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

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

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

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

The purpose of our study was to identify possible risk factors of patients with GCT of the long bones after curettage and packing the bone cavity with bone cement or bone allografts. We retrospectively reviewed the records of 249 patients with GCT of the limbs treated at Musculoskeletal Oncology Department of our institution between 1990 and 2013, confirmed histologically and recorded in the Bone Tumor Registry. We reviewed 219 cases located in the lower limb and 30 of the upper limb. This series includes 135 females and 114 males, with mean age 32 years (ranging 5 to 80 yrs). According to Campanacci's grading system, 190 cases were stage 2, 48 cases stage 3, and 11 cases stage 1. Treatment was curettage (intralesional surgery). Local adjuvants, such as phenol and cement, were used in 185 cases; whereas in the remaining 64 cases the residual cavity was filled with allografts or autografts only. Oncological outcome shows 203 patients alive and continuously disease-free (CDF), 41 patients NED1 after treatment of local recurrence (LR), 2 patients NED1 after treatment of lung metastases, 2 AWD with lung metastases. One patient died of unrelated causes (DOD). LR rate was 15.3% (38 pts). Lung metastases rate was 1.6% (4 pts). In patients treated by curettage and cement (185 cases) LR was 12% (22 pts). Conversely, in patients treated curettage and bone allografts it was higher (16/64 cases), with an incidence of 25% of cases (p=0.004). Oncological complications seemed to be related with site, more frequently occurring in the proximal femur (p=0.037). LR occurred only in stage 2 or 3 tumors without statistical significance (p>0.05). The mean interval between the first surgical treatment and LR was 22 months (range: 3–89 mos). However, in the multivariate analysis no significant statistical effect on local recurrence rate could be identified for gender, patient's age, Campanacci's grading, or cement vs allografts. The only independent risk factor related to the local recurrence was the site, with a statistical significance higher risk for patients with GCT of the proximal femur (p= 0.008). Our observation on the correlation of tumor location and risk of local recurrence is new. Therefore, special attention must be given to GCTs in the proximal femur. In fact, primary benign bone tumors in the proximal femur are difficult to treat due to the risk of secondary osteonecrosis of the femoral head or pathologic fracture. Numerous methods of reconstructions have been reported. Among these, total hip arthroplasty (THA) or bipolar hip arthroplasty (BHA) should be avoided when possible as more cases are observed in young patients. Therefore, we do not suggest different approach for the proximal femur. GCT in the proximal femur is much more difficult to treat than in other sites, but if curettage is feasible, the best way is to save the joint with a higher risk of local recurrence, knowing that the sacrifice of the hip articulation in case of recurrence is always possible with THA or BHA

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

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

To present the oncological outcome of eleven patients with stage-3 GCT of bone. Thirty-nine cases of GCT who were treated the past nine years at our department were reviewed. Five tumors were classified as stage I, twenty-three tumors as stage II and eleven as stage III tumors. In stage I or II tumors we proceeded to an intraoperative biopsy (frozen biosy).In cases where the intraoperative pathological findings confirmed our diagnosis of GCT we proceeded to operative management. In cases where the intraoperative pathologist’s findings were not clear as well as in cases of stage III tumors we performed only a traditional open biopsy proceeding surgery in a second stage. In stage III tumors we aimed wide margins. Ten of these patients underwent wide surgical excision and limb salvage, while in one patient curettage with cementation was the treatment of choice in order to obtain a fair functional outcome. With a minimum follow up of 3 years, we had no case of local recurrence in cases treated with wide excision and limb salvage. One stage III GCT treated with curettage recurred. Two stage III tumors metastized to the lung. The average interval from initial operation to lung metastasis was six months. Treating GCT with the above management minimizes diagnostic failures. Literature shows local recurrence rate as high as 50% in stage III GCTs. The present study shows that recurrence rate can be significantly reduced and good functional outcome can be achieved by carefully planning approach and wide excision of the tumor

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

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

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

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

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

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

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

The October 2013 Oncology Roundup. 360 . looks at: En bloc resection, irradiation and re-implantation; Metastasis and osteosarcoma; Mobile spine and osteosarcoma; Denosumab miraculous for GCT; Fevers, megaprostheses and sarcomas; PET and prognosis; Canine sarcomas not so different?; Bone cement and giant cell tumours

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

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

The February 2013 Children’s orthopaedics Roundup. 360 . looks at: the human genome; new RNA; cells, matrix and gene enhancement; the histology of x-rays; THR and VTE in the Danish population; potential therapeutic targets for GCT; optimising vancomycin elution from cement; and how much sleep is enough

Aim. To analyse our results after en-block resection of aggressive GCT during 20 years period. Methods. We review 86 patients with skeletal GCT during the last 20 years, from 1990 until 2009, retrospectively. In the cases of latent and active type, extended curettage and bone graft or cement were our treatment of choice, while in aggressive ones we performed en block resection and reconstruction by fibular autograft (e.g. in distal part of radius) or fusion/hinge joint prosthesis (e.g. in GCT around the knee joint). We describe the recurrences, metastases and complications according to treatment. Results. There was no recurrence in 18 cases of en block resection and segmental bone defects were reconstructed with fibular autograft (5), joint fusion (4) and hinge joint arthroplasty (9). We had 2 cases of pulmonary metastasis that underwent resection of the metastasis. In one case, internal fixation failed and the graft broke; thus revision was performed. The rest 68 cases underwent extended curettage and bone graft (51) or cement (17). We had 7 cases of recurrence, 6 treated with repeated curettage and bone cement and one with en lock resection. No death or major complication was reported. Conclusions. In comparison of en block resection with extended curretage, the recurrence rate is greater with the latter; however it results in good control of the disease with less morbidity. In recent years, the invention of hinge knee prosthesis has increased the quality of patients' life in whom we could not preserve the involved joint