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The identification of a plasma membrane 3,3',5-triiodo-L-thyronine binding protein on the cultured Swarm rat chondrosarcoma chondrocyte and the lack of its up-regulation by insulin in vitro.

Primary cultures of Swarm rat chondrosarcoma chondrocytes were examined for the presence of T3 plasma membrane binding proteins and their possible regulation by insulin. Incubation of this tumor cell with [125I]T3 at 4 C yielded saturable and reversible binding of the radioligand. As assessed by LIGAND computer analysis, the binding data in one experiment revealed two classes of [125I]T3 binding sites with association constants of 2.2 X 10(9) M-1 and 4.8 X 10(6) M-1, and binding capacities of 4.9 X 10(3) and 1.9 X 10(6) sites per cell, respectively. Whole cells and a preparation enriched for plasma membrane were affinity labeled with N-bromoacetyl-[125I]T3 (N-BrAc-[125I] T3), and the molecular weights of the radiolabeled proteins were analyzed both by sodium dodecyl sulfate polyacrylamide gel electrophoresis and by Sephadex G-200 gel filtration chromatography. One major chondrosarcoma protein of 55,000 mol wt and two minor proteins of 47,000 and 33,000 mol wt bound N-BrAc-[125I]T3, suggesting that the mol wt of the T3 binding protein was 55,000. As assessed by isoelectric focusing, the 55,000 mol wt protein had an isoelectric point of 5.1. The radiolabeled 55,000 mol wt chondrosarcoma protein was immunoprecipitated with anti-T3 and anti-GH3 plasma membrane T3 antisera. The high degree of homology between this chondrocyte N-BrAc-[125I]T3 binding protein and the protein on rat GH3 cells was demonstrated by a comparison of the peptide maps of Staphylococcus aureus V8 protease and elastase digested radiolabeled binding protein. Although culture of the chondrocytes in medium containing insulin resulted in an approximate 400% increase in plasma membrane [125I]insulin binding, no significant increase in [125I]T3 binding was observed. Thus, expression of the T3 plasma membrane binding protein was similar to that observed previously for the insulin-like growth factor-II receptor on these chondrosarcoma chondrocytes in not being influenced by the concentration of insulin in the culture medium.

Affinity Labels↗

Radiotherapeutic factors in the management of cervical-basal chordomas and chondrosarcomas.

OBJECTIVE: To define prognostic factors for local control and survival in 90 consecutive patients treated by fractionated photon and proton radiation for chordoma or chondrosarcoma of the cranial base and upper cervical spine. METHODS: Between December 1995 and December 2000, 90 patients (median age, 51.3 yr; range, 10-85 yr; male/female ratio, 3:2) were treated by a combination of high-energy photons and protons. Sixty-four patients had a chordoma, and 26 had a chondrosarcoma. The proton component was delivered by the 201-MeV proton beam of the Centre de Protontherapie d'Orsay. The median total dose delivered to the gross tumor volume (GTV) was 67 cobalt Gray equivalents (range, 22-70 cobalt Gray equivalents). RESULTS: With a median follow-up of 34 months (range, 3-74 mo), treatment of 25 tumors failed locally. The 3-year local control rates were 69.2% (+/-6.0%) and 91.6% (+/-8.4%) for chordomas and chondrosarcomas, respectively. According to multivariate analysis, a small tumor volume excluded from the 95% isodose line (P = 0.032; relative risk [RR], 0.098; 95% confidence interval [CI], 0.01-0.81) and a controlled tumor (P = 0.049; RR, 0.19; 95% CI, 0.04-0.99) were independent favorable prognostic factors for overall survival. On multivariate analysis, a high minimum dose (P = 0.02; RR, 2.8; 95% CI, 1.2-6.6), a high tumor control probability (P = 0.02; RR, 3.8; 95% CI, 1.2-12.5), a high dose delivered to 95% of the GTV (P = 0.03; RR, 3.4; 95% CI, 1.15-10.2), a high GTV encompassed by the 90% isodose line (P = 0.01; RR, 3.29; 95% CI, 1.29-8.44), and a small GTV excluded from the 90% isodose line (P = 0.036; RR, 0.4; 95% CI, 0.1-0.9) were independent favorable prognostic factors for local control. CONCLUSION: In chordomas and chondrosarcomas of the cranial base and cervical spine treated by surgical resection and then by high-dose photon and proton irradiation, local control is mainly dependent on the quality of radiation, especially dose uniformity within the GTV. Special attention must be paid to minimize underdosed areas because of the close proximity of critical structures and to redefine and possibly escalate dose constraints to tumor targets in future studies in view of the low toxicity observed to date.

