Search

Aims: To assess complications and failure mechanisms of osteoarticular allograft reconstructions for primary bone tumours., Patients and Methods: We retrospectively evaluated 38 patients (28 men, 74%) who were treated at our institution with osteoarticular allograft reconstruction between 1989 and 2010. Median age was 19 years (interquartile range 14 to 32). Median follow-up was 19.5 years (95% confidence interval (CI) 13.0 to 26.1) when 26 patients (68%) were alive. In addition, we systematically searched the literature for clinical studies on osteoarticular allografts, finding 31 studies suitable for analysis. Results of papers that reported on one site exclusively were pooled for comparison., Results: A total of 20 patients (53%) experienced graft failure, including 15 due to mechanical complications (39%) and three (9%) due to infection. In the systematic review, 514 reconstructions were analysed (distal femur, n = 184, 36%; proximal tibia, n = 136, 26%; distal radius, n = 99, 19%; proximal humerus, n = 95, 18%). Overall rates of failure, fracture and infection were 27%, 20%, and 10% respectively. With the distal femur as the reference, fractures were more common in the humerus (odds ratio (OR) 4.1, 95% CI 2.2 to 7.7) and tibia (OR 2.2, 95% CI 1.3 to 4.4); infections occurred more often in the tibia (OR 2.2, 95% CI 1.3 to 4.4) and less often in the radius (OR 0.1, 95% CI 0.0 to 0.8)., Conclusion: Osteoarticular allograft reconstructions are associated with high rates of mechanical complications. Although comparative studies with alternative techniques are scarce, the risk of mechanical failure in our opinion does not justify routine employment of osteoarticular allografts for reconstruction of large joints after tumour resection. Cite this article: Bone Joint J 2017;99-B:522-30., (©2017 The British Editorial Society of Bone & Joint Surgery.)

Aims: The purpose of this retrospective study was to differentiate between the MRI features of normal post-operative change and those of residual or recurrent disease after intralesional treatment of an atypical cartilage tumour (ACT)/grade I chondrosarcoma., Patients and Methods: We reviewed the case notes, radiology and histology of 75 patients, who had been treated for an ACT/grade I chondrosarcoma by curettage, phenolisation and bone allografting between 1994 and 2005. The first post-operative Gd-enhanced MRI scan was carried out within one year of surgery. Patients had a minimum of two scans and a mean follow-up of 72 months (13 to 169). Further surgery was undertaken in cases of suspected recurrence., Results: In 14 patients (18.6%) a second procedure was undertaken after a mean period of 59 months (8 to 114). Radio frequency ablation (RFA) was used in lesions of < 10 mm and curettage, phenolisation and bone grafting for those ≥ 10 mm. Only six of these (8% of total) had a histologically-proven recurrence. No increase in tumour grade was seen at time of recurrence., Conclusion: Based on this study, we have been able to classify the post-operative MRI appearances into four groups. These groups differ in follow-up, and have a different risk of recurrence of the lesion. Follow-up and treatment vary for the patients in each group. We present a flow diagram for the appropriate and safe follow-up for this specific group of patients. Cite this article: Bone Joint J 2016;98-B:1674-81., (©2016 The British Editorial Society of Bone & Joint Surgery.)

Background: Favorable reports on the use of massive allografts to reconstruct intercalary defects underline their place in limb-salvage surgery. However, little is known about optimal indications as reports on failure and complication rates in larger populations remain scarce. We evaluated the incidence of and risk factors for failure and complications, time to full weight-bearing, and optimal fixation methods for intercalary allografts after tumor resection., Methods: A retrospective study was performed in all four centers of orthopaedic oncology in the Netherlands. All consecutive patients reconstructed with intercalary (whole-circumference) allografts after tumor resection in the long bones during 1989 to 2009 were evaluated. The minimum follow-up was twenty-four months. Eighty-seven patients with a median age of seventeen years (range, 1.5 to 77.5 years) matched inclusion criteria. The most common diagnoses were osteosarcoma, Ewing sarcoma, adamantinoma, and chondrosarcoma. The median follow-up period was eighty-four months (range, twenty-five to 262 months). Ninety percent of tumors were localized in the femur or the tibia., Results: Fifteen percent of our patients experienced a graft-related failure. The major complications were nonunion (40%), fracture (29%), and infection (14%). Complications occurred in 76% of patients and reoperations were necessary in 70% of patients. The median time to the latest complication was thirty-two months (range, zero to 200 months). The median time to full weight-bearing was nine months (range, one to eighty months). Fifteen grafts failed, twelve of which failed in the first four years. None of the thirty-four tibial reconstructions failed. Reconstruction site, patient age, allograft length, nail-only fixation, and non-bridging osteosynthesis were the most important risk factors for complications. Adjuvant chemotherapy and irradiation had no effects on complication rates., Conclusions: We report high complication rates and considerable failure rates for the use of intercalary allografts; complications primarily occurred in the first years after surgery, but some occurred much later after surgery. To reduce the number of failures, we recommend reconsidering the use of allografts for reconstructions of defects that are ≥15 cm, especially in older patients, and applying bridging osteosynthesis with use of plate fixation.

Background: Neoadjuvant chemotherapy improves outcome in osteosarcoma. Determination of optimum regimens for survival, toxicity and prognostic factors requires randomised controlled trials to be conducted., Patients and Methods: Between 1983 and 2002, the European Osteosarcoma Intergroup recruited 1067 patients with localised extremity osteosarcoma to three randomised controlled trials. Standard treatment in each was doxorubicin 75 mg/m(2) and cisplatin 100 mg/m(2). Comparators were addition of methotrexate (BO02/80831), a multidrug regimen (BO03/80861) and a dose-intense schedule (BO06/80931). Standard survival analysis methods were used to identify prognostic factors, temporal and other influences on outcome., Results: Five- and 10-year survival were 56% (95% confidence interval 53% to 59%) and 52%, respectively (49% to 55%), with no difference between trials or treatment arms. Median follow-up was 9.4 years. Age range was 3-40 years (median 15). Limb salvage was achieved in 69%. Five hundred and thirty-three patients received the standard arm, 79% completing treatment. Good histological response to preoperative chemotherapy, distal tumour location (all sites other than proximal humerus/femur) and female gender were associated with improved survival., Conclusions: Localised osteosarcoma will be cured in 50% of patients with cisplatin and doxorubicin. Large randomised trials can be conducted in this rare cancer. Failure to improve survival over 20 years argues for concerted collaborative international efforts to identify and rapidly test new treatments.

Chondrosarcomas are resistant to conventional chemo- and radiotherapy. A subset of chondrosarcomas arises secondarily in the benign tumour syndromes enchondromatosis (EC) and multiple osteochondromas (MO), and prevention of tumour development would greatly improve prognosis. We therefore investigated the effect of selective COX-2 inhibition on chondrosarcoma growth. COX-2 expression was studied in central- and peripheral cartilaginous tumours. The effect of COX-2 inhibition was assessed in four high-grade chondrosarcoma cell lines using celecoxib and NS-398 treatment. COX-2 activity (prostaglandin E(2) (PGE(2)) ELISA) and cell viability were measured. The (prophylactic) effect of celecoxib on chondrosarcoma growth in vivo was studied for 8 weeks using a xenograft model of cell line CH2879 in immunoincompetent nude mice. High COX-2 protein expression was mainly found in solitary peripheral chondrosarcoma and in enchondromatosis-related central chondrosarcoma, which was confirmed by qPCR. After 72h of celecoxib treatment, a significant decrease in cell viability was observed in three chondrosarcoma cell lines. In vivo, celecoxib initially slowed tumour growth in chondrosarcoma xenografts; however, after prolonged treatment relapsed tumour growth was observed. Tumour volume was negatively associated with celecoxib serum levels, and seemed smaller in the high-dose prophylactic treatment group. We confirmed the expression of COX-2 in 65% of chondrosarcomas, and COX-2 inhibition by celecoxib diminished cell viability in vitro. The initial response and the decrease in tumour volume with increased celecoxib serum levels in vivo supported a role for celecoxib, although relapsed tumour growth after 6 weeks was worrisome. Also the role of high-dose prophylactic celecoxib in preventing the development of benign and malignant cartilage tumours in EC and MO patients deserves further investigation., (Copyright (c) 2009 Elsevier Ltd. All rights reserved.)

