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

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 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. 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

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. 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

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

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

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

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

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

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

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

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

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

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

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

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

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

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