Adolescent↗

Radiosurgery for cranial base chordomas and chondrosarcomas.

OBJECTIVE: To evaluate the efficacy and toxicity of radiosurgery in the treatment of cranial base chordoma and chondrosarcoma. METHODS: We reviewed 29 patients with cranial base chordoma (n = 25) or chondrosarcoma (n = 4) who underwent stereotactic radiosurgery between September 1990 and December 2002. The median patient age was 45 years (range, 10-81 yr). Nineteen patients also had radiation therapy before or in conjunction with radiosurgery (median dose, 50.4 Gy). The median tumor volume was 14.4 cm3 (range, 0.6-65.1 cm3). The median tumor margin dose was 15 Gy (range, 10-20 Gy); the median maximum radiation dose was 30 Gy (range, 20-40 Gy). Median clinical and imaging follow-up periods were 4.8 and 4.5 years, respectively. RESULTS: Seven chordoma patients (28%) had tumor progression (in-field, n = 3; out-of-field, n = 4), whereas 18 had stable disease or tumor shrinkage. No patient with a chondroid chordoma had tumor enlargement. The actuarial tumor control rates were 89 and 32% at 2 and 5 years, respectively. All 4 patients with chondrosarcoma had tumor control. Clinically, 7 patients (24%) had improvement of pretreatment symptoms, 16 (55%) remained stable, and 6 (21%) worsened. Three patients with tumor progression died. Ten patients (34%) had radiation-related complications. Complications included cranial nerve deficits (n = 6), radiation necrosis (n = 5), and pituitary dysfunction (n = 3). Patients having radiosurgery alone had no toxicity. CONCLUSION: Cranial base chordomas and chondrosarcomas remain a formidable management challenge. Radiosurgery as an adjunct to surgical resection provides in-field tumor control for some patients, but radiation-related complications are relatively high, especially when radiosurgery is combined with fractionated radiation therapy.

Chondrosarcoma↗

The endoscopic transnasal transsphenoidal approach for the treatment of cranial base chordomas and chondrosarcomas.

OBJECTIVE: We report our experience with endoscopic transsphenoidal or extended endoscopic transsphenoidal approaches for the treatment of cranial base lesions such as clival chordomas and chondrosarcomas. METHODS: Between May 1998 and April 2004, 11 patients (four were recurrences because they previously had been treated with surgery and/or radiotherapy) underwent transnasal transsphenoidal endoscopic surgery for cranial base chordomas and chondrosarcomas at the Neurosurgical Department of Bellaria Hospital in Bologna. The transsphenoidal endoscopic approach and the ethmoid-pterygo-sphenoidal endoscopic approach were used to accomplish resection of the lesions involving the clivus and extending up to the parasellar region and to the petrous apex, or within the cavernous sinus. RESULTS: Patient follow-up periods ranged from 15 to 69 months (mean, 27 mo). Three patients died of chordoma progression at 20, 14, and 10 months, respectively, after endoscopic treatment. One patient experienced two recurrences; the first was treated using a new endoscopic approach, whereas the second, 1 year later, was treated by means of a far lateral approach. Four patients underwent postoperative proton beam radiotherapy, whereas one underwent a conventional megavoltage x-radiation therapy. However, postoperative radiotherapy was not administered in the two patients treated for cranial base chondrosarcoma. CONCLUSION: The flexibility of this new technique with respect to the classical microscopic transsphenoidal approach permits us to widen the horizon of surgical management of aggressive cranial base tumors such as clival chordomas and chondrosarcomas.

Adult↗

Cardiac chondrosarcoma producing parathyroid hormone-related protein.

Chondrosarcoma is a malignant tumor characterized by the formation of cartilage. A case of primary cardiac chondrosarcoma of the left atrium developed in a middle-aged male. The preoperative serum concentrations of C-parathyroid hormone-related protein (PTHrP) and calcium were high (413.2 pmol/L and 12.2 mg/dl, respectively), but normalized after resection of the tumor, which measured 7 x 5 x 3.5 cm. The tumor was histopathologically diagnosed as chondrosarcoma, composed of outer atypical chondroid cells and inner pleomorphic and spindle mesenchymal cells mimicking malignant fibrous histiocytoma. Half of the cartilaginous tumor cells and a few pleomorphic cells showed cytoplasmic immunoreactivity for PTHrP. The tumor is a possible example of the functional pleiotropy of chondrosarcoma.

Chondrosarcoma↗

A review of the behaviour of chondrosarcoma of bone.

Sixty-two cases of chondrosarcoma of bone were reviewed and histologically graded as low, medium or high-grade tumours. After excluding patients dead from unrelated causes or lost to follow-up, forty cases were available for ten-year follow-up and fifty-eight for five-year follow-up. The rates of survival, recurrence and metastasis were analysed according to the histological grading. Recurrence was further analysed according to the adequacy of treatment. The results were compared with those previously reported in the literature. There was a ten-year survival rate of 58 per cent. Recurrence developed in 58 per cent and was uncontrollable in 29 per cent. The recurrence rate was 87 per cent with inadequate treatment and 15 per cent with adequate treatment. Recurrences outside the limb bones usually proved uncontrollable; recurrences in the limb bones were amenable to further, and if necessary repeated, operations. High-grade chondrosarcoma had a metastatic risk of 75 per cent and eventual mortality of 88 per cent. Medium-grade chondrosarcoma had a metastatic risk of 14 per cent and a mortality of 60 per cent. Low-grade chondrosarcoma had a metastatic risk of 5 per cent and a mortality of 29 per cent.

Adult↗

Chondrosarcoma in association with primary hyperparathyroidism.

We describe two female patients, 66 and 36 years of age, with both primary hyperparathyroidism and chondrosarcoma. Case 1 had a chondrosarcoma of the right scapula, and case 2 had chondrosarcoma of the left proximal tibia. Both patients underwent surgical resection of their chondrosarcoma and subsequent parathyroid surgery. Histological analysis of the excised parathyroid in case 1 showed a parathyroid carcinoma and in case 2 showed a parathyroid adenoma. Including these two patients, there is now a total of six cases that have been reported in the literature describing the association between hyperparathyroidism and bone malignancy. We believe that this small number makes it unlikely that there is an association between these two conditions, although we speculate that there may be an underlying genetic basis.

Adult↗

Management of primary spinal chondrosarcoma: report of two cases causing cord compression.

Chondrosarcomas are malignant tumors that rarely grow inside the spinal canal. Prognosis depends on histological features, patient's age and surgical margins free from tumor. Response to radio and chemotherapy is poor. Ideal treatment consists of total "en-block" resection, not always achievable due to limitation of location, compromise of stability and risk of inducing neurological deficits. Two cases of spinal chondrosarcoma causing cord compression are reported, located in the cervical and thoracic spine. Microsurgical technique consisted of initial debulking followed by removal of margins until limits free from tumor were obtained. Total resection was accomplished and neurological function improved in both cases. Follow-up has been seven and one year respectively, with no evidence of recurrence and preserved neurological functions. Association between chondrosarcoma and estrogen-dependent tumor has been confirmed in this report. Although "en-block" resection of a chondrosarcoma should be tried whenever possible, tumor fragmentation should be considered in difficult cases, as in the present report, in which a long period free from recurrence with good quality of life can be obtained.

Adult↗

Clinicopathology of chondrosarcoma.

We conducted a clinicopathological analysis of chondrosarcomas in 17 patients treated in our institute. The 5- and 10-year overall survival rates of the patients were 72.3% and 61.9%, respectively. The significant prognostic factors were size and histologic grade of the tumor. Sex, age, location of the primary tumor, or the presence of a preceding exostosis did not affect the treatment results significantly. Chondrosarcomas of histologic grades I and II did not metastasize, while all grade III and dedifferentiated chondrosarcomas metastasized to the lung. The local recurrence rate depended on the surgical margin. Wide excision with an adequate surgical margin is important to achieve local control of the chondrosarcoma.

Adolescent↗

Laryngeal chondrosarcoma in Sweden.

Between 1958 and 1972, 5 cases of posterior cricoid chondrosarcoma were reported to the Swedish Cancer Registry. These cases, and one recently observed case of laryngeal chondrosarcoma, are presented in this study of one female and five male patients. The tumours grow slowly and recur locally, but have not metastasized, and none of the patients has died from tumour disease. The clinical and morphological findings indicate that these tumours represent secondary chondrosarcomas developing from pre-existing benign ecchondromas. The reason for the uniformity as to localization is not known. The microscopic appearance varied in different parts of the same tumour. The presently obtained data and review of the literature indicate that laryngeal chondrosarcomas are extremely rare, locally invasive, but usually not metastasizing tumours. Conservative laryngeal operation is suggested as primary treatment. Total laryngectomy is necessary only after local recurrences involving a major portion of the cricoid cartilage.

Aged↗

Chondrosarcoma of the head in children.

Chondrosarcoma usually manifests in adult and elderly patients and involves primarily the long bones of the extremities and the osseous pelvis. Children and adolescents may be affected, however. In the young, these neoplasms tend to grow in atypical anatomic sites. A review of clinical experience at a pediatric institution disclosed three chondrosarcomas, including one of mesenchymal type, arising in tissues of the head in patients aged 15, 9, and 13 years. From a review of the pertinent literature as well as clinical experience, it appears that pediatric pathologists are apt to encounter chondrosarcomas rarely, and in those cases the clinical and pathologic features are at variance with those described for chondrosarcoma in adult patients. Low-grade lesions may pursue an indolent course, necessitating prolonged surveillance.

Adolescent↗

Proton radiation therapy for chordomas and chondrosarcomas of the skull base.

OBJECT: Local tumor control, patient survival, and treatment failure outcomes were analyzed to assess treatment efficacy in 58 patients in whom fractionated proton radiation therapy (RT) was administered for skull base chordomas and chondrosarcomas. METHODS: Between March 1992 and January 1998, a total of 58 patients who could be evaluated were treated for skull base tumors, 33 for chordoma and 25 for chondrosarcoma. Following various surgical procedures, residual tumor was detected in 91% of patients; 59% demonstrated brainstem involvement. Target dosages ranged from 64.8 and 79.2 (mean 70.7) Co Gy equivalent. The range of follow up was 7 to 75 months (mean 33 months). In 10 patients (17%) the treatment failed locally, resulting in local control rates of 92% (23 of 25 patients) for chondrosarcomas and 76% (25 of 33 patients) for chordomas. Tumor volume and brainstem involvement influenced control rates. All tumors with volumes of 25 ml or less remained locally controlled, compared with 56% of tumors larger than 25 ml (p = 0.02); 94% of patients without brainstem involvement did not experience recurrence; in patients with brainstem involvement (and dose reduction because of brainstem tolerance constraints) the authors achieved a tumor control rate of 53% (p = 0.04). Three patients died of their disease, and one died of intercurrent disease. Actuarial 5-year survival rates were 100% for patients with chondrosarcoma and 79% for patients with chordoma. Grade 3 and 4 late toxicities were observed in four patients (7%) and were symptomatic in three (5%). CONCLUSIONS: High-dose proton RT offers excellent chances of lasting tumor control and survival, with acceptable risks. In this series all small- and medium-sized tumors with no demonstrable brainstem involvement have been controlled; all such patients are alive. Surgical debulking enhanced delivery of full tumoricidal doses, but even patients with large tumors and disease abutting crucial normal structures benefited.

Actuarial Analysis↗

Mesenchymal chondrosarcoma of the hyoid bone: a case report.

Mesenchymal chondrosarcoma is a rare tumor that is distinctly different from classic chondrosarcoma. The prognosis of this tumor is poor, with a high incidence of locoregional and distant metastases. It shows a predilection for the head and neck, however mesenchymal chondrosarcoma of hyoid bone has rarely been reported. We experienced a case of mesenchymal chondrosarcoma of the hyoid bone in a 39-year-old woman. She underwent excision of the tumor by right hemihyoidectomy. Histologically, a combination of cellular zones composed of undifferentiated small cells and chondroid zones typically presented a bimorphic appearance. CD99 (DN16) immunohistochemical stain demonstrated that all undifferentiated small cells had strong reactivity with a distinct membranous pattern. There was microscopic tumor extension to the resection margin of the hyoid bone, however, no evidence of reccurence is noted at follow-up of 4 months with neck CT.

Adult↗

Overexpression of p53 and absent genetic mutation in clear cell chondrosarcoma.

Clear cell chondrosarcoma is one of the extremely rare chondrosarcomas. The pathogenesis and the molecular genetic events, which contribute to the development of clear cell chondrosarcoma, are not well elucidated, due in part to the lack of sufficient tumor tissue available. To characterize the involvement of the p53 gene abnormality in this disease, we analyzed expression and sequence alteration of p53 by immunohistochemical analysis of the protein expression and quantitative DNA/PCR and PCR-SSCP assays of the gene in 28 paraffin-embedded tissue specimens. Immunohistochemical analysis demonstrated that 7 (25%) showed patchy positive nuclear staining for p53 and 5 (18%) showed diffuse positive nuclear staining patterns. Sixteen (57%) were negative for p53 immunostaining. Quantitative DNA/PCR analysis revealed that none of the cases we studied showed significantly reduced levels of p53 amplification (<0.50), strongly suggesting an allelic deletion of the p53 gene. In contrast, however, DNA/PCR-SSCP analysis failed to detect any types of mutations resulting in amino acid substitution within exons 5-9 regions of the gene. Taken together, our data suggest that genetic alteration of p53 is a relatively rare event in clear cell chondrosarcomas but a substantial fraction of this type of tumors carries abnormal overexpression of p53, which might result from an as yet unidentified mechanism(s).

Chondrosarcoma↗

Overexpression of p53 and rare genetic mutation in mesenchymal chondrosarcoma.

Mesenchymal chondrosarcoma is extremely rare and accounts for less than 2% of all chondrosarcomas. The pathogenesis and the molecular genetic events which contribute to the development of mesenchymal chondrosarcoma are not well elucidated, due in part to the lack of sufficient tumor tissue available. To characterize the involvement of the p53 gene abnormality in this disease, we analyzed expression and sequence alteration of p53 by immunohistochemical analysis of the protein expression and quantitative DNA/PCR and PCR-SSCP assays of the gene in 33 paraffin-embedded tissue specimens. Immunohistochemical analysis demonstrated that 19 (61.3%) of 31 had nuclear overexpression of p53 while 7 (22.6%) showed cytoplasmic expression. The remaining 5 (16.1%) were negative for p53 staining. The nuclear positivity of p53 was observed within a range of 22-64% (mean 37.3%) of tumor cells and showed a positive staining in mesenchymal components as well as chondroid components. Quantitative DNA/PCR analysis revealed that 6 (18.2%) of the 33 specimens carried significantly reduced or undetectably low levels of p53 indicating the genomic deletion of the gene in these tumors. In contrast, however, DNA/PCR-SSCP analysis failed to detect any types of mutations resulting in amino acid substitution within exons 5-9 regions of the gene. Taken together, our data suggests that genetic alteration of p53 is a relatively rare event in mesenchymal chondrosarcomas but substantial fraction of this type of tumors carries abnormal overexpression of p53, which might result from as yet unidentified epigenetic mechanism(s).

Chondrosarcoma, Mesenchymal↗

Conservative surgery for chondrosarcoma of the first metacarpal bone.

A rare case of a chondrosarcoma of the first metacarpal bone is presented. The lesion was radiographically interpreted initially as an enchondroma and treated conventionally by curettage and cancellous autologous bone grafting. After final histology, a low-grade chondrosarcoma was reported. A resection of the entire first metacarpal bone was performed, followed by reconstruction using an autologous corticocancellous bone graft and plate fixation, creating arthrodeses of the adjacent joints. Although isolated enchondromas are considered to have no malignant potential, histological examination is essential to rule out malignancy. A preoperative biopsy should be recommended in lesions suspected to be chondromas. Chondrosarcomas are rarely located in bones of the hand, where they are usually treated by amputation. With the case presented we wish to advocate that cases of low-grade, intraosseous chondrosarcoma (stage IA) can be treated by conservative surgery, especially when it is located in the thumb.

Adult↗

DNA ploidy alterations detected during dedifferentiation of periosteal chondrosarcoma.

DNA ploidy of a case with dedifferentiated periosteal chondrosarcoma was analyzed by DNA cytofluorometry. The diagnosis of primary periosteal chondrosarcoma was made on the basis of the radiographic and histological findings. At 4 years after marginal resection, the tumor recurred locally and metastasized to various organs. The patient died of disease 2 years later. Histologically, there were two components, chondrosarcoma and malignant fibrous histiocytoma, in the recurrent and metastatic tumors. DNA ploidy analysis of multiple samples revealed that the primary lesion was composed of many diploid cells with some tetraploid and octaploid cells, whereas in the dedifferentiated area, there were many aneuploid cells which were not recognized in any area of the primary tumors. This case illustrated that DNA ploidy alteration of euploidy to aneuploidy is closely correlated with the process of dedifferentiation in chondrosarcoma.

Adult↗

[The comparative biochemical and morphological characteristics of chondrosarcoma and giant-cell tumor of the bone].

Spectrometry has been employed to assess the levels of collagenase, catepsin D, trypsin-like proteinases and their inhibitors as well as bone acid and alkaline phosphatase both in the center and along the periphery of giant cell tumor of bone (GCTB) and chondrosarcoma. The levels of collagenase, trypsin-like proteinases and their inhibitors in the center of chondrosarcoma were much higher while those of alkaline phosphatase--lower than along tumor periphery. The catepsin D and acid phosphatase concentrations of the center and periphery of chondrosarcoma were similar. It was suggested that an extremely low concentration of trypsin-like inhibitors may contribute to degradation of the matrix in tissues adjacent to chondrosarcoma and, consequently, to tumor invasion development.

Acid Phosphatase↗