Background: Osteosarcoma is the most prevalent primary malignant bone tumour in children and young adults, with poor survival in 40% of patients. To identify the signalling pathways involved in tumourigenesis, we compared gene expression in osteosarcoma with that in its presumed normal counterparts., Methods: Genome-wide expression profiles were generated from 25 high-grade central osteosarcoma prechemotherapy biopsies, 5 osteoblastomas, 5 mesenchymal stem cell (MSC) populations and these same MSCs differentiated into osteoblasts. Genes that were differentially expressed were analysed in the context of the pathways in which they function using the GenMAPP programme., Results: MSCs, osteoblasts, osteoblastomas and osteosarcomas clustered separately and thousands of differentially expressed genes were identified. The most significantly altered pathways are involved in cell cycle regulation and DNA replication. Several upstream components of the Wnt signalling pathway are downregulated in osteosarcoma. Two genes involved in degradation of beta-catenin protein, the key effectors of Wnt signalling, Axin and GSK3-beta, show decreased expression, suggesting that Wnt signalling is no longer under the control of regular signals. Comparing benign osteoblastomas with osteosarcomas identified cell cycle regulation as the most prominently changed pathway., Conclusion: These results show that upregulation of the cell cycle and downregulation of Wnt signalling have an important role in osteosarcoma genesis. Gene expression differences between highly malignant osteosarcoma and benign osteoblastoma involve cell cycle regulation.

Giant cell tumour of bone (GCTB) is a benign bone tumour known for the unpredictable clinical behaviour of recurrences and, in rare instances, distant metastases. It consists of uniformly distributed osteoclastic giant cells in a background of mononuclear rounded and spindle-shaped cells. Cytogenetically, telomeric associations are the most common chromosomal aberrations, which, however, are normally almost exclusively found in high-grade malignancies. GCTB has often been regarded as a polyclonal tumour, but more recently a recurrent specific aberration was reported, which suggests a possible role for disturbed telomere maintenance. Here we further investigate telomere maintenance in GCTB using 19 samples from 19 patients. A combination of immunofluorescence and FISH was performed, applying antibodies directed against promyelocytic leukaemia body-related antigen and hTERT and using telomere peptide nucleic acid probes. The TRAP assay and telomere restriction fragment length analysis were performed for functional detection of telomerase activity and alternative telomere lengthening. Both osteoclastic giant cells and mononuclear cells showed positivity for hTERT and promyelocytic leukaemia body-related antigen. In most mononuclear cells, co-expression was present. The TRAP assay demonstrated heterogeneous telomerase activity, while telomere restriction fragment length analysis showed non-heterogeneous telomere lengths, indicating the absence of alternative telomere lengthening. Confocal microscopy showed stereometric co-localization of nucleolin with promyelocytic leukaemia body-related antigen in association with telomeres in the spindle-shaped cells. hTERT was more diffusely distributed throughout the nucleus. Our results show that GCTB demonstrates remarkable telomere maintenance of activated telomerase and inactivated alternative telomere lengthening in the presence of normal mean telomere restriction fragment lengths. These findings strongly suggest that these aggregates, while activating telomerase, are part of a structural telomere protective-capping mechanism rather than of a telomere-lengthening mechanism. Telomere maintenance could be considered an important key factor in the pathogenesis of GCTB., (Copyright (c) 2008 Pathological Society of Great Britain and Ireland)

Background: Dedifferentiated chondrosarcoma has a very poor prognosis. Because of its rarity, there are few large studies of outcome which might identify potential prognostic factors. In particular there remains uncertainty about the value of chemotherapy for this condition., Method: A retrospective study was done using data supplied by members of the European Musculo Skeletal Oncology Society (EMSOS). We obtained data on 337 patients from nine European centres with this rare condition, with details on patients, treatment and outcome which were then analysed in an attempt to identify prognostic features., Results: The median age was 59 years and there was a slight predominance of males (53%). The most common sites were the femur and pelvis. Twenty-nine percent of patients with a long bone tumour had a pathological fracture. 71 patients (21%) had metastases at the time of diagnosis and these patients had a median survival of 5 months with a 10% chance of survival at 2 years. For the 266 patients without metastases at diagnosis, 254 underwent surgery with 79% having limb salvage. Thirty-one percent of these 266 patients had chemotherapy with 47% of those under 60 receiving it. In this group of 266 patients, overall survival was 28% at 10 years and poor prognostic factors were the presence of a pathological fracture at diagnosis, a pelvic location and increasing age. Local recurrence and overall survival were related to inadequate margins of excision. We did not find that the histological subtype, size of the tumour or the use of chemotherapy significantly affected outcome. For all patients the overall survival was 24% at 5 years., Conclusions: The prognosis for patients with dedifferentiated chondrosarcoma remains dismal. Surgery with clear margins remains the principal treatment for this condition. Further use of chemotherapy should be within a trial or treatment protocol.

Mutational inactivation of EXT1 or EXT2 is the cause of hereditary multiple osteochondromas. These genes function in heparan sulphate proteoglycan (HSPG) biosynthesis in the Golgi apparatus. Loss of heterozygosity of the EXT1 locus at 8q24 is frequently found in solitary osteochondromas, whereas somatic mutations are rarely found. We investigated the expression of EXT1 and EXT2 (quantitative RT-PCR) and of different HSPGs (immunohistochemistry) in solitary and hereditary osteochondromas and in cases with malignant progression to secondary peripheral chondrosarcoma, in relation to possible mutations and promoter methylation. The mutation status of patients with multiple osteochondromas correlated with decreased EXT1 or EXT2 expression found in their resected tumours. We could not show somatic point mutations or promoter hypermethylation in 17 solitary tumours; however, EXT1 expression was decreased in 15 cases, whereas EXT2 was not. Intracellular accumulation of syndecan-2 and heparan sulphate-bearing isoforms of CD44 (CD44v3) was found in most tumours, which concentrated in the Golgi apparatus as shown by confocal microscopy. This contrasted with the extracellular expression found in normal growth plates. In conclusion, mutational inactivation of either EXT1 or EXT2 leads to loss of mRNA expression of the corresponding gene. We hypothesize that loss of EXT expression disrupts the function of the EXT1/2 complex in HSPG biosynthesis, resulting in the intracellular accumulation of HSPG core proteins that we found in these tumours., (Copyright (c) 2007 Pathological Society of Great Britain and Ireland.)

Primary high-grade intramedullary osteosarcoma of the extremities is a clinically aggressive bone tumour. There is an ongoing effort to further improve efficacy of neo-adjuvant chemotherapy and reduce chemotoxicity by trying to identify osteosarcoma patients who are at risk of treatment failure as well as to identify those who can do with less chemotherapy. In only 5% of patients, first distant metastasis or local relapse occurs 5 years or more after initial treatment for osteosarcoma. Patients and physicians can therefore easily erroneously consider a patient with osteosarcoma cured if he or she is disease-free for more than 5 years following diagnosis and treatment. To investigate if these rare late relapsing patients are characterised by specific clinico-pathological features, we examined clinical and histological variables of late relapse (first local recurrence or metastasis 5 years or more after initial diagnosis) out of a total of 2,243 patients, with a special interest in the histological osteosarcoma subtype. In total, 33 patients had a documented relapse 5 years or more after diagnosis. Half of the patients had good response (>or=90% necrosis) to pre-operative chemotherapy and the other half a poor response (<90% necrosis) and late relapses seemed to be more frequently proportionately in those who had a good initial response to chemotherapy. The occurrence of late relapse did not appear to be associated with age or gender. Although not statistically significant, there was a trend for patients with a chondroblastic subtype of osteosarcoma, or a location in the tibia or fibula, to have a higher risk for late relapse.

