant Cell Tumor (GCT). Osteoarthritis (OA) may be a consequence of the lesion itself or its treatment. Total Knee Arthroplasty (TKA) is a treatment option for end stage knee arthritis. In the current study we describe the short term follow up of three patients that underwent TKA for treatment of GCT related OA between 2006–2007. Method. The records of 180 consecutive patients treated for giant cell tumor of the knee between 1989 and 2007 in our institution were reviewed. Three patients were identified that had total knee arthroplasty following treatment of giant cell tumor of the knee, confirmed by tissue biopsy. The review included all clinical notes, pathology and operative reports. Outcomes were assessed based on knee scores and functional scores calculated according to the clinical rating system of The Knee Society, with the assignment of a maximum of 100 points for each. Patient ages range from 29–75 years of age. Assessment occurred pre-operatively as well as post-operatively at six weeks, three months, six months and then yearly. The development of osteoarthritis with severe knee pain was the primary indication for performing TKA. Results. Patients had a low mean preoperative knee score of 23, with mean function score of 50. All patients reported severe pain preoperatively. Mean range of motion was five degrees of fixed flexion contracture to to 75 degrees of flexion. Intraoperatively, there were no complications, although mean tourniquet time was prolonged in comparison to standard TKA at 106.7 minutes. This reflects a procedure of greater complexity than routine TKA. At last follow up at a mean of 35.5 months the mean knee score was 58, mean function score was 93, mean pain score of two (none to moderate), and mean range of motion was zero to 93 degrees. No recurrences of GCT were noted in any of the cases. Conclusion. In the cases we currently report, the preoperative pain scores as well as functional scores have all improved following TKA. While the range of motion did not seem to improve significantly and one patient developed TKA instability requiring revision surgery to resolve the issue, no other complications or recurrences of the GCT were noted. Thus while range of motion was inferior to routine TKA, this procedure can provide a pain-free, well functioning knee joint in a patient with arthritis secondary to GCT. In summary, our experience with TKA for osteoarthritis secondary to giant cell tumor of the knee is a reliable treatment option providing acceptable range of motion, pain and functional score results for patients


The Bone & Joint Journal
Vol. 95-B, Issue 6 | Pages 838 - 845
1 Jun 2013
Oliveira VC van der Heijden L van der Geest ICM Campanacci DA Gibbons CLMH van de Sande MAJ Dijkstra PDS

Giant cell tumours (GCTs) of the small bones of the hands and feet are rare. Small case series have been published but there is no consensus about ideal treatment. We performed a systematic review, initially screening 775 titles, and included 12 papers comprising 91 patients with GCT of the small bones of the hands and feet. The rate of recurrence across these publications was found to be 72% (18 of 25) in those treated with isolated curettage, 13% (2 of 15) in those treated with curettage plus adjuvants, 15% (6 of 41) in those treated by resection and 10% (1 of 10) in those treated by amputation. We then retrospectively analysed 30 patients treated for GCT of the small bones of the hands and feet between 1987 and 2010 in five specialised centres. The primary treatment was curettage in six, curettage with adjuvants (phenol or liquid nitrogen with or without polymethylmethacrylate (PMMA)) in 18 and resection in six. We evaluated the rate of complications and recurrence as well as the factors that influenced their functional outcome. At a mean follow-up of 7.9 years (2 to 26) the rate of recurrence was 50% (n = 3) in those patients treated with isolated curettage, 22% (n = 4) in those treated with curettage plus adjuvants and 17% (n = 1) in those treated with resection (p = 0.404). The only complication was pain in one patient, which resolved after surgical removal of remnants of PMMA. We could not identify any individual factors associated with a higher rate of complications or recurrence. The mean post-operative Musculoskeletal Tumor Society scores were slightly higher after intra-lesional treatment including isolated curettage and curettage plus adjuvants (29 (20 to 30)) compared with resection (25 (15 to 30)) (p = 0.091). Repeated curettage with adjuvants eventually resulted in the cure for all patients and is therefore a reasonable treatment for both primary and recurrent GCT of the small bones of the hands and feet. Cite this article: Bone Joint J 2013;95-B:838–45


The Bone & Joint Journal
Vol. 100-B, Issue 12 | Pages 1626 - 1632
1 Dec 2018
Medellin MR Fujiwara T Tillman RM Jeys LM Gregory J Stevenson JD Parry M Abudu A

Aims. The aim of this paper was to investigate the prognostic factors for local recurrence in patients with pathological fracture through giant cell tumours of bone (GCTB). Patients and Methods. A total of 107 patients presenting with fractures through GCTB treated at our institution (Royal Orthopaedic Hospital, Birmingham, United Kingdom) between 1995 and 2016 were retrospectively studied. Of these patients, 57 were female (53%) and 50 were male (47%).The mean age at diagnosis was 33 years (14 to 86). A univariate analysis was performed, followed by multivariate analysis to identify risk factors based on the treatment and clinical characteristics. Results. The initial surgical treatment was curettage with or without adjuvants in 55 patients (51%), en bloc resection with or without reconstruction in 45 patients (42%), and neoadjuvant denosumab, followed by resection (n = 3, 3%) or curettage (n = 4, 4%). The choice of treatment depended on tumour location, Campanacci tumour staging, intra-articular involvement, and fracture displacement. Neoadjuvant denosumab was used only in fractures through Campanacci stage 3 tumours. Local recurrence occurred in 28 patients (25%). Surgery more than six weeks after the fracture did not affect the risk of recurrence in any of the groups. In Campanacci stage 3 tumours not treated with denosumab, en bloc resection had lower local recurrences (13%), compared with curettage (39%). In tumours classified as Campanacci 2, intralesional curettage and en bloc resections had similar recurrence rates (21% and 24%, respectively). After univariate analysis, the type of surgical intervention, location, and the use of denosumab were independent factors predicting local recurrence. Further surgery was required 33% more often after intralesional curettage in comparison with resections (mean 1.59, 0 to 5 vs 1.06, 0 to 3 operations). All patients treated with denosumab followed by intralesional curettage developed local recurrence. Conclusion. In patients with pathological fractures through GCTB not treated with denosumab, en bloc resection offers lower risks of local recurrence in tumours classified as Campanacci stage 3. Curettage or resections are both similar options in terms of the risk of local recurrence for tumours classified as Campanacci stage 2. The benefits of denosumab followed by intralesional curettage in these patients still remains unclear


The Journal of Bone & Joint Surgery British Volume
Vol. 94-B, Issue 7 | Pages 882 - 888
1 Jul 2012
van der Heijden L Gibbons CLMH Dijkstra PDS Kroep JR van Rijswijk CSP Nout RA Bradley KM Athanasou NA Hogendoorn PCW van de Sande MAJ

Giant cell tumours (GCT) of the synovium and tendon sheath can be classified into two forms: localised (giant cell tumour of the tendon sheath, or nodular tenosynovitis) and diffuse (diffuse-type giant cell tumour or pigmented villonodular synovitis). The former principally affects the small joints. It presents as a solitary slow-growing tumour with a characteristic appearance on MRI and is treated by surgical excision. There is a significant risk of multiple recurrences with aggressive diffuse disease. A multidisciplinary approach with dedicated MRI, histological assessment and planned surgery with either adjuvant radiotherapy or systemic targeted therapy is required to improve outcomes in recurrent and refractory diffuse-type GCT. Although arthroscopic synovectomy through several portals has been advocated as an alternative to arthrotomy, there is a significant risk of inadequate excision and recurrence, particularly in the posterior compartment of the knee. For local disease partial arthroscopic synovectomy may be sufficient, at the risk of recurrence. For both local and diffuse intra-articular disease open surgery is advised for recurrent disease. Marginal excision with focal disease will suffice, not dissimilar to the treatment of GCT of tendon sheath. For recurrent and extra-articular soft-tissue disease adjuvant therapy, including intra-articular radioactive colloid or moderate-dose external beam radiotherapy, should be considered


Orthopaedic Proceedings
Vol. 92-B, Issue SUPP_III | Pages 444 - 444
1 Jul 2010
Lehner B Dimitrakopoulou-Strauß A Weiss S Witte D
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Following intralesional resection of giant cell tumour local recurrence happens in up to 40% depending on type of treatment. Common plain radiography or Magnetic resonance tomography (MRI) often has the problem not to discriminate between scar and recurrent tumour tissue in the cement-tissue border of lesions treated with cement packing. The value of Positron emission tomography (PET) for diagnosis of tumour and recurrence was investigated in these patients. In 19 patients with giant cell tumour dynamic PET using F18-Fluordeoxyglucose for estimation of FDG turnover was carried out. PET was performed before surgery and as follow up. In all patients giant cell tumour was treated by curettage followed by burring and cement packing. Giant cell tumour was shown by histology in all patients. All giant cell tumours showed a specific PET pattern with a very high standard uptake value (SUV) of 4.8 in median. In follow up after surgery this value dropped to 0.3. In one case also pulmonary metastasis could be demonstrated. Recurrence was suspected in the follow up in 5 patients by MRI or plain radiography. In all these patients PET could show an elevated SUV above 4.0. In these 5 patients surgery was performed and recurrence could be proven by histology. In one patient MRI showed signs of recurrence but PET showed a SUV of 1.3. In the revision surgery no tumour could be found. In one patient MRI was negative but PET showed a SUV of 5.2 indicating re-recurrent tumour which could be demonstrated by histology. We conclude that PET is a very helpful tool not only in the first line diagnosis of giant cell tumour but also in diagnosis of metastatic disease and especially for detection of recurrent tumour


The Bone & Joint Journal
Vol. 101-B, Issue 3 | Pages 272 - 280
1 Mar 2019
Verspoor FGM Mastboom MJL Hannink G van der Graaf WTA van de Sande MAJ Schreuder HWB

Aims. The aim of this study was to evaluate health-related quality of life (HRQoL) and joint function in tenosynovial giant cell tumour (TGCT) patients before and after surgical treatment. Patients and Methods. This prospective cohort study run in two Dutch referral centres assessed patient-reported outcome measures (PROMs; 36-Item Short-Form Health Survey (SF-36), visual analogue scale (VAS) for pain, and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC)) in 359 consecutive patients with localized- and diffuse-type TGCT of large joints. Patients with recurrent disease (n = 121) and a wait-and-see policy (n = 32) were excluded. Collected data were analyzed at specified time intervals preoperatively (baseline) and/or postoperatively up to five years. Results. A total of 206 TGCT patients, 108 localized- and 98 diffuse-type, were analyzed. Median age at diagnosis of localized- and diffuse-type was 41 years (interquartile range (IQR) 29 to 49) and 37 years (IQR 27 to 47), respectively. SF-36 analyses showed statistically significant and clinically relevant deteriorated preoperative and immediate postoperative scores compared with general Dutch population means, depending on subscale and TGCT subtype. After three to six months of follow-up, these scores improved to general population means and continued to be fairly stable over the following years. VAS scores, for both subtypes, showed no statistically significant or clinically relevant differences pre- or postoperatively. In diffuse-type patients, the improvement in median WOMAC score was statistically significant and clinically relevant preoperatively versus six to 24 months postoperatively, and remained up to five years’ follow-up. Conclusion. Patients with TGCT report a better HRQoL and joint function after surgery. Pain scores, which vary hugely between patients and in patients over time, did not improve. A disease-specific PROM would help to decipher the impact of TGCT on patients’ daily life and functioning in more detail. Cite this article: Bone Joint J 2019;101-B:272–280


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XXXVII | Pages 257 - 257
1 Sep 2012
Maric M Bergovec M Viskovic A Kolundzic R Smerdelj M Orlic D
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AIM. To present our experience in patients treated under primary diagnosis giant cell tumor of bone at Department Orthopaedic Surgery Zagreb University School of Medicine in a 15-year period from 1995 to 2009. METHODS. We performed a retrospective study of all patients treated in our Department because of giant cell tumor of bone (GCT) from 1995 to 2009. The mean age of our patients was 29,9 years (range: 14 to 70 years). Sex distribution showed prevalence in female (F:M=23:12=66%:34%). All together, 39 patients were operated under primary diagnosis of GCT. Four patients were lost in follow-up. In total, 35 patients were included in study. Diagnosis of GCT was made according to clinical, imaging and histological findings, and distributed by Campanacci's classification. RESULTS. Not including diagnostic biopsy, 84 operations were performed on 35 patients. Fourteen patients (40%) had GCT grade 1, fourteen (40%) had GCT grade 2, and seven (20%) had GCT grade 3. From the first symptoms to diagnosis there was an average duration of 7 months (range: 0 to 24 months), where the main symptoms were pain and swelling of affected bone and/or joint. GCT was localized in distal femur (n=12, 34%), proximal tibia (n=10, 29%), distal tibia (n=4, 11%), distal radius (n=3, 9%), and other locations (n=6, 17%). Patients with less aggressive GCT (grades 1 and 2) were treated with marginal excision: excochleation and reconstruction with bone transplant (n=12, 34%). In patients with locally more aggressive tumor (grades 2 and 3), “en bloc” resection and reconstruction with tumor endoprosthesis or bone transplant was performed (n=22, 63%). Due to localization of tumor, one patient was treated with radiation (3%). Complications were recorded in 12 patients (34%), and are shown as total number and percentage of all complications. Complications were the most common in knee region, proximal tibia (n=4, 33%) and distal femur (n=3, 25%). Also, the complications occured more frequently after “en bloc” resection (n=7, 58%). GCT classified as gradus 2 had most complications (n=5, 42%) till GCT classified as gradus 3 had least (n=3, 25% of complications, 9% of all). We recorded and treated local recurrence of tumor (n=6, 50%), infection (n=2, 17%), and mehanical complications of endoprosthesis (n=2, 17%). Due to local recurrences, in 2 patients underlying osteosarcoma was revealed, and they were treated with amputation. CONCLUSION. Each patient with GCT should be treated individually. Regardless non-malignant attribute, local behaviour of tumor determines treatment approach according to treatment principles of malignant tumor of bone. Number of complications in our patients is relatively high, recorded in one third of our patients, which matches the literature in announced studies


Orthopaedic Proceedings
Vol. 95-B, Issue SUPP_29 | Pages 11 - 11
1 Aug 2013
Duze J Pikor T Kyte R
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It has become standard practice in our unit to treat large giant cell tumours with intralesional curettage, burring, a locking plate and adjuvant liquid nitrogen & PMMA cementation. 24 patients have been treated in this fashion over the past 7 years. We have had 2 recurrences to date, both recent. These 2 cases of large Campanacci type 2 & 3 giant cell tumour of the distal femur & proximal tibia, successfully treated with megaprosthetic replacement are reported. One patient had lung metastases, which appeared stable and were being closely monitored for progress. Histopathology had been reviewed and giant-cell rich osteosarcoma definitely excluded. Osteoclastic inhibitory chemotherapy was instituted 6 weeks post-op


Orthopaedic Proceedings
Vol. 92-B, Issue SUPP_I | Pages 67 - 67
1 Mar 2010
Grimer R Carter S Stirling A Spooner D
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Aim: To investigate the outcome of our management of patients with giant cell tumour of the sacrum and draw lessons from this. Method: Retrospective review of medical records and scans for all patients treated at our unit over the past 20 years with a giant cell tumour (GCT) of the sacrum. Results: Of 517 patients treated at our unit for GCT over the past 20 years, only 9 (1.7%) had a GCT in the sacrum. 6 were female, 3 male with a mean age of 34 (range 15–52). All but two tumours involved the entire sacrum and there was only one purely distal to S3. The mean size was 10cm and the most common symptom was back or buttock pain. Five had abnormal neurology at diagnosis but only one presented with cauda equina syndrome. The first four patients were treated by curettage alone but two patients had intra-operative cardiac arrests and although both survived all subsequent curettages were preceeded by embolization of the feeding vessels. Of 7 patients who had curettage, 3 developed local recurrence but all were controlled with a combination of further embolisation, surgery or radiotherapy. One patient elected for treatment with radiotherapy and another had excision of the tumour distal to S3. All the patients are alive and only two patients have worse neurology than at presentation, one being impotent and one with stress incontinence. All are mobile and active at a follow up between 2 and 21 years. Conclusion: GCT of the sacrum can be controlled with conservative surgery rather than sacrectomy. Embolisation and curettage are the preferred first option with radiotherapy as a possible adjunct. Spino-pelvic fusion may be needed if the sacrum collapses


