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National cancer database report on chondrosarcoma of the head and neck.

BACKGROUND: Management of chondrosarcoma of the head and neck is largely based on single-institution reports with small numbers accrued over several decades. METHODS: The American College of Surgeons' National Cancer Data Base included 400 cases of chondrosarcoma of the head and neck diagnosed between 1985 and 1995. Chi square analyses of selected contingency tables and Wilcoxon regression analyses of selected survival stratifications were performed. RESULTS: Histologic types included conventional (80.8%), myxoid (10.5%), and mesenchymal (8.8%). The mesenchymal and myxoid subtypes were rare among white patients (17.1%) and more common among African-American (31.8%) and Hispanic patients (44.9%). Treatment was most commonly surgery alone (59.5%) and surgery with irradiation (21.0%). Disease-specific survival was 87.2% at 5 years and 70.6% at 10 years. Worse 5-year survival was associated with higher grade (67.3%), regional or distant spread (71.0%), and the myxoid (45.0%) or mesenchymal (53.2%) subtypes. CONCLUSIONS: Chondrosarcoma of the head and neck encompasses a variety of lesions that differ substantially by demographic and tumor characteristics. Individual tumors can be classified further according to site of origin, histologic subtype, and tumor grade, which can be used to predict biologic behavior and prognosis.

Adult↗

3-D surface charges modulate protrusive and contractile contacts of chondrosarcoma cells.

Up to now, most of the studies addressing the critical roles played by protrusive and contractile cell-matrix contacts in cell adhesion, guidance, migration, matrix assembly, and activation of signaling molecules have been performed on two-dimensional surfaces. Here, we analysed the organization of chondrosarcoma cell contacts in a new three-dimensional environment made of titanium beads. Surface charges were modified by deposition of polyelectrolyte multilayer films built up by alternated polycations poly-(L-lysine) or poly(allylamine hydrochloride) and polyanions poly-(L-glutamic acid) or poly(sodium 4-styrenesulfonate). Negatively charged 3-D titanium surfaces amplified the occurrence and length of cell protrusions. These protrusions had pseudopod characteristics extended to 200 microm in length, growing off the substratum to distant beads. Pseudopod formation is inhibited by the exocytosis inhibitor concanamycin A and is triggered by a secreted factor. Chondrosarcoma cells adhering on uncoated or on negatively charged surfaces contained discrete focal spots of vinculin and actin cables. In cells plated onto these surfaces, phosphorylation of p44/42 MAPK/ERK was twofold increased. In contrast, no cytoskeletal vinculin and actin organization was observed when the surface was positively charged. These data suggest that chondrosarcoma cells adapt a more stable adhesion on uncoated or negatively charged surfaces. This point may be critical in tissue engineering strategies designed for cartilage repair.

Actins↗

Chondrosarcoma of calcanaeum in a 12-year-old male patient: a case report.

Chondrosarcoma is distinctly uncommon and tends to be located often in the extremities in young patients more than in its adult counterpart. Cartilaginous tumors involving the small bones of the hands and feet are benign tumors such as enchondromas, chondromyxoid fibroma (CMF), and chondroblastoma. Chondrosarcomas involving calcanaeum in young adults are largely covered in the literature as single case reports. A young 12-yr-male patient presented with complaints of pain and mild swelling in the ankle. Radiological examination revealed a dense irregular lesion in the calcanaeum. Fine-needle aspiration was performed and a possibility of chondrosarcoma was suspected, which later was confirmed on histopathological examination. The cytopathologist should be aware of the occurrence of malignant chondroid tumors in the younger age group at this rare site. Correlation to radiological findings is essential in these cases.

Biopsy, Fine-Needle↗

Biochemical characterization of long-term culture of the Swarm rat chondrosarcoma chondrocytes in agarose.

Difficulty in maintaining phenotypic stability of the Swarm rat chondrosarcoma in long-term monolayer cultures has prompted investigation of alternative conditions that would enable extended maintenance of these cells, permitting use of the tumor as a model system for the long-term study of proteoglycan metabolism. Morphological analysis of the growth of the chondrosarcoma chondrocytes in agarose has shown stability of the culture over a 20 day period with respect to the ability of the cells to proliferate and synthesize an Alcian blue-positive extracellular matrix. The present study confirms these findings through analysis of the growth characteristics of the culture and the pattern of proteoglycan and collagen synthesis. The chondrocytes actively synthesize a proteoglycan-rich matrix at a rate dependent on the initial plating density and concentration of serum in the culture medium. These factors similarly affect the proliferative capabilities of the culture as demonstrated by the growth curves obtained at different culture conditions. During 20 days in culture, the cells synthesize an aggregating chondroitin sulfate proteoglycan and collagen type II, typical of cartilage and this chondrosarcoma. In addition, small molecular weight proteoglycans were found to be present at concentrations of up to 10% of the total proteoglycan population. Degradative rates are slow, the proteoglycan half-life is about 30 days, but can be enhanced with retinol, reducing the half-life to 2 days.