Periosteal osteosarcoma is a rare primary malignant bone tumour. Treatment is by surgical excision, but controversy remains about the value of chemotherapy. The members of the European Musculo Skeletal Oncology Society (EMSOS) collaborated to produce a dataset of 119 patients. The predominant site for the tumour was the femur, followed by the tibia. All but 2 patients underwent surgery, with 9 requiring amputation and the others having limb salvage. A total of 81 patients had chemotherapy, of whom 50 had neoadjuvant chemotherapy. There was no standard chemotherapy regime, but all patients receiving chemotherapy were given doxorubicin combined with at least one other agent. The overall survival was 89% at 5 years and 83% at 10 years. Eight patients developed local recurrence, of whom 5 died. Survival was related to appearance of local recurrence (P < 0.0001) but no other single factor. The use of chemotherapy was not shown to be a prognostic factor, but was used in two-thirds of the patients in this study.

Epidiaphyseal intercalary reconstruction has become possible for bone tumors that extend into the epiphysis because advances in magnetic resonance imaging and chemotherapy allow close resection while sparing the juxtaarticular bone and joint. In a retrospective study, we questioned whether epidiaphyseal reconstructions around the knee had a clinical outcome (measured as long-term survival, complication rate, and functional score) comparable with metadiaphyseal and diaphyseal reconstructions. Between 1988 and 1999, 14 epidiaphyseal, nine metaphyseal, and 12 diaphyseal reconstructions were done, and the median followup was 7.2 years. Kaplan-Meier analysis showed a 10-year survival rate of 79% for epidiaphyseal reconstructions, which did not differ from an 89% rate for metadiaphyseal and a 75% rate for diaphyseal reconstructions. Epidiaphyseal complications included two infections, five fractures, and three nonunion treatments. Complications for all 35 grafts included three infections, 12 fractures, and nine nonunion treatments. Ultimately, six grafts failed, with infection and length of resection as predisposing factors. All epiphyseal osteotomies had tumor-free margins and no local recurrences. The mean Musculoskeletal Tumor Society score for each type of intercalary reconstruction was between 23 and 24. Because the epidiaphyseal reconstruction avoids complications associated with joint reconstruction and the results are comparable with those of other types of intercalary grafts, these reconstructions should be considered if at least 1 cm of tumor-free juxtaarticular bone can be maintained.

There are limited data that define the role of chemotherapy in the treatment of high-grade spindle cell sarcomas of bone, other than osteosarcoma or malignant fibrous histiocytoma (MFH-B). This prospective study evaluates the effect of doxorubicin and cisplatin on these tumours. Thirty-seven patients, age 65 years, with spindle cell sarcoma of bone, except osteosarcoma or MFH-B, were included. Chemotherapy consisted of doxorubicin and cisplatin every 3 weeks for six cycles. Resection was performed after three cycles. In 15 patients with metastases, response assessment showed three complete responses (CR), four stable disease (SD), five progression; three were not evaluable. Median time to progression was 30 months (95% Confidence Interval (CI), 8-51 months) for the operable non-metastatic patients; median survival 41 months (95% CI, 16-82 months). Median time to progression in the metastatic group was 10 months (95% CI, 0-18 months) and median survival was 14 months (95% CI, 4-45 months). This study suggests a limited role for doxorubicin and cisplatin in metastatic high-grade spindle cell sarcoma of bone, other than osteosarcoma or MFH-B cases.

The aim of our study was to determine whether or not the tyrosine kinase receptor, HER2 (also known as ErbB2/Her2/neu), is overexpressed in human osteosarcomas (OS). We studied 15 biopsy and 18 resection specimens at the mRNA and protein levels. HER2 status in the OS specimens was assessed by immunohistochemistry (IHC) and quantitative Real-Time Polymerase chain reaction (PCR). In moderately immunopositive cases fluorescent in situ hybridisation (FISH) analysis was used in order to identify any possible gene amplification. 27 samples were evaluable for IHC and only 1 case showed a moderately positive membrane staining. The remaining samples showed no staining or focal cytoplasmic staining (2 samples). In the moderately positive case, FISH analysis showed no HER-2 gene amplification. There was also no overexpression of HER2 mRNA suggesting this sample was a false-positive immunostain. HER2 mRNA expression was present in all samples at a similar level to that in the breast cancer cell line, MCF7, which does not overexpress HER2 and was used as a negative control. In conclusion, this study shows that HER2 mRNA or membranous HER2 protein overexpression is absent in human OS. We noted various inconsistencies in previous published studies, with regard to methodology and the interpretation of the results based on poor methodology. We therefore conclude that the positive data with regard to HER2 overexpression reported in these previous studies is not reliable. Our results suggest that the monoclonal antibody trastuzumab (Herceptin(R)), directed against the HER2-receptor, is not likely to be an effective therapeutic agent in OS.

Chondroblastoma (CB) is a rare benign tumour (<1% of all bone tumours) involving epiphyseal long bones (male:female 1.5:1). During development, and in the postnatal period, IHh/PTHrP and FGF signalling molecules control the space and timing of chondrocyte differentiation. Considering the close relationship of CB with the growth plate (age and location), the expression of proteins involved in epiphyseal growth regulation was studied. Twelve cases of CB were retrieved. Immunohistochemistry was performed using antibodies against fibroblast growth factor-2 (FGF-2), fibroblast growth factor receptor-1 (FGFR-1), FGFR-3, bcl-2, p21, parathyroid hormone-related peptide (PTHrP), and parathyroid hormone-related peptide receptor (PTHR1). Three observers evaluated haematoxylin and eosin (H&E)-stained and immunostained slides independently. Semi-quantitative estimation of the matrix, the type of matrix, and immunostaining was performed. Cellular and matrix-rich areas were evaluated separately. Diverse amounts and types of matrix were present in different tumours, as well as within individual tumours. Signalling molecules were expressed in 50-100% of the cases. Higher levels of expression were found in cellular areas than in matrix-rich areas, especially for PTHR1, bcl-2, and FGFR-3. CB is an unusual entity affecting specific sites, showing that both IHh/PTHrP and FGF signalling are active. Higher expression was found in cellular than in matrix-rich areas, as in the proliferating/pre-hypertrophic growth plate zone in comparison with the hypertrophic/calcifying zone. Previous studies have shown the same molecules to be expressed with a similar pattern in chondrosarcomas. The sum of the evaluated features indicates that CB is a neoplasm originating from a mesenchymal cell committed towards chondrogenesis via active growth plate signalling pathways., (Copyright 2004 John Wiley & Sons, Ltd.)

The European Musculo Skeletal Oncology Society (EMSOS) has carried out a retrospective review of patients over the age of 40 years with osteosarcoma. 481 patients from 12 centres or multicentric groups were included. 42 patients had osteosarcoma arising in Paget's disease, median survival was 9 months. Patients with axial or metastatic tumours also did badly whilst 41 patients with radiation-induced osteosarcoma had a prognosis paralleling conventional osteosarcoma matched for patient age and site of the tumour. 238 patients had high grade non-metastatic osteosarcoma and had a survival of 46% at 5 years. Older patients had less chemotherapy and fared worse. Osteosarcoma in the elderly is a curable condition and warrants intensive treatment with chemotherapy and surgical resection.

Low-grade surface tumours of bone may theoretically be treated by hemicortical resection, retaining part of the circumference of the cortex. An inlay allograft may be used to reconstruct the defect. Since 1988 we have performed 22 hemicortical procedures in selected patients with low-grade parosteal osteosarcoma (6), peripheral chondrosarcoma (6) and adamantinoma (10). Restricted medullary involvement was not a contraindication for this procedure. There was no evidence of local recurrence or distant metastasis at a mean follow-up of 64 months (27 to 135). Wide resection margins were obtained in 19 patients. All allografts incorporated completely and there were no fractures or infections. Fractures of the remaining hemicortex occurred in six patients and were managed successfully by casts or by osteosynthesis. The functional results were excellent or good in all except one patient. Hemicortical procedures for selected cases of low-grade surface tumours give excellent oncological and functional outcomes. There was complete remodelling and fewer complications when compared with larger intercalary procedures. The surgery is technically demanding but gives good clinical results.