The Bone & Joint Journal
Vol. 102-B, Issue 2 | Pages 177 - 185
1 Feb 2020
Lim CY Liu X He F Liang H Yang Y Ji T Yang R Guo W

Aims. To investigate the benefits of denosumab in combination with nerve-sparing surgery for treatment of sacral giant cell tumours (GCTs). Methods. This is a retrospective cohort study of patients with GCT who presented between January 2011 and July 2017. Intralesional curettage was performed and patients treated from 2015 to 2017 also received denosumab therapy. The patients were divided into three groups: Cohort 1: control group (n = 36); cohort 2: adjuvant denosumab group (n = 9); and cohort 3: neo- and adjuvant-denosumab group (n = 17). Results. There were 68 patients within the study period. Six patients were lost to follow-up. The mean follow-up was 47.7 months (SD 23.2). Preoperative denosumab was found to reduce intraoperative haemorrhage and was associated with shorter operating time for tumour volume > 200 cm. 3. A total of 17 patients (27.4%) developed local recurrence. The locoregional control rate was 77.8% (7/9) and 87.5% (14/16) respectively for cohorts 2 and 3, in comparison to 66.7% (24/36) of the control group. The recurrence-free survival (RFS) rate was significantly higher for adjuvant denosumab group versus those without adjuvant denosumab during the first two years: 100% vs 83.8% at one year and 95.0% vs 70.3% at two years. No significant difference was found for the three-year RFS rate. Conclusion. Preoperative denosumab therapy was found to reduce intraoperative haemorrhage and was associated with shorter operating times. Adjuvant denosumab was useful to prevent early recurrence during the first two years after surgery. Cite this article: Bone Joint J 2020;102-B(2):177–185


Orthopaedic Proceedings
Vol. 84-B, Issue SUPP_III | Pages 207 - 207
1 Nov 2002
Gross M Mohan R
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Introduction: Good results have been reported with curettage and cementation in the treatment of giant cell tumours of bone. There is a fear of potential degenerative changes with the long-term presence of methyl methacrylate in a weight bearing subchondral location. Purpose of the study: To prospectively study the effectiveness of treatment of giant cell tumours by curettage, high speed burring and cementation. Patients and methods: A single surgeon treated 37 giant cell tumours with meticulous curettage and high speed burring followed by cementation of the resulting cavity. The tumours were graded radiologically after the method of Campanacci et al. All the patients were prospectively followed up clinically by MSTS scoring system and radiologically. Results: There were 22 women and 15 men with a mean age at operation of 34 years (range 17–72). 26 of the tumors were around the knee. 4 patients were Campanacci grade I, 22 grade II and 11 grade III. In 8 patients with pathological fractures, cementation was supplemented by internal fixation. Mean follow-up was 3.3 years (1.7–14). There were 4 recurrences. All the recurrences occurred within the first year. There have been no degenerative changes in the adjacent joint. All the patients scored either excellent or good in the MSTS scoring system. Conclusions: Curettage, high speed burring followed by cementation is a useful method in the treatment of giant cell tumours. The advantages include relatively low recurrence rate (10% in our series), immediate stability allowing early mobilization and easier and early radiological diagnosis of recurrence


Orthopaedic Proceedings
Vol. 92-B, Issue SUPP_III | Pages 444 - 444
1 Jul 2010
Kuerzl G Maurer-Ertl W Leithner A Liegl-Atzwanger B Dobnig H Windhager R
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Multifocal osteolytic lesions of the skeletal system are a challenge regarding diagnosis especially when multi-nucleated giant cells which are not specific for a tumour entity are found in the histological specimen. Therefore multiple differential diagnosis have to be considered such as metastases, primary malignant bone tumours, multicentric giant cell tumour of bone and brown tumours of primary hyperparathyroidism. A 49 year old woman underwent medical investigation in an external surgical department due to right hip pain after a fall. The radiologic skeletal status surprised with multiple osteolytic pelvic lesions and one tumour in the left scapula and first histological diagnosis described a giant cell tumour of bone with malignant aspects. After confirmation of this diagnosis by a second histopathological inquiry accomplished by a bone tumor specialist the patient was transferred to our tumour centre. To exclude the differential diagnosis of brown tumours a close look on the parathormon level was done which revealed an exorbitantly high serum amount of 922.7 pg/ml (normal 15–65 pg/ml). Further examination confirmed a parathyroid adenoma. After its extirpation serum levels of parathormon decreased and two months after therapy with high dose calcium substitution radiologic controls show a decline of osteolysis with bone consolidation. Brown tumours of hyperparathyroidism have always to be considered as a rare differential diagnosis of multiple giant cell containing tumours. The disease cannot be distinguished by the histological pattern but can very easily be excluded by normal parathormon levels. First step of therapy in brown tumours should be surgical extirpation of parathyroid adenomas or carcinomas followed by an endocrinological regime. Only failure of this treatment requires further surgical stabilisation of the bone lesions


Orthopaedic Proceedings
Vol. 93-B, Issue SUPP_I | Pages 79 - 79
1 Jan 2011
Sharma R Dramis A Tillman R Grimer R Carter S Abudu A Jeys L
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Introduction: Giant cell tumor (GCT) is a benign but locally aggressive tumor that primarily affects the epiphyses of long bones of young adults. Pulmonary metastases in giant cell tumor are rare. We report our experience of treating pulmonary metastatic GCT of bone over the last 24 years between 1984–2007. Methods: A retrospective review of patients’ records and oncology database of patients with metastatic GCT. Results: We had 471 patients with GCT of bone out of which 7 patients developed pulmonary metastases (1.48%). Six patients following diagnosis and initial treatment and one with pulmonary metastases present at the diagnosis. There were 4 males and 3 females aged between 23 to 40 years (median, 27 years). All patients had GCT around the knee (distal femur/proximal tibia). All patients eventually required Endoprosthetic Replacement apart from one who was treated with curettage only. The time of pulmonary metastases from initial diagnosis was 16–92 months (median, 44.6 months). All patients who developed metastases in the postoperative period had thoracotomy for excision of the pulmonary metastases. Two patients received chemotherapy for control of the local recurrence. At an average follow up of 151 months (27–304 months), all patients were alive. Discussion: Pulmonary metastases have been reported as 1% to 9% in GCT. Because of its rarity, very little is known about the long-term outcome and the best treatment for the pulmonary lesions. The mortality rates recorded for patients with pulmonary metastatic GCT range from 0% to 37%. In our series the mortality rate was 0% and metastases 1.48%. It seems that surgical resection of pulmonary metastases gave excellent rate of survival


Orthopaedic Proceedings
Vol. 90-B, Issue SUPP_II | Pages 399 - 399
1 Jul 2008
Malik A Lakshmanan P Gerrand C Haslam P
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Background: Giant-cell tumour (GCT) of bone is a benign but aggressive tumour, usually treated by radical surgical curettage. Surgical treatment of GCT involving the ischium is associated with a high local recurrence rate. We describe a case in which serial arterial embolisation and bisphosphonate treatment resulted in radiological healing of the tumour. So far we have avoided surgical treatment. Case Report: A 40-year-old lady was referred to the bone tumour unit following a fall. A plain radiograph of the pelvis revealed a lytic lesion in the ischium, extending into the posterior column of the acetabulum and associated with a pathological fracture. Biopsy confirmed a diagnosis of GCT. Given the anatomic location, the tumour was treated with serial arterial embolisation and intravenous zoledronate infusions. Follow up at one-year shows healing of the lesion, with no radiological evidence of recurrence. The patient has so far avoided surgery. Discussion: Serial arterial embolisation has been described in the treatment of giant cell tumours in anatomical regions where surgery is likely to be associated with significant morbidity, such as the sacrum. There is a sound theoretical basis for the use of bisphosphonates in this disease; they have been shown to cause apoptosis of the osteoclast-like giant cells and interfere with osteoclast recruitment. As far as we are aware this is the first case described in which embolisation and bisphosphonate treatment appears to have led to healing and stabilisation of the lesion. The durability of this response remains uncertain


Orthopaedic Proceedings
Vol. 92-B, Issue SUPP_III | Pages 443 - 443
1 Jul 2010
Alberghini M Kliskey K Krenacs T Picci P Athanasou NA
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Giant cell tumour of bone (GCTB) is a primary tumour of bone characterised by a proliferation of mononuclear stromal cells and infiltrating macrophages and osteoclast-like giant cells. GCTB has a variable and unpredictable course and can produce metastatic lesions, mostly in the lungs, in up to 3% of cases. Whether these represent tumour implants rather than true neoplastic secondaries is uncertain. In this study, we analysed morphological and immunophenotypic features of primary GCTBs which metastasised to the lung as well as the metastatic lesions themselves in order to determine if these would provide a clue as to the mechanism of lung metastasis in GCTB. 17 cases of primary GCTB which metastasised to the lung and the lung metastases in these cases were obtained from IOR, Bologna. Morphologically, primary tumours showed variable features, often containing both giant cell-rich and mononuclear stromal cell-rich areas. Mononuclear cells showed frequent mitotic activity and a degree of nuclear pleomorphism; none of the tumours showed cytological features of malignancy. The tumours were highly vascular and frequently contained dilated thin-walled blood vessels and large areas of haemorrhage. GCTB lung metastases were generally small and contained osteoclast-like giant cells and mononuclear stromal cells which showed typical mitotic activity; cytologically, the metastatic tumours were relatively bland and showed little nuclear pleomorphism. Expression of HLA-DR (an allele of which has been associated with a more aggressive GCTB phenotype) and smooth muscle actin (SMA) was noted in stromal cells in primary and secondary GCTBs; frequently, the same pattern of SMA expression was seen in both primary and secondary lesions. Osteoclasts were vitronectin receptor+, CD14-HLA-DR- in both primary and secondary GCTBs. Our findings indicate that mononuclear stromal cells in lung metastases of GCTB often recapitulate the immunophenotype of the primary tumours from which they derive. Taken with the morphological finding that many primary GCTBs are highly vascular and contain areas of haemorrhage, it is possible that the lung “secondaries” of GCTB more likely represent tumour implants than true neoplastic metastases


Orthopaedic Proceedings
Vol. 88-B, Issue SUPP_II | Pages 300 - 300
1 May 2006
Bandi S Narreddy J Birudavolu C Ravishankar P Reddy V Sagar S
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Objective: To report the use of a pedicled patellar transplant (d’ Aubigne procedure) in the reconstruction of femoral condyle for unicondylar giant cell tumours, in developing countries where facilities for custom made prostheses are not widely available. Case Report: A 28 year old male presented with 5 month history of left knee joint swelling and pain and 1 month history of inability to walk. X-ray showed eccentric, expansile lytic lesion of the lateral femoral condyle associated with a pathological fracture of the subchondral bone. A diagnosis of Enniking’s stage-III Giant cell tumour was made based on the x-ray and histopathology findings. Due to the associated subchondral fracture, joint reconstruction using custom made prosthesis was considered as an ideal option. But, as this prosthesis was not available, d’ Aubigne procedure was considered as an alternative, in order to preserve the joint. Femoral condyle was removed “en bloc” with the tumour. Patella was prepared with intact vastus lateralis and fixed in continuity and in level with the medial condyle. Gap between the patella and femoral shaft was filled by combined cancellous and cortical grafts from iliac crest and tibia. Post operative course was uneventful. After a follow up of 2 years there was no recurrence and the range of flexion was 90° without any instability and pain. Conclusion: In patients with unicondylar giant cell tumours with subchondral fractures, arthrodesis can be avoided and the joint can be preserved using pedicled patellar transfer, when arthroplasty can not be carried out


Orthopaedic Proceedings
Vol. 85-B, Issue SUPP_I | Pages 51 - 51
1 Jan 2003
Goto T Yokokura S Arai M Matsuda K Yamamoto A Kawano H Iijima T Takatori Y Nakamura K
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Tartrate-resistant acid phosphatase is contained in multinucleated giant cells of giant cell tumour of bone (GCT) and chondroblastoma (CBL) as well as in osteo-clasts. Yet few studies have so far been done regarding serum acid phosphatase (AcP) level in patients of GCT or CBL. The purpose of this study is to elucidate the clinical significance of serum AcP as a tumour marker for GCT and CBL. Serum AcP value was examined in nine GCT patients and three CBL patients before and after surgery. In the GCT cases, serum AcP values before surgery were high in five cases. They were 14.0 IU/L, 68.7 IU/L, 45.9 IU/L, 21.9 and 31.3 IU/L (normal value; 7.1–12.6 IU/L). They decreased after surgery to 7.7 IU/L (55% of the preoperative value), 8.2 IU/L (12%), 7.8 IU/L (17%), 6.1 IU/L (28%) and 10.0 IU/L (32%), respectively. Serum AcP values before surgery were within normal limits in the remaining four GCT cases. Even in these four cases, postoperative serum AcP level was lower than the preoperative level. Postoperative/preoperative AcP ratios in these four cases were 67%, 80%, 69% and 76%. In the CBL cases, serum AcP values were high in all cases. They were 15.1 IU/L, 13.1 IU/L and 13.7 IU/L. They decreased after surgery to 10.3 IU/L (68% of the pre-operative value), 10.2 IU/L (78%) and 9.7 IU/L (71%), respectively, all within normal limits. Therefore, it is concluded that serum AcP is a useful tumour marker for GCT and CBL in diagnosing the tumour as well as in evaluating the efficacy of treatment


Orthopaedic Proceedings
Vol. 92-B, Issue SUPP_III | Pages 445 - 445
1 Jul 2010
Yurttaş Y Başbozkurt M Kürklü M Demiralp B Özkan H Bilgiç S
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Giant cell tumor of the tendon sheath (nodular synovitis) is a benign soft tissue tumor, usually affecting older women, that most often occurs in the interphalangeal joints of the fingers, wrist or knee. Malign giant cell tumor of the tendon sheath is rare. We present a case of a 56-year-old woman presented with a slow-growing, painless mass on the anteromedial aspect of the ankle 5 year duration. Apparent rapid enlargement of the mass was observed and went under surgery. The resected tumor, measuring 50x21x28 mm.cm, was encapsulated and located on the tibialis anterior tendon sheath of the ankle. The tumor was intracapsular and its margins was clear. We performed radioterapy. The patient was quite well at the last follow-up 12 months after wide excision. It seems likely that may expect the good outcome, superficial location and the minority of the tumor composed of malignant component. However, long-term follow-up is mandatory, due to the poor prognosis


Orthopaedic Proceedings
Vol. 91-B, Issue SUPP_I | Pages 136 - 136
1 Mar 2009
Fabbri N Farfalli G Gamberi G Benassi S Briccoli A Mercuri M
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Introduction: Giant Cell Tumor (GCT) is rarely associated with lung metastases (1–4%). No prognostic factors have been reliably associated with the occurrence of lung metastases. Since high levels of urokinase-type plasminogen activation system have been associated with cancer metastasis, purpose of this study was to investigate its expression in patients with giant cell tumor and the relationship with outcome. Materials and Methods: Expression of urokinase-type plasminogen activation system was evaluated by immunohistochemistry in the primary lesion of 65 patients with GCT. This included urokinase-type plasminogen activator (u-PA), plasminogen activator inhibitor type 1 (PAI-1), and u-PA receptor (u-PAR). Patient population consisted of 12 cases that developed lung metastases and 53 cases that did not show metastases at last follow-up. Clinical outcome of the 2 groups was retrospectively reviewed and correlated with u-PA, PAI-1 and u-PAR expression levels. Results: Overexpression of u-PA, PAI-1 and u-PAR was more frequent in the metastatic (92%) than non-metastatic (21%) group (p< 0.0005). Incidence of local recurrence was higher in the metastatic (67%) than non-metastatic (30%) group (p=0,024). Risk of re-recurrence after 1st local recurrence was more than 4 times higher in the metastatic than non-metastatic group (p=0.05). No differences were observed in the 2 groups with respect to age, sex, site, stage, treatment, follow-up and mortality. Conclusions: Overexpression of urokinase-type plasminogen activation system in this study associated with an increased risk of lung metastases, local recurrence and local re-recurrence. Evaluation of urokinase-type plasminogen activation system expression levels may identify a subgroup of patients with increased risk of relapse


