Background: Chondrosarcoma is the second most frequent primary malignant tumor of bone. The biologic evolution of these tumors is slow, requiring long follow up for meaningful survival analysis. Methods: The clinicopathologic profiles of 84 (41 male, 45 female/M: F, 1:1.09) chondrosarcomas of the upper limb from the Scottish Bone Tumor Registry (1940–2000) are presented. Results: The mean age at presentation was 54.8Yrs (range 12–85yrs).The proximal humerus was the most frequent anatomical site (30.2%).21% lesions involved the scapula, and 34% small bones of the hand. Local pain was the most frequently reported initial symptom. All patients were followed up for a minimum 60 mts. Radiographically; chondrosarcomas had a characteristic appearance of bone expansion and cortical thickening. The cumulative 5 year survival was 82.5%. Local recurrence developed in19.7 % (mean 40 mts after initial presentation), and distal metastasis in 16.2%.Hand tumors rarely had metastasis. Tumor breach at time of surgery increased risk of local recurrence. Histological grade was an important factor in predictor of local recurrence and metastasis. Discussion: Chondrosarcomas are highly diverse tumors ranging from slow growing non- metastasizing lesions to highly aggressive metastasizing sarcomas. With adequate initial surgical intervention, chondrosarcoma is primarily a local disease with a low metastatic rate. Hand lesions have best prognosis

Introduction. Enchondromas located in the phalangeal bones may be more cellular than non-digital locations necessitating clinical and radiological correlation to determine diagnosis. Atypical enchondromas have increased cellularity and atypia relative to simple enchondromas but no evidence of permeation. Chondrosarcomas of the phalanges are thought to have a more indolent course than chondrosarcomas in other locations. The aim of the study was to determine the outcome of atypical enchondromas and grade 1 chondrosarcomas of the phalanges treated surgically. Methods. Data was collected prospectively on patients with a cartilage lesion of the phalanges. Typical enchondromas, grade 2 or 3 chondrosarcomas and patients with Ollier's disease were excluded. Results. There were twenty two cases of atypical enchondroma or grade 1 chondrosarcoma. Ten of the patients were female and twelve male with a mean age of 41. There were fourteen atypical enchondromas and eight grade 1 chondrosarcomas. Sixteen of the lesions were in the hand and six were in the foot. Seventeen tumours, including four cases of grade 1 chondrosarcoma, were treated with extended curettage utilising a high speed burr. Five cases were managed by digital amputation as the degree of bone loss precluded retention of the phalanx. At a mean follow up of 30 months there has been one case of local recurrence occurring in an atypical enchondroma of the foot. There have been no cases of local recurrence in the four cases of grade 1 chondrosarcoma treated by curettage. There have been no cases of distant metastasis. All patients remain under long term clinical review. Discussion. There are few published results on the treatment of atypical enchondromata and low-grade chondrosarcomas of the phalanges. In selected cases extended curettage has a low recurrence rate in the treatment of atypical enchondromata and grade 1 chondrosarcomas of the phalanges

Chondrosarcomas are uncommon primary malignant cartilaginous tumours, even less common in spine. Surgical excision is the only mode of successful treatment as these tumours are resistant to conventional chemotherapy and radiation therapy. We share our experience of 22 cases of chondrosarcomas of the spine with special reference to their recurrence and survival. We identified 20 conventional and 2 dedifferentiated chondrosarcomas from the Scottish Bone Tumour Registry database between 1964 and 2009. Radiology and histopathology were documented. The mean follow-up was 5.2 years. There were 14 men and 8 women with a mean age of 50.1 years. There were 7 under the age of 40 years (31.8%). The majority of lesions occurred in the thoracic spine (16), followed by sacrum (3), lumbar (2) and cervical spine (1). The overall local recurrence rate was 45.4% (10/22 cases-once in 5, twice in 2 and thrice in 3 patients). Four patients presented with pulmonary metastases leading to death. The estimated overall 5- and 10-year survival rates were 31.8% and 18.1% respectively. We found that 1/3. rd. of chondrosarcomas of the spine occured below 40 years of age and 3/4. th. in the thoracic spine. Every other case was associated with local recurrence with a 32% 5-year and 18% 10-year survival rates

Aim

We investigated low grade intramedullary chondrosarcomas to see if curettage and cementation remains a strong alternative treatment to local resection.

