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1.
Ann R Coll Surg Engl ; 94(8): e240-2, 2012 Nov.
Article in English | MEDLINE | ID: mdl-23131213

ABSTRACT

Laryngeal chondrosarcomas are a very rare malignancy with less than 150 cases reported in the literature. Of these, the epiglottis is the most unusual primary neoplastic subsite. Uncertainties arise owing to the extremely rare nature of the condition with regard to treatment and investigation for metastases in overtly low grade cases. We present the case of a 62-year-old woman with a low grade chondrosarcoma, arising from the tip of the epiglottis, presenting with dysphagia but no other symptoms.


Subject(s)
Chondrosarcoma/surgery , Epiglottis , Laryngeal Neoplasms/surgery , Rare Diseases/surgery , Chondrosarcoma/ultrastructure , Deglutition Disorders/etiology , Deglutition Disorders/pathology , Female , Humans , Laryngeal Neoplasms/ultrastructure , Magnetic Resonance Imaging , Microscopy, Electron, Scanning , Middle Aged , Rare Diseases/pathology , Treatment Outcome
2.
Med Mol Morphol ; 42(3): 180-4, 2009 Sep.
Article in English | MEDLINE | ID: mdl-19784746

ABSTRACT

A case of extraskeletal myxoid chondrosarcoma (ESMC), which developed in the right thigh of a middle-aged Japanese woman, was studied using immunohistochemistry, conventional electron microscopy, and the quick-freezing and deep-etching (QF-DE) method. In addition to typical light microscopic findings of ESMC, conventional electron microscopy indicated that the tumor cells had features of chondrocytes. Immunohistochemically, the tumor cells showed a positive immunoreaction for S100 protein. A diagnosis of ESMC was made. An interesting observation was the ultrastructural features of collagen fibrils in the myxoid matrix highlighted by the QF-DE method. These collagen fibrils consisted of relatively thin collagen (20-35 nm) with pleated surface structures. The surface striation at 65 nm was obscure. We consider that such a finding of collagen fibrils identified by the QF-DE method is one of the characteristics of the myxoid matrix of ESMC, and this is useful for the differential diagnosis of myxoid soft tissue tumors.


Subject(s)
Chondrosarcoma/diagnosis , Chondrosarcoma/pathology , Freeze Etching/methods , Soft Tissue Neoplasms/diagnosis , Soft Tissue Neoplasms/pathology , Chondrosarcoma/ultrastructure , Female , Humans , Microscopy, Electron , Middle Aged , Soft Tissue Neoplasms/ultrastructure , Thigh/pathology
3.
Med Mol Morphol ; 42(3): 185-8, 2009 Sep.
Article in English | MEDLINE | ID: mdl-19784747

ABSTRACT

Clear cell chondrosarcoma (CCC) is a rare neoplasm. We report here a case of CCC. A 67-year-old Japanese man presented with right arthralgia for 1 year, and histological examination of the subsequent surgical resection of the right femoral bone showed the finding of CCC. Ultrastructurally, most organelles were observed in the perinuclear area. Clear neoplastic cells contained many glycogen particles in the area of the cytoplasm lacking organelles, although glycogen particles overall seemed to be evenly distributed in the cytoplasm. Some mitochondria, Golgi complex, actin-like filaments, and rough endoplasmic reticulum were also demonstrated in the cytoplasm of clear cells. Well-developed microvilli were also seen on the surface of neoplastic cells. These structures in neoplastic cells corresponded notably to structures of normal chondrocytes. Finally, our ultrastructural findings support further evidence that clear cells in CCC may show chondrocyte differentiation and a lack of an organelles area as well as abundant glycogen particles, may contribute to the clear cell morphology in CCC.