Orthopaedic Proceedings
Vol. 87-B, Issue SUPP_III | Pages 299 - 299
1 Sep 2005
Gitelis S Saiz P Virkus W Piasecki P Shott S
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Introduction and Aims: The treatment of Giant Cell Tumor (GCT) of bone ranges from resection to intra-lesional excision. The latter procedure preserves the joint and function. The purpose of this paper is to review functional and oncological outcomes for GCT treated by intralesional excision. Method: The medical records including radiology and pathology of 40 consecutive patients with GCT were retrospectively reviewed. Demographics, complications, tumor local control were determined. Functional evaluation using the MSTS system was performed on 23 patients. The data was subject to statistical analysis. Results: Forty patients (19M/21F). Mean age 28 years. Sites: femur 17, tibia 14, radius five, other four. Mean follow-up 90.3 months (26–178). Functional outcome: 93.2% (50–100). Complications: DJD two, fracture one. Recurrence: five (12.5%). Recurrence sites: Tibia two, femur one, radius one, and talus one. Recurrence treatment: 1/5 resection, 4/5 repeat intralesional excision. Recurrence outcome: 5/5 NED (mean 58.2 months). Conclusion: GCT treated by intralesional excision had excellent functional and oncological outcomes. The joint was preserved in most patients (95%) except due to recurrence 1 and fracture 1. The recurrences were successfully treated by repeat excision in 4/5 patients. Intralesional excision should be considered the preferred treatment for most giant cell tumors


Orthopaedic Proceedings
Vol. 90-B, Issue SUPP_III | Pages 466 - 467
1 Aug 2008
Cocciuti N Kyte R
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Giant cell tumours of bone involving the lower limb are characteristically close to the knee joint and pose a challenge in their treatment with respect to functional outcome, risk of recurrence and complications. Various treatment modalities exist, but it is widely accepted that intra-lesional curettage followed by local adjuvants and cementation of the defect may protect the integrity of the nearby joint and maintain function and stability. Many studies have reported on the use of various adjuvants and different methods of filling the defect left by intralesional curettage as well as fixation of impending or simultaneous pathological fractures with plate and screws. Up to 12 weeks, or more, of non weight bearing has been advised post-op, particularly in the larger lesions. We have encountered no evidence of the use of locking plates in augmenting reconstruction with PMA bone cement, particularly when a large lesion, displaying a very thin cortical envelope is encountered, and where there may be concern for knee strength and stability post-op. We surmised that the addition of such a rigid construct would be of benefit in aiding a faster rehabilitation. At our institution we have treated 3 patients in this manner: two patients had large giant cell tumours of the proximal tibia and one involving the distal femur. They were treated with intralesional curettage, liquid nitrogen, and bone cementation but in all three cases, we augmented the cement filler with a locking plate. Although we have a limited sample size, and our mean follow-up is only 12 months, it has been our experience that this approach may provide an immediately stable knee, rapid rehabilitation with return to full weight bearing within 4–6 weeks and very good post-operative function by 3 months post-op, with few complications


Orthopaedic Proceedings
Vol. 92-B, Issue SUPP_III | Pages 440 - 440
1 Jul 2010
Gibbons C Jones F Taylor R Knowles H Hogendoorn P Wass J Balke3 M Gebert3 C Athanasou NA
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Giant cell tumour of bone (GCTB) is an expansile osteolytic tumour of bone which contains numerous osteoclast-like giant cells. GCTB is a locally aggressive tumour which can cause extensive bone destruction that can be difficult to control surgically, up to 35% of cases recurring after simple curettage. Bisphosphonates are anti-resorptive agents that have proved effective in the treatment of a number of osteolytic conditions. In keeping with its known effect on osteoclasts, we found that the aminobisphosphonate zoledronate abolished in vitro lacunar resorption in cultures of osteoclasts isolated from GCTB. The effect of zoledronate and other bisphosphonates on 15 cases of recurrent primary GCTB, four of which had metastasised to the lung, was assessed clinically. Most recurrent tumours did not exhibit progressive enlargement and, in some cases, both primary and metastatic GCTBs showed a degree of radiological improvement following treatment However, tumours did not diminish in size and, in some cases, no apparent treatment effect was noted. Our findings provide in vitro evidence for the use of bisphosphonates to inhibit the progressive osteolysis associated with GCTB. In vivo, these agents produced a degree of clinical and radiological improvement in some cases. This study reports results from three European centres where bisphosphonates are being used to treat recurrent GCTB and highlights the fact that these centres are all employing different clinical indications and different regimes of bisphosphonate treatment. Bisphosphonates have significant side effects and indications for treatment and standardisation of drug type and dosage regimes (and measurement of agreed outcome measures to determine treatment efficacy) should be established before these agents are included as part of a treatment protocol to control GCTB tumour growth and osteolysis


Orthopaedic Proceedings
Vol. 87-B, Issue SUPP_I | Pages 10 - 10
1 Mar 2005
Robertson I
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This is a retrospective study of 14 cases from clinical records and the Bone Tumour Registry over the last 20 years. The mean follow-up time was 27 months (3 to 60). Two of the cases were referred elsewhere for final treatment and the relevant clinical records were obtained by correspondence with the treating doctor. Most tumours occurred about the knee, with two in the distal femur and five involving the proximal tibial metaphysis. Three were in the forearm and one in the humerus. Once diagnosis had been made on clinical and radiological grounds, the tumours were curetted. Cryosurgery was used in four cases and phenol in two. Structural integrity was restored by autogenous bone grafting in most cases. Two of these were vascularised free grafts. Two patients had arthrodeses (one ischiofemoral and one wrist) and two were referred for custom-made joint replacements. There was only one local recurrence. Of the adverse outcomes, three required late amputations, one for varus malunion and recurrence, and two for nonunion and chronic sepsis. Giant cell tumour of bone has a low rate of recurrence. The treatment challenge is to avoid sepsis and graft collapse. Large bone grafts often fail to incorporate fully, which can lead to angular deformities. A combination of bone cement, reinforced with Ender rods with bone cement to the subchondral surface, promises to be a more satisfactory method in and around the knee


The Bone & Joint Journal
Vol. 97-B, Issue 11 | Pages 1566 - 1571
1 Nov 2015
Salunke AA Chen Y Chen X Tan JH Singh G Tai BC Khin LW Puhaindran ME

We investigated whether the presence of a pathological fracture increased the risk of local recurrence in patients with a giant cell tumour (GCT) of bone. We also assessed if curettage is still an appropriate form of treatment in the presence of a pathological fracture. We conducted a comprehensive review and meta-analysis of papers which reported outcomes in patients with a GCT with and without a pathological fracture at presentation. We computed the odds ratio (OR) of local recurrence in those with and without a pathological fracture. . We selected 19 eligible papers for final analysis. This included 3215 patients, of whom 580 (18.0%) had a pathological fracture. The pooled OR for local recurrence between patients with and without a pathological fracture was 1.05 (95% confidence interval (CI) 0.66 to 1.67, p = 0.854). Amongst the subgroup of patients who were treated with curettage, the pooled OR for local recurrence was 1.23 (95% CI 0.75 to 2.01, p = 0.417). . A post hoc sample size calculation showed adequate power for both comparisons. . There is no difference in local recurrence rates between patients who have a GCT of bone with and without a pathological fracture at the time of presentation. The presence of a pathological fracture should not preclude the decision to perform curettage as carefully selected patients who undergo curettage can have similar outcomes in terms of local recurrence to those without such a fracture. Cite this article: Bone Joint J 2015;97-B:1566–71


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_3 | Pages 64 - 64
1 Mar 2021
Aoude A Lim Z Perera J Ibe I Griffin A Tsoi K Ferguson P Wunder J
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Benign aggressive tumors are common and can be debilitating for patients especially if they are in peri-articular regions or cause pathological fracture as is common for giant cell tumor of bone (GCT). Although GCT rarely metastasize, the literature reports many series with high rates of local recurrence, and evidence about which risk factors influence recurrence is lacking. This study aims to evaluate the recurrence rate and identify local recurrence risk factors by reviewing patient data from a single high-volume orthopedic oncology center. A retrospective analysis of all patients treated for GCT at a tertiary orthopedic oncology center was conducted. In total 413 patients were treated for GCT between 1989 and 2017. Multiple patient and tumour characteristics were analysed to determine if they influenced local recurrence including: age, gender, anatomical site, Campanacci stage, soft tissue extension, presence of metastasis, pathologic fractures, and prior local recurrence. Additional variables that were analysed included type of treatment (en bloc resection or aggressive intralesional curettage) and use of local adjuvants. The main outcome parameters were local recurrence- free survival, metastasis-free survival and complications. Patients treated with Denosumab were excluded from analysis given its recently documented association with high rates of local recurrence. “There were 63/413 local recurrences (15.3%) at a mean follow-up of 30.5 months. The metastatic rate was 2.2% at a mean 50.6 months follow-up and did not vary based on type of treatment. Overall complication rate of 14.3% was not related to treatment modality. Local recurrence was higher (p=0.019) following curettage (55/310; 17.7%) compared to resection (8/103; 7.8%) however, joint salvage was possible in 87% of patients (270/310) in the curettage group. Use of adjuvant therapy including liquid nitrogen, peroxide, phenol, water versus none did not show any effect on local recurrence rates (p= 0.104). Pathological fracture did not affect local recurrence rates regardless of treatment modality (p= 0.260). Local recurrence at presentation was present in 16.3% (58/356) patients and did not show any significance for further local recurrence (p= 0.396). Gender was not associated with local recurrence (p=0.508) but younger patient age, below 20 years (p = 0.047) or below 30 years (p = 0.015) was associated with higher local recurrence rates. GCT in distal radius demonstrated the highest rate of local recurrence at 31.6% compared to other sites, although this was not significant (p=0.098). In addition, Campanacci stage and soft tissue extension were not risk factors for recurrence. The overall GCT local recurrence rate was 15.3%, but varied based on the type of resection: 17.7% following joint sparing curettage compared to 7.8% following resection. Local recurrence was also higher with younger patient age (30 years or less) and in distal radius lesions. In addition, neither Campanacci stage, soft tissue extension or presence of a pathologic fracture affected local recurrence. Most patients with GCT can undergo successful curettage and joint sparing, while only a minority require resection +/− prosthetic reconstruction. Even in the presence of soft tissue extension or a pathologic fracture, most joints can be salvaged with curettage


Orthopaedic Proceedings
Vol. 92-B, Issue SUPP_IV | Pages 603 - 603
1 Oct 2010
Lovse T Glehr M Leithner A Maurer-Ertl W Pechmann M Windhager R
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Introduction: Giant cell tumor of bone is a semimaligne tumor which locally recurs very often but rarely metastasises. En bloc resection of the distal radius with reconstruction using a homologeous allograft, curettage with PMMA blomb, and allograft arthrodesis are established methods. The aim of the study was to evaluate the functional outcome of our patients with the DASH-Score and the Mayo Wrist Score. Materials and Methods: In the last 7 years six patients were treated at our clinic due to a giant cell tumor of the distal radius. Two patients were primary treated with an en bloc resection. The other four were primary treated with curettage and filled up with PMMA cement plomb (Phenol was used in every case). In two of these cases a secondary en bloc resection was performed for local recurrence. For evaluation of function in daily live we used the DASH Score and the MAYO wrist score. Results: The mean bone resection length was 5,25cm (5–6 cm). All four patients treated with en bloc resection (primary or secondary) had no recurrence but in two out of that cases a re-operation was necessary because of non union. At a mean follow up from 27 months (4–95) there were no recurrences or metastases at all. The flexion/extension of the wrist in currettaged radius was 60° and 80° compared with 38° and 68° in reconstructed radius. The pronation/suppination was 90°/90° in the currettaged ones versus 77°/77° in the allograft replaced ones. The functional outcome evaluated with Mayo Wrist Score and DASH score showed an exellent outcome for both groups (84/7,7 Allograft < -> 85/10 Currettage). Discussion: Functional outcome of distal radius resection reconstruction using an allograft is highly satisfactory compared with the literature, however we experienced a high risk for pseudoarthrosis. For prevention of non union simultan bone grafting at the index operation could be advisable. The functional outcome proof no disadvantages in daily life and daily work compared to curettage. Thus allograft reconstruction of the distal radius represents a valuable alternative to arthrodesis


Orthopaedic Proceedings
Vol. 92-B, Issue SUPP_III | Pages 443 - 443
1 Jul 2010
Penna V Babeto E Toller E Becker R Pinheiro C Pires L Valsechi M Kerr L Peitl P Rahal P Morini S
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The giant cell tumor of bone (GCT) is a locally aggressive intraosseous neoplasm, with an uncertain biological behavior, constituted of giant multinuclear cells spread over tumoral tissue with a nucleus presenting the same features of the ovoid and fusiform cells forming its stroma. The local recurrence of GCT is often observed, mainly in the first three years after treatment, giving a rate of recurrence ranging in 20 to 50% of cases. Further aggravating the recurrence is the fact that after the relapse, the patient often also presents metastases in other organs. The aim of this study was to identify and to characterize differentially expressed genes that can be used in the prognostic, treatment and understanding of this physiopathology. To identify novel genes differentially expressed in GCT, we have applied rapid subtractive hybridization (RaSH). Samples of GCT and normal tissues were obtained at Tumor Bank of Barretos Cancer Hospital. After RNA extraction and cDNA synthesis the samples were submitted to Rapid hybridization Subtraction (RaSH) methodology for subtractive libraries elaboration. The RaSH subtractive libraries reveals the presence of 619 different clones including both normal and tumor tissues were identified. Of these, 450 in tumor sample and 169 in control tissue. Four biomarkers candidates were selected for validation: ZAK, KTN1, NEB, and ROCK1 genes, whose functions are, related to cell cycle checkpoint, transport of organelles, cytoskeletal matrix and cell adhesions. The validation of selected differentially expressed genes was performed using real time PCR. The putative molecular markers found in this work may help to find the basis for a molecular comprehension of GCT, thus improving diagnosis, treatment and outcome for patients with this tumor


Orthopaedic Proceedings
Vol. 92-B, Issue SUPP_III | Pages 444 - 444
1 Jul 2010
Noort-Suijdendorp AV Kroep J Gelderblom H Hogendoorn P Taminiau A Dijkstra P
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Giant cell tumour of bone (GCT) is a primary osteolytic neoplasm, histopathologically characterized by osteoclast-like giant cells and clinically characterized by local bone destruction and high recurrence rates. There is a need to identify risk factors for recurrence. In order to reduce the recurrence rate we initiated an international, multicenter, randomised phase II trial with adjuvantzoledronic acid as compared to standard care for high risk GCT patients. One hundred and sixteen GCT patients, treated at the LUMC from 1971 to 2006, with a minimal follow-up of a year, were retrospectively analysed for the following risk factors for local recurrence: GCT grade III and tumour involvement into soft tissue caused by ingrowth or fracture. Resection was used as treatment in 21 patients (group A), intralesional surgery with cement or adjuvant in 24 (group B) and intralesional surgery with cementation and adjuvant in 71 patients (group C). GCT recurred in 5% (1/21) in group A. Risk factors were found in 90% of patients without recurrence (18/20). Group B shows a recurrence of 25% (6/24). Risk factors were found in 83% (5/6) of recurring GCTs, compared with 28% in patients without recurrence. In group C, a recurrence rate of 23% (16/71) was found. Risk factors were present in 94% (15/16) of recurrences, compared to 36% (20/55) in patients without recurrence. Soft tissue involvement and GCT grade 3 and up are risk factors for recurrence in GCT. Recurrence rates are lowest when resection is used. Risk factors may influence the choice of treatment. High risk patients may benefit from resection or systemic treatment with adjuvant therapy