Chondrosarcoma of bone is a surgical disease and excision with wide margins is the optimum treatment. Sometimes the size or location of the tumour at the time of diagnosis mean that only a marginal excision can be achieved. The effect of the margin of excision on outcome is investigated.

Introduction: Both enchondromas and chondrosarcomas are mesenchymal neoplasms which originate from cartilage cells, and they occur mainly in the extremities. Both these tumours are resistant to chemotherapy and radiotherapy, and surgery is the only treatment option. In the last few years limb saving procedures have become the treatment of choice. Intra-operative cryosurgery has been introduced as a local adjuvant therapy for skeletal benign and low-grade malignant tumours. It is applied after curettage of the lesion to destroy any remaining tumour cells, and to enlarge the oncological margin of resection. Since the introduction of cryosurgery as an adjuvans, oncological and functional results of this extremity sparing surgery are significantly enhanced.

Patients and Methods: A retrospective study was conducted to evaluate the oncological and functional results, and the complications of cryosurgical treatment.

Data were prospectively collected from the tumour register and patient records. Functional scores of the affected limbs were assessed according to the Musculo-Skeletal Tumour Society scoring system.

Results: Between 1994 and 2003 123 patients (47 men, 76 women, average age 49 years; range 13–83 yrs) were treated with curettage and cryosurgery for an Enneking stage 3 enchondroma (75 patients) or a low-grade chondrosarcoma (55 patients).

The minimal follow up was two years, and the average follow up 50 months (range 24–119 months).

At follow up three recurrences had occurred in patients treated for enchondroma. One residual tumour was diagnosed in a patient with chondrosarcoma grade Ib. All patients were treated again with curettage and cryosurgery and disease free at the latest follow-up.

Of the 37 complications the most common were a fracture at the surgical site (18), fracture of osteosynthesis (6), 3 wound infection (3), delayed soft tissue healing (3), and transient nerve palsy (3).

Functional MSTS scores increased in time to an average of 28 points (94%) at two year follow up. No significant difference in scores were found regarding to localisation of the lesion, age or gender. A significant discrepancy in functional scores was observed between patients who did suffer from one or more complications and patients who did not.

Conclusion: We believe that the use of cryosurgery is an excellent adjuvant therapy after curettage to achieve local control of aggressive enchondromas and low grade chondrosarcomas. It avoids the need for segmental resection, making reconstruction of the bony defect easier and therefore results in excellent functional outcome. Due to the initial high fracture rate osteosynthesis at the surgical site is used more often, and weight baring mobilisation is postponed until full consolidation is reached.

Aims

Due to its indolent clinical behaviour, the treatment paradigm of atypical cartilaginous tumours (ACTs) in the long bones is slowly shifting from intralesional resection (curettage) and local adjuvants, towards active surveillance through wait-and-scan follow-up. In this retrospective cohort study performed in a tertiary referral centre, we studied the natural behaviour of ACT lesions by active surveillance with MRI. Clinical symptoms were not considered in the surveillance programme.

Aims

The preoperative grading of chondrosarcomas of bone that accurately predicts surgical management is difficult for surgeons, radiologists, and pathologists. There are often discrepancies in grade between the initial biopsy and the final histology. Recent advances in the use of imaging methods have shown promise in the ability to predict the final grade. The most important clinical distinction is between grade 1 chondrosarcomas, which are amenable to curettage, and resection-grade chondrosarcomas (grade 2 and 3) which require en bloc resection. The aim of this study was to evaluate the use of a Radiological Aggressiveness Score (RAS) to predict the grade of primary chondrosarcomas in long bones and thus to guide management.

Aims

Socioeconomic and racial disparities have been recognized as impacting the care of patients with cancer, however there are a lack of data examining the impact of these disparities on patients with bone sarcoma. The purpose of this study was to examine socioeconomic and racial disparities that impact the oncological outcomes of patients with bone sarcoma.