Subject(s)
Bone Neoplasms/ultrastructure , Chondrosarcoma/ultrastructure , Aged , Bone Neoplasms/pathology , Bone Neoplasms/surgery , Chondrosarcoma/pathology , Chondrosarcoma/surgery , Femur Head/pathology , Femur Head/surgery , Humans , Male
4.
Int J Mol Med ; 24(4): 427-35, 2009 Oct.
Article in English | MEDLINE | ID: mdl-19724881

ABSTRACT

Dedifferentiated chondrosarcoma (CS) is a rare, highly malignant variant of CS in which a high-grade sarcoma coexists with a low-grade chondroid tumor. In this study, a novel dedifferentiated CS cell line, MS0812, was spontaneously established from mutated human embryonic muscle cells. Several features of the cell line were investigated, including growth characteristics, cytogenetics, electron microscopic features, expression of various antigenic markers and tumor formation. MS0812 has been cultured continuously for more than 3 years. The growth characteristics of MS0812 are similar to the immortalized cell lines as reported. The cell line exhibited complex karyotypes and hyperploidy, the chromosome number ranged from 50 to 158. MS0812 was positive for vimentin, desmin and muscle actin, indicating their muscle origin. With specific inductive condition, MS0812 differentiates into neural cells and adipocytes. Deletion of the p16 gene, which seemed to play a major role in the malignant phenotype of this cell line, was confirmed by PCR and immunocytochemistry. MS0812 formed tumors in nude mice, and the tumor revealed a fibrosarcoma with chondroid components, which were consistent with dedifferentiated CS as reported. Chondroid components showed metachromasia by Alcian blue and toluidine blue and were S100 and collagen-II positive. To our knowledge, this is the first report of the establishment of a human dedifferentiated chondrosarcoma from mutated human embryonic muscle cells, and it is a useful model for the study of the molecular pathogenesis of dedifferentiated CS.


Subject(s)
Cell Differentiation/physiology , Chondrosarcoma/genetics , Chondrosarcoma/pathology , Actins/metabolism , Adipogenesis/genetics , Adipogenesis/physiology , Animals , Cell Differentiation/genetics , Cell Line, Tumor , Chondrosarcoma/metabolism , Chondrosarcoma/ultrastructure , Desmin/metabolism , Female , Humans , Karyotyping , Mice , Mice, Nude , Microscopy, Electron, Transmission , Mutation , Polymerase Chain Reaction , Pregnancy , Vimentin/metabolism
5.
Ultrastruct Pathol ; 31(4): 293-302, 2007.
Article in English | MEDLINE | ID: mdl-17786830

ABSTRACT

A middle-aged Japanese woman visited the Orthopedics Department of Nihon University Nerima Hikarigaoka Hospital complaining of pain in the left hip joint that had started approximately 8 months earlier. Following several examinations, including imaging diagnoses, an incisional biopsy demonstrated a malignant acetabular bone tumor, which was removed and examined by a quick-freezing and deep-etching (QF-DE) method, conventional electron microscopy, and light microscopy. Histologically, the tumor was a chondrosarcoma with marked myxoid changes. An interesting extracellular matrix was observed by the QF-DE method. The myxoid area consisted of a fine meshwork of proteoglycans (PG) without obvious aggrecans, which resembled that of PG usually present in the pericellular matrix of normal cartilage. Thin collagen fibrils with pleated surface structures of regular periodicity were also seen, which were sparsely distributed in wide areas except for the pericellular matrix. These collagen fibrils were of the type that are mainly located in the pericellular side of the territorial matrix in normal cartilage. A myxoid matrix consisting of thin collagen fibrils on the background of pericellular type PG suggested that the myxoid matrix in the chondrosarcoma resembled those of the pericellular and pericellular sides of the territorial matrices in normal cartilage.