Orthopaedic Proceedings
Vol. 92-B, Issue SUPP_III | Pages 444 - 444
1 Jul 2010
Lovse T Maurer-Ertl W Pechmann M Glehr M Leithner A Windhager R
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Giant cell tumor of the distal radius is associated with a high local recurrence rate. En bloc resection of the distal radius and reconstruction using osteoarticular allograft, curettage with PMMA blomb, and allograft arthrodesis are established methods. The aim of the study was to evaluate the functional outcome of our patients with the DASH-Score and the Mayo Wrist score. In the last 7 years six patients were treated at our department due to a giant cell tumor of the distal radius. Two patients were primary treated with an en bloc resection. The other four were primary treated with curettage packing of the defect with polymethylmethacrylate. In two of these cases a secondary en bloc resection was performed for local recurrence. For evaluation of function in daily live we used the DASH score and the MAYO wrist score. The mean bone resection length was 5,25cm (5–6 cm).All four patients treated with en bloc resection (primary or secondary) had no recurrence but in two out of that cases a re-operation was necessary because of non union. At a mean follow up from 27 months (4–95) there were no recurrences or metastases at all. The flexion/extension of the wrist in currettaged radius was 60°/80° compared with 38°/68° in reconstructed radius. The pronation/suppination was 90°/90° in the currettaged ones versus 77°/77° in the allograft replaced ones. The functional outcome evaluated with Mayo Wrist Score and DASH score showed an excellent outcome for both groups (84/7,7 Allograft < -> 85/10 Currettage). Functional outcome of distal radius resection reconstruction using an allograft is highly satisfactory compared with the literature, however we experienced a high risk for pseudoarthrosis. For prevention of non union simultaneous bone grafting at the index operation could be advisable. Thus allograft reconstruction of the distal radius represents a valuable alternative to arthrodesis


Orthopaedic Proceedings
Vol. 88-B, Issue SUPP_II | Pages 331 - 332
1 May 2006
Manaute JR Laakso RB Lòpez JG Lopez-Barea F
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Introduction and purpose: Benign giant cell tumours (GCT) are locally aggressive and may transform into primary sarcomatous tumours (1–3%) following recurrence (10–15%) and lung metastases (1–6%) even with benign histology. However, survival in these cases is high (96–100% of transformations and 15–50% of metastases). Recurrences after en-block resection are less common (0–5%), but curettage together with bone graft and/or adjuvant therapy achieves acceptable recurrence rates (0–34%) with lower morbidity. The purpose of this study is to analyse our results after en-block resection and curettage. Materials and methods: Retrospective series of 19 patients with GCT operated on between 1988 and 2002 with en-block resection and local reconstruction or curettage and allograft or cement. Location: proximal tibia (3), distal femur (4), hip (3), proximal humerus (2) and distal radius (6). We describe the recurrences, metastases, deaths and complications according to treatment. Results: There were no recurrences in 9 cases of en-block resection and we performed local reconstruction with a prosthesis (3), allograft (5) or VFG (1). The rest (10) underwent curettage with cement (2) or allograft (8). We had one recurrence treated with en-block resection and prosthesis. There were no metastases, deaths or other complications. Conclusions: Although there were no recurrences with the en-block resection, curettage resulted in acceptable control of the disease with less morbidity. As a general rule, we tried to preserve the joint even with lesions in advanced stages


Orthopaedic Proceedings
Vol. 85-B, Issue SUPP_I | Pages 46 - 46
1 Jan 2003
Khwaja H Cole A Gibbons C Cooke P Athanasou N
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Giant Cell Tumour of the Tendon Sheath is a benign tumour of synovial origin most frequently affecting the upper limb. Up to 11% exhibit radiographic evidence of cortical erosion and intra-osseous expansion. In the upper limb recurrence rates of between 10–50% following excision have been reported. However, GCT-TS is rarely described in the foot and ankle and its behaviour is ill understood. 17 cases of this rarely described tumour in the foot and ankle are presented, describing their clinical presentation, histopathology, treatment and outcome. Analysis of all cases of histopathologically proven GCT-TS of the foot and ankle from the Oxford Tumour Registry, was conducted between the periods of January 1984 to December 1999. 22 cases were identified of which 17 cases had adequate records to allow analysis of patient demographics, duration of symptoms, preoperative investigations, presumed diagnosis, precise site of origin, post operative complications and recurrence rates. The mean age of presentation was 28 (8–53). 10 cases were female and 7 male. 76% cases occurred in the foot, all of which arose adjacent to the phalanges or heads of the metatarsals. 14% occurred in relation to the ankle or sub-talar joint. 82% presented with a painless swelling. The duration of symptoms ranged from 6 months to 8 years. Only one patient complained of sensory symptoms. Pre-operative investigations included radiographs in 64% with 3 cases having an additional MRI scan. The MRI scans of GCT-TS have characteristic changes on T1 and T2 images. The presumed preoperative diagnosis was incorrect in 82%. 36% of radiographs taken showed changes including cortical erosion and speckled calcification. A local excision was performed in 15 cases, an amputation in one and a wide local excision in one case only. There have been no recurrences during the follow up period of between 1–12 years. GCT-TS of foot and ankle is rare and is commonly misdiagnosed. Despite only a local excision being performed in more than 80% of this series there were no recurrences. Plain radiographs may show cortical erosion or speckled calcification in up to 36% and MRI is helpful in further defining the anatomy of the lesion, allowing planned excision and reducing the risk of recurrence


Orthopaedic Proceedings
Vol. 91-B, Issue SUPP_II | Pages 252 - 252
1 May 2009
Rabinovich A Thornhill O Colterjohn N Cowan R Ghert M Simunovic N Singh G
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Giant cell tumor (GCT) of bone is an osteolytic tumor that is locally aggressive and potentially metastatic. The pathogenesis of GCT is poorly understood. The purpose of this study was to harvest and culture primary cell lines from clinical specimens of GCT of bone and identify specific bone degradation proteases (matrix metalloproteinases: MMP-2, MMP-9) produced by the neoplastic stromal cells in vitro. With approval by the McMaster University Biohazards and Ethics Review Boards, we acquired consent from five patients with GCT of bone, and harvested specimens intraoperatively. The specimens were chopped in DMEM containing 10% Fetal Bovine Serum, 2 mM L-glutamine, 100 U/ml penicillin and 100 mg/ml streptomycin. The cell suspensions were incubated at thirty-seven degrees (5% CO2 and 95% air) and cultivated. The cells were grown to confluence and taken through several passages until only proliferative cells were present. Immunocytochemistry with TRAP (Tartrate Resistant Acid Phosphatase) was used to confirm the stem cell origin of the propagative cells. Protein electrophoresis with embedded gelatin was used for detecting protease activity (MMP-2, MMP-9) on cell lysates and medium. P-aminophenyl mercuric acetate (APMA) was used to activate and ethylenediaminetetraacetic acid (EDTA) was used to block MMP-2 and MMP-9 activity. Our controls included serum free media, Human Osteosarcoma and Fibroblast cell lines. Immunocytochemistry with TRAP confirmed that our propagative cells were not hematopoietic in origin but rather mesenchymal. Protein electrophoresis on cell lysates and medium identified the protease activity of MMP-2 and MMP-9 with lytic bands at appropriate molecular weights. APMA activated MMP-2 more than MMP-9, as indicated by increased relative density of bands. EDTA blocked the activity of both MMPs. Our study confirmed the ability to cultivate the neoplastic stromal cells of GCT of bone from clinical specimens. Protein electrophoresis showed that activated MMP-2 and MMP-9 are secreted from the neoplastic stromal cells in vitro, suggesting a role for the tumor cells in bone destruction. These results are intriguing, as novel therapies in specific MMP inhibitors are currently underway for numerous disease processes


Orthopaedic Proceedings
Vol. 92-B, Issue SUPP_II | Pages 281 - 281
1 May 2010
Peirò A Gracia I Oller B Pellejero R Cortés S Moya E Rodriguez R Doncel A Majò J
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Goals: Sarcomatous degeneration of giant cell tumours (GCT) occurs rarely. It occurs in less than 1% of the cases, and most of them are GCT previously treated with radiotherapy. The goal of this presentation is to review the CGT cases treated at our unit that have evolved towards malignization. Methods: Retrospective study of 96 GCT treated at our Hospital between 1983 and 2005. 5 presented sarcomatous degeneration in their evolution. These were the cases of 3 men and 2 women with a mean age of malignization of 42 years (32 years – 54 years). The median follow-up period was 155 months (5 months – 209 months). 3 cases affected the distal femur, one case affected distal radius and one case affected proximal humerus, with a slight tendency to the right hemibody. The primary treatment for GCT in these patients was curettage and bone graft. Only one case had received previous radiotherapy. In the same period of time we had two cases of lung dissemination of CGT with typical histology, without previous malignization of tumour. Results: Malignization takes place, on average, at the 1.8th recurrence (1.3). Histologically, we find 3 osteosarcomas and 2 indifferentiated tumours. Three patients developed distant dissemination; 2 patients died due to lung metastases, with a mean time between the first surgery and the sarcomatous degeneration of 90 months (40 monts – 183 months) and a mean time between malignization and mestastases of 22.3 months (9 months – 34 months) The treatment, once the malignization was diagnosed, consisted in wide resection and substitution with mega-arthroplasty in cases of distal femur and osteoarticular graft at the shoulder. 2 cases required amputation of the affected limb due to irresecable recurrence in soft tissues. Conclusions: There is no predictive criteria of which type of primary typical CGT will evolve into sarcoma. The malignization always has as a result high grade sarcomas, with a high tendency to hematogenous dissemination. When lung metastases appear the survival prognosis is a number of months. We must suspect malignization of a benign CGT when one of the relapses shows a very rapid growth with radiologic aggressive characteristics; in these cases we prefer wide resection of the tumour instead of curettage and thus we prevent the possible sarcomatous degeneration


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XIV | Pages 54 - 54
1 Apr 2012
Dadia S Gortzak Y Kollender Y Bickels J Meller I
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Aim. Giant cell tumour (GCT) of bone is a benign but locally aggressive tumour. Although topical adjuvants have been used in the past, local recurrence following intralesional excision of GCT of bone continues to remain a problem. The use of bisphosphonates as an anti-osteoclastic agent in the management of osteolytic bone metastases is well accepted. Therefore our study aims to retrospectively demonstrate whether the administration of bisphosphonate as an adjuvant can control aggressive local recurrence of GCT and prevent wide resections of bones or amputations. Method. A retrospective study was performed between 2004 and 2010. 6 patients were diagnosed with aggressive local recurrence of appendicular GCT. All patients were treated for the primary tumour by surgical curettage and cryoablation followed by cementation or biological reconstruction. In 5 patients the tumour was located in the distal radius and in one in the first metacarpal bone. All recurrences were in the bone with large soft-tissue extension. After histological diagnosis – by CT core needle biopsy – the patients were treated by intravenous bisphosphonate, followed by clinical & radiological assessments. Results. Average follow-up of 42 months, ranging from 12 to 72 consecutive months. All patients showed good response to bisphosphonate treatment: lesions become calcified gradually as shown in x-rays & CT scans, reduction in size of soft tissue components, patient reported relief of pain & improvement of the affected limb. All treated patients did not report any untoward effects. Conclusion. In the current study bisphosphonate treatment is found to be an effective treatment for local control of aggressive local recurrence of GCT of the extremities and can therefore be a good alternative to wide resections of bone and complicated reconstructions. Functional results are shown to be promising as well. The study results need further investigation & a larger scale of patients


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XXXVII | Pages 302 - 302
1 Sep 2012
Van Der Heijden L Van De Sande M Nieuwenhuijse M Dijkstra P
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Background. Giant cell tumours of bone (GCT) are benign bone tumours with a locally aggressive character. Local recurrence is considered the main complication of surgical treatment and is described in up to 50% of patients. Intralesional curettage with the use of adjuvants like phenol or polymethylmetacrylate (PMMA) is recommended as initial treatment, significantly decreasing the risk of recurrence. However, risk factors for local recurrence in skeletal GCT have not yet been firmly established and a golden standard for local therapy remains controversial. Objective. The identification of risk factors predisposing for an increased risk of local recurrence. In addition, different surgical techniques are compared to identify the optimal surgical approach for the identified risk factors. Methods. In a retrospective study all 215 patients with bone GCT treated between 1964 and 2009 in one centre were included, of which 193 were suitable for analysis. All patients had minimal follow-up of 12 months (mean 115; range 12–445). Using a Kaplan Meier survival analysis recurrence free survival rates were calculated. Cox-regression was used to determine the influence of different types of therapy, the use of adjuvants, and various patient and tumour characteristics. Results. The mean local recurrence rate for all patients was 35.2% (n=68, 95%CI: 28.3–42.1). Recurrence rate after wide resection was 0.17 (n=6, 95%CI: 0.04–0.29), after curettage with adjuvants 0.32 (n=42, 95%CI 0.24–0.41) and after curettage alone 0.74 (n=20, 95%CI: 0.57–0.91, p < 0.001). Soft tissue extension (Hazard Ratio: 3.8, p < 0.001), localisation in radius and ulna (HR: 2.6, p=0.013), and surgical experience (HR: 2.2, p=0.022) were identified as significant general risk factors for local recurrence. For intralesional resection, Campanacci grade III (HR: 3.9, p=0.019) and location in axial skeleton (HR: 3.3, p=0.016) additionally significantly increased this risk. Comparing treatments our data showed that curettage followed by adjuvants was superior to curettage alone (p < 0.004), and the application of both phenol and PMMA did not present a significantly better outcome than curettage and PMMA alone (HR: 1.07, p=0.881). Conclusion. Of all possible risk factors only soft tissue extension, localisation in radius and ulna and non-radical resections significantly influenced the risk of local recurrence for all treatments. In addition, we found that high-grade tumours and localisation in the axial skeleton were additional risk factors for local recurrence after intralesional surgery. Although wide resection increases patient morbidity, it can be the therapy of choice in high risk patients. Intralesional therapy can be advised for low recurrence risk patients using curettage and PMMA only, whereas our study could not confirm the predicted effect of phenol as an additional adjuvant


Orthopaedic Proceedings
Vol. 92-B, Issue SUPP_I | Pages 67 - 67
1 Mar 2010
Gibbons C Kliskey K Sabokbar A Lau WS Sun SG Athanasou N
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Introduction: Osteoclast-like multinucleated giant cells (MNGCs) are found in a number of soft tissue sarcomas including malignant fibrous histiocytoma and leiomyosarcoma. The nature of these MNGCs is poorly understood and the cellular mechanisms underlying their accumulation in sarcomas is not known. Methods: We analysed by immunohistochemistry the expression of osteoclast, macrophage and smooth muscle markers by mononuclear and multinucleated cells in two cases of giant cell-rich leiomyosarcoma. We also characterised the role of mononuclear stromal cells and tumour-associated macrophages in the formation of MNGCs by RT-PCR, cell culture studies and immunohistochemistry/histochemistry for macrophage, osteoclast and smooth muscle markers. Results: MNCGs in giant cell-rich leiomyosarcoma expressed an osteoclast-like phenotype, being negative for smooth muscle actin and CD14 but positive for tartrate-resistant acid phophatase (TRAP), CD45, CD68 and vitronectin receptor (VNR). Scattered mononuclear cells expressing an osteoclast-like antigenic phenotype were also noted. An analysis of 25 conventional (non-giant cell-containing) leiomyosarcomas found isolated CD68+ MNGCs in three cases (approximately 12%); all of these cases were Grade-II/III leiomyosarcomas in which there was a prominent tumour-associated macrophage (TAM) infiltrate. Leiomyosarcoma TAMs isolated from two cases of conventional leiomyosarcoma and cultured in the presence of the osteoclastogenic factors RANKL and M-CSF differentiated into TRAP+/VNR+ MNGCs that were capable of lacunar resorption. RT-PCR studies showed that cultured leiomyosarcoma mononuclear stromal cells expressed RANKL, OPG and TRAIL. Discussion: These findings show that the MNGCs which are found in leiomyosarcomas are osteoclast-like in nature and that these MNGCs are formed from TAMs by a RANKL dependent mechanism which involves an interaction with RANKL-expressing mononuclear stromal cells. A similar mechanism is likely to account for MNGC accumulation in other soft tissue sarcomas