Purpose: In patients with an osteosarcoma, the prognosis is still poor. The aim of the present study was to investigate whether routinely tested biochemical parameters or additional parameters on bone scintigraphy could be identified which can select prognostic subgroups at the time of diagnosis., Methods: A retrospective study was performed in 115 consecutive patients (70 male, 45 female) (mean age: 25.6 years; range: 3.50-78.0 years) who were referred for bone scintigraphy prior to treatment from March 1986 to September 2000 because of a newly diagnosed osteosarcoma. All bone scans were reassessed for the intensity and pattern of uptake and a bone-scan index. All pre-treatment general, histological, biochemical, and scintigraphic data were correlated with clinical outcome during follow-up., Results: During follow-up 54 patients died. Tumour volume and GGT showed significance as independent variables for metastases. Patients with metastases demonstrated a significantly lower survival rate (23% 5-year survival) than patients without metastases (98% 5-year survival). Tumours of the humerus and femur had a significantly lower survival rate. With respect to significant biochemical parameters (ALP, GGT, ASAT), it was not possible to determine a cut-off value that could be used to differentiate between high- and low-risk patients. Additional parameters assessed on bone scintigraphy were not important for prognostic stratification., Conclusion: The strongest predictor of survival in osteosarcoma is the presence or absence of metastasis. Some biochemical parameters have prognostic value, but they cannot be used for the unequivocal identification of subgroups. Additional scintigraphic parameters are irrelevant for prognostic stratification.

From the European Osteosarcoma Intergroup study 202 patients were assessed with respect to their surgical treatment. Although treated in three different centres the survival of the three groups was identical (57% at five years). Two of the centres had rates of limb salvage of 85% and 83%, respectively, while the third had a rate of 49%. The corresponding risks of local recurrence were 13.3%, 6.8% and 2.5%, with all local recurrences arising in limbs with attempted limb salvage. Local recurrence was closely related to the adequacy of the margins of excision and to the chemotherapeutic response. Patients who had undergone limb-salvage surgery and who developed local recurrence still had a better survival than those who had primary amputation (37% v 31% survival at five years). Of patients who relapsed, 31% of those with local recurrence alone were cured by further treatment, as compared with only 10% of those with metastases. Limb-salvage surgery with effective chemotherapy remains the optimum treatment for osteosarcoma.

A 40 year old man with hereditary multiple exostoses (HME), affecting predominantly his left proximal tibia, distal femur, and proximal femur, underwent resection of an osteochondroma near the trochanter major of his left proximal femur because of malignant transformation of the cartilaginous cap towards secondary peripheral chondrosarcoma. The patient had a history of a papillary thyroid carcinoma four years previously. At examination of the resected specimen, a third malignant tumour, an intermediate grade osteosarcoma (grade II/IV), was found in the osseous stalk of the osteochondroma. Although no mutations were found in the EXT1 and EXT2 genes, the genes involved in HME, or in exons 5-8 of the p53 gene, the development of three malignancies before the age of 40 suggests that this patient is genetically prone to malignant transformation.

In the present study different methods for determining the volume of a tumor were evaluated. For 12 models, the real volume, the volume according to measurement of the surface area on MRI, an ellipsoid and a cylindrical approximation of the volume, as well as the maximum diameter, were determined. There appeared to be a good correlation between all calculated volumes and the real volume. The error (mean: 17%) and the standard deviation (SD: 14%) on this error were smallest if the volume was determined by means of determination of the surface area. The ellipsoid approximation resulted in a smaller error (mean: 0%) but a higher standard deviation (SD: 27%). The cylindrical approximation resulted in unacceptable deviations (mean: 51%; SD: 40%). Volume was significantly related to the maximal diameter to the power of 2.3. Volume calculated according to this power resulted in an error of 18%. Standard deviation in this case however was unacceptable (SD: 89%). Volume calculation based upon the determination of the surface area has given the best and most reliable results. Ellipsoid approximation was less reliable, but faster and cheaper. Cylindrical approximation was unacceptable. Size, expressed as maximal diameter of the tumor, was also unacceptable as a parameter for volume.

A continuous ambulatory activity monitor allows objective measurement of the amount and intensity of physical activity. We examined the reliability and validity of this device in the assessment of seven aspects of function over a period of 24 hours in 20 patients who had undergone limb salvage or amputation for a tumour in the leg. The test-retest reliability was determined by undertaking identical assessments on two separate days. The measurements were compared with other indicators of functional status and quality of life in order to determine the validity of the monitor. Its reliability was satisfactory, with intraclass correlation coefficients ranging from 0.65 to 0.91. Significant correlations were seen between the 'time spent walking' and the Musculoskeletal Tumor Society rating scales and the Rand-36 physical functioning score. There was also a significant association between the 'movement intensity during walking' and the Musculoskeletal Tumor Society score. The satisfactory reliability and validity of the monitor shows considerable promise for its use as a device for measuring physical activity objectively in patients after surgery for limb-salvage or an amputation.

The aim of this study was to assess the effect of local recurrence on survival in primary osteosarcoma. 559 patients entered into two randomised trials of the European Osteosarcoma Intergroup who received surgery for primary operable high-grade osteosarcoma of the extremities were included in this analysis. Proportional hazards modelling techniques were used to assess the relative importance of sex, age, site, surgery performed and local recurrence. The last of these was considered as a time-dependent covariate. 42/559 (8%) patients had a local recurrence. In the multivariate analysis, local recurrence was found to greatly increase the risk of death (hazard ratio (HR)=5.10, 95% confidence interval (CI) 3.51-7.41). Site and surgery performed also had a significant influence within this model. Using the technique of landmark analysis, with the landmark time set at 18 months, local recurrence alone had a significant influence on survival (HR=4.60, 95% CI 2.80-7.57). Local recurrence is an indicator of poorer survival for patients with operable primary osteosarcoma.

Background and Objectives: In large malignancies of the distal femur, limb salvage may not be feasible. Amputation is often the treatment of choice. A Van Ness-Borggreve rotationplasty is an alternative when the sciatic nerve is free of tumour. The appearance of the rotated lower leg is poor, which justifies a general concern about the psychosocial functioning of these patients. The aim of the study was to assess the medium- and long-term effects on quality of life (QOL) after rotationplasty., Methods: A self-report questionnaire included the SF-36, the Social Support List, and selected items from the European Organisation for Research and Treatment of Cancer (EORTC) questionnaires as well as study-specific questions. The questionnaire was mailed to 34 patients at once. All patients were older than 16 years and at least 1 year postsurgery (mean 6.3 years). The response rate was 96%., Results: Patients' physical functioning was poorer than that of healthy peers but better in comparison to chronically ill patients. Levels of psychosocial functioning, general QOL, and social support were highly comparable with those of healthy peers. One-third to one-half of the patients reported negative effects of the surgery on initiating social and/or intimate contacts, body image, and sexuality. With respect to physical functioning, two-thirds of patients engaged actively in sports. Patients reported wearing the prosthesis continuously and were, in general, satisfied with its fit., Conclusions: Given the relatively high levels of QOL and psychosocial functioning of these patients, these results indicate that rotationplasty is a good alternative in the treatment of patients with a large malignancy of the distal femur.

Purpose: To differentiate between benign and malignant cartilaginous tumors with fast contrast material-enhanced magnetic resonance (MR) imaging., Materials and Methods: In 37 patients, fast contrast-enhanced MR images were obtained in eight enchondromas, 11 osteochondromas, and 18 chondrosarcomas. Start of enhancement-early, within 10 seconds after arterial enhancement; delayed, between 10 seconds and 2 minutes; late, after 5 minutes on spin-echo images-and progression of enhancement were represented with three types of time-signal intensity curves. Findings were correlated with the surgical specimen in 27 cases, curettage material in three cases, and biopsy combined with long-term follow-up findings in seven cases., Results: Start of enhancement and the combination of start and progression of enhancement correlated significantly (P <.001) with benign and malignant tumors. Early enhancement was seen in chondrosarcoma, not seen in enchondroma, and seen in osteochondroma only when growth plates were unfused. The sensitivity was 89%, specificity 84%, positive predictive value 84%, and negative predictive value 89%. Differentiation of malignancy from benignity on the basis of early and exponential enhancement was possible with a sensitivity of 61%, specificity 95%, positive predictive value 92%, and negative predictive value 72%., Conclusion: Preliminary results show that in the adult population fast contrast-enhanced MR imaging may assist in differentiation between benign and malignant cartilaginous tumors.

We present an overview of the imaging modalities in bone tumors. The imaging strategies of preoperative work-up, monitoring the effect of chemotherapy and the detection of recurrences by long-term follow-up are discussed.

Dedifferentiated chondrosarcoma is defined as a high-grade, anaplastic sarcoma adjacent to a low-grade malignant cartilage-forming tumour. Controversy remains as to whether the anaplastic and cartilaginous components are derived from a common precursor cell, or whether they represent separate genotypic lineages (collision tumour). Both components of a case of dedifferentiated chondrosarcoma were therefore separately investigated by loss of heterozygosity (LOH) analysis, comparative genomic hybridization (CGH), DNA flow cytometry, and p53 analysis. Both showed p53 overexpression and an identical somatic 6 bp deletion in exon 7 of p53. Combination of the CGH and LOH results revealed that both components had lost the same copy of chromosome 13. These results provide compelling evidence in this case for a common origin, instead of the 'collision tumour' theory. Certain genotypic alterations were not shared. The anaplastic component showed severe aneuploidy, LOH at additional loci, and amplification and deletion of several chromosome parts. In contrast, the cartilaginous component had lost chromosomes 5, 22, 17p and part of 16p and revealed an amplification of 17q. The LOH and CGH results further demonstrated that the two components had lost a different copy of chromosome 4. Thus, a substantial number of genetic alterations have occurred after the diversion of the two components, indicating that the separation of the two clones, derived from a single precursor, was a relatively early event in the histogenesis of this case of dedifferentiated chondrosarcoma., (Copyright 1999 John Wiley & Sons, Ltd.)

Background: Enchondroma is the most common primary benign bone tumor of the hand, especially the phalanges, whereas chondrosarcoma is uncommon at this site. Although phalangeal chondrosarcoma may have ominous histologic features, its biologic behavior is relatively indolent., Methods: Thirty-five cases of phalangeal lesions previously diagnosed as chondrosarcoma were studied. Histologic and tumor-biologic parameters (Ki-67 and p53 immunohistochemistry) were investigated and correlated with clinical behavior., Results: All cases were characterized by unequivocal malignant histologic features (Grade 2 or higher) or Grade 1 malignant histologic features combined with the presence of cortical destruction and soft tissue extension. The median age of the patients at the time of diagnosis was 67 years (range 21-87 years), with a slight female predominance. Occurrence in the hand was more common than in the foot, with the proximal phalanx affected most often. Treatment varied from local therapy (curettage or local excision) in 16 patients to amputation or exarticulation in 19 cases. Follow-up ranged from 8-432 months for 28 patients. Ten of 15 tumors treated by local therapy recurred whereas none of 13 tumors treated by radical surgery recurred. The median survival was 20.8 years; none of 28 patients developed metastases nor died of disease. Both the type of treatment and localization in the proximal phalanx were associated independently with local recurrence., Conclusions: Phalangeal chondrosarcoma behaves as a locally aggressive lesion and, in contrast to chondrosarcomas located elsewhere, rarely metastasizes. Treatment is indicated only because of its locally destructive growth. The authors believe that given the excellent survival data, curettage with adequate follow-up should be considered as the treatment of choice if technically feasible, especially in those cases in which amputation would lead to a significant loss of hand function.

Chondrosarcomas are malignant cartilaginous tumors arising centrally in bone (central chondrosarcoma), or secondarily within the cartilaginous cap of a hereditary or sporadic exostosis (peripheral chondrosarcoma). Loss of heterozygosity (LOH) was studied by microsatellite analysis at the loci harboring the EXT genes (implicated in hereditary multiple exostoses), the EXT-like genes, and at 9p21, 13q14, 17p13, and chromosome 10. Nineteen of 20 peripheral chondrosarcomas showed LOH at all loci tested, while only 3 of 12 central chondrosarcomas exhibited LOH, restricted to 9p21, 10, 13q14, and 17p13. LOH at 9p21 did not appear to involve the CDKN2A gene, as assessed by SSCP analysis. DNA flow cytometry demonstrated a wide variation in the ploidy status in peripheral chondrosarcomas (DNA indexes, 0.56-2.01), whereas central chondrosarcomas were predominantly peridiploid. Near-haploidy found in peripheral chondrosarcomas could explain part of the high LOH percentages. Ki-67 immunohistochemistry suggested a higher proliferation rate in peripheral chondrosarcomas. Our results indicate that peripheral chondrosarcomas, arising secondarily to an exostosis, may obtain genetic alterations during malignant transformation, with subsequent genetic instability as demonstrated by a high percentage of LOH and a wide variation in ploidy status. In contrast, peridiploidy and a low percentage of LOH in central tumors suggest that a different oncogenic molecular mechanism may be operative., (Copyright 1999 Wiley-Liss, Inc.)

Purpose: To prospectively analyze the value of fast, dynamic, subtraction magnetic resonance (MR) imaging in the characterization of musculoskeletal tumors., Materials and Methods: In 175 consecutive patients with a musculoskeletal mass, dynamic contrast-enhanced subtraction MR imaging was performed after administration of 0.1 mmol per kilogram of body weight gadopentetate dimeglumine or gadoteridol. A turbo gradient-echo technique was used, with a temporal resolution of 1-3 seconds. The interval between arterial and early tumor enhancement, the pattern (peripheral or diffuse) of enhancement, and the progression of tumor enhancement, as visualized on time-signal intensity curves, were assessed. MR enhancement features were related to the histopathologic diagnoses., Results: Differentiation of benign from malignant soft-tissue masses was possible with a sensitivity of 91% and specificity of 72% based on start of enhancement, a sensitivity of 73% and specificity of 97% based on peripheral or diffuse enhancement, and a sensitivity of 86% and specificity of 81% based on progression of enhancement. Benign bone tumors could not be accurately differentiated from malignant bone tumors on the basis of the three defined parameters (sensitivity, 63%-76%; specificity, 50%-76%)., Conclusion: Dynamic, contract-enhanced, subtraction MR images may be useful to differentiate malignant from benign soft-tissue masses.

In the fifties, patients with a malignant bone tumour were treated with radiotherapy, sometimes supplemented by resection, as recommended by the Bone Tumour Committee established in 1953. In the seventies, improvement of imaging techniques and chemotherapy made limb-saving surgery possible. Currently, 70% of patients with a malignant tumour of the locomotor apparatus are treated by limb saving, oncologically justified surgery. The surgical defects can be repaired with the aid of an endoprosthesis, or bone homografting or autografting. Children are often treated with an operation involving 180% rotation of the ankle to function as the knee, combined with a prosthesis. Adults are sometimes treated with this technique, but also with internal ('standard') prostheses and donor bone. The future will have to make clear which technique is to be preferred in which situation. Probably, typing and prognosis of various tumours may improve, leading to better insight into the treatment. Centralization of the treatment of rare tumours may also contribute to improvement of the treatment and its scientific research.

Objective: To identify specific features of chondroblastic osteosarcoma on gadopentetate dimeglumine (Gd)-enhanced magnetic resonance (MR) imaging., Design and Patients: Nine patients with chondroblastic osteosarcoma and a control group of 20 patients with conventional central osteosarcoma were included in this study. The histopathological findings of the surgical specimens were compared with enhancement patterns on static Gd-enhanced MR images., Results: In chondroblastic osteosarcoma septonodular and peripheral rim enhancement represented tumour with a pure chondroid matrix. Non-enhancing and heterogeneous enhancing areas represented tumour with both chondroid and osteoid matrix. In the tumours in the control group enhancement was predominantly heterogeneous but in one it was homogeneous. All these areas corresponded to necrotic or viable osteoid tumour tissue or fibrovascular tissue in areas of necrosis., Conclusion: Gd-enhanced MR imaging can assist in obtaining diagnostic biopsy material of chondroblastic osteosarcoma by identifying both osteoid- and chondroid-forming areas.

Objective: To analyse to what extent MR imaging based decisions were correct in determining the surgical procedure in patients with osteosarcoma of the distal femur., Design: We compared the findings on MR imaging that determined the surgical strategy with the actual surgical findings or histopathological specimen. We assessed to what extent MR images could be used to determine the surgical procedure in patients with osteosarcoma., Patients: Between 1985 and 1992, 34 patients with an osteosarcoma were treated. Two patients had a low-grade osteosarcoma. Thirty-two patients with a high-grade osteosarcoma of the distal femur (17 stage IIB, 15 stage III) were included in this study. Surgical options consisted of either limb salvage surgery or ablative surgery, which included the Van Nes-Borggreve rotationplasty. Limb salvage surgery consisted of extra-articular or transarticular resection, followed by reconstruction. Surgery was planned depending on the local extent of the tumour as depicted on the MR studies, coupled with data from the biopsy, age, patient compliance and histological grade. Follow-up was available in all patients. Nine of 17 patients graded as IIB were alive with an average follow-up of 68 months (range 46-109 months), of whom one has metastases. No local recurrence was encountered., Results: If no tumour involvement on MR imaging was found and this was used as a determining factor, this proved to be correct at subsequent analysis. We found that in eight of 11 cases, when MR images suggested a close relationship between tumour and nerve, an oncologically safe plane could be achieved during surgery. In three, a free plane could not be accomplished, as confirmed at histopathological examination. Hence, when nerve involvement was equivocal on MR imaging we found it valuable to reassess nerve involvement during surgery and reconsider limb salvage surgery. When the decisive factor was the vascular involvement and tumour extension was read as equivocal, it was possible to obtain a oncologically safe plane in six of 13 cases. When comprehensive tumour involvement of any structure was noted pre-operatively, it proved to be correct at histopathological examination, except for one case of assumed vascular involvement that proved to be free., Conclusions: If no tumour involvement of a structure was found on MR imaging and this was used as a determining factor, this proved to be correct. When nerve involvement was equivocal on MR imaging we found it valuable to reassess nerve involvement during surgery and reconsider limb salvage surgery. Extensive tumour involvement of any structure, as shown by MR imaging, could be used correctly as a decisive argument in planning a surgical procedure.

Objective: The purpose of this study was to evaluate clinical symptoms and radiographic features that allow radiologists to differentiate between enchondroma and central grade 1 chondrosarcoma. Such differentiation is important because of differences in management., Materials and Methods: Clinical symptoms and location and size of 35 enchondromas and 43 central grade 1 chondrosarcomas were analyzed. Radiographic features were assessed independently by three observers. The chi-square test and linear discriminant analysis were used to identify features with discriminating strength. Kappa values were calculated to validate the consistency of observations among observers. A consensus diagnosis made by histology and long-term follow-up was used as the standard., Results: No statistically significant correlation was found between clinical symptoms and the benign or malignant nature of the neoplasms. Grade 1 chondrosarcomas were more likely to be found in the axial skeleton and in flat bones. Also, chondrosarcomas were significantly larger than enchondromas (p < .001). Ill-defined margins and lobulated contours were the only morphologic features seen on radiographs that allowed significant discrimination (p = .004 and .009, respectively). An optimal combination of four radiographic features still left 72 of the 78 lesions with a 10-90% probability of malignancy, indicative of poor discriminating power. Kappa values generally showed poor to fair agreement., Conclusion: Location in the axial skeleton and size greater than 5 cm are the most reliable predictors of central grade 1 chondrosarcoma. Morphologic features seen on radiographs and clinical symptoms do not improve the ability to differentiate between enchondromas and central grade 1 chondrosarcomas.

MR imaging has had an unparalleled impact on the treatment of patients with musculoskeletal sarcoma. Basically, the high accuracy of local staging has made the introduction of reconstructive and limb salvage procedures instead of amputation of disarticulation available to the majority of patients with musculoskeletal sarcoma. Pre-operative work-up with MRI is not only more accurate, but also much faster and cheaper than the conventional work-up. Staging is the single most important reason for performing MR imaging in patients with musculoskeletal tumours. The impact of MR specificity is less dramatic but the benefit to the patient is an increased safety margin. When diagnostic errors with devastating consequences are made nowadays, it is usually because the proper protocol has not been followed. A patient with a potentially malignant, or equivocal, musculoskeletal mass deserves to have a combined radiographic-MRI examination prior to invasive procedures. MRI does not currently have a major impact on chemotherapy decisions and colour Doppler ultrasound has a higher accuracy than MRI. However, selected cases, i.e. intraosseous tumours, dynamic Gd-enhanced MRI, can replace colour Doppler ultrasound.

Adamantinoma of long bones is a rare skeletal tumor of unknown origin with epithelial and fibrous elements. The ill-defined distinction between the two components in some cases earlier led to the assumption that these might be derived from the same (mesenchymal) stem cell. In this study, we investigated the distribution of extracellular matrix components in 21 adamantinomas by immunohistochemistry, to gain information on the interaction between the epithelial and fibrous parts of the tumor. Collagens I and III, and fibronectin were generally present in the (osteo-)fibrous tissue of adamantinoma but lacked in the epithelial aggregates. There was a clear relation between the identification of the epithelial and fibrous components at the histological level, and the staining for basement membrane proteins collagen IV and laminin. Prominent areas with cohesive epithelial growth were surrounded by continuous basement membranes, whereas less distinct epithelial islands contained membrane interruptions or had no surrounding basement membrane at all. Tenascin stained intensely surrounding demarcated epithelial aggregates, but weakly or absent more distantly. Osteofibrous dysplasia (OFD)-like tumors displayed local spicular density or pericellular staining of basement membrane factors in fields of isolated keratin-positive cells. These findings suggest that in adamantinoma individual epithelial cells transform from the osteofibrous tissue and thereafter form clusters of epithelium, as can be recognized in classic adamantinoma. This is in analogy to the development of the glandular component of biphasic synovial sarcoma. The fibrous part of adamantinoma is, however, believed to be of benign nature. These results further substantiate the hypothesis of osteofibrous dysplasia being a potential precursor lesion of adamantinoma.

Obtaining a histologic diagnosis is crucial in patients presenting with a tumor or a tumorous condition of the bone. The incisional surgical and the closed trocar biopsy are the most frequently used techniques for obtaining a representative tissue sample for histologic evaluation. This study reports on the reliability of 270 Jamshidi trocar biopsies performed on 258 patients with osseous tumors and tumorlike lesions. All patients were evaluated clinically and radiographically by a team consisting of an orthopaedic surgeon, a radiologist, and a surgical pathologist. In nearly all cases the biopsy and the resection were performed by the same orthopaedic surgeon. The biopsy site was determined in accordance with the planned subsequent resection surgery. Overall, an accurate diagnosis could be reached in 90.7% of the total number of 270 Jamshidi biopsies and in 95% of the 258 patients. The failure rate of the 270 biopsies was 9.3%. No specific contraindications with regard to the kind of lesion were found. Except for the pelvis, the localization of the lesion did not influence the rate of success. The high accuracy of the trocar biopsy, combined with the advantages of this technique over the incisional surgical biopsy, makes it a safe, fast, and adequate technique for obtaining a histologic sample of a bone tumor.

Objective: The objective of this study was to assess the effectiveness of conventional radiography in predicting histopathologic response in patients with osteogenic sarcoma who were treated with preoperative chemotherapy., Design and Patients: The radiographs of 22 patients with an osteogenic sarcoma, taken before and after neoadjuvant chemotherapy, were reviewed. Tumour location, size, radiographic appearance, margination, cortical destruction and periosteal reaction were evaluated. The findings were correlated with the histopathologic response of the surgical specimen., Results: None of the findings proved to be of predictive value for the histopathologic response. Increase in tumour diameter and increase in ossification and/or calcification, which were seen in more than half of the patients, did not correlate with response., Conclusion: Conventional radiographs do not contribute to the identification of good or poor responders.

Adamantinoma of long bones is a rare malignant tumor composed of cells with epithelial characteristics in various differentiation patterns surrounded by fibrous cells. Evidence as to whether this neoplasm should be designated as an epithelial bone tumor or a biphasic sarcoma with both epithelial and mesenchymal features is lacking. In this study the nature of the mesenchymal and epithelial components of adamantinoma was investigated by DNA flow cytometry, DNA image cytometry, p53 immunohistochemistry, and polymerase chain reaction-based loss of heterozygosity detection at the p53 locus. Specimens from 6 of 15 patients (40%) analyzed by flow cytometry had an aneuploid DNA index. Image cytometry analysis of Feulgen-stained paraffin sections of 6 aneuploid and 2 diploid tumors revealed that aneuploid nuclei were detected in cells with an epithelial phenotype only, whereas all fibrous cells were diploid. Immunohistochemistry for p53 on specimens from 25 patients revealed moderate or strong immunoreactivity in 12 tumors (48%) restricted to the epithelial cells. Loss of heterozygosity at the p53 locus could be confirmed in the epithelial component of an immunohistochemically p53-positive tumor. Additionally, sections of 7 lung metastases were studied histologically. Only keratin-positive epithelial cells, predominantly in the spindle cell pattern, were present in these metastases, whereas the osteofibrous tissue present in the primary tumors was not detected. These results suggest that either adamantinoma consists of a malignant epithelial part with a reactive osteofibrous stroma or that the malignant epithelial cells develop next to a proliferating benign fibrous component. Additional analysis of common genetic abnormalities in the fibrous and epithelial cells of adamantinoma is therefore indicated.

Objective: This study analyzed the value of dynamic contrast-enhanced and subtraction MR images in detecting residual viable tumor before surgery, with emphasis on timing of enhancement, in patients with high-grade osteosarcoma and Ewing's sarcoma after neoadjuvant chemotherapy., Subjects and Methods: Twenty-one patients with proved osteosarcoma or Ewing's sarcoma were treated with neoadjuvant chemotherapy followed by surgery. After IV administration of gadopentetate dimeglumine, dynamic enhancement patterns on preoperative MR images were compared with corresponding areas on histologic sections of the resected specimens. On dynamic subtraction images obtained with high temporal resolution (1.5-3 sec), the interval between arrival of the bolus of contrast agent in an artery and start of tumoral enhancement was used to distinguish residual viable tumor. Early enhancing foci (interval artery-tumor < 6 sec) and late or nonenhancing areas seen on MR images were correlated with the histopathologic findings in these areas of the resected specimens., Results: Early and progressively enhancing structures seen on MR images corresponded to feeding arteries, physeal vessels, or residual viable tumor at specific preferential sites on corresponding histologic sections of the resected specimens. Tumor foci as small as 3-5 mm2 could be detected on dynamic MR images. Remnant viable tumor was often located subperiosteally and at the margins of the tumor. Occasionally, active periosteal reaction without presence of viable tumor contributed to early enhancement. Late and gradually enhancing or nonenhancing areas corresponded histopathologically to regions of chemotherapy-induced necrosis, mucomyxoid degeneration, or fibrosis. Alternatively, late or nonenhancing areas were associated with reactive changes such as edema, hemorrhage, or osteomyelitis or with tumor-related extracellular matrices such as abundant osteoid or chondroid. Viable tumor areas with scarce formation of matrix on microscopy, such as small cell osteosarcoma areas or Ewing's sarcoma, showed early enhancement with rapid washout of contrast agent on the dynamic MR images., Conclusion: Fast dynamic contrast-enhanced sequences are essential for identifying residual tumor before surgery. A short time interval of less than 6 sec between arterial enhancement and tumoral enhancement strongly correlates with presence of viable tumor. Both therapy-related alterations of tissue and tumor-related matrices must be considered when late or lack of enhancement is noted on dynamic MR images.

Current treatment for osteoid osteomas is usually surgical excision of the nidus. We treated 18 patients with osteoid osteoma by percutaneous thermocoagulation of the nidus under computed-tomography guidance. The procedure was technically successful in all cases and there were no complications. Patients were discharged on the following morning and resumed normal activities immediately. All patients but one remained pain free during follow-up (range 3-15 months). A second thermocoagulation treatment relieved the recurrent symptoms in this patient. Percutaneous thermocoagulation appears to be effective for osteoid osteomas, and is a minimally invasive alternative to surgical resection.

Objective: The purpose of this study was to use color Doppler flow imaging to predict the response to preoperative chemotherapy in patients with Ewing's sarcoma or high-grade osteosarcomas early in treatment., Subjects and Methods: Color Doppler flow imaging was done in 31 patients before, during, and after chemotherapy. In each phase of treatment, semiquantitative changes in intratumoral blood flow, changes in maximum intratumoral Doppler shifts, and changes in resistive indexes of arteries feeding limbs that contained tumors relative to contralateral normal arteries were compared with the histopathologic response, as evaluated on the resected specimens., Results: Before chemotherapy, pathologic flow was found in the extraosseous component of all but two patients. Resistive indexes in arteries that fed tumors were significantly lower (p < .001) than the resistive indexes in the contralateral normal arteries. Histopathologic response could not be predicted on the basis of the initial measurements of Doppler shifts and resistive indexes taken before or after the first cycle of chemotherapy. Histopathologic response could be predicted after the second cycle of chemotherapy. After the second cycle of chemotherapy, the resistive index in the arteries that fed tumors increased in eight of nine good respondents but did not change or decreased in eight of nine poor respondents (p = .03). Lower intratumoral Doppler shifts were measured in six of 10 good respondents but also in five of 13 poor respondents (p = .07). After the full course of chemotherapy, persistent lower resistive indexes were measured in the arteries that fed tumors in all poor respondents but one. Intratumoral flow and Doppler shifts further decreased in all good respondents but one. Changes in Doppler shifts (p = .001) and resistive indexes (p < .001) were statistically significant between good and poor respondents, irrespective of the tumor type studied., Conclusion: Decreased or unaltered resistive index in the arteries that feed tumors in addition to persistent intratumoral flow and high-frequency Doppler shifts after two cycles of chemotherapy suggest poor histologic response to chemotherapy in osteosarcoma and Ewing's sarcoma. An increased resistive index after two cycles is indicative of good response.

The magnetic resonance (MR) changes after one cycle of chemotherapy were compared with the prechemotherapy studies in 39 patients with osteosarcoma, in order to identify MR changes which can be used to assess early response to chemotherapy. Measurements of total tumour volume, signal intensity, and tumour enhancement of the intra- and extraosseous tumour component were performed. Change in the amount of oedema was subjectively assessed. Changes observed were correlated with histopathological response. Changes in tumour volume and of the signal intensity of the extraosseous tumour component on T2-weighting were the only two parameters which correlated significantly (P < 0.05) with histopathological response. Increase of tumour volume is the most significant parameter and indicates poor response (sensitivity 89%, specificity 73%). Only one good responder showed increase of tumour volume. Decreased or stable tumour volume was observed in both good and poor responders. Increase of signal intensity was found exclusively in five poor responders (sensitivity 100%, specificity 23%). Decreased or stable signal intensity was observed in both good and poor responders. Changes in the amount of oedema and contrast enhancement could not predict response at an early stage. We conclude that increase of tumour volume and increase of T2 signal intensity of extraosseous tumour can be predictive for poor response. MR criteria are not helpful in the early identification of good responders.

A uniform classification of response to chemotherapy is essential to allow comparison of local effect and ultimate prognosis between different therapy schedules. We define a histological grading system for assessment of the response to chemotherapy in Ewing's sarcoma, based on the amount and architectural pattern of residual histologically viable-appearing tumour, the preferential sites of minimal residual tumour and the amount of tumour necrosis. Twenty-six consecutive patients with a biopsy-proven Ewing's sarcoma were treated with chemotherapy prior to surgery. The effect of chemotherapy was evaluated microscopically on the specimens obtained after surgery. Response to chemotherapy was classified as minimal or no effect (< 10% tumour necrosis), moderate effect (solid areas of remnant viable tumour), minimal residual disease, and no evidence of disease (100% tumour necrosis or well-vascularized fibrous tissue). The subperiosteal area in particular and, less frequently, soft tissues and intramedullary compartment were identified as sites of predilection for persistence of microscopic viable tumour foci, frequently depicted as pseudo-rosettes in a characteristic scattered pattern. Although it is not well known whether morphological viability of these residual clusters in Ewing's sarcoma indicates biological viability, accurate preoperative local staging, with special attention to preferential sites of residual viable tumour, is essential. The proposed grading system can be used to standardize assessment of chemotherapy in trials, and may serve as a standard for non-invasive monitoring of preoperative chemotherapy with magnetic resonance imaging.

The records of thirty-two patients who had had an adamantinoma of the long bones were examined to investigate the relationship between the clinical presentation, the histological subtype, and the method of treatment, and the clinical result. All histological patterns of differentiation that are characteristic of adamantinoma were observed, including the basaloid, spindle-cell, tubular, squamous, and osteofibrous dysplasia-like subtypes. Follow-up data were available for twenty-eight (88 per cent) of the thirty-two patients. These patients were followed for a mean duration of 122 months (range, eleven months to twenty-nine years and two months). Nine patients (32 per cent), all of whom had been managed with an intralesional or marginal procedure, had a local recurrence of the tumor after a mean disease developed in three of the nine patients. In five other patients, metastasis developed without having been preceded by a local recurrence. Thus, the over-all rate of metastasis was 29 per cent (eight patients). The mean duration of survival for the patients who had metastasis was twelve years and eight months. Statistical analysis of various clinicopathological variables revealed intralesional or marginal excision to be the most significant risk factor for a local recurrence or metastasis (p < 0.001). Two patients who had had a presumed osteofibrous dysplasia-like adamantinoma, which contained few isolated keratin-positive epithelial cells within the stroma at the time of presentation, had a full-blown adamantinoma at the time of the local recurrence. Although the clinical course that was observed may be the result of a sampling error, it poses questions as to the regressive nature of osteofibrous dysplasia-like adamantinoma. On the basis of our findings and the data in the literature, we believe that an osteofibrous dysplasia-like adamantinoma may be a precursor lesion of the classic type of adamantinoma.

Magnetic resonance (MR) imaging was performed in 26 patients with Ewing's sarcoma of bone preceding and following neoadjuvant chemotherapy, to assess tumour response non-invasively prior to surgery. T1- and T2-weighted spin echo images were obtained. Changes including intra- and extramedullary signal intensities, tumour demarcation, tumour volume and the appearance of residual extramedullary tumour were compared with histopathology of the resected specimens. Reduction of tumour volume was significantly higher in good responders. Other single parameters did not correlate with histologic tumour response. However, when several MR parameters summarized in a classification system were combined, a positive correlation with histopathologic response was found. A limited decrease of tumour volume (< 25%) and/or residual soft tissue mass following chemotherapy correlated with a poor response. An inhomogeneous, well-defined cuff of abnormal tissue encircling the bone and/or radiological disappearance of the soft tissue tumour component following chemotherapy correlated with good response. Twenty-three out of 26 patients were correctly classified by MR as good or poor responders. Minimal residual disease (< 10% of the entire tumour volume), observed histologically, could not be identified with MR imaging. Tumour volume reduction and residual extramedullary tumour, rather than changes of signal intensity, are major features for evaluating the response to chemotherapy in Ewing's sarcoma.

In the period 1984-1991, 33 lower limb reconstructions were performed with an uncemented Kotz modular femur tibia reconstruction (KMFTR) prosthesis after resection of 32 malignant bone tumors and 1 benign giant cell tumors. Tumor localization was proximal femur in 12, distal femur in 17, and proximal tibia in 4. The mean age of the patients was 38 years. 28 patients with a minimum follow-up of 1 year were studied after 3 (1-8) years. 7 patients were reoperated because of complications. Good or excellent results were obtained in 6 of the 10 proximal and 13 of the 14 distal femur reconstructions. In 2 of the 4 patients undergoing combined distal femur and proximal tibia resection, a deep infection developed, and above-knee amputation was performed. One local recurrence occurred after proximal femur resection.

To evaluate the incidence, quantity, and presentation of intra- and extraosseous edema accompanying benign and malignant primary bone lesions, the magnetic resonance (MR) studies of 63 consecutive patients with histologically proven primary bone tumors were reviewed. MR scans were assessed for the presence and quantity of marrow and soft tissue edema and correlated with peroperative findings, resected specimens and follow-up data. The signal intensity and enhancement of tumor and edema prior to and after intravenous administration (if any) of gadolinium-labeled diethylene triamine pentaacetate (Gd-DTPA) was analyzed. Marrow edema was encountered adjacent to 8 of 39 malignant tumors and 14 of 24 benign lesions. Soft tissue edema was found accompanying 28 of 39 malignancies and 10 of 24 benign disorders. On unenhanced T1-weighted MR images tumor and edema were difficult to differentiate. Tumor inhomogeneity made this differentiation easier on T2-weighted sequences. In 36 patients the contrast medium Gd-DTPA was used. Edema was present in 27 of these patients and the respective enhancement of tumor and edema could be compared. Edema always enhanced homogeneously, and in most cases it enhanced to a similar degree as or more than tumor. Marrow and, more specifically, soft tissue edema is a frequent finding adjacent to primary bone tumors. The mere presence and quantity of marrow and soft tissue edema are unreliable indicators of the biologic potential of a lesion. Unenhanced MR scans cannot always differentiate between tumor and edema, but the administration of Gd-DTPA is of assistance in differentiating tumor from edema.(ABSTRACT TRUNCATED AT 250 WORDS)

Purpose: To prospectively evaluate color Doppler flow imaging (CDFI) with spectral analysis versus dynamic gadolinium-enhanced magnetic resonance (MR) imaging and three-phase bone scintigraphy in monitoring the effect of chemotherapy on bone sarcomas., Materials and Methods: Seventeen osteosarcomas and five Ewing sarcomas were examined with these imaging techniques before and after chemotherapy. Results were compared with the histopathologic response., Results: Before chemotherapy, high systolic Doppler frequency shifts (DFSs) and/or low-impedance Doppler signals were found in all but one tumor. Resistive indexes (RIs) in tumor-feeding arteries were substantially lower than in contralateral normal arteries. After chemotherapy, DFSs disappeared in five of seven good respondents and remained substantial in all but one poor respondent. RIs increased substantially in all good respondents and decreased or showed minor changes only in all but one poor respondent., Conclusion: CDFI with spectral analysis has an advantage over the other two techniques in monitoring the efficacy of chemotherapy in bone sarcomas because of its superior accuracy, noninvasive nature, availability, and low cost.