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PubMed1981

Chondrosarcoma growth: influence of diabetes, caloric restriction, and insulin treatment.

Diabetes and malnutrition result in decreased somatomedin production and cartilage growth in rats. The growth and metabolism of the Swarm rat chondrosarcoma are dramatically affected by somatomedins. Data presented here show that streptozotocin diabetes and diet restriction inhibit in vivo chondrosarcoma growth. Tumors grown in diabetic rats were significantly smaller than tumors grown in diet-restricted rats showing the same changes in body weight. Insulin treatment increased the rate of tumor growth in diabetic rats. Tumors grown in rigidly controlled diabetic rats were as large as tumors grown in nondiabetic controls. Diet restriction and diabetes reduced the capacity of the serum of the rat to stimulate alpha-amino[14C]isobutyrate uptake and [3H]uridine incorporation into RNA in chondrosarcoma pieces grown in nondiabetic rats. This somatomedin activity of the serum was restored by treating diabetic rats with insulin. There was a significant correlation between the in vitro stimulatory effect of a particular serum pool on chondrosarcoma metabolism and in vivo chondrosarcoma growth in the animals from whom the serum was obtained. These studies demonstrate that the in vivo growth of malignant chondrocytes is similar to that of normal chondrocytes with respect to the role of nutrition and insulin.

Animals↗

PubMed1993

Dedifferentiated chondrosarcoma of the larynx with regional and distant metastases.

Chondrosarcoma of the larynx is an unusual tumor, with only approximately 200 cases having been reported. This tumor is relatively nonaggressive and tends to remain localized in the larynx. Two cases with aggressive clinical behavior manifested by regional or distant metastasis are presented. In the first case, cervical node metastasis appeared 6 months after total laryngectomy. A dedifferentiated chondrosarcoma was identified by pathologic examination. In the other case, clavicular metastasis developed 7 years after initial local excision. Despite additional treatments, the patient later developed cervical node, lung, and vertebral metastasis. Transformation from low-grade to dedifferentiated chondrosarcoma was verified by pathologic examination. We believe this case to be the first reported laryngeal chondrosarcoma with bone metastasis. A review of the literature regarding regional and/or distant metastasis of laryngeal chondrosarcoma, including the present observations, reveals a total of 20 cases. In all cases, tumor grade has been directly correlated with the development of metastasis.

Chondrosarcoma↗

PubMed2006

Differentiating clinical and radiographic features of enchondroma and secondary chondrosarcoma in the foot.

BACKGROUND: Enchondroma is the most common benign tumor of the bones of the foot. Chondrosarcoma in this area is relatively rare with malignant transformation from enchondroma occurring rarely. In contrast to similar tumors in the appendicular skeleton, it is difficult to distinguish between these two tumors when they occur in the foot. METHODS: We reviewed the medical records and radiographs of all patients with enchondroma and chondrosarcoma arising from enchondroma (secondary chondrosarcoma) from the radiologic archives at the Armed Forces Institute of Pathology (AFIP) and identified those patients with tumors involving the bones of the foot. There were 755 patients with enchondroma of which 34 (4.8%) involved the foot; there were 340 patients with secondary chondrosarcoma and 14 (4.1%) involved the foot. We compared clinical and radiographic features of both these lesions. We also compared interobserver differences not only for diagnosis but also for the presence of scalloping, fracture, cortical destruction, and mineralized matrix. RESULTS: Size and location were statistically significant variables differentiating the two tumors (p = 0.03). Enchondromas had a mean size of 2.7 cm(2). Lesions that occurred in the hindfoot and midfoot were more likely to be malignant compared to those in the forefoot. In comparing interobserver reliability, most disagreement occurred regarding the presence or absence of matrix with the examiners concurring only 51% of the time. With regard to diagnosis, the examiners' accuracy was 71% and 80%. Their accuracy increased only to 83% when they agreed. CONCLUSION: Our findings suggest that it is difficult to differentiate enchondroma from secondary chondrosarcoma in the foot. Concern for malignant change is warranted for cartilage bone tumors of the foot if they exceed 5 cm(2), or if they arise in the midfoot or hindfoot. In these cases, we recommend either biopsy or close clinical followup.

Adult↗

PubMed1980

Hormone responsiveness of a transplantable rat chondrosarcoma. I. In vitro effects of growth hormone-dependent serum factors and insulin.