Orthopaedic Proceedings
Vol. 92-B, Issue SUPP_III | Pages 444 - 444
1 Jul 2010
Noort-Suijdendorp AV Dijkstra P Taminiau A
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Giant cell tumors (GCT) of the sacrum have a high recurrence rate, up to 33%. Treatment of Giant Cell Tumors (GCT) of the sacrum has many options. Although curettage is more often performed than partial sacral resection the indications are not well described. Large resection in the sacral area is limited, and adequate local adjuvant therapy potentially damages the nervous system. Therefore the type of surgical treatment of sacral GCT is still under debate. The purpose of this study was to compare clinical outcome after surgical treatment in GCT of the sacrum using two different surgical techniques: curettage and Extended Cortical Excision (ECE). Pre-operative embolisation was routinely performed, followed by curettage or PSR followed by reconstruction if indicated. Between 1994–2005 11 patients were treated for GCT of the sacrum. Eight were female, 3 men. The median age was 43.5 (14–66) years. The median follow-up period was 60 (6–156) months. Five patients were eventually treated by ECE. The other patients were operated on using different techniques, mainly curettage and/or adjuvant therapy. Two patients died disease-related 42 and 6 months after primary treatment, both metastasized. All other patients are alive and currently disease-free. Six patients had a recurrence, after 33 (4–140) months. Three patients had a recurrence twice. Three patients received radiotherapy, 1 as palliative treatment and 2 as (adjuvant) therapy for recurrence. No recurrences were seen after ECE compared to 86% (6/7) after curettage only, and 50% (2/4) after curettage with adjuvant therapy. Extended cortical excision may improve the recurrence rate in sacral GCT


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XXX | Pages 4 - 4
1 Jul 2012
van de Sande M van der Heijden L Gibbons M Dijkstra P
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Introduction. Local recurrence of Giant cell tumours of bone (GCT) is considered the main complication of surgical treatment (50%). Intra-lesional curettage with adjuvants like phenol or polymethylmethacrylate (PMMA) is recommended as initial treatment, decreasing the risk of recurrence. However, risk factors for local recurrence in skeletal GCT have not yet been firmly established and a golden standard for treatment remains controversial. Aim of this study is identification of risk factors for recurrence in GCT, specifically after intra-lesional curettage with or without adjuvants. Methods. In a retrospective single-institution study 191 patients treated for GCT between 1964 and 2009 were included. Mean follow-up was 111 months (range 12-415). The recurrence-free survival and hazards for different treatment strategies and various patient and tumour characteristics were determined. Results. Overall risk of recurrence was 36.1% (n=66, 95% CI: 28.3-42.1). Recurrence rate after wide resection was 20%, after curettage with adjuvants 33% and after curettage alone 77%. Hogendoorn-grade III (Hazard Ratio: 5.7, p⋋0.001), localisation in axial skeleton (HR: 3.7, p⋋0,001), primary treatment in a non-specialised centre (HR: 2.8, p⋋0.001) and extension into soft tissue (HR: 2.0, p=0.02) were significant risk factors for local recurrence. Curettage with adjuvants proved superior to curettage alone (p⋋0.004 p=0.07, HR: 0.54), but the application of both PMMA and phenol did not present a significantly better outcome than PMMA alone (HR: 1.07, p=0.9). Discussion. Of all possible risk factors only soft tissue extension and localisation in distal radius significantly influenced the risk of local recurrence for all treatments. We found that high-grade tumours and localisation in the axial skeleton were additional risk factors for local recurrence after intra-lesional surgery. Although wide resection increases morbidity, it can be the therapy of choice in high risk patients. Intra-lesional therapy can be advised for low risk patients using curettage adjuvants and PMMA


Orthopaedic Proceedings
Vol. 92-B, Issue SUPP_III | Pages 443 - 443
1 Jul 2010
Balke M Ahrens H Streitbuerger A Koehler G Winkelmann W Gosheger G Hardes J
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Although the recurrence rate of giant cell tumors of bone (GCTB) is relatively high exact data on treatment options for the recurrent cases is lacking. The possible surgical procedures range from repeated intralesional curettage to wide resection. 214 patients with histologically certified GCTB have been treated at the authors department from 1980 to 2007. 67 patients with at least one local recurrence were included in this study. The mean follow-up was 77.3 months. The data was evaluated according the re-recurrence rate with regard to the surgical procedure for the recurrence. The mean time until the first local recurrence was 22.0 months; the mean number of recurrences per patient was 1.4. The recurrence occurred in 69.7 % (46 out of 66 patients) within the first two years. If after intralesional procedures (curettage or intralesional resection) no adjunct was used the re-recurrence rate was 58.8 % (10 out of 17 patients) and decreased to 21.7 % (5 out of 23 patients) if a combination of all adjuncts (PMMA + burring) was used. The likelihood of re-recurrence was reduced by the factor 5.508 which was clearly significant (p = 0.016). In case of wide resection no re-recurrence occurred. Seven patients (10.5 %) developed pulmonary metastases. Fourteen patients (20.9 %) finally received an endoprosthesis; 12 due to tumor recurrence, 2 due to secondary arthritis. Recurrent GCTB can be treated by further curettage with additional burring and cementing with an acceptable re-recurrence rate of 21.7 %. The rate of patients finally needing an endoprosthesis is 20.9 %. Due to the high rate of pulmonary metastases recurrent GCTB may be considered as a severe disease


Orthopaedic Proceedings
Vol. 84-B, Issue SUPP_III | Pages 217 - 217
1 Nov 2002
Nakamura Y Ozeki S Yasumura K Koike H Jinnai M Nohara Y
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Introduction: The confocal laser-scanning microscope (CSLM) was recently introduced. We have invented a new transmission type of double pass CSLM. This study is the first report of valuable pathological information related to bone tumor being derived using such microscopy. Methods: The most remarkable characteristic of this microscope is the use of two laser beams twice passing through the specimen. This laser microscope can detect signals from coloring sources such hematoxylin eosin (HE) stain and obtain clear images of the organelles. The images presented here were built up as electronic signals, processed by computer analysis, and stored in frame memory. Specimens of the giant cell tumor stained with HE were examined directly by the phase contrast mode of this microscope and computer analysis was performed. Double pass CSLM and conventional microscopic views were then compared. Results: We successfully observed sharply and sensitively positive fine granules in our laser microscopes provided higher magnification, resolution and contrast than did conventional ones. CSLM provides high magnification, contrast, resolution and can be used to observe living cells in culture in real time. With the combination of double pass CSLM and computer analysis, clear images of the subcellular organelles of various cells were successfully visualized. Conclusion: This study suggests that double pass CSLM is an important tool for analyzing the cellular ultrastructure, physiology, and function of bone tumor. Double pass CSLM is also a powerful new instrument for orthopedics, complementing light and electron microscopy


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XXX | Pages 5 - 5
1 Jul 2012
Gaston C Bhumbra R Watanuki M Abudu A Carter S Jeys L Tillman R Grimer R
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Introduction. The role of adjuvants in curettage for giant cell tumours (GCT) is still controversial. Our aim was to determine if adjuvant cementation lowers local recurrence (LR) rates for GCTs treated with curettage. Methods. Detailed curettage has been the principal treatment for GCT for the past 30 years. Cement was used from 1996 onwards for tumours where there was concern about structural stability. We investigated factors affecting LR and also the incidence of complications for treatment with or without cement. Results. From 1975 to 2008, 330 patients with GCT were treated primarily with curettage. Eighty-four (25%) received adjuvant treatment with acrylic bone cementation. Cement was only used in Campannacci grade 2 or 3 GCTs. LR for curettage was 30% compared with 14% for curettage plus cementation. (p = 0.001). LR was halved by the use of cement for both stage 2 and stage 3 tumours (Stage 2, 8% LR with cement, 21% without (p=0.02); Stage 3, 19% with cement, 48% without (p⋋0.001)). On multivariate analysis both stage and use of cement were independent significant factors in predicting LR. Site was not significant although the distal tibia and proximal humerus had lower risk of LR than other sites. Cement was however associated with a higher risk for subsequent joint replacement surgery. In patients without LR, 18% with cement needed a joint replacement compared to 2% without. In patients with LR, 75% with cement required a joint replacement, compared to 44% without. Discussion. Although adjuvant cementation seems to give better local control for curettage of GCT, it is associated with an increased need for subsequent joint replacement


Orthopaedic Proceedings
Vol. 87-B, Issue SUPP_I | Pages 76 - 77
1 Mar 2005
Maruthainar K Dunstan E Hamilton P Unwin P Cannon SR Briggs TWR
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We performed a retrospective analysis of massive endoprostheses inserted at our unit in the management of Giant Cell Tumours of the distal femur with a minimum follow up of 5 years. Methods. Twenty-five massive articulating endoprostheses were inserted between 1986 and 1998 at our unit. The case notes and radiographs of all patients were reviewed. A functional and radiological analysis was performed using the MTOS and ISOLS scoring systems. Kaplan-Meier Cumulative Survival Graphs were created for amputation and revision for septic and aseptic loosening. Two patients had died (8%) from unrelated causes. No cases were lost to Follow Up. Results. Massive replacements were performed for stage 3 (aggressive), pathological fracture (30%) or recurrent disease. The mean follow up was twelve years (range 5–18 years). The average age at time of insertion was 37 years; no patients were skeletally immature. Fifteen implants were fixed hinge devices and ten were rotating hinge devices with HA collars (since 1993). No cases were revised for sepsis. There had been no cases of recurrent disease or amputation. There have been six (26%) revisions for aseptic loosening. Only one of these occurred in the rotating hinge and HA collar group. In the fixed hinge group (38% aseptic loosening rate) revision occurred after an average of six years. There have also been five re-bushings all of which have occurred in the fixed hinge group. The average MTOS score was 74 (range 47–97). Conclusion. Young patients with fixed hinged devices developed a high incidence of aseptic loosening. They also had a significant rate of re-bushing. Results of the rotating hinge prosthesis with HA collar were much more promising. Functional scores were good after a period of twelve years despite the young age group


Orthopaedic Proceedings
Vol. 86-B, Issue SUPP_II | Pages 131 - 132
1 Feb 2004
Doncel-Cabot A Gracia-Alegría I Majò-Buigas J
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Introduction and Objectives: Giant cell tumour (GCT) of the bone is an “aggressive tumor characterized by highly-vascularized tissue consisting of ovoid or fusiform cells and the presence of numerous gigantic osteoclast-like cells distributed uniformly throughout the tumor tissue” (WHO). The aim of this report is to present our experience over the past 19 years (1983–2002) with GCT of the bone treated in our unit. Materials and Methods: From January 1983 to January 2002, we have treated 67 cases of GCT of the bone, excluding all cases with less than 12 months of follow up. Age at presentation ranged 10 to 17 years. There was a higher incidence from 20 to 40 years of age. There was a moderately higher rate in women compared to men (1.5:1). The most common locations were the distal epiphysis of the femur, proximal epiphysis of the tibia, and the distal end of the radius. This type of tumour generally localises to the epiphysis and subsequently invades the metaphysis. Localization to the axial skeleton is rare. Radiologic diagnosis was achieved by simple local radiology, CT scan, and MRI. Histopathologic diagnosis was done by means of biopsy using a trocar guided by an image intensifier. In cases of central localization, we obtained the sample by CT-guided biopsy. The treatment of choice is aggressive curettage (high-velocity burr) and filling with frozen cancellous chips. Radiation therapy is useful in cases of localization that are not accessible by surgery. Results: GCT of the bone possesses several unique characteristics, which make it different from other intermediate tumors: a high rate of recurrence (up to 50%), the possibility of sarcomatous degeneration, and the possibility of pulmonary metastasis (even in non-malignant cases). We believe the ideal treatment is resection of the bone where the tumour is located (useful on the head of the fibula, distal end of the ulna, ribs, some bones of the hand and feet, and the patella). In view of its usual localization near the knee (50%), our usual treatment is aggressive curettage (high-speed burr) and filling with frozen cancellous chips. We have treated 26 recurrent cases out of 67 patients treated in our unit (38.8%). Of these, approximately 50% were referred from other centres. Treatment of recurrence has generally been aggressive curettage and addition of allografts. Sarcomatous degeneration occurred in 3 cases (4.5%), all of which were high grade sarcomas of the malignant fibrous histiocytoma type. One case survived following amputation of the extremity, and the other 2 cases died as a result of pulmonary metastasis. Discussion and Conclusions: Alternative local treatment methods exist for GCT of the bone such as cryosurgery, phenolization, and cementing. However, we cannot comment on these methods due to a lack of experience with them. The aim of all these methods is to cauterize the tumour bed. We prefer aggressive curettage and filling with cancellous bone in an attempt to use a more biological treatment


Orthopaedic Proceedings
Vol. 92-B, Issue SUPP_III | Pages 443 - 443
1 Jul 2010
Albertini U Piana R Gino G Boux E Marone S Boffano M Linari A Faletti C del Prever EB
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Giant cell tumor (GCT) of bone is an aggressive tumor with high rate of recurrence. Bad prognosis factors were inquired, without a definite identification: type of treatment, soft tissue invasion, high proliferation rate at histology, pathologic fracture. From January 2000 to February 2008, 38 patients affected by GCT were treated in a regional reference centre, 17 male, mean age 32 (range 16–69, median 29); one patient had 2 localizations (tarsal bone and proximal tibia); 3 were recurrences previously treated in other hospitals. Seven cases were in upper limb, 1 case in the sacrum, 30 in lower limb (20 around the knee); fracture at presentation was present in 6 cases; bone aneurismal cyst (ABC) was associated in 4 cases. Five cases in stage 3 were treated by bone resection followed in 4 cases by allograft and/or prosthesis (no reconstruction in 1 proximal fibula excision); 33 cases were treated by curettage, local chemical (phenole) and mechanical adjuvants (burring), filling with bone grafts in 13 cases, cement in 8 cases, cement and allografts in subchondral area in 11 cases. The sacral lesion was only curetted. Seven patients developed a local recurrence, in 2 patients twice, for a total of 9 recurrences (19% of treatments). Recurrences occurred in 2 proximal tibia, in 2 distal femurs, in 1 proximal femur, in 1 distal radius and in 1 proximal fibula. The first treatment was bone grafts in 3 cases (23% of recurrence), bone cement and grafts in 2 cases (18% of recurrence), cement in 1 case (12% of recurrence), resection in the proximal fibula with severe soft tissue invasion. Two patients with associated ABC developed a recurrence and two with fracture at presentation. In this study, increased rate of recurrences occurred with pathologic fracture at presentation, soft tissue invasion and ABC association


The Journal of Bone & Joint Surgery British Volume
Vol. 72-B, Issue 3 | Pages 486 - 489
1 May 1990
Wray C Macdonald A Richardson R

We report a case of benign giant cell tumour which over a 20-year period has given rise to pulmonary and bony metastases. The indolent nature of these metastases is remarkable, with considerable implications for the long-term management of such cases


