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 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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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)

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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