Serum somatomedins and insulin stimulate transport processes and macromolecular synthesis in cartilage. The in vitro effects of serum somatomedins and insulin on amino acid transport and macromolecule synthesis in the Swarm rat chondrosarcoma were studied to determine if malignant transformation alters the responsiveness of chondrocytes to these factors. Amino acid transport was assessed by alpha-aminoisobutyrate uptake. Macromolecule synthesis was estimated by radiolabeled precursor incorporation into RNA, total proteins, and proteoglycan. Serum from normal rats and GH-treated hypophysectomized rats stimulates alpha-aminoisobutyrate uptake and macromolecule synthesis in the rat chondrosarcoma. Hypophysectomized rat serum stimulates these events marginally or not at all. Thus, the chondrosarcoma responds in vitro to GH-dependent serum factors. Additionally, insulin stimulates in vitro amino acid transport and macromolecule synthesis in the rat chondrosarcoma. These data demonstrate that, in vitro, the Swarm rat chondrosarcoma is a hormone-responsive tumor.

Aminoisobutyric Acids↗

PubMed1995

Chordomas and chondrosarcomas of the cranial base: results and follow-up of 60 patients.

The management of chordomas and chondrosarcomas involving the cranial base remains controversial. The options for therapy include biopsy, partial resection, radical resection, and various forms of radiotherapy. In this article, we analyze the outcome of 60 patients with cranial base chordoma or chondrosarcoma treated with extensive surgical resection between 1984 and 1993. Forty-six patients had chordomas, and 14 had low-grade chondrosarcomas; 50% of these patients had been treated previously. Preoperative studies included computed tomography, magnetic resonance imaging, cerebral angiography, and balloon occlusion test of the internal carotid artery, as indicated. Magnetic resonance imaging was performed on all patients during follow-up. The surgical approaches used for tumor resection were predominantly the following: subtemporal, transzygomatic, transcavernous, and transpetrous apex; subtemporal and infratemporal; extended frontal; and extreme lateral transcondylar. Staged operations with a combination of approaches were used when necessary (52% of cases) to remove a tumor more completely. Statistical analysis was done by the chi 2 test and correlation matrix. Sixty-seven percent of the patients had total or near-total resection. Twenty percent of the patients received postoperative radiotherapy. Eleven patients died during the postoperative follow-up period, nine with chordomas and two with chondrosarcomas. Three patients died because of systemic complications within 3 months after surgery, five died because of tumor recurrence, one died from unrelated causes, and two died from late complications of radiotherapy. The recurrence-free survival rate for all tumors was 80% at 3 years and 76% at 5 years. Chondrosarcomas had a better prognosis than chordomas (recurrence-free survival rates, 90% at 5 years and 65% at 5 years, respectively; P = 0.09). Patients who had undergone previous surgery had a greater risk of recurrence (5-year recurrence-free survival rate, 64%) than did patients who had not undergone previous surgery (5-year recurrence-free survival rate, 93%; P < 0.05). Patients with total or near-total resection had a better 5-year recurrence-free survival rate (84%) than did patients with partial or subtotal resection (64%) (P < 0.05). Postoperative leakage of cerebrospinal fluid was the most frequent complication (30% of patients) and was found to increase the risk of permanent disability. Patients who had undergone previous radiotherapy had a greater risk of death in the postoperative period (within 3 months of their operations) and during follow-up. However, total or near-total resection did not increase the rate of postoperative disability.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗

PubMed1982

Periosteal chondrosarcoma and periosteal osteosarcoma. Two distinct entities.

This review of 27 cases serves to emphasis that periosteal chondrosarcoma and periosteal osteosarcoma are two distinct entities. Clinically, periosteal chondrosarcoma is less painful than periosteal osteosarcoma and runs a slower course. Radiographically, periosteal chondrosarcoma tends to affect the metaphysis and contains granular or "popcorn" opacities; while periosteal osteosarcoma more often affects the mid-diaphysis and shows lytic lesions with some spicules of reactive bone perpendicular to the underlying cortex. Histologically, periosteal chondrosarcoma shows lobular well-differentiated cartilage with Grade I or II (rarely Grade III) malignancy; periosteal osteosarcoma has a chondroid matrix with some osteoid component and Grade II or III malignancy. The prognosis in periosteal chondrosarcoma is good; conservative surgery is usually effective and metastases are very uncommon. In periosteal osteosarcoma the prognosis is less satisfactory but is better than that of other osteosarcomata; wide surgical excision is, however, needed and the incidence of metastases is about 15 per cent.

Adolescent↗

PubMed2002

Diagnosis and prognosis of chondrosarcoma of bone.

The mechanisms of chondrosarcoma development are just beginning to be unraveled. The distinction between benign and low-grade malignant cartilaginous tumors is difficult and is based mainly on radiological and clinicopathological features. In this review, the conventional chondrosarcomas are subdivided into central and secondary peripheral chondrosarcomas, based on their different genetic and clinicopathological background. Thus far, no diagnostic markers have been identified for central tumors. Bcl-2 is a good diagnostic marker that can be used in the distinction between osteochondroma and low-grade secondary peripheral chondrosarcoma. For the prognosis of chondrosarcomas, the best and most commonly used marker at present is histological grade. Several molecular markers, recapitulated in this paper, have been tested to see if they aid in determining diagnosis and predicting prognosis, but most are not independent of histological grade.

Biomarkers, Tumor↗

PubMed1980

De novo protein synthesis by human chondrosarcoma in cell and organ culture: evidence of unusually high collagen production by a neoplastic tissue.

Protein synthesis by human chondrosarcoma tissue and normal articular cartilage was studied in organ and primary monolayer cell culture systems. Protein synthesis by cell cultures was evaluated at 2.7 and 21 days after plating. When compared to normal, incorporation of 3H-proline and 35S-methionine into proteins was elevated in chondrosarcoma samples under both culture conditions. Hydroxyproline analyses of tissue hydrolysates indicated that chondrosarcoma samples contained significantly less collagen than normal articular cartilage, yet were incorporating significantly greater amounts of 3H-proline into 3H-hydroxyproline. Collagen production by cell cultures was assessed by digestion of samples with purified clostridial collagenase. Chondrosarcoma cells produced more collagenase-sensitive protein than normal cells at all intervals. SDS polyacrylamide gel analyses of all preparations showed two collagenase-sensitive proteins with apparent molecular weights of 165,000 and 175,000. Decreased synthesis of another major protein, apparent molecular weight 210-220,000 was noted in chondrosarcoma preparations in both culture systems.

Bone Neoplasms↗

PubMed1996

DNA flow cytometric analysis of chest-wall chondroma and chondrosarcoma.

DNA flow cytometric analysis was performed for prediction of malignancy potential, and hence of outcome, in 17 patients aged 29-76 (mean 52) years with cartilaginous tumour of the chest wall. Histologically there were nine chondromas and eight chondrosarcomas. The chondrosarcomas (3 grade I, 4 grade II, 1 grade III) were significantly larger than the chondromas (13.6 +/- 7.8 vs 4.2 +/- 2.0 cm, p < 0.001). DNA flow cytometry was performed on paraffin-embedded blocks of resected tumour. In eight of the 17 tumours (6 chondromas, 1 grade I and 1 grade II chondrosarcoma) measurement of DNA content failed because of low cellularity and severe calcification. Aneuploid DNA content was detected only in three chondrosarcomas (2 grade II, 1 grade III). The synthetic phase fraction was less than 15% in all the studied chondromas, but exceeded 25% in four of six chondrosarcomas. This case series though small, may indicate a trend towards association between higher histologic grading and greater incidence of aneuploidy with higher synthetic phase fraction. Tumour size, histologic grade, DNA ploidy and adequacy of surgical resection are the main influences on prognosis.

Adult↗

PubMed1994

Periosteal osteosarcoma and parosteal chondrosarcoma evaluated by double immunohistochemical staining. Report of 2 cases.

Differentiation of periosteal osteosarcoma and parosteal (periosteal) chondrosarcoma by conventional histology may be difficult. One case each of clinically and histologically proven periosteal osteosarcoma and parosteal chondrosarcoma were evaluated by a double-immunohistochemical staining method using proliferating cell nuclear antigen (PCNA) and S-100 protein (S-100). Conventional histology showed proliferation of both osteoblastic and chondroblastic cells in the periosteal osteosarcoma, while there was a growth of only chondroblastic tumor cells in the parosteal chondrosarcoma. Immunohistochemical studies indicated that the nuclei of chondroblastic cells recognized by S-100 were PCNA-negative, while osteoblastic stromal cells were PCNA-positive in the periosteal osteosarcoma. In contrast, chondroblastic cells in the parosteal chondrosarcoma were both S-100- and PCNA-positive. Our findings suggest that periosteal osteosarcoma is characterized by the proliferation of osteoblastic stromal cells, whereas parosteal chondrosarcoma is characterized by the proliferation of chondroblastic cells. This method of double immunohistochemical staining, using PCNA and S-100, may be useful in differentiating these chondroblastic tumors.

Adolescent↗

PubMed1995

Low risk of recurrence of enchondroma and low-grade chondrosarcoma in extremities. 80 patients followed for 2-25 years.

We analyzed the clinical course in 40 patients with enchondroma and 40 with low-grade chondrosarcoma of the extremities after a median follow-up of 7 years. 13 patients with enchondroma and 2 with chondrosarcoma had only open biopsy and they had no signs of further progression of the lesions. Among 23 patients with enchondroma and 23 with chondrosarcoma who were treated by intralesional curettage, 3 had local recurrences. The 10-year local recurrence rate was 0.04 in the enchondroma group and 0.09 in the chondrosarcoma group. There were no metastases. The results imply that enchondroma and low-grade chondrosarcoma of the extremities should be treated with limited surgery. The morbidity associated with en bloc resection and reconstruction can apparently be obviated without jeopardizing the limb or survival.

Adolescent↗

PubMed2000

Mutational alterations of the p16CDKN2A tumor suppressor gene have low incidence in mesenchymal chondrosarcoma.

Mutational inactivation of the cyclin-dependent kinase inhibitors (CDKIs) (p16INK4A/MTS1) tumor suppressor gene has been found in a variety of human tumor types. To investigate the involvement of CDKI abnormality in mesenchymal chondrosarcoma, alterations of CDKIs were examined in human mesenchymal chondrosarcoma tissues using a quantitative DNA/PCR, PCR-SSCP. Seven of 33 specimens (21.2%) showed abnormally low levels of p16CDKN2A amplification, suggesting that the allelic deletion of the gene might be a less frequent event in progression of this tumor. To detect subtle sequence alterations such as point mutations, SSCP analysis of the entire coding region of the p16CDKN2A gene, exons 1, 2, and 3 regions, showed no altered SSCP patterns in 33 mesenchymal chondrosarcoma specimens. A low incidence of genetic alterations of the p16CDKN2A was found in mesenchymal chondrosarcoma. Through this study, we conclude that alteration of the p16CDKN2A gene does not participate significantly in the tumorigenesis of mesenchymal chondrosarcoma.

Base Sequence↗

PubMed1999

Gene therapy of chondrosarcoma using retrovirus vectors encoding the herpes simplex virus thymidine kinase gene.

Human chondrosarcoma cells (HCS-TG) were transduced with the gene for a herpes simplex virus thymidine kinase (HSV-tk) or Escherichia coli beta-galactosidase (lacZ). We investigated the cytotoxicity of human chondrosarcoma bearing an HSV-tk gene after treatment with ganciclovir. Chondrosarcoma cells bearing an HSV-tk gene were more sensitive than non-transduced cells. Coculturing with chondrosarcoma cells bearing both an HSV-tk gene (HCS-TG-tk) and lacZ gene (HCS-TG-Z) in various ratios showed a bystander effect. Chondrosarcoma implanted in nude mice were injected with HCS-TG-tk cells. After 4 weeks, the growth of tumors was significantly prevented.

Animals↗

PubMed2001

Low incidence of genetic alterations of the p16CDKN2a in clear cell chondrosarcoma.

Mutational inactivation of the cyclin-dependent kinase inhibitors (CDKIs) (p16CDKN2a) tumor suppressor gene has been found in a variety of human tumor types. To investigate the involvement of CDKI abnormality in clear cell chondrosarcoma, alterations of CDKIs were examined in clear cell chondrosarcoma tissues using a quantitative DNA/PCR, PCR-SSCP. Two of 38 specimens (5.2%) we analyzed showed abnormally low levels of p16CDKN2a amplification, suggesting that the allelic deletion of the gene might be low frequent event in progression of this tumor. For detection of subtle sequence alterations such as point mutations, we performed SSCP analysis of the entire coding region of the p16CDKN2a gene. No altered SSCP patterns were found in 38 clear cell chondrosarcoma specimens. This study reflects the very low incidence of genetic alterations of the p16CDKN2a gene in clear cell chondrosarcoma. Therefore, we conclude that the alteration of the p16CDKN2a gene is not involved significantly in the development of clear cell chondrosarcoma.

Bone Neoplasms↗

PubMed2004

Comparative analysis of imbalances in genomic DNA and mRNA expression levels in chondrosarcoma-derived cell line FSCP-1.

Malignant cell transformation results from multiple biological alterations including chromosomal abnormalities, oncogene activation, loss of suppressor gene function and a imbalance in cell regulating processes. The aim of our study was to combine gene expression and genomic analysis to evaluate the cellular phenotype of a chondrosarcoma cell line, which is potentially a useful in vitro model system for physiological and/or neoplastic chondrocytes. cDNA-array, quantitative PCR and comparative genomic hybridization (CGH) technologies were used to analyze gene expression profiles of chondrosarcoma cell line FSCP-1 in correlation to changes of DNA copy number on corresponding chromosomal sections. Gene expression analysis revealed similarities, but also great differences in between the chondrosarcoma cell line and physiological chondrocytes. In particular the proliferative activity was up-regulated and molecules involved in matrix synthesis and turnover down-regulated. CGH analysis revealed a heterogeneous pattern of DNA gains or losses. The c-myc oncogene, located on 8q24.12-q24.13, was the only gene with a marked up-regulation located on a chromosome section with a gain of DNA copy number. The inability of the chondrosarcoma cell line FSCP-1 to maintain an adequate matrix turnover as well as a notable proliferative activity is similar to neoplastic chondrosarcoma in vivo. The limited correlation between the CGH analysis and the gene expression pattern supports the notion that also in neoplastic cells most genes are not primarily regulated by the gene dosage, but by cellular regulation pathways. However, genes such as c-myc might represent significant exceptions potentially relevant for the clinico-biological behavior of the neoplasms.

Bone Neoplasms↗

PubMed1999

Skeletal and extraskeletal myxoid chondrosarcoma: related or distinct tumors?

Skeletal myxoid chondrosarcoma is a histologic variant of conventional skeletal myxoid chondrosarcoma, whereas extraskeletal myxoid chondrosarcoma is a distinct entity characterized by a reciprocal t(9;22) translocation resulting in fusion of the EWS and CHN genes. Rarely, extraskeletal myxoid chondrosarcoma can occur in bone, and it is difficult to describe such tumors, unambiguously, using the present nomenclature. Designation as "chordoid sarcoma of bone" would distinguish these cases from conventional skeletal myxoid chondrosarcoma.

Bone Neoplasms↗

PubMed2002

Identification and initial characterization of 6,000 expressed sequenced tags (ESTs) from rat normal-growing cartilage and swarm rat chondrosarcoma cDNA libraries.

Chondrosarcoma is the second most common type of skeletal malignancy with a survival rate at five years for histological grade III of only 29 percent. The development of a reliable chondrosarcoma animal model could enable the study of tumor growth and progression, the effect of the host on tumor behavior, and the effectiveness of various therapeutic modalities. The Swarm rat chondrosarcoma is a tumor tissue line that has been maintained through the years by serial subcutaneous injections, and the histochemical characteristics of the tumor have remained essentially similar in all transplants over the years. This study was designed to initiate the characterization of the Swarm rat chondrosarcoma model by gene expression profiling as compared to normal-growing rat cartilage. Analysis of the gene expression from both libraries revealed a complex pattern of gene expression, including many genes not yet reported to be expressed by chondrocytes. It suggests that the biochemical characterization of growing cartilage and chondrosarcoma reported to date has only begun to describe the complexity of these tissues.

Animals↗

PubMed2003

[Clinical analysis of 9 cases chondrosarcoma in nasal cavity and paranasal sinuses].

OBJECTIVE: To improve the diagnosis and treatment levels of the chondrosarcoma in nasal cavity and paranasal sinuses. METHOD: Nine patients with chondrosarcoma in nasal cavity and paranasal sinuses were investigated. Diagnosis, treatment and prognosis were analyzed respectively. RESULT: The clinic pathologic features of chondrosarcoma in nasal cavity and paranasal sinuses were complex and various. The lesions were wide and close to the skull base in 4 patients with secondary chondrosarcoma, poorer prognosis was noted. Irregular and molted calcifications were radiographic findings of chondrosarcoma. Eight patients were diagnosed after explorative operation by partial or total resection of tumor. Histological grade I were the commonest. CONCLUSION: Histological, clinical features and computed tomography should be paid attention to the disease and early explorative operation and resection will make contribution to the definite diagnosis and prognosis.

Adult↗