Orthopaedic Proceedings
Vol. 93-B, Issue SUPP_III | Pages 266 - 266
1 Jul 2011
Klenke FM Wenger DE Inwards CY Sim FH
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Purpose: Giant cell tumor (GCT) of bone is a rare, usually benign, primary skeletal lesion. The disease’s clinical course may be complicated by local recurrence subsequent to surgical treatment or the development of benign pulmonary metastases. Intra-lesional curettage is the standard treatment of primary GCT of bone. However, the value of intralesional procedures in recurrent GCT has not been well established. Method: Forty-six patients with recurrent GCT of long bones treated between 1983 and 2005 were followed retrospectively. Minimum follow-up was three years; mean follow-up was 11.1 (±4.8) years. Results: Wide resections were performed in 18 patients. Intralesional, joint preserving procedures were performed in 28 patients. Subsequent recurrence occurred in nine patients (20%). Wide resection was performed if joint salvage was not achievable due to expansion of the tumor. Reconstructions following wide resection included arthroplasty (n=4), osteoarticular allograft (n=3), APC (n=1) and fibular autograft reconstruction of the wrist (n=3). Amputations were performed in two patients. Patients undergoing wide resections for local recurrence had a significantly smaller risk of subsequent recurrence as compared to patients treated with intra-lesional surgery (6% versus 32%, hazard ratio: 0.28, p< 0.05). In patients treated with intralesional surgery, application of polymethylmethacrylate (PMMA) in addition to local phenol treatment significantly reduced the risk of subsequent recurrence (PMMA + phenol: 7% vs. Phenol: 25%, hazard ratio: 0.23, p< 0.05). Soft tissue expansion was not associated with an increased risk of subsequent recurrence. At follow-up, all patients with subsequent recurrence were without local disease after additional intralesional surgery (n=3) or wide resection (n=5). Metachronous benign pulmonary metastases evolved in five cases. There was no correlation between the development of pulmonary metastases and the type of treatment of recurrent disease found. Conclusion: In recurrent disease of GCT of long bones and the possibility to salvage the adjacent joint intra-lesional surgery is the treatment of choice independent of whether soft tissue expansion is present. Intra-lesional surgery does not increase the risk of development benign pulmonary metastases. In cases with extensive tumor formation and without the possibility to preserve the adjacent joint wide resection has a high chance for long-term recurrence free disease


Orthopaedic Proceedings
Vol. 96-B, Issue SUPP_11 | Pages 103 - 103
1 Jul 2014
Avnet S Salerno M Zini N Gibellini D Baldini N
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Summary. We demonstrate that osteoclast-like cells of GCT result from the spontaneous fusion and differentiation of CD14+ cells of the monoblastic lineage by an autocrine mechanism mediated by RANKL, rather than induced by stromal cells. This process is further enhanced by the simultaneous impairment of the negative feed-back regulation of osteoclastogenesis by interferon β. Introduction. Giant cell tumor of bone (GCT) is a benign osteolytic lesion with a complex histology, comprising prominent multinucleated osteoclast-like cells (OC), mononuclear stromal cells (SC), and monocyte-like elements. So far, most studies have focused on SC as the truly transformed elements that sustain osteoclast differentiation, while less attention has been paid on the monocyte-like cell fraction. On the contrary, we have previously shown that SC are non-transformed element that can induce osteoclastogenesis of monocytes at levels that do not exceed that of normal mesenchymal stromal cells. We therefore focused on CD14+ monocyte-like cells as an alternative key candidate for the pathogenesis of GCT. Methods. We isolated CD14+ enriched cell fraction from tumor samples by immunomagnetic separation. We analyzed CD14+ cells for ultrastructural morphology, mRNA levels of haematopoietic, monocytic, and dendritic markers, and for RANKL, and M-CSF. Due to the very high number of OC in GCT, we hypothesised that the IFN-b pathway might be impaired. In fact, IFN-b functions as a negative-feedback regulator that inhibits osteoclast differentiation. We assayed IFN-b mRNA and protein expression in both cultures and tumor samples. Finally, we verified the ability of CD14+ cells to spontaneously form osteoclasts. Results. In the CD14+ enriched fraction we identified two different cell populations, both positive for TRACP activity and negative for Ki-67 nuclear localization, one with an undefined histotype and the other showing characteristics of the monoblastic lineage, mainly monoblasts and promonocytes. Isolated cells were positive for CD45, MSE-1, RANK, CD14, and CD80, and negative for CD144, and were able to spontaneously form collagen-resorbing multinucleated cells, a process that was strongly impaired by the addition of osteoprotegerin. The expression of RANKL and M-CSF mRNA in cultured cells demonstrated the presence of an autocrine circuit inducing osteoclast formation. Finally, we found very low expression of IFN-b both in the in vitro formed OC and in tissue samples. Conclusions. These data show that CD14+ cells in GCT are monocyte-like cells that can spontaneously form bone-resorbing multinucleated cells through impaired IFN-b expression. Taken together, these data raise questions regarding the role of the CD14+ cell component and of their regulating mechanisms that may be relevant for the development of effective therapeutic strategies


Orthopaedic Proceedings
Vol. 90-B, Issue SUPP_II | Pages 399 - 399
1 Jul 2008
Navadgi B Rao SK
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Purpose of the Study: To study the results of resection of giant cell tumour around the knee and limb salvage by distraction osteogenesis using Ilizarov construction over intramedullary nail. Summary: The treatment of GCT has ranged from curettage and en-bloc resection. It has always been a challenge to reconstruct the resected gap especially across the joints. We have done juxta articular resection of the tumour followed by interlocking nailing across the resected gap as first stage. In the second stage simple Ilizarov construct was used for transportation of bone across the resected gap. Results and Discussion: There were 6 male and 2 females. The mean age at presentation was 27 years. 3 lesions were in proximal tibia and 5 in the distal femur. The mean length of bone defect was 13.9 cm. With trifocal distraction the mean duration of Ilizarov external fixation was 90 days. We used colour doppler to asses the quality of regenerate during follow-ups. Mean duration of follow up was 44 months. A good quality of regenerate was seen at last follow up and all patients were fully weight bearing. Allografts are an alternative to endoprosthetic reconstruction but high incidence of complications such as fracture, deformity and infection makes the outcome unpredictable. The treatment option of reconstructing the resected gap with endoprosthesis is limited in our Indian subcontinent set up because of limited resource and availibility. The advantage include, the method we used has given us best alternative which allowed us to fill the large resected gap without the need of massive bone grafts. The distraction from both sides of resected gap has reduced the transportation time and use of DCP plate across the docked bone has allowed us to remove the fixator earlier. The regenerate had sufficient biological strength and durability. The disadvantages include the long duration of external fixation and related problems such as pin tract infections and frustration of patients due to the long period of treatment. Conclusion: Resection of tumour across the joint especially around the knee and recostruction by distraction osteogenesis using Ilizarov construct over the nail to fill the large gaps without using grafts is very encouraging


Orthopaedic Proceedings
Vol. 90-B, Issue SUPP_II | Pages 399 - 399
1 Jul 2008
Bhagat S Pillai D Sharma H Naik M Amin P Pandit J Shah M
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Objective: To analyse long term outcome of pedicled patellar implantation in treating the defect of the knee joint after the excision of giant cell tumor of distal femur. Methods: The geometry of patella has lead to its use for condylar reconstruction following resection for giant cell tumour around knee. 15 such patients were treated at our institute and followed up for a mean period of 7.3 years. Average age at presentation was 14.8 years. All patients had plain x-rays, angiography as needed, CT scan and MRI to check integrity of articular cartilage and ACL. Size of lesion was measured on CT. Predominant lateral condyle involvement was found in 6 and medial in 9 patients. The patella was dissociated with a slip of quadriceps attached to its proximal superior-medial pole and rotated to place it horizontally in the zone of resection. Firm osteosynthesis to intact condyle and autogenous bone grafting was carried out. Results: Grafts consolidated at a mean of 10.8 months. All joints were fairly stable and 70% had movement of 90 degrees without pain. 11 patients had excellent outcome with ability to carry on occupations involving manual labour. There were reoperations for 2 deep infections, 1 recurrence leading to arthrodesis, 1 supracondylar fracture, 2 arthrolysis and 1 valgus osteotomy. 4 patients had arthritic changes and extensor leg at 6 years follow up. No AVN changes or extensor mechanism problems occurred. Using chi square test for log rank analysis significant relationship was found between size of lesion and range of motion (P=0.03) as well as articular cartilage grading and development of arthrosis. The rate of healing was faster than other series reporting free patella grafting. Conclusion: Patellar implantation is a suitable way to repair the defect of the knee with better immediate functional results subsequently delaying eventual prosthesis surgery


Orthopaedic Proceedings
Vol. 93-B, Issue SUPP_I | Pages 77 - 77
1 Jan 2011
Puri A Gulia A Agarwal MG Srinivas CH
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Objectives: To analyse functional outcome of giant cell tumor (GCT) distal radius treated with en bloc excision and reconstruction with ulnar translocation and wrist arthrodesis. Methods: Between June 2005 and March 2008 fourteen patients of Campanacci grade 3 GCT distal radius treated with en bloc excision were reconstructed with ulnar translocation (radial transposition of ulna) and wrist arthrodesis. Seven (50%) patients had recurrent disease. Average resection length was 7.9 cm (range 5.5cm–15 cm). Twelve cases were fixed with a plate and in 2 an intramedullary nail was used. Union at both junctions was evaluated and functional assessment done using MSTS score. Results: All 14 patients had followed up till bony union. Eleven patients were available at time of final review with an average follow up of 24.5 months (range 13–48 months). Average time for union at ulnocarpal junction was 4 months and ulnoradial junction was 5 months. No case required any additional procedure to augment union. Three cases had a soft tissue recurrence and one had pulmonary metastasis. Average range of prono supination was 80 degrees, one patient with synostosis had complete restriction of prono supination. Average MSTS Score at last follow up was 26 (86.6%). Conclusions: Ulnar translocation provides a local vascularised bone graft to bridge the defect after excision of distal end radius tumors without the need for microvascular procedures. Unlike centralization of the ulna it retains prono supination while maintaining good hand function


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XXI | Pages 183 - 183
1 May 2012
P. WC K. LS A. EP A. MG P. CF J. SW B. AM T. G
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Objectives. A defect following resection of Giant Cell Tumour of the distal radius (GCT-DR) is reconstructed by either vascularised free fibular transfer (VFF) or non-vascularised structural iliac crest transfer (NIC). The purpose of this study was to compare these procedures. Methods. Twenty-seven patients at two centres were identified, 14 underwent VFF and 13 NIC. The two groups were comparable for age, sex, and tumour grade. Functional outcomes were assessed with TESS, MSTS, and DASH. In the VFF group, ankle joint morbidity was assessed with the Ankle Osteoarthritis Scale. In the NIC group, iliac crest morbidity was assessed with a short questionnaire. Results. Two local recurrences occurred in the VFF group and one in the NIC group. Following the index surgery, three patients in the VFF group underwent surgery for cosmesis, hardware removal or tendon release, and one is scheduled for tendon release. In the NIC group two infections required debridement, one of which went on to free fibular transfer, but there were no re-operations for union or donor site morbidity. The surgical time was significantly shorter for NIC. Functional scores showed no differences between the groups on any of the parameters studied for the upper limb (Mann-Whitney test). The Anke OA scale and the iliac crest morbidity questionnaire revealed only a few mild problems with donor site morbidity in either group. Conclusion. Both VFF and NIC are effective surgical techniques that result in a well-functioning wrist arthrodesis. VFF should be considered when there is a significant skin defect, as it allows the inclusion of a vascularised skin paddle, or when the osseous defect is too long for NIC. We were unable to demonstrate any difference in functional scores between VFF and NIC. As the re-operation rate is less for NIC and surgical time is shorter, we recommend NIC whenever possible


Orthopaedic Proceedings
Vol. 104-B, Issue SUPP_13 | Pages 99 - 99
1 Dec 2022
St George S Clarkson P
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Diffuse-type Tenosynovial Giant-Cell Tumour (d-TGCT) of large joints is a rare, locally aggressive, soft tissue tumour affecting predominantly the knee. Previously classified as Pigmented Villonodular Synovitis (PVNS), this monoarticular disease arises from the synovial lining and is more common in younger adults. Given the diffuse and aggressive nature of this tumour, local control is often difficult and recurrence rates are high. Current literature is comprised primarily of small, and a few larger but heterogeneous, observational studies. Both arthroscopic and open synovectomy techniques, or combinations thereof, have been described for the treatment of d-TGCT of the knee.

There is, however, no consensus on the best approach to minimize recurrence of d-TGCT of the knee. Some limited evidence would suggest that a staged, open anterior and posterior synovectomy might be of benefit in reducing recurrence. To our knowledge, no case series has specifically looked at the recurrence rate of d-TGCT of the knee following a staged, open, posterior and anterior approach. We hypothesized that this approach may provide better recurrence rates as suggested by larger more heterogeneous series.

A retrospective review of the local pathology database was performed to identify all cases of d-TGCT or PVNS of the knee treated surgically at our institution over the past 15 years. All cases were treated by a single fellowship-trained orthopaedic oncology surgeon, using a consistent, staged, open, posterior and anterior approach for synovectomy. All cases were confirmed by histopathology and followed-up with regular repeat MRI to monitor for recurrence. Medical records of these patients were reviewed to extract demographic information, as well as outcomes data, specifically recurrence rate and complications. Any adjuvant treatments or subsequent surgical interventions were noted.

Twenty-three patients with a minimum follow-up of two years were identified. Mean age was 36.3 at the time of treatment. There were 10 females and 13 males. Mean follow-up was seven and a half years. Fourteen of 23 (60.9%) had no previous treatment. Five of 23 had a previous arthroscopic synovectomy, one of 23 had a previous combined anterior arthroscopic and posterior open synovectomy, and three of 23 had a previous open synovectomy. Mean time between stages was 87 days (2.9 months). Seven of 23 (30.4%) patients had a recurrence. Of these, three of seven (42.9%) were treated with Imatinib, and four of seven (57.1%) were treated with repeat surgery (three of four arthroscopic and one of four open).

Recurrence rates of d-TGCT in the literature vary widely but tend to be high. In our retrospective study, a staged, open, anterior and posterior synovectomy provides recurrence rates that are lower than rates previously reported in the literature. These findings support prior data suggesting this approach may result in better rates of recurrence for this highly recurrent difficult to treat tumour.


Orthopaedic Proceedings
Vol. 104-B, Issue SUPP_12 | Pages 64 - 64
1 Dec 2022
St George S Clarkson P
Full Access

Diffuse-type Tenosynovial Giant-Cell Tumour (d-TGCT) of large joints is a rare, locally aggressive, soft tissue tumour affecting predominantly the knee. Previously classified as Pigmented Villonodular Synovitis (PVNS), this monoarticular disease arises from the synovial lining and is more common in younger adults. Given the diffuse and aggressive nature of this tumour, local control is often difficult and recurrence rates are high. Current literature is comprised primarily of small, and a few larger but heterogeneous, observational studies. Both arthroscopic and open synovectomy techniques, or combinations thereof, have been described for the treatment of d-TGCT of the knee.

There is, however, no consensus on the best approach to minimize recurrence of d-TGCT of the knee. Some limited evidence would suggest that a staged, open anterior and posterior synovectomy might be of benefit in reducing recurrence. To our knowledge, no case series has specifically looked at the recurrence rate of d-TGCT of the knee following a staged, open, posterior and anterior approach. We hypothesized that this approach may provide better recurrence rates as suggested by larger more heterogeneous series.

A retrospective review of the local pathology database was performed to identify all cases of d-TGCT or PVNS of the knee treated surgically at our institution over the past 15 years. All cases were treated by a single fellowship-trained orthopaedic oncology surgeon, using a consistent, staged, open, posterior and anterior approach for synovectomy. All cases were confirmed by histopathology and followed-up with regular repeat MRI to monitor for recurrence. Medical records of these patients were reviewed to extract demographic information, as well as outcomes data, specifically recurrence rate and complications. Any adjuvant treatments or subsequent surgical interventions were noted.

Twenty-three patients with a minimum follow-up of two years were identified. Mean age was 36.3 at the time of treatment. There were 10 females and 13 males. Mean follow-up was seven and a half years. Fourteen of 23 (60.9%) had no previous treatment. Five of 23 had a previous arthroscopic synovectomy, one of 23 had a previous combined anterior arthroscopic and posterior open synovectomy, and three of 23 had a previous open synovectomy. Mean time between stages was 87 days (2.9 months). Seven of 23 (30.4%) patients had a recurrence. Of these, three of seven (42.9%) were treated with Imatinib, and four of seven (57.1%) were treated with repeat surgery (three of four arthroscopic and one of four open).