Animals↗

Multidrug resistance-1 and p-glycoprotein in human chondrosarcoma cell lines: expression correlates with decreased intracellular doxorubicin and in vitro chemoresistance.

We report on two chondrosarcoma cell lines, FS and AQ, that may be used as models of multidrug resistance in chondrosarcoma. Multidrug resistance-1 expression was assayed with reverse transcription-polymerase chain reaction. Immunostaining for the multidrug resistance-1 product, P-glycoprotein, was performed with the monoclonal antibody C494. Intracellular levels of doxorubicin were measured by fluorescent emission at 590 nm after 1 hour of incubation with the agent and again after 1, 2, and 4-hour washout periods. Chemosensitivity was assayed by staining micropellet cultures of AQ and FS cells with fluorescein acetate before and after the cells were exposed to varying doses of doxorubicin for 48 hours. Cytotoxicity was assessed by comparison of computer-processed images before and after treatment. The FS cell line was positive for multidrug resistance-1 expression, stained heavily for P-glycoprotein, and had significantly lower intracellular levels of doxorubicin than the AQ cell line, which was negative for multidrug resistance-1 and P-glycoprotein. Chemosensitivity testing showed that the FS cell line was significantly more resistant to doxorubicin than was the AQ cell line at all doses tested. Our results show that multidrug resistance-1 expression in a human chondrosarcoma cell line results in resistance to doxorubicin in vitro.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Chondrosarcoma of the first metatarsal.

Chondrosarcoma of the first metatarsal was observed in an 84-year-old man. Chondrosarcoma of the small bones of the foot is comparatively rare. These tumors generally arise de novo rather than from a preexisting benign cartilage lesion. Pedal chondrosarcoma presents as a painful enlarging mass. Radiographs show lytic destruction of bone with or without calcification. The histological grade, location of the tumor, and adequacy of surgical excision are the major determinants of long-term survival.

Aged↗

Chondrosarcoma of the head and neck--the value of computed tomography.

Chondrosarcomas of the head and neck represent a small percentage and differ in their treatment and prognosis compared with chondrosarcomas elsewhere. Four different cases of chondrosarcoma are presented. One arose intracranially, two in the jaws, one of which followed irradiation for a retinoblastoma, and the last represents chondrosarcomatous transformation in cervical spine Paget disease which is exceptionally rare. Computer tomography (CT) plays an important role in delineating the extent of the tumor with visualization of bony destruction, associated soft-tissue mass, and calcification, information which is extremely important for surgical and therapeutic planning. CT can be vital in suggesting the best possible site for biopsy which is particularly important in this group of neoplasms where the histological diagnosis may be difficult.

Adult↗

Role of radionuclide imaging in the diagnosis of chondrosarcoma.

The diagnosis of chondrosarcoma may be difficult if there is an atypical radiographic appearance or an inconclusive biopsy. Radionuclide bone scans of 13 patients with chondrosarcoma were reviewed to assess if a pattern of scan features could be recognised in association with this tumour. A combination, including increased blood pool activity, moderate intensity of uptake, patchy uptake with cortical predominance of activity, minimal distortion of bony outline, and a well-defined scintigraphic margin, occurred regularly in the series. Recognition of this characteristic pattern of scintigraphic features in cases of suspected chondrosarcoma may assist in the diagnostic assessment.

Adolescent↗

Tumor-specific cytotoxic T lymphocyte responses against chondrosarcoma with HLA haplotype loss restricted by the remaining HLA class I allele.

Although loss of HLA expression by malignant cells has also been demonstrated, it has not been clarified how the loss of HLA expression observed in vitro actually results in immune escape. We demonstrated two major findings: (i) a part of chromosome 6 coding for HLA haplotypes was deleted from the genome of chondrosarcoma cell line, OUMS-27; furthermore, immunohistostaining for HLA-A11 showed that the original chondrosarcoma tissue lost the expression of HLA-A11, implicating that HLA haplotype loss was already present in the original tumor tissue and (2) HLA class I-restricted and autologous tumor-specific cytotoxic T cells (CTL) were generated from peripheral blood lymphocytes of the patient with chondrosarcoma, from whom OUMS-27 originated. This CTL line was maintained by weekly stimulation with OUMS-27, and lysed OUMS-27 in an HLA-A24 dependent manner but did not either K562 or autologous (EBV)-transformed B cells. These observations indicated that OUMS-27 and its original tumor are still immunogenic and can present antigen peptides with the remaining HLA-A24, even if HLA expression is partially lost. Tumor specific immunotherapy can be applied to the treatment of malignancies, even if HLA expression is partially lost.

