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Mesenchymal chondrosarcoma of the vagus nerve.

Mesenchymal chondrosarcoma is a rare, aggressive, malignant neoplasm, which arises from extraskeletal sites in 30-40 per cent of cases. It is extremely rare in children. We present a novel case of childhood mesenchymal chondsarcoma arising from the vagus nerve in the neck, resulting in paralysis of the right vocal fold. The clinicopathologic features and management of this case are described along with a brief discussion on the aetiology of vocal fold paralysis in this age group. Current literature on extraskeletal presentation of mesenchymal chondrosarcoma is reviewed.

Child↗

Canine mesenchymal chondrosarcoma of the ribs.

The tumor of the thoracic cavity, which arose from the ribs, was diagnosed as mesenchymal chondrosarcoma. No distant metastasis was observed. Histologically, the tumor was characterized by the nests of well-defined cartilaginous tissue within a proliferation of primitive mesenchymal cells. Additionally, the deformed blood vessels compressed by the proliferating mesenchymal cells exhibited clear stag-horn appearance. Immunohistochemically, most neoplastic cells that formed multifocal cartilaginous islands were positive for S-100 protein, while the surrounding mesenchymal cells were negative. This is the first report of canine mesenchymal chondrosarcoma of the ribs.

Animals↗

Chondrosarcoma developing in synovial chondromatosis. A case report.

Synovial chondromatosis is a rare condition in which osteocartilaginous nodules are formed by synovial metaplasia and become intra-articular loose bodies. It is usually monarticular, most commonly affecting the knee and is regarded as invariably benign. There are reports of malignant change, but only the two case studies of Mullins, Berard and Eisenberg (1965) and of Dunn et al. (1974) fully document the development of chondrosarcoma in this condition. We report a patient with a long history of histologically proven synovial chondromatosis in whom the condition became clinically aggressive and underwent malignant transformation to chondrosarcoma.

Adult↗

Chondrosarcoma of the soft tissues. Two different sub-groups.

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.

Adult↗

Experience in the treatment of dedifferentiated chondrosarcoma.

Dedifferentiated chondrosarcoma is a rare, highly malignant variant of chondrosarcoma in which a high-grade spindle-cell sarcoma coexists with a lower-grade chondroid tumour. We have reviewed our experience with this neoplasm in 22 patients, all of whom were treated using modern oncological principles of planned resection and chemotherapy. Despite this the median survival was under nine months and only 18% were alive at five years. Those patients who received chemotherapy, and in whom wide margins of excision were achieved at operation, did best. It is essential to have an accurate preoperative diagnosis in order to plan treatment which may offer a better prospect of cure.

Adolescent↗

Chondrosarcoma in a family with multiple hereditary exostoses.

Multiple hereditary exostoses is an autosomal dominant skeletal disorder in which there are numerous cartilage-capped excrescences in areas of actively growing bone. The condition is genetically heterogeneous, and at least three genes, ext1, ext2 and ext3 are involved. The reported risk for malignant transformation to chondrosarcoma has been from 0.6% to 2.8%. We have reviewed six generations of a family with 114 living adult members, 46 of them with multiple exostoses. Four have had operations for chondrosarcoma, giving the risk for malignant transformation as 8.3% in this family. Clinical and radiological examination revealed two additional patients with a suspicion of malignancy, but in whom the histological findings were benign. Reported elsewhere in detail, genetic linkage analysis mapped the causative gene to chromosome 11 and molecular studies revealed a guanine-to-thymine transversion in the ext2 gene. Patients with multiple hereditary exostoses carry a relatively high risk of malignant transformation. They should be informed of this possibility and regularly reviewed.

Adolescent↗

Surgical treatment and outcome of conventional pelvic chondrosarcoma.

We reviewed 124 patients with a conventional pelvic chondrosarcoma who had been treated over a period of 20 years. We recorded the type of tumour (central or peripheral), type of operation (limb salvage surgery or hemipelvectomy), the grade of tumour, local recurrence and/or metastases, in order to identify the factors which might influence survival. More satisfactory surgical margins were achieved for central tumours or in those patients treated by hemipelvectomy. However, grade 1 tumours, whatever the course, did not develop metastases or cause death, while grade 3 tumours had the worst outcome and prognosis. Central, high-grade tumours require aggressive surgical treatment in order to achieve adequate surgical margins, particularly in those lesions located close to the sacroiliac joint. By contrast, grade 1 peripheral chondrosarcomas may be treated with contaminated margins in order to reduce operative morbidity, but without reducing survival.

Bone Neoplasms↗

Primary chondrosarcoma in the liver of a dog.

Primary chondrosarcoma was found in the quadrate lobe of the liver of a 6-year-old, intact, male Golden Retriever. At 6 months after partial hepatectomy, recurrence in the liver occurred. The dog died of its systemic metastases 10 months thereafter. Histologically, the hepatic mass revealed neoplastic chondrocytes with abundant chondroid matrix, and there were few myxoid areas where the cellularity and pleomorphism of the neoplastic cells were more prominent. The neoplastic cells were positive for periodic acid-Schiff and were immunohistochemically positive for vimentin and S-100 protein; the matrix was deeply stained for alcian blue and was metachromatic for toluidine blue stain. This tumor might be derived from pluripotent mesenchymal cells in the connective tissue of the liver. To the best of our knowledge, in all mammalians, including humans, this is the first report of extraskeletal chondrosarcoma primarily arising in the liver.

Animals↗

[Chondrosarcoma of the orbit. Report of a case].

A case of chondrosarcoma of the orbit is reported. The patient complained of marked deterioration of her vision, pain and presented exophatalmus of the left eye. Chondrosarcoma of the orbit are rare and this is the first case reported in the Brazilian literature. Diagnostic and prognostic are discussed.

Carotid Arteries↗

Collagenase specificity in chondrosarcoma metastasis.

The treatment of some mesenchymal malignancies has made significant gains over the past few decades with the development of effective systemic therapies. In contrast, the treatment of chondrosarcoma has been limited to surgical resection, with the most significant prognostic indicators being surgical margins and histologic grade. We have reported that MMP-1/TIMP-1 gene expression serves to prognosticate for tumor recurrence in this group of patients. This led to the hypothesis that collagenase activity facilitates cell egression from the cartilaginous matrix. In the current study we examine the specificity of collagenase gene expression in archival human chondrosarcoma samples using semi-quantitative PCR. Messenger RNA was affinity extracted and subject to reverse transcription. The subsequent cDNA was amplified using novel primers and quantitated by densitometry. Ratios of gene expression were constructed and compared to disease-free survival. The data demonstrate that the significance of the MMP-1/TIMP-1 ratio as a predictor of recurrence is confirmed with a larger number of patients. Neutrophil collagenase or MMP-8 was observed in only 5 of 29 samples. Collagenase-3 or MMP-13 was observed in all samples but the level did not correlate with disease-free survival. Since the collagenases have similar activity for fibrillar collagens and cleave the peptide in the same location, post-transcriptional regulatory mechanisms may account for the observed specificity. The determination of the MMP-1/TIMP-1 gene expression ratio not only serves to identify those patients at risk for recurrence but may also serve as a novel therapeutic avenue as an adjunct to surgical resection.

Bone Neoplasms↗

Inhibitory effects of transforming growth factor-beta1 pretreatment on experimental pulmonary metastasis of MCS-1 Chinese hamster mesenchymal chondrosarcoma cells.

Recent studies have suggested that transforming growth factor(TGF)-beta1 acts as a multifunctional regulator of cell growth, and also modifies tumor progression and metastasis. In the present study, we investigated the effects of TGF-beta1 on the proliferation and experimental pulmonary metastasis of MCS-1. MCS-1 are undifferentiated type cloned tumor cells established from a mesenchymal chondrosarcoma which spontaneously occurred in the soft tissue of a female Chinese hamster. MCS-1 cells were pretreated with TGF-beta1 (0, 0.05, 0.5, 2, 10 ng/ml) for 72 hours in a medium containing 1% fetal bovine serum, then tested for in vitro growth by the MTT method, in vivo growth by subcutaneous inoculation into athymic nude mice (1 x 10(6) cells/mouse) and experimental pulmonary metastasis by injection into the lateral tail vein of athymic nude mice (5 x 10(4) cells/mouse). TGF-beta1 significantly inhibited in vitro growth of MCS-1, depending on its concentrations, and also experimental metastasis with maximal inhibition at 0.5 or 2 ng/ml treatment compared to untreated controls. TGF-beta1, however, was ineffective for in vivo subcutaneous growth of MCS-1. These results indicated that TGF-beta1 might be an inhibitor of metastasis of mesenchymal chondrosarcomas including other types of non-epitherial cartilage or bone formation tumors.

Animals↗

Chondrosarcoma of bone: an assessment of outcome.

BACKGROUND: The data on 227 patients who had been managed for a chondrosarcoma at one institution were reviewed to determine the nature of the lesions, the predictors of outcome, and whether there were any ways to change the treatment approaches to improve the results. METHODS: The patients were followed for a mean duration of six years (range, three to twenty-five years). The mean age of the patients was forty-seven years (range, nine to eighty-four years). The most prevalent sites of the tumors were the femur (seventy-eight), the pelvis (fifty-one), and the humerus (thirty-nine). The tumors were divided into two groups according to histological grade. Eighty-six tumors (sixteen atypical enchondromas and seventy grade-1 chondrosarcomas) that were locally destructive but were associated with a low likelihood of metastasis were considered to be low-grade. The remaining 141 lesions, which were locally destructive, potentially metastatic, and capable of causing death, were thought to be high-grade. One hundred and three of these 141 lesions were grade 2, and thirty-eight were grade 3 (eighteen of the thirty-eight were grade 3 only, and twenty were both grade 3 and dedifferentiated). Two hundred and twenty-four patients were managed with resection and a limb-sparing procedure; the remaining three patients had an amputation. Postoperative adjuvant radiation was used for fifty-six patients; chemotherapy, for thirty-five; and both radiation and chemotherapy, for nineteen. Flow cytometric patterns were analyzed for 105 patients. RESULTS: The patients who had a high-grade tumor were older than those who had a low-grade tumor (mean age [and standard deviation], 50+/-17.0 years compared with 40+/-15.9 years; p < 0.001). Pathological fracture, metastasis, local recurrence, and death were more prevalent in the group that had a high-grade lesion (p < 0.001). Predictors of metastasis and death in that group of patients included local recurrence, a pelvic location of the tumor, a tumor that was more than 100 cubic centimeters in size, a ploidic abnormality (aneuploidy coupled with a high mean DNA index), a histological grade of 3, and a dedifferentiated type of tumor (p < 0.001). CONCLUSIONS: Although the data are suggestive, with the numbers available for study we could not detect a significant difference in the rates of pulmonary metastasis and death between the patients who had a grade-3 lesion and those who had a grade-3 lesion that was also dedifferentiated. However, the interval between diagnosis and death was 32+/-22.8 months for the patients who had a grade-3 lesion compared with 5+/-3.7 months for those who had a grade-3 lesion that was also dedifferentiated (p < 0.001). Overall, patients who had had a resection with wide margins (margins extending outside the reactive zone) had a longer duration of survival than did those who had had a so-called marginal resection (margins extending outside the tumor but within the reactive zone) or an intralesional resection (margins within the lesion) (p < 0.04). Adjunctive chemotherapy or radiation, or both (which, it must be noted, was used, without a protocol, in a relatively small number of patients), after an intralesional resection, for recurrent disease, or for distant metastasis did not appear to alter the outcome.

Adolescent↗

Primary chondrosarcoma of the lung--a case report with immunohistochemical study.

A case of primary chondrosarcoma of the lung is presented. The tumor, located in the medial segment of the right lower lobe, was successfully resected surgically. Clinical survey did not reveal any primary lesion elsewhere. The tumor consisted of myxomatous, chondromatous, and fibrous lesions. Immunohistochemical study revealed that tumor cells were positive for S-100 protein and vimentin, and negative for other antisera which characterize epithelial tumors. With these clinical, histological, and immunohistochemical studies we diagnosed the tumor as a primary chondrosarcoma of the lung.

Aged↗

Chondrosarcoma of the esophagus.

A 46-year-old man had a large noncalcified tumor in the wall of the thoracic esophagus narrowing its lumen by projection of numerous firm nodular masses. The pathologic diagnosis was chondrosarcoma. Malignant degeneration of a tracheobronchial cartilaginous remnant is the main consideration in this first recorded case of esophageal chondrosarcoma.

Chondrosarcoma↗

Radionuclide bone scanning of medullary chondrosarcoma.

Technetium-99m methylene diphosphonate bone scans of 18 medullary chondrosarcomas of bone were correlated with pathologic macrosections of the resected tumors. There was increased scan uptake by all 18 tumors, and the uptake in 15 scans corresponded accurately to the anatomic extent of the tumors. Only three scans displayed increased uptake beyond the true tumor margins; thus, the "extended pattern of uptake" beyond the true tumor extent is much less common in medullary chondrosarcomas than in many other primary bone tumors. Therefore, increased uptake beyond the apparent radiographic margin of the tumor suggests possible occult tumor spread. Pathologically, there was intense reactive new bone formation and hyperemia around the periphery of all 18 tumors, and there were foci of enchondral ossification, hyperemia, or calcification within the tumor itself in nearly every tumor. Three scans displayed less uptake in the center of the tumors than around their peripheries. One of these tumors was necrotic in the center, but the other two were pathologically no different from tumors that displayed homogeneous uptake on the scan.

Bone Neoplasms↗

Scintigraphy of benign exostoses and exostotic chondrosarcomas.

Technetium-99m diphosphonate scintigraphy of 11 benign exostoses and nine exostotic chondrosarcomas was correlated with pathologic macrosections of the resected tumors. Increased uptake in benign exostoses occurred in areas of enchondral ossification, and uptake in chondrosarcomas occurred in areas where ossification, osteoblastic activity, and hyperemia were found. Uptake was not related to amorphous cartilage calcification. Radiopharmaceutical uptake, therefore, correlated with areas of ossification visible radiographically, and large masses of nonossifying cartilage were not detected. Radionuclide bone imaging did not contribute to the preoperative anatomic evaluation of these tumors, and it did not always distinguish benign from malignant lesions.

Adolescent↗

The human chondrosarcoma HCS-2/8 cell line is responsive to BMP-7, but not to IL-1beta.

Cultures of primary chondrocytes as in vitro model systems for studying the cellular behavior of chondrocytes are notoriously difficult to cultivate and propagate. One way to circumvent these problems appears to be the use of immortalized/immortal chondrocytic cell lines. In the present study, we were interested whether the chondrosarcoma derived HCS-2/8 cells are suitable for studying major cellular reaction pattern in response to key anabolic (BMP-7) and catabolic (IL-1beta) factors. Therefore, we used cDNA array and real-time PCR technology in order to evaluate gene expression triggered by stimulation with IL-1beta (0,1-100 ng/ml) and BMP-7 in confluent monolayer cultures. HCS-2/8 cells hardly responded to IL-1beta, but showed good responsiveness to BMP-7. We found 12 genes up- and 17 significantly down-regulated by BMP-7 (out of 340 investigated genes). Besides the expected activation of anabolic genes chondrocytic cells after BMP-stimulation try to neutralize activation of the BMP-signalling cascade by expressing intra- and extracellular BMP-antagonists. Chondrosarcoma derived cell lines are a potential substitute for primary articular chondrocytes promising consistent expression of a differentiated chondrocyte phenotype with sufficient proliferative capacity. However, as shown by this study one needs to carefully select the cell line depending on the effects which one intends to study. In this respect, HCS-2/8 cells are a validated tool for studying BMP-effects on chondrocytes, but not e.g. effects of interleukin-1.

Bone Morphogenetic Protein 7↗

Microtubular aggregates in the rough endoplasmic reticulum of a myxoid chondrosarcoma.

A tumor with the light microscopic and histochemical characteristics of myxoid chondrosarcoma is examined ultrastructurally. Instead of the usual features of chondroblasts, the tumor cells exhibited prominent collections of long straight microtubules within the endoplasmic reticulum. This finding is compared with other previously reported tubular aggregates. The differential diagnosis and ultrastructure of myxoid chondrosarcoma are also discussed.

Chondrosarcoma↗