Recurrence rates of d-TGCT in the literature vary widely but tend to be high. In our retrospective study, a staged, open, anterior and posterior synovectomy provides recurrence rates that are lower than rates previously reported in the literature. These findings support prior data suggesting this approach may result in better rates of recurrence for this highly recurrent difficult to treat tumour.


The Journal of Bone & Joint Surgery British Volume
Vol. 72-B, Issue 4 | Pages 723 - 724
1 Jul 1990
Farooque M Biyani A Adhikari A


Orthopaedic Proceedings
Vol. 92-B, Issue SUPP_II | Pages 279 - 279
1 May 2010
Moghtadaei M Akbarian E Farahini H Zangi M Pazouki M
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Background: Polymethylmethacrylate (PMMA) is a potent stimulant of inflammatory response. This study investigated the role of Prostaglandin E2 (PGE2), Platelet activating factor (PAF) and histamine and their specific antagonists in bone changes. Materials: 120 white-male-wistar rats were divided into ten groups. Using sterile technique, a 2mm drill hole was made in the tibia 1cm distal to the knee joint bilaterally. The left tibia was filled with Simplex particulate cement polymer (PMMA) and the right tibia was used as control. The first nine groups respectively received terfenadine 1mg/kg, 10mg/kg and 25mg/kg, alprazolam 0.08mg/kg, 0.32mg/kg and 0.64mg/kg, and naproxen 1mg/kg, 5mg/kg and 25mg/kg; however, the tenth group received no drug and served as control. The animals were killed after 16 weeks and implant areas were harvested aseptically and studied by one pathologist. Results: Our study revealed that the cellular reaction in the left side was statistically more than the right one in all cases (p< 0.05). Also, a significant decrease in histiocytes and giant cells was seen just in those groups that had received 10mg/kg and 25mg/kg of terfenadine, 0.32mg/kg and 0.64mg/kg of alprazolam and 5mg/kg and 25mg/kg of naproxen (P< 0.05) while administration of 1mg/kg naproxen resulted in significant decrease only in giant cells (P< 0.05) but not in histiocytes. Discussion: Previous studies have suggested that particulate debris, PGE2 production and inflammatory response are associated with arthroplasty loosening. This experiment has demonstrated that the increased cellular reaction by the membrane surrounding particulate cement polymer can be suppressed by administration of PGE2, PAF and histamine specific inhibitors. The use of these agents may be indicated in retarding the bone loss associated with early prosthetic loosening


Orthopaedic Proceedings
Vol. 93-B, Issue SUPP_III | Pages 351 - 351
1 Jul 2011
Ioannou M Papanastassiou I Kottakis S Demertzis N
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To present the oncological outcome of eleven patients with stage-3 GCT of bone.

Thirty-nine cases of GCT who were treated the past nine years at our department were reviewed. Five tumors were classified as stage I, twenty-three tumors as stage II and eleven as stage III tumors.

In stage I or II tumors we proceeded to an intraoperative biopsy (frozen biosy).In cases where the intraoperative pathological findings confirmed our diagnosis of GCT we proceeded to operative management. In cases where the intraoperative pathologist’s findings were not clear as well as in cases of stage III tumors we performed only a traditional open biopsy proceeding surgery in a second stage. In stage III tumors we aimed wide margins. Ten of these patients underwent wide surgical excision and limb salvage, while in one patient curettage with cementation was the treatment of choice in order to obtain a fair functional outcome.

With a minimum follow up of 3 years, we had no case of local recurrence in cases treated with wide excision and limb salvage. One stage III GCT treated with curettage recurred. Two stage III tumors metastized to the lung. The average interval from initial operation to lung metastasis was six months.

Treating GCT with the above management minimizes diagnostic failures. Literature shows local recurrence rate as high as 50% in stage III GCTs. The present study shows that recurrence rate can be significantly reduced and good functional outcome can be achieved by carefully planning approach and wide excision of the tumor.


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XXXVII | Pages 310 - 310
1 Sep 2012
Savadkoohi D Siavashi B Rezanezhad SS Seifi M Savadkoohi M
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Aim

To analyse our results after en-block resection of aggressive GCT during 20 years period.

Methods

We review 86 patients with skeletal GCT during the last 20 years, from 1990 until 2009, retrospectively. In the cases of latent and active type, extended curettage and bone graft or cement were our treatment of choice, while in aggressive ones we performed en block resection and reconstruction by fibular autograft (e.g. in distal part of radius) or fusion/hinge joint prosthesis (e.g. in GCT around the knee joint). We describe the recurrences, metastases and complications according to treatment.


Orthopaedic Proceedings
Vol. 90-B, Issue SUPP_I | Pages 30 - 30
1 Mar 2008
Jeys L Suneja R Carter S Grimer R
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To identify the incidence of a cortical breech on the initial presentation X-rays of patients with distal femoral GCTs, and whether this lead to a higher rate of local recurrence of tumour, a prospective database is kept of all patients seen in the unit. Initial presentation X-rays on 54 patients with distal femroal GCTs were reviewed. The size of the tumour was estimated by measuring the largest dimensions of the tumour (depth, breadth & height). The volume of the distal femur was estimated using the same X-ray and computer programme. The X-rays were then carefully studied for evidence of a cortical breach. The records were also checked for evidence of subsequent locally recurrent disease and subsequent surgery.

X-rays were reviewed on 54 patients (29 male, 25 female), range of 18–72 years. All patients had a biopsy-proven GCT of the distal femur, X-rays (prior to biopsy) were reviewed. 34 (63%) patients with a cortical breech on X-ray. The mean tumour volume: distal femoral volumes (TV:DFV) was statistically greater between those patients with a cortical breach and those without, using ANOVA (p< 0.0001). There were 13 patients with local recurrent disease but no statistical difference in subsequent local recurrence rates between the two patient groups. There was also no statistical differences between the number of operations for those who presented with a cortical breach or without. There was no evidence that more radical surgery was required if a patient presented with a cortical breach.

The risk of cortical breech in patients with GCTs of the distal femur is dependant upon the tumour volume to distal femur volume ratio. If the ratio is above 54% then present with a cortical breech on X-ray is likely (95% confidence interval).There is no evidence those patients with a cortical breach have a higher rate of local recurrence, an increased number of operations or more radical surgery.

Conclusion: The risk of cortical breech in patients with GCTs of the distal femur is dependent upon the tumour volume to distal femur volume ratio.


Orthopaedic Proceedings
Vol. 99-B, Issue SUPP_1 | Pages 46 - 46
1 Jan 2017
Errani C Leone G Cevolani L Spazzoli B Frisoni T Donati D
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The purpose of our study was to identify possible risk factors of patients with GCT of the long bones after curettage and packing the bone cavity with bone cement or bone allografts.

We retrospectively reviewed the records of 249 patients with GCT of the limbs treated at Musculoskeletal Oncology Department of our institution between 1990 and 2013, confirmed histologically and recorded in the Bone Tumor Registry. We reviewed 219 cases located in the lower limb and 30 of the upper limb. This series includes 135 females and 114 males, with mean age 32 years (ranging 5 to 80 yrs). According to Campanacci's grading system, 190 cases were stage 2, 48 cases stage 3, and 11 cases stage 1. Treatment was curettage (intralesional surgery). Local adjuvants, such as phenol and cement, were used in 185 cases; whereas in the remaining 64 cases the residual cavity was filled with allografts or autografts only.

Oncological outcome shows 203 patients alive and continuously disease-free (CDF), 41 patients NED1 after treatment of local recurrence (LR), 2 patients NED1 after treatment of lung metastases, 2 AWD with lung metastases. One patient died of unrelated causes (DOD).

LR rate was 15.3% (38 pts). Lung metastases rate was 1.6% (4 pts). In patients treated by curettage and cement (185 cases) LR was 12% (22 pts). Conversely, in patients treated curettage and bone allografts it was higher (16/64 cases), with an incidence of 25% of cases (p=0.004). Oncological complications seemed to be related with site, more frequently occurring in the proximal femur (p=0.037). LR occurred only in stage 2 or 3 tumors without statistical significance (p>0.05). The mean interval between the first surgical treatment and LR was 22 months (range: 3–89 mos). However, in the multivariate analysis no significant statistical effect on local recurrence rate could be identified for gender, patient's age, Campanacci's grading, or cement vs allografts. The only independent risk factor related to the local recurrence was the site, with a statistical significance higher risk for patients with GCT of the proximal femur (p= 0.008).

Our observation on the correlation of tumor location and risk of local recurrence is new. Therefore, special attention must be given to GCTs in the proximal femur. In fact, primary benign bone tumors in the proximal femur are difficult to treat due to the risk of secondary osteonecrosis of the femoral head or pathologic fracture.

Numerous methods of reconstructions have been reported. Among these, total hip arthroplasty (THA) or bipolar hip arthroplasty (BHA) should be avoided when possible as more cases are observed in young patients.

Therefore, we do not suggest different approach for the proximal femur. GCT in the proximal femur is much more difficult to treat than in other sites, but if curettage is feasible, the best way is to save the joint with a higher risk of local recurrence, knowing that the sacrifice of the hip articulation in case of recurrence is always possible with THA or BHA.


Bone & Joint 360
Vol. 12, Issue 4 | Pages 35 - 37
1 Aug 2023

The August 2023 Oncology Roundup360 looks at: Giant cell tumour of bone with secondary aneurysmal bone cyst does not have a higher risk of local recurrence; Is bone marrow aspiration and biopsy helpful in initial staging of extraskeletal Ewing’s sarcoma?; Treatment outcomes of extraskeletal Ewing’s sarcoma; Pathological complete response and clinical outcomes in patients with localized soft-tissue sarcoma treated with neoadjuvant chemoradiotherapy or radiotherapy; Long-term follow-up of patients with low-grade chondrosarcoma in the appendicular skeleton treated by extended curettage and liquid nitrogen; Cancer-specific survival after limb salvage versus amputation in osteosarcoma; Outcome after surgical treatment of dermatofibrosarcoma protuberans: does it require extensive follow-up, and what is an adequate resection margin?; Management of giant cell tumours of the distal radius: a systematic review and meta-analysis


The Bone & Joint Journal
Vol. 105-B, Issue 5 | Pages 551 - 558
1 May 2023
Wang H Ji T Qu H Yan T Li D Yang R Tang X Guo W

Aims. The aim of this study was to determine the rate of indocyanine green (ICG) staining of bone and soft-tissue tumours, as well as the stability and accuracy of ICG fluorescence imaging in detecting tumour residuals during surgery for bone and soft-tissue tumours. Methods. ICG fluorescence imaging was performed during surgery in 34 patients with bone and soft-tissue tumours. ICG was administered intravenously at a dose of 2 mg/kg over a period of 60 minutes on the day prior to surgery. The tumour stain rate and signal-to-background ratio of each tumour were post hoc analyzed. After tumour resection, the tumour bed was scanned to locate sites with fluorescence residuals, which were subsequently inspected and biopsied. Results. The overall tumour stain rate was 88% (30/34 patients), and specific stain rates included 90% for osteosarcomas and 92% for giant cell tumours. For malignant tumours, the overall stain rate was 94%, while it was 82% for benign tumours. The ICG tumour stain was not influenced by different pathologies, such as malignant versus benign pathology, the reception (or lack thereof) of neoadjuvant chemotherapies, the length of time between drug administration and surgery, the number of doses of denosumab for patients with giant cell tumours, or the tumour response to neoadjuvant chemotherapy. The overall accuracy rate of successfully predicting tumour residuals using fluorescence was 49% (23/47 pieces of tissue). The accuracy rate after en bloc resection was significantly lower than that after piecemeal resection (16% vs 71%; p < 0.001). Conclusion. A high percentage of bone and soft-tissue tumours can be stained by ICG and the tumour staining with ICG was stable. This approach can be used in both benign and malignant tumours, regardless of whether neoadjuvant chemotherapy is adopted. The technique is also useful to detect tumour residuals in the wound, especially in patients undergoing piecemeal resection. Cite this article: Bone Joint J 2023;105-B(5):551–558


Bone & Joint 360
Vol. 13, Issue 3 | Pages 40 - 42
3 Jun 2024

The June 2024 Oncology Roundup. 360. looks at: Chondrosarcoma of the femur: is local recurrence influenced by the presence of an extraosseous component?; Diagnostic challenges in low-grade central osteosarcoma; Single osteotomy technique for frozen autograft (pedicled freezing) in patients with malignant bone tumours; Unplanned resection for small superficial soft-tissue sarcomas: disastrous or simply bad?; Inactivation and replantation of the knee joint: an infeasible surgical method; Active surveillance of diffuse-type tenosynovial giant cell tumours: a retrospective, multicentre cohort study


Bone & Joint 360
Vol. 12, Issue 4 | Pages 16 - 20
1 Aug 2023

The August 2023 Knee Roundup. 360. looks at: Curettage and cementation of giant cell tumour of bone: is arthritis a given?; Anterior knee pain following total knee arthroplasty: does the patellar cement-bone interface affect postoperative anterior knee pain?; Nickel allergy and total knee arthroplasty; The use of artificial intelligence for the prediction of periprosthetic joint infection following aseptic revision total knee arthroplasty; Ambulatory unicompartmental knee arthroplasty: development of a patient selection tool using machine learning; Femoral asymmetry: a missing piece in knee alignment; Needle arthroscopy – a benefit to patients in the outpatient setting; Can lateral unicompartmental knees be done in a day-case setting?


Orthopaedic Proceedings
Vol. 100-B, Issue SUPP_15 | Pages 105 - 105
1 Nov 2018
Kubo Y Motomura G Ikemura S Hatanaka H Fukushi J Hamai S Yamamoto T Nakashima Y
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Similar to the radiological findings in rapidly destructive arthrosis of the hip joint (RDA), subchondral insufficiency fracture of the femoral head (SIF) can result in progressive femoral head collapse of unknown etiology. We thus examined the osteoclast activity in hip joint fluid in SIF with progressive collapse in comparison to that in RDA. Twenty-nine hip joint fluid samples were obtained intraoperatively with whole femoral heads from 12 SIF patients and 17 RDA patients. SIF cases were classified into subgroups based on the presence of ≥2mm collapse on preoperative radiographs: SIF with progressive collapse (n=5) and SIF without progressive collapse (n=7). The levels of tartrate-resistant acid phosphatase (TRACP)-5b, interleukin-8, vascular endothelial growth factor (VEGF), and matrix metalloproteinase (MMP)-9 were measured. Numbers of multinuclear giant cells at the subchondral region were assessed histopathologically using mid-coronal slices of each femoral head specimen. Median levels of all markers and median numbers of multinuclear giant cells in SIF with progressive collapse were significantly higher than those in SIF without progressive collapse, while there were no significant differences in SIF with progressive collapse versus RDA. Regression analysis showed that the number of multinuclear giant cells correlated positively with the level of TRACP-5b in joint fluid. This study suggests an association of increased osteoclast activity with the existing condition of progressive collapse in SIF, which was quite similar to the findings in RDA. Therefore, high activation of osteoclast cell may reflect the condition of progressive collapse in SIF as well as RDA


Orthopaedic Proceedings
Vol. 90-B, Issue SUPP_II | Pages 399 - 399
1 Jul 2008
Mahendra A Singh OP Khanna M Kumar P
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Giant cell tumor of bone is a benign lesion that is ‘locally aggressive and potentially malignant’. The most common specific location of ‘GCT’ is about the knee (50–65%), followed by the distal radius (10–12%), sacrum (4–9%) and proximal humerus (3%–8%). The pelvis is recognized as an infrequent site of involvement accounting for as few as 2% to 3% of all giant cell tumors. Giant cell tumors often can reach an alarming size in the pelvis jeopardizing the surrounding structures. Treatment options described in literature for pelvic giant cell tumors include radiation therapy; surgery with intralesional margin; surgery with an intralesional margin and physical adjuvants, and surgery with wide margins. Following Type II (Periacetabular) resections the two preferred modes of reconstruction are either Saddle Prosthesis or Ilio femoral fusion. But, in patients with extensive periacetabular involvement with tumor extension into ilium the type II resection has to be combined with a Type I (Ilial) resection. This may result in insufficient ilium being available for reconstruction to consider either a iliofemoral fusion or a saddle prosthesis. In such situations we recommend Sacroiliofemoral fusion as a novel variation of iliofemoral arthrodesis. We present two cases of GCT of pelvis with significant periacetabular involvement treated by Sacroiliofemoral fusion. A follow up at 2 years in both cases showed no recurrences, mean MSTS of 21 & TESS of 70. This paper discusses the various treatment options for such extensive periacetbular giant cell tumors, operative technique for sacroiliofemoral fusion, outcome evaluation after 2 years by MSTS & Toronto Extremity Salvage scores