Aged↗

Chondrocyte and chondrosarcoma cell integrins with affinity for collagen type II and their response to mechanical stress.

Mechanical stress is an important regulator of chondrocyte functions but the mechanisms by which chondrocytes sense mechanical signals are unknown. Receptors for matrix molecules are likely involved in the mechanical signaling. In the first part of this study we identified integrins with affinity for the cartilage-specific collagen type II. We report that the collagen-binding integrins alpha 1 beta 1 and alpha 2 beta 1 isolated from bovine chondrocytes or human chondrosarcoma cells bound collagen type II as judged from affinity chromatography. The integrins alpha 3 beta 1 or alpha 9 beta 1 did not bind collagen type II-Sepharose. In the second part of the study we investigated the effect of mechanical stress on expression of matrix molecules and integrin subunits. Chondrocytes and chondrosarcoma cells, cultured on uncoated flexible silicone membranes in the presence of serum, were exposed to mechanical stress by the Flexercell system. Dynamic stimulation of chondrocytes for 3 h increased the mRNA expression of collagen type II and aggrecan as judged by Northern blotting, while the beta 1-integrin subunit was not changed. When chondrosarcoma cells were exposed to mechanical stimulation under the same conditions, mRNA expression of alpha 5 was found to increase while beta 1, alpha 2, and alpha v did not increase to significant levels. In another study the effect of mechanical stress on integrins was investigated when the cells were cultured on collagen type II-coated flex-dishes. Three hours of dynamic stress increased the mRNA expression of alpha 2-integrin subunit while the level of mRNA for integrin subunits beta 1, alpha 1, alpha 5, and alpha v showed no or small changes, indicating that matrix components may modulate the expression of integrins during mechanical stress.

Aggrecans↗

Giant-cell tumor and chondrosarcomas: grading, treatment and results (studies of 209 and 131 cases).

The Author reviews 209 cases of giant-cell tumor (follow-up 3-42 years in 130 cases) and 131 chondrosarcomas (70 central, 50 peripheral, 11 periosteal; follow-up 10-32 years in 63 cases). Giant-cell tumors are graded into three radiographic types (calm, active, aggressive) and three histologic types (typical, aggressive, sarcoma). Chondrosarcomas were also graded into three radiographic and three histologic types (grades I, II, III). Incidence and mutual relationships of radiographic and histologic grades are presented. In recurrences it is possible to observe a progression of malignancy in giant-cell tumor and - more often - in chondrosarcomas. Results are related to the radiographic and histologic grading and to the type of treatment. Indications for treatment are given according to the experience gained from this study. The Author enumerates the surgical techniques he has found most suitable for the conservative treatment of these tumors when resection is indicated.

Bone Neoplasms↗

Extensive skeletal metastases from chondrosarcoma without pulmonary involvement.

Among 251 patients who presented to our orthopedic oncology unit over the last 20 years with chondrosarcoma, we identified two patients with low to intermediate grade conventional chondrosarcoma who developed multifocal bone metastases in the absence of pulmonary spread. The metastatic lesions were of a similar histologic grade to the primary site. One of the patients had synchronous foci, while the other developed the bone lesions 3 years after initial presentation. The unusual behavior of these cases, as well as the possibility that they may represent instances of multicentric chondrosarcoma, is discussed.

Adult↗

Chondrosarcoma of the first metatarsal--primary or secondary to enchondroma?

Enchondromas are said to be extremely rare precursors of secondary chondrosarcomas. Peripheral enchondromas of the hand and foot may be considered as benign, even when the histomorphological study reveals pleomorphic features with atypical nuclei. Our case deals with a 56 year old woman who had an enchondroma of the first metatarsal. Its distinct histopathological signs of focal malignant transformation were only seen in later review. Nine months after curettage and autologous bone-grafting a chondrosarcoma was diagnosed. The enbloc-resection of the medial foot provided adequate surgical treatment of the chondrosarcoma.

Bone Transplantation↗

Maffucci's syndrome combined with dedifferentiated chondrosarcoma.

We report a rare case of Maffucci's syndrome combined with dedifferentiated chondrosarcoma in the right shoulder girdle developing from pre-existing enchondroma. In this case, magnetic resonance imaging was useful in diagnosing dedifferentiated chondrosarcoma before surgery. T2-weighted imaging was used to distinguish between the cartilaginous component and the dedifferentiated one. Histologically, there was enchondroma in the humerus and grade 2 chondrosarcoma in the scapula. Further, the dedifferentiated tumor had three mesenchymal elements: osteosarcoma, malignant fibrous histiocytoma, and fibrosarcoma. This histological heterogenicity may be due to mesodermal dysplasia of Maffucci's syndrome.

Aged↗

Chordoid sarcoma (extraskeletal myxoid chondrosarcoma).

Evaluation of a series of 12 chordoid sarcomas suggests that there is a wider range of histological features in this entity then previously appreciated. Six of the lesions had a typical tumor cell organization and a mixture of cellular and myxoid stromal components, while the remaining cases were atypical because of a more solid growth pattern. Four of the 12 cases, that included both typically myxoid and more cellular examples, had small foci with hyalinized stroma segragating individual or small groups of tumor cells with and without lacunar spaces. Two atypical cases revealed more extensive and obvious chondrocytic differentiation in recurrent or metastatic lesions and in one of these, the histological pattern was that of mesenchymal chondrosarcoma. Ultrastructural examination of three cases revealed fine structural features of both the tumor cell population and extracellular matrix compatible with chondrocytic differentiation. Results of light and electron microscopy of this series of chordoid sarcoma add further support for categorizing this tumor with other malignant chondrocytic neoplasms. It is probable that chordoid sarcoma and extraskeletal myxoid chondrosarcoma represent the same entity and that this lesion has a close histogenetic relationship to mesenchymal chondrosarcoma.

Adult↗

Chondroid chordoma versus low-grade chondrosarcoma of the base of the skull: can immunohistochemistry resolve the controversy?

The classification of cartilaginous tumors of the skull base, including chondroid chordoma and chondrosarcoma remains the subject of controversy. Critical review of the literature and our own experience of chordomas and cartilaginous tumors of the skull base led to the following conclusions: 1) Chondrosarcoma of the skull base is a distinct clinicopathological entity. The immunohistochemical staining pattern (cytokeratin negative, epithelial membrane antigen (EMA) negative) can be helpful in distinguishing it from chordoma with chondroid differentiation (cytokeratin positive, EMA positive). 2) The chondroid chordomas originally described by Heffelfinger et al. may have included some true chondrosarcomas with focal areas of myxoid chordomalike appearance. 3) Focal chondroid differentiation in chordoma is not such a rare phenomenon. Further study is needed to define whether chordoma with chondroid foci should be separated out from conventional chordoma as a distinct entity with a better prognosis.

Adolescent↗

Silver-stained nucleolar organizer proteins in chondrosarcoma.

Silver-stained nucleolar proteins (AgNORs) were counted in primary chondrosarcomas of three histologic grades and in metastatic chondrosarcomatous lesions in the lung. The AgNOR numbers of neoplastic cells in primary tumors increased stepwise from grade 1 (4.42 +/- 1.11) through grade 2 (4.94 +/- 1.31) to grade 3 (6.97 +/- 1.10). There was a significant difference in AgNOR numbers between grade 3 and both grades 1 and 2 (p less than 0.001). Furthermore, the mean number of AgNORs in metastatic lesions (9.75 +/- 0.83) was significantly higher than that in primary sites (p less than 0.001). The number of AgNORs therefore reflects the grade of the chondrosarcoma. The results in the present study indicate that silver colloid staining is a useful technique for determining the histologic grade and evaluating the proliferative activity of chondrosarcomas.

Antigens, Nuclear↗

Bone scintigraphic and CT evaluation of chondrosarcoma of the rib: correlation with histological grade in 6 cases.

OBJECTIVE: The objective of this study is to assess the value of CT and bone scintigraphic findings for grading of rib chondrosarcoma. METHODS: Included in this study were six cases of histologically proven chondrosarcoma of the rib, in which bone scintigraphy and/or CT was performed. Correlation of histologic grade (I-III), tumor size on CT, CT grading (modified Brown's system), the pattern (nodular or peripheral, presence or absence of extended uptake pattern) and the intensity (Simon and Kirchner's grade, 0-4) of scintigraphic uptake were assessed. RESULTS: CT grade was III, except for one case of dedifferentiated chondrosarcoma. Scintigraphic grade was 3 or 4 in all the cases. CONCLUSION: The patterns of CT and bone scintigraphic findings more likely reflect the size of the mass and ossification, and are not well correlated with the histological grading.

Adult↗