Subject(s)
Acetabulum/pathology , Artifacts , Bone Neoplasms/ultrastructure , Chondrosarcoma/ultrastructure , Freeze Etching/methods , Microscopy, Electron, Transmission , Comorbidity , Female , Humans , Middle Aged , Schizophrenia/pathology
6.
Biophys J ; 92(5): 1784-91, 2007 Mar 01.
Article in English | MEDLINE | ID: mdl-17158567

ABSTRACT

Atomic force microscopy has rapidly become a valuable tool for quantifying the biophysical properties of single cells. The interpretation of atomic force microscopy-based indentation tests, however, is highly dependent on the use of an appropriate theoretical model of the testing configuration. In this study, a novel, thin-layer viscoelastic model for stress relaxation was developed to quantify the mechanical properties of chondrosarcoma cells in different configurations to examine the hypothesis that viscoelastic properties reflect the metastatic potential and invasiveness of the cell using three well-characterized human chondrosarcoma cell lines (JJ012, FS090, 105KC) that show increasing chondrocytic differentiation and decreasing malignancy, respectively. Single-cell stress relaxation tests were conducted at 2 h and 2 days after plating to determine cell mechanical properties in either spherical or spread morphologies and analyzed using the new theoretical model. At both time points, JJ012 cells had the lowest moduli of the cell lines examined, whereas FS090 typically had the highest. At 2 days, all cells showed an increase in stiffness and a decrease in apparent viscosity compared to the 2-h time point. Fluorescent labeling showed that the F-actin structure in spread cells was significantly different between FS090 cells and JJ012/105KC cells. Taken together with results of previous studies, these findings indicate that cell transformation and tumorigenicity are associated with a decrease in cell modulus and apparent viscosity, suggesting that cell mechanical properties may provide insight into the metastatic potential and invasiveness of a cell.


Subject(s)
Chondrosarcoma/chemistry , Microscopy, Atomic Force/methods , Actins/chemistry , Actins/ultrastructure , Cell Line, Tumor , Chondrosarcoma/ultrastructure , Elasticity , Humans , Models, Biological , Neoplasm Invasiveness , Viscosity
7.
Pathol Int ; 55(8): 453-63, 2005 Aug.
Article in English | MEDLINE | ID: mdl-15998372

ABSTRACT

Extraskeletal myxoid chondrosarcoma (EMC) is a rare soft-tissue sarcoma characterized by distinctive morphological and cytogenetical features. As its name implies, EMC was believed to represent a variant of soft-tissue chondrosarcoma owing to its histological resemblance to chondroblastic tissue in the early stages of cartilage development or chondroid tumors such as skeletal chondrosarcoma. However, the chondroid nature has been a subject of controversy, and its line of differentiation remains to be determined. Consequently, the tumor is provisionally classified into a group of tumors of uncertain differentiation in the revised World Health Organization classification of tumors of soft tissue and bone. Moreover, immunohistochemical and ultrastructural features of neural or neuroendocrine differentiation have been recently reported in a subset of EMC, providing a new insight into their histogenetic nature. Chromosomal rearrangements involving 9q22, such as t(9;22)(q22;q12), and resultant NR4A3 fusion genes are tumor-type specific or pathognomotic for this entity and are assumed to play an important role in the development of EMC. Although the biological mechanisms and functions are largely unknown, the NR4A3-related pathway is considered a potential molecular target for future therapeutic intervention. Because of its protracted but resilient nature, a tenacious and long-term follow up is necessary for any patient.


Subject(s)
Chondrosarcoma/pathology , Chromosome Aberrations , Soft Tissue Neoplasms/pathology , Chondrosarcoma/genetics , Chondrosarcoma/ultrastructure , Humans , Microscopy, Electron , Soft Tissue Neoplasms/genetics , Soft Tissue Neoplasms/ultrastructure , Translocation, Genetic , Trisomy
8.
Virchows Arch ; 446(3): 287-99, 2005 Mar.
Article in English | MEDLINE | ID: mdl-15731924

ABSTRACT

The permanent human cell line C3842 was established from a secondary chondrosarcoma in a typical case of Ollier's disease. In the present study, we analyzed the morphological, cytogenetic and molecular biological characteristics of the cultured cells in comparison with the original tumor and investigated the invasion properties of the tumor model using functional imaging of proteolysis, matrigel assay and chick chorioallantoic membrane assay. C3842 cells exhibit the typical features of malignant cartilage tumor cells in vitro, including the expression of collagen types II, IX, XI and aggrecan. The proteolytic ability of C3842 cells is attributed to the expression of several proteases, such as cathepsin B, urokinase plasminogen activator and matrix-metalloproteinase-2, which enable the cells to degrade collagen type I and to permeate matrigel matrix. In accordance with the biological features in vivo, C3842 cells are not able to invade through the epithelium of the chick chorioallantoic membrane. In conclusion, the cell line C3842 provides the first model of a secondary chondrosarcoma in Ollier's disease in vitro, which is characterized by distinct features of such malignant cartilage tumors.


Subject(s)
Bone Neoplasms/complications , Cell Line, Tumor/physiology , Chondrosarcoma/complications , Enchondromatosis/complications , Adult , Animals , Bone Neoplasms/pathology , Bone Neoplasms/ultrastructure , Cell Line, Tumor/ultrastructure , Chondrosarcoma/pathology , Chondrosarcoma/ultrastructure , Chorioallantoic Membrane , Chromosome Aberrations , Humans , Immunohistochemistry , In Situ Hybridization, Fluorescence , Male , Neoplasm Invasiveness , Polymorphism, Single-Stranded Conformational , Reverse Transcriptase Polymerase Chain Reaction
9.
Iowa Orthop J ; 24: 33-5, 2004.
Article in English | MEDLINE | ID: mdl-15296203

ABSTRACT

Chondrosarcoma remains one of the most difficult clinical conundrums of orthopaedic pathology, with wide variation in clinical course. The natural history of chondrosarcoma ranges from slow indolent growth without metastasis over years to rapid proliferation and lethal metastasis. Molecular regulatory events in the growth of these neoplasms are poorly understood. Of the Swarm rat chondrosarcoma, originating from a single neoplasm in a Sprague-Dawley rat more than thirty-five years ago, two populations were identified with different growth properties. These two Swarm chondrosarcoma lines were characterized for growth properties, histomorphometric and ultrastructural integrity, and the ability for proteoglycans to form aggregates with hyaluronan. After careful comparison, no obvious clues to the variation in growth rate were noted. Further molecular analyses may lead to better understanding of the differential growth properties of these cell lines. Understanding the mechanisms involved in differential growth rates may lead to clinically applicable clues to predict clinical behavior of chondrosarcomas in humans.


Subject(s)
Bone Neoplasms/pathology , Cell Line, Tumor/pathology , Chondrosarcoma/pathology , Animals , Bone Neoplasms/ultrastructure , Cell Line, Tumor/ultrastructure , Chondrosarcoma/ultrastructure , Female , Rats , Rats, Sprague-Dawley
10.
Cell Motil Cytoskeleton ; 56(3): 147-58, 2003 Nov.
Article in English | MEDLINE | ID: mdl-14569595

ABSTRACT

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.


Subject(s)
Cell Communication , Cell Culture Techniques/methods , Chondrosarcoma/ultrastructure , Pseudopodia/ultrastructure , Actins/metabolism , Blotting, Western , Cell Adhesion/physiology , Cell Line, Tumor , Chondrosarcoma/metabolism , Fluorescent Antibody Technique , Humans , Mitogen-Activated Protein Kinase 3 , Mitogen-Activated Protein Kinases/metabolism , Titanium , Tubulin/metabolism , Vinculin/metabolism
11.
Lab Invest ; 83(6): 877-87, 2003 Jun.
Article in English | MEDLINE | ID: mdl-12808123