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_7 | Pages 82 - 82
4 Apr 2023
Kokozidou M Gögele C Pirrung F Hammer N Werner C Kohl B Hahn J Breier A Schöpfer M Meyer M Schulze-Tanzil G
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Although autografts represent the gold standard for anterior cruciate ligament (ACL) reconstruction, tissue-engineered ACLs provide a prospect to minimize donor site morbidity and limited graft availability. This given study characterizes the ligamentogenesis in embroidered poly(L-lactide-co-ε-caprolactone) (P(LA-CL)) / polylactic acid (PLA) constructs using a dynamic nude mice xenograft model. (P(LA-CL))/PLA scaffolds remained either untreated (co) or were functionalized by gas fluorination (F), collagen foam cross-linked with hexamethylene diisocyanate (HMDI) (coll), or gas fluorination combined with the foam (F+coll). Cell free constructs or those seeded for 1 week with lapine ACL ligamentocytes were implanted into nude mice for 12 weeks. Following explantation, biomechanical properties, cell vitality and content, histopathology of scaffolds (including organs: liver, kidney, spleen), sulphated glycosaminoglycan (sGAG) contents and biomechanical properties were assessed. Implantation of the scaffolds did not negatively affect mice weight development and organs, indicating biocompatibility. All scaffolds maintained their size and shape for the duration of the implantation. A high cell viability was detected in the scaffolds prior to and following implantation. Coll or F+coll scaffolds seeded with cells yielded superior macroscopic properties when compared to the controls. Mild signs of inflammation (foreign-body giant cells, hyperemia) were limited to scaffolds without collagen. Microscopical score values and sGAG content did not differ significantly. Although remaining stable in vivo, elastic modulus, maximum force, tensile strength and strain at Fmax were significantly lower in the in vivo compared to the samples cultured 1 week in vitro, but did not differ between scaffold subtypes, except for a higher maximum force in F+coll compared with F samples (in vivo). Scaffold functionalization with fluorinated collagen foam provides a promising approach for ACL tissue engineering. (shared first authorship). Acknowledgement: The study was supported by DFG grants SCHU1979/9-1 and SCHU1979/14-1


The Bone & Joint Journal
Vol. 101-B, Issue 2 | Pages 170 - 177
1 Feb 2019
Puri A Gulia A Hegde P Verma V Rekhi B

Aims. The aims of this study were to evaluate the efficacy of preoperative denosumab in achieving prospectively decided intention of therapy in operable giant cell tumour of bone (GCTB) patients, and to document local recurrence-free survival (LRFS). Patients and Methods. A total of 44 patients received preoperative denosumab: 22 to facilitate curettage, 16 to facilitate resection, and six with intent of converting resection to curettage. There were 26 male and 18 female patients. The mean age was 27 years (13 to 47). Results. The mean number of denosumab treatments was five (2 to 7) per patient. In 42 of 44 patients (95%), denosumab helped to achieve prospectively decided intention. A total of 41 patients were available for follow-up at a mean follow-up of 34 months (24 to 48). There were 12 local recurrences (29%), in 11 patients (11/25, 44%) who had curettage and in one patient (1/16, 6%) who had resection. The mean time to local recurrence was 16 months (8 to 25). The LRFS was 76% at two years: 94% for cases with resection and 64% for cases with curettage (p = 0.013). Conclusion. Although local control rates are unlikely to improve with use of preoperative denosumab, a short preoperative course of denosumab can facilitate surgery in certain cases of operable GCTB, with a high risk of local recurrence making curettage or resection technically easier. It may also help in converting a lesion requiring resection to a lesion that could possibly be treated with curettage


Orthopaedic Proceedings
Vol. 102-B, Issue SUPP_2 | Pages 72 - 72
1 Feb 2020
Hall D Garrigues G Blanchard K Shewman E Nicholson G Pourzal R
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Introduction. The combined incidence of anatomic (aTSA) and reverse total shoulder arthroplasties (rTSA) in the US is 90,000 per annum and rising. There has been little attention given to potential long-term complications due to periprosthetic tissue reactions to implant debris. The shoulder has been felt to be relatively immune to these complications due to lower acting loads compared to other joint arthroplasties. In this study, retrieved aTSAs and rTSAs were examined to determine the extent of implant damage and to characterize the nature of the corresponding periprosthetic tissue responses. Methods. TSA components and periprosthetic tissues were retrieved from 23 (eleven aTSA, twelve rTSA). Damage to the implants was characterized using light microscopy. Head/stem taper junction damage was graded 1–4 as minimal, mild, moderate or marked. Damage on polyethylene (PE) and metal bearing surfaces was graded 1–3 (mild, moderate, marked). H&E stained sections of periprosthetic soft tissues were evaluated for the extent and type of cellular response. A semi-quantitative system was used to score (1=rare to 4=marked) the overall number of particle-laden macrophages, foreign body giant cells, lymphocytes, plasma cells, eosinophils, and neutrophils. Implant damage and histopathological patterns were compared between the two TSA groups using the Mann-Whitney and Spearman tests. Results. The PE bearing surfaces of aTSAs were dominated by three-body wear and plastic deformation, whereas the rTSA PE components exhibited mainly polishing and scratching. Metal surface damage occurred in a few cases of both groups. Only one aTSA case exhibited marked taper corrosion. In both groups the primary nature of the inflammatory response was a moderate to marked macrophage response to wear particles (78% of cases). The particle-laden macrophages tended to occur in broad sheets and contained metal, PE, bone cement and suture debris. The extent of macrophage and foreign body giant cell responses was greater in the aTSA group (p≤0.001). Metal particles were seen in 63% of aTSAs and 83% of rTSAs. In the aTSA group, bone cement was seen in all cases and suture was observed in 9 cases, and their presence was larger compared to the rTSA group (p≤0.022). There was no difference in the number of other cell types between the groups. A mild lymphocyte response and chromium-phosphate debris was present within the tissue of the aTSA case with marked corrosion, which may be indicative of an early stage adverse local tissue reaction (ALTR) analog to total hip replacements with taper corrosion. Conclusion. Both groups exhibited a strong macrophage response to a combination of different types of implant debris—PE, metal, bone cement and suture. The prevalence of a marked macrophage response was larger in the aTSA group which may be explained by the larger overall presence of cement and suture within this group. PE particles may differ in size between groups due to different acting wear mechanisms which may also affect the extent of the macrophage response. Although corrosion within modular junctions was overall rare, the presence of one case with marked corrosion shows that taper corrosion and subsequent ALTRs are possible in TSAs. For any figures or tables, please contact authors directly


Orthopaedic Proceedings
Vol. 84-B, Issue SUPP_I | Pages - 15
1 Mar 2002
Clarke S Brooks R Hobby J Wimhurst J Myer B Shore S Rushton N
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This study investigated the relationship between histological, clinical and radiological features of aseptically loose total joint replacements (TJRs) and synovial fluid levels of interleukin (IL)-1b, IL-6, IL-8 and IL-10. Tissue and synovial fluid samples were retrieved from patients undergoing primary (hip; n=15: knee; n=13), or revision of aseptically loose TJRs (hip; n=14: knee; n=9). The presence of inflammatory cells, blood vessels and wear debris in the tissue were assessed on a relative scale. Revision TJRs were assessed for sepsis, migration of the implant, gross loosening and the degree of radiolucency. Cytokine levels in the synovial fluid samples were determined by ELISA. All cytokines were increased in synovial fluid from revision TJRs compared to primary replacements, as were the degree of macrophage and giant cell infiltration (p< 0.01). There was a significant positive correlation between the presence of macrophages and giant cells with the levels of IL-1b, IL-8 and IL-10 (p< 0.05) but not IL-6. The amount of wear debris was related to the presence of macrophages and giant cells (p< 0.01) but not to any of the cytokines. There were no relationships between any of the clinical parameters and the presence of wear debris or the levels of any cytokine with the exception of IL-6 and gross loosening (p< 0.01). Similarly there were no differences between hips and knees for any of the parameters except IL-6, for which higher levels were found in hips (p< 0.05). The results suggest that macrophages and giant cells are responsible for the majority of IL-1b, IL-8 and IL-10 production but another cell type is contributing to IL-6 production. Furthermore, IL-6 does not fit the pattern of the other cytokines as it is upregulated in hip joints compared to knees and correlates with the presence of gross loosening. This may suggest a unique role for IL-6 that requires further investigation


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_16 | Pages 15 - 15
1 Dec 2021
Mohamed H
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Abstract. Background. Benign osteolytic lesions of bone represent a diverse group of pathological and clinical entities. The aim of this study is to highlight the importance of intraoperative endoscopic assessment of intramedullary osteolytic lesions in view of the rate of complications during the postoperative follow up period. Methods. 69 patients (median age 27 years) with benign osteolytic lesion had been prospectively followed up from December 2017 to December 2018 in a university hospital in Cairo, Egypt and in a level-1 trauma center in United Kingdom. All patients had been treated by curettage with the aid of endoscopy through a standard incision and 2 portals. Histological analysis was confirmed from intraoperative samples analysis. All patients had received bone allografts from different donor sites (iliac crest, fibula, olecranon, etc). None of them received chemo or radiotherapy. Results. Most of lesions were enchondroma (n=29), followed by Aneurysmal bone cyst (ABC) (n=16), Fibrodysplasia (n=13), Chondromyxoid fibroma (n=3), simple bone cyst (n= 3), non-ossifying fibroma (n= 3), giant cell tumour (n= 1) and chondromyxoid fibroma (n = 1). Site of lesion varied from metacarpals (n = 29), femur (n= 1), lower leg (n= 31), and upper limb (n=18). Complications happened only in 9 cases (pathological fractures (n=2), infection (n= 1), recurrence (n=3, all aneurysmal bone cyst), residual pain (n= 3, all in tibia). None of cases developed malignant transformation. Conclusion. Endoscopy is recommended in management of benign osteolytic bone lesions; as it aids in better visualization of the hidden lesions that are missed even after doing apparently satisfactory blind curettage. From our study the recurrence rate is 2% compared to the known 12–18% recurrence rate in the blind technique from literature


Bone & Joint 360
Vol. 4, Issue 2 | Pages 28 - 30
1 Apr 2015

The April 2015 Oncology Roundup. 360 . looks at: New hope for skull base tumours; Survival but at what cost?; Synovial sarcoma beginning to be cracked?; Wound complications facing soft-tissue sarcoma surgeons; Amputation may offer no survival benefit over reconstruction; Giant cell tumour in the longer term; Intralesional treatment comparable with excision in GCT of the radius?; Imaging prior to oncological referral; And finally…


Bone & Joint 360
Vol. 1, Issue 2 | Pages 27 - 28
1 Apr 2012

The April 2012 Oncology Roundup. 360 . looks at chondrosarcoma of the cervical spine, if excision margins matter, radiation-induced sarcomas, giant cell tumours and bone cement, enchondromatosis and malignant change, axial or appendicular Ewing’s sarcoma, and diagnosing a sarcoma


Bone & Joint 360
Vol. 1, Issue 4 | Pages 27 - 29
1 Aug 2012

The August 2012 Oncology Roundup. 360. looks at: prolonged symptom duration; peri-operative mortality and above-knee amputation; giant cell tumour of the spine; surgical resection for Ewing’s sarcoma; intercalary allograft reconstruction of the femur for tumour defects; and an induced membrane technique for large bone defects


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_13 | Pages 140 - 140
1 Nov 2021
Reifenrath J Kempfert M Kampmann A Angrisani N Glasmacher B Menzel H Welke B Willbold E
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Introduction and Objective. In the elderly population, chronic rotator cuff tears are often associated with high re-rupture rates after surgical tendon refixation. Implant materials, especially in combination with additives are supposed to positively influence healing outcome. Furthermore, adequate mechanical properties are crucial. In order to realize degradable implants with high specific surface area, polycaprolactone (PCL) was chosen as basic material and processed by electrospinning to achieve a high surface area for growth factor implementation and subsequent cell attachment. Materials and Methods. PCL (M. n. approx. 80,000 g/mol) was used to generate fibre mats by electrospinning (relative collector velocity 8 m/s; flow rate of 4 ml/h). Mechanical analysis was performed according to EN ISO 527–2:2012 with test specimen 1BA (5 mm in diameter). Maximum force at failure (Fmax) as well as stiffness were evaluated. For preclinical in vivo testing, a coating with CS-g-PCL was performed to increase cellular adhesion and biological integration. Native and TGF-ß3 loaded mats were examined in a chronic rat tendon defect model with dissection of the M. infraspinatus, four week latency and following refixation at the humerus with different PCL-fibre mats (approval Nr. 33.12–42502–04–15/2015). After 8 weeks, rats were finalized and tendon-bone insertions were analyzed biomechanically and via histological methods. Results. Electrospun PCL-fibre mats (n = 6) showed maximum forces of 2.19 ± 0.8 N and a stiffness of 0.38 ± 0.12 N/mm. Native rat infraspinatus tendons showed Fmax values of 28.4 ± 7.2 N and a stiffness of 11.8 ± 4.9 N/mm. After implantation, Fmax of the implant-tendon-regenerate was significantly lower in CS-g-PCL - fibre mat groups compared to native control tendons (mean 52 % of native tendon value). Functionalization with TGF-ß3 led to increased Fmax (78 % of the native tendon value). However, differences were not statistically significant. Histological evaluation revealed no differences between non loaded and TGF-ß3 loaded mats. The implants were strongly disintegrated. Granulation tissue and a high number of foreign body giant cells were present. Conclusions. Although mechanical properties of fabricated mats were low, loading of the fibre mats influenced the biomechanical outcome of refixed tendons, presumably due to their high potential for binding biological active substances like TGF-ß3. However, in ongoing studies these cell reactions, especially regarding polarization of macrophages and foreign body cells need to be characterized. This research project has been supported by the German Research Foundation “Graded Implants FOR 2180 – tendon- and bone junctions” WE 4262/6-2 and parts were published in J Tissue Eng Regen Med. 2020 Jan;14(1):186–197. doi: 10.1002/term.2985


Orthopaedic Proceedings
Vol. 85-B, Issue SUPP_II | Pages 114 - 114
1 Feb 2003
Maruthainar N Zambakidis C Harper G Calder DA Cannon SR Briggs TWR
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The aim of surgery in the treatment of tumours of the distal radius is to achieve satisfactory clearance whilst best preserving function of the hand and wrist. Since 1992 a technique of distal radial tumour excision with reconstruction by autologous free fibula strut grafting has been employed in the treatment of thirteen patients at our unit. The procedure employs fixation of the non-vascularised fibula shaft to the proximal radius by step-cuts and a dynamic compression plate. The fibula head substitutes for the distal limit of the radius and articulates with the carpus. We have treated 10 cases of primary or recurrent giant cell tumour and cases of osteosarcoma, chondrosarcoma and Ewings’ sarcoma by this technique. The patients were reviewed at a mean of 50 months post surgery, with assessment of their functional outcome and measurement of the range of wrist movement and grip strength. The patient with Ewings tumour had died of meta-static disease 62 months post grafting. Three patients treated for giant cell tumour had required further surgery, two of these had forearm amputation for malignant transformation. In comparison to the unoperated wrist, range of movement was well preserved. The power of grip strength was 57% of the contralateral wrist and hand. These results compare well with published rates of recurrence of benign giant cell tumour treated by other methods. This technique would seem to offer an acceptable functional result without compromise of the tumour prognosis