Chondrosarcoma are rare malignant tumors. About the biological characteristics of chondrosarcoma is little-known [. 2. ]. Endothelin and its receptors are involved in regulating angiogenesis and metastatic dissemination [. 1. ]. The aim of this study is first to identify if chondrosarcoma are expressing endothelin-1 (ET-1) and the endothelin-receptors and thereupon to identify potential molecular markers for new target therapies. Another aim is to determine if endothelin is a prognostic factor in chondrosarcoma. 32 cases were investigated clinically and histopathologically. The expression of vascular endothelial growth factor (VEGF), Endothelin-1, Endothelin-Receptor-A (ETR-A) and Endothelin-Receptor-B (ETR-B) were determined. All data were analyzed by Fisher’s exact test (p< 0,05). All tumors show an expression of either ET-1, ETR-A or ETR-B. Chondrosarcomas with grade (G) I are mostly expressing less than 10-% ET-1 in cells, Chondrosarcomas G II are expressing in most cases between 10–50% and nearly all Chondrosarcoms G III more than 50%. In addition ET-1-expression is correlating with the histological grading. The patients also show a significant high metastatic dissemination probability at the time when tumor samples present more than 10%-storing ET-1-cells. The intensity of ET-1-expression is correlating with VEGF, which is the most important angiogenetic factor in tumors. Chondrosarcomas are expressing ET-1, ETR-A and ETR-B. ET-1 seems to play a role in the angiogenesis of chondrosarcoma. Increased expression of ET-1 is accompanied with a high probability of metastatic dissemination. Endothelin receptor antagonists, which are used for example in prostate and breast cancer, can represent a potential therapy for chondrosarcoma [. 1. ]. Experiments on animals and clinical studies are required

Chondrosarcomas arising from soft tissues are rare. Two different varieties are described, myxoid and mesenchymal. We have collected nine cases of the tumour, five myxoid and four mesenchymal, from a review of 513 cases of chondrosarcoma seen between 1904 and 1988. We report the principal clinical, radiographical and histological differences between the two varieties and discuss their surgical treatment and prognosis

Chondrosarcomas are malignant neoplasms that form an exclusively chondroid matrix. These generally slow-growing cartilage-based tumors most commonly occur in patients between 30 and 60 years old. In this article, we describe our retrospective clinical study, performed on 21 patients (11 males and 10 females) who were affected by conventional chondrosarcoma (Grade 1) and underwent surgery between 1997 and 2008. The patients’ average age was 45,5 (29 to 71 years old) with an average follow-up of 68,4 months. All low grade chondrosarcomas were treated with curettage, phenolization and reconstruction with acrylic bone cement. Assessment of the limb functional recovery in treated patients has been performed through the Musculoskeletal Tumour Society scoring system (MSTS). Patients’ average score six months after surgery was 76, 4% (between 61% and 87%) - low scores were reported in four patients following to complications (three fractures and one local recurrence). Another evalutation has been carried out through the MSTS scoring system at the end of our study, showing a value improvement, with an average score of 79.9% (between 63.3% and 88%). In conclusion, we see large intralesional curettage with chemical adjuvants (phenol and polimetilmetacrilate) as an effective treatment for low-grade chondrosarcoma of bones, allowing for a better patients’ compliance and a faster functional recovery. It is important, however, to prepare a surgical strategy according to the results of an accurate biopsy and a correct interpretation of the radiological imaging

Chondrosarcomas are notorious for their resistance to conventional chemo- and radiotherapy, indicating there are no curative treatment possibilities for patients with inoperable or metastatic disease. We therefore explored the existence of molecular targets for systemic treatment of chondrosarcoma using kinome profiling. Peptide array was performed for 4 chondrosarcoma cell lines and 9 primary chondrosarcoma cultures. Acitivity of kinases was verified using immunoblot and active Src- and PDGFR signaling were further explored using imatinib and dasatinib on chondrosarcoma cell lines and primary cultures. The AKT1/GSK3B pathway was clearly active in chondrosarcoma. In addition, the PDGFR pathway and the Src kinase family were active. PDGFR and Src kinases can be inhibited by imatinib and dasatinib, respectively. While imatinib did not show any effect on chondrosarcoma cell cultures, dasatinib showed a decrease in cell viability at nanomolar concentrations in 3 out of 5 chondrosarcoma cultures. Whereas inhibition of phosphorylated Src (Y419) was found both in responsive and non-responsive cells, caspase-3 related apoptosis was found only in cell line GIST882, suggesting that the mechanism of decreased cell viability in chondrosarcoma by dasatinib is caspase-3 independent. In conclusion, using kinome profiling we found the Src pathway to be active in chondrosarcoma. Moreover, in the chondrosarcoma cell lines and primary cultures we showed that the inhibitor of the Src pathway, dasatinib, may provide a potential therapeutic benefit for chondrosarcoma patients which are not eligible for surgery

Chondrosarcoma is the second most frequent primary malignant tumour of bone, representing approximately 25% of all primary osseous neoplasms. Chondrosarcomas are a group of tumours with highly diverse features and behavior patterns, ranging from slow-growing non-metastasizing lesions to highly aggressive metastasizing sarcomas. As radio and quimio-resistant tumours, the surgery constitutes the unique chance of cure. Nowadays, besides the curative intention, the reconstructive surgery is also a priority in order to save the limb and optimize the function. This case report is about a young woman, of 24 years old, with hip-related pain and a large mass in the left pelvis. The imagiologic study showed a large mass of about 8 cm of large diameter, starting at the anterior wall of the acetabulum, involving the pubic arcs and with matrix calcification. The core needle biopsy confirmed the presence of a chondrosarcoma, staged as a IIB of Enneking. Because of its size and localization the limb salvage surgery has been a challenge. The surgery included a broad approach of the left hemipelvis, with wide excision of the tumour, reconstruction of the abdominal wall with a propylene prothesis and reconstruction of the hemipelvis with a “custom-made” prothesis with preservation of the femoral neurovascular bundle. The patient started to walk with total bearing after three months and had a normal gait and a nearly normal life during eleven months. Fifteen months after the surgery lung metastasis and local recurrence were diagnosed and she died six months after. Conclusion: The surgery is our unique weapon in the “combat” against the chondrosarcoma. The reconstructive surgery must be a concern to give to our patients the best functional result and quality of life

Aim. Multiple (hereditary) osteochondroma (MO) is a rare autosomal dominant disease. Previous reports show that the risk of a malignant degeneration varies between 5-25%, but these are often combined with data on other cartilaginous diseases. The aim of this study was to establish clinical and radiological parameters that could identify a group of MO patients who are at risk for peripheral chondrosarcoma. Methods. A database of 64 MO patients surgically treated between 1980-2009 was established. For 24 patients full radiological (including MRI), surgical and pathological records were complete. This group contained 14 osteochondroma patients and 10 chondrosarcoma patients. Non-parametric tests and Kaplan-Meier survival analysis were used to establish a cartilage-cap thickness cut off point and a volume cut off point. Results. A total of 450 osteochondromas were seen in 64 patients, most common sites were the distal femur (14%) and the proximal tibia (12%). Eighteen patients developed a chondrosarcoma (28%), the most common sites were the ribs (22%) and the proximal femur (17%). Between osteochondromas and chondrosarcomas there was no significant difference in clinical symptoms like pain (10% vs 29% p=0,472) and growth (25% vs 30% p=0,669). The median cartilage-cap thickness was 5mm (range 1-12) for benign and the median cartilage-cap thickness was 40mm (range 15-130) malignant lesions, with a cut-off point at 8mm. Chondrosarcomas had a larger median volume of 227cm3 (range 2-147) compared to 51cm3 (range 37-545) in the osteochondroma group, with a cut-off point at 175cm3. Conclusion. Clinical symptoms (pain and growth) are non-reliable indicators for malignancy. In MO patients a cartilage-cap thickness larger than 8mm or a tumour-volume larger than 175cm3 should be considered malignant. Lower thickness of the cartilage cap than earlier reported and volume measurement both based on MRI, are indicators for malignant degeneration and should be implemented in screening protocols

Chondrosarcomas are malignant hyaline cartilage tumours of bone. They are clinically resistant to conventional chemo- and radiotherapy and the underlying mechanism is poorly studied. Chemoresistance is a multifactorial process and the inaccessibility due to abundant hyaline cartilaginous matrix surrounding the cells, presence of multi-drug resistance pumps, and expression of anti-apoptotic proteins such as BCL2, have been suggested. Our aim was to study chemoresistance mechanisms in chondrosarcoma. We first studied the sensitivity of chondrosarcoma cell lines (SW1353, CH2879, JJ012, OUMS27) and 2 primary cultures for doxorubicin and cisplatin. We used a 3D pellet model of CH2879 to study doxorubicin incorporation. To investigate whether chondrosarcoma cells could be resensitised to chemotherapy we tested the BH3 mimetic ABT737 inhibiting anti-apoptotic BCL2 family proteins. Cell viability was assessed using a WST assay for mitochondrial activity. Dose response curves showed that chondrosarcoma cell lines and cultures are partially resistant to doxorubicin, while primary cultures were completely resistant to cisplatin. In 3D cell pellets, with morphology strongly resembling high grade chondrosarcoma, doxorubicin incorporation was confirmed. Chondrosarcoma cells responded to ABT737 with a >60% reduction in cell viability at high concentrations (25μM). Combination treatment allowing 2 days between ABT737 and chemotherapy addition led to a complete reduction of cell viability in all cell cultures. In conclusion, chondrosarcoma cell lines show a partial response to doxorubicin and less response to cisplatin. The incorporation of doxorubicin in the cells in a 3D pellet model indicates that resistance is not caused by inaccessibility of the cells for the drugs nor by multi-drug resistance pump activity. By combining BCL2 inhibition with Doxorubicin treatment, a complete reduction of cell viability was obtained. This suggests that BCL2 overexpression plays an important role in chemoresistance of chondrosarcoma, and turning on the apoptotic machinery by BCL 2 inhibition can render them chemosensitive

Chondrosarcomas are hyaline cartilage-forming tumours which can be classified according to malignancy through histological grading. Grade I chondrosarcomas rarely metastasize whereas in grade III chondrosarcoma metastasis is observed in 71% of cases. There is, so far, no clear molecular marker allowing an objective classification of chondrosarcoma. The aim of this project was to identify such marker genes through the comparison of gene expression of chondrosarcoma and normal hyaline cartilage and through the correlation of expression profiles to histological grading. The mRNA of 19 chondrosarcomas with different histological grades and of eight normal cartilage samples was analysed. Gene expression profiles were assessed on a customised cDNA array including 230 cartilage- and stem cell-relevant genes. Data were analysed by hierarchical clustering and significance analysis of microarrays. Results were confirmed by real-time RT-PCR. Gene expression profiles clearly discriminated between normal and neoplastic cartilage. Between them, 73 differentially expressed genes were identified. The genes higher expressed in cartilage included several genes encoding matrix proteins. Among the genes higher expressed in chondrosarcoma, molecules involved in PTH and BMP signalling were found. Genes differentially expressed between tumours of different grade were identified. Among others, galectin 1 was significantly higher expressed in highly malignant tumours compared to grade I tumours. This correlation could be confirmed at protein level by immunohistological analysis. The comparative analysis of normal cartilage and chondrosarcoma gene expression showed that there are important molecular differences between the matrix of normal and neoplastic cartilage. Our results furthermore confirm that genes implicated in the regulation of the growth plate were expressed in chondrosarcoma. Remarkably, we identified galectin 1 as a marker correlating to malignancy on the level of gene and protein expression. More extended studies on this functionally polyvalent molecule would be necessary to establish it as a marker for malignancy in chondrosarcoma

Aims

Our aim was to develop and validate nomograms that would predict the cumulative incidence of sarcoma-specific death (CISSD) and disease progression (CIDP) in patients with localized high-grade primary central and dedifferentiated chondrosarcoma.