ABSTRACT

Chondrosarcomas are malignant cartilage-forming tumors that represent the second most common malignant solid tumor of bone. These biologically poorly understood neoplasms vary considerably in clinical presentation and biologic behavior. Chemotherapy and radiation therapy are generally ineffective. Here we describe the establishment and characterization of a new human chondrosarcoma cell line named ch-2879, and we compare the cell line with its tumor of origin. The cell line was established from a recurrent grade 3 chondrosarcoma of the chest wall and characterized by growth kinetics and morphologic studies. Immunocytochemistry and RT-PCR were performed to examine the expression of cartilage-specific phenotypes. Genetic characterization was performed using cytogenetics, fluorescence in situ hybridization, flow cytometry, and molecular techniques for analysis of the genes implicated in cell cycle control, amplification of MDM2, CDK4, and Cyclin D1, and mutations in the p53 gene. ch-2879 cells were subcultured for more than 80 passages. They expressed vimentin, HNK-1, HBA-71, Ki-67, cyclin D1, Fli-1, S-100, p21, p27, and p53 and were negative for cytokeratin, EMA, p14, p16, MDM2, Rb, and c-erb-b2 antigens. Cytogenetically the recurrent tumor showed a hyperhaploid karyotype with clonal numerical and structural abnormalities. The sole structural abnormality was a chromosome derivative of a t(1;21) translocation. The cell line at passage 3 showed two populations: the hyperhaploid and an exactly duplicated, hypotriploid population. After the 18th passage, only the hypotriploid population was present. The cells expressed collagen 2. Molecular comparison of the primary and recurrent tumor evidenced an in vivo molecular change consisting of a deletion of 9p21 genes in the recurrence, probably caused by a selection process. Because of its gene expression profile, including expression of genes implicated in chondrogenesis in uncoated plastic dishes, this cell line may prove useful for cellular and molecular studies as well as studies of chondrosarcoma characterization and treatment.


Subject(s)
Bone Neoplasms/genetics , Bone Neoplasms/pathology , Chondrosarcoma/genetics , Chondrosarcoma/pathology , Bone Neoplasms/ultrastructure , Cell Culture Techniques/methods , Chondrosarcoma/ultrastructure , Chromosome Aberrations , Flow Cytometry , Humans , Karyotyping , Metaphase , Microscopy, Electron , Tumor Cells, Cultured
12.
Diagn Cytopathol ; 28(1): 13-7, 2003 Jan.
Article in English | MEDLINE | ID: mdl-12508176

ABSTRACT

A consecutive series of 47 chondrosarcomas was reviewed to identify the most useful criteria for cytological diagnosis, and grading in comparison to histology grade. This series includes 39 evaluable cases, including 2 patients with Ollier's disease and 2 with extraskeletal chondrosarcomas. Eight cases were excluded because of lack of histologic confirmation (3). nondiagnostic cytology (4). and one inconclusive histologic diagnosis. The cytologic diagnosis of these tumors was based on the identification of chondrocytes and a chondromyxoid stroma. The chondrocytes often showed double nuclei (34/39) and macronucleoli (20/39). Nuclear atypia in terms of distinct variation in size was less common (16/39). Cytoplasmic granules and vacuoles were often seen (34/39 and 29/39, respectively). In smears, chondroid fragments and a chondromyxoid background were seen in a majority of cases (36/39 and 30/39, respectively). By grade, concordance with histology was present in 4/7 grade I tumors, 26/29 grades II-III, and 5/5 grade IV, respectively.


Subject(s)
Bone Neoplasms/diagnosis , Chondrosarcoma/diagnosis , Adolescent , Adult , Aged , Biopsy, Needle , Bone Neoplasms/ultrastructure , Cell Nucleus/pathology , Chondrosarcoma/ultrastructure , Cytoplasm/pathology , Female , Humans , Male , Reproducibility of Results , Retrospective Studies , Soft Tissue Neoplasms/diagnosis , Soft Tissue Neoplasms/ultrastructure
13.
Br J Cancer ; 86(8): 1303-9, 2002 Apr 22.
Article in English | MEDLINE | ID: mdl-11953889

ABSTRACT

A rare immunohistochemical study using 28 surgical sections of human chondrosarcoma revealed that 67.9% of tumour cells had weak (10-40%) or strong (>40%) positive immunoreaction for peroxisome proliferator-activated receptor-gamma. The expression of peroxisome proliferator-activated receptor-gamma mRNA and protein in human chondrosarcoma cell line OUMS-27 was also determined by reverse transcription-polymerase chain reaction and immunocytochemistry, respectively. Furthermore, the effects of peroxisome proliferator-activated receptor-gamma ligands on cell proliferation and survival were investigated in OUMS-27 cells. Pioglitazone, a selective ligand for peroxisome proliferator-activated receptor-gamma, and 15-deoxy-Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)), a putative endogenous ligand for peroxisome proliferator-activated receptor-gamma, inhibited the proliferation of OUMS-27 cells in a dose-dependent manner. The mechanism of cytotoxic effects of 15d-PGJ(2) was via apoptosis as shown by DNA fragmentation using TUNEL stain and DNA ladder formation, and by ultrastructural analysis using transmission electron microscopy. Flow-cytometric analysis using annexin-V-fluorescein and propidium iodide detected the early change of apoptosis, as well as necrosis of OUMS-27 cells at 4 h after co-incubation with 15d-PGJ(2). These results suggest that peroxisome proliferator-activated receptor-gamma may play a significant role in the pathogenesis of chondrosarcoma, and peroxisome proliferator-activated receptor-gamma ligands, especially 15d-PGJ(2), may be of therapeutic value in the treatment of human chondrosarcoma.


Subject(s)
Apoptosis , Chondrosarcoma/metabolism , Chondrosarcoma/pathology , Prostaglandin D2/analogs & derivatives , Receptors, Cytoplasmic and Nuclear/metabolism , Thiazolidinediones , Transcription Factors/metabolism , Apoptosis/drug effects , Cell Cycle/drug effects , Cell Division/drug effects , Cell Survival , Chondrosarcoma/ultrastructure , Flow Cytometry , Humans , Male , Microscopy, Electron , Pioglitazone , Prostaglandin D2/pharmacology , RNA, Messenger/genetics , RNA, Messenger/metabolism , Receptors, Cytoplasmic and Nuclear/antagonists & inhibitors , Receptors, Cytoplasmic and Nuclear/genetics , Reverse Transcriptase Polymerase Chain Reaction , Thiazoles/pharmacology , Transcription Factors/antagonists & inhibitors , Transcription Factors/genetics , Tumor Cells, Cultured
14.
Histopathology ; 39(5): 514-24, 2001 Nov.
Article in English | MEDLINE | ID: mdl-11737310

ABSTRACT

AIMS: Extraskeletal myxoid chondrosarcoma is a rare low-grade soft-tissue sarcoma with locally aggressive and metastasizing potential. Extraskeletal myxoid chondrosarcoma has distinctive clinical, light microscopic, immunophenotypic, cytogenetic and ultrastructural features. Evidence that extraskeletal myxoid chondrosarcoma often shows neuroendocrine features was first provided by Chhieng et al. on the basis of an immunohistochemical and ultrastructural study of seven cases. Our study aims to further confirm by immunohistochemistry and ultrastructural studies, including immunoelectron microscopy, that extraskeletal myxoid chondrosarcoma indeed may show neuroendocrine differentiation. METHODS AND RESULTS: Fifteen cases of extraskeletal myxoid chondrosarcoma and seven control cases of skeletal chondrosarcomas were studied. Extensive immunohistochemical analysis was performed in all cases and ultrastructural studies were done in 11 extraskeletal myxoid chondrosarcomas and three skeletal chondrosarcomas. Immunoelectron microscopy was performed on one case each of extraskeletal myxoid chondrosarcoma and skeletal chondrosarcoma. Extraskeletal myxoid chondrosarcomas expressed neuron-specific enolase (100%), synaptophysin (87%), S100 (50%), PGP 9.5 (40%), and epithelial membrane antigen (25%). Co-expression of synaptophysin and PGP 9.5 was observed in six tumours. Skeletal chondrosarcomas showed expression of S100 protein, vimentin and neuron-specific enolase in all cases. Synaptophysin, chromogranin and PGP 9.5 were not expressed in any skeletal chondrosarcoma case. Ultrastructurally, extraskeletal myxoid chondrosarcoma was characterized by distinct cords of cells immersed in a glycosaminoglycan-rich matrix. The cells were rich in mitochondria, had well-developed Golgi apparatus and there were numerous smooth vesicles. In three cases there were easily found 140-180 nm diameter membrane-bound dense-core granules in cell bodies and in processes, unrelated to the Golgi, compatible with neurosecretory granules. Fewer such granules were present in the remaining extraskeletal myxoid chondrosarcoma cases, three of which also contained intracisternal tubules typical of extraskeletal myxoid chondrosarcoma. The skeletal chondrosarcomas had scalloped cell surfaces, prominent rough endoplasmic reticulum focally distended with secretory product, and lacked neurosecretory granules. Intermediate filaments were prominent in both extraskeletal myxoid chondrosarcoma and skeletal chondrosarcomas. Immunoelectron microscopy showed synaptophysin expression in the extraskeletal myxoid chondrosarcoma but not in the skeletal chondrosarcoma case. CONCLUSIONS: This study confirms that a substantial proportion of extraskeletal myxoid chondrosarcomas show immunophenotypic and/or ultrastructural evidence of neuroendocrine differentiation, and are unlikely to be related to conventional skeletal chondrosarcomas.


Subject(s)
Chondrosarcoma/pathology , Soft Tissue Neoplasms/pathology , Adult , Aged , Bone Neoplasms/metabolism , Bone Neoplasms/pathology , Bone Neoplasms/ultrastructure , Carcinoma, Neuroendocrine/metabolism , Carcinoma, Neuroendocrine/pathology , Carcinoma, Neuroendocrine/ultrastructure , Chondrosarcoma/metabolism , Chondrosarcoma/ultrastructure , Chromogranins/analysis , Female , Humans , Immunohistochemistry , Male , Microscopy, Electron , Middle Aged , Mucin-1/analysis , Phosphopyruvate Hydratase/analysis , S100 Proteins/analysis , Soft Tissue Neoplasms/metabolism , Soft Tissue Neoplasms/ultrastructure , Synaptophysin/analysis , Thiolester Hydrolases/analysis , Ubiquitin Thiolesterase , Vimentin/analysis
15.
Otolaryngol Pol ; 54(6): 703-8, 2000.
Article in English | MEDLINE | ID: mdl-11265380

ABSTRACT

Most common among the laryngeal sarcomas is the chondrosarcoma. The difficulties in differentiation between benign and malignant behavior of cartilaginous tumors are responsible for the danger of misinterpretation of chondrosarcoma as chondroma. A case of a laryngeal chondrosarcoma is presented examined by light and electron microscopy to determine if the ultrastructure of chondrosarcoma could be helpful in the correct diagnosis. The cells and their formation play a more important role than the extracellular matrix in the differentiation of tumor's behavior. As special criterias of malignancy by electron microscopy are the presence of dominant mitochondria, fat vacuoles, dilated rough endoplasmatic reticulum and the irregular shape of chondrocytes. The knowledge of the ultrastructure of chondrosarcomas may be helpful to distinguish between a benign chondroma and low-grade chondrosarcoma, especially when only small tumor biopsies are valuable.


Subject(s)
Chondrosarcoma/ultrastructure , Laryngeal Neoplasms/ultrastructure , Aged , Cell Nucleus/ultrastructure , Chondrocytes/ultrastructure , Chondrosarcoma/blood supply , Collagen/ultrastructure , Cytoplasm/ultrastructure , Endoplasmic Reticulum, Rough/ultrastructure , Extracellular Matrix/ultrastructure , Humans , Laryngeal Neoplasms/blood supply , Male , Microscopy, Electron , Mitochondria/ultrastructure
16.
Virchows Arch ; 435(5): 524-30, 1999 Nov.
Article in English | MEDLINE | ID: mdl-10592057

ABSTRACT

Extraskeletal myxoid chondrosarcoma is a rare malignant soft tissue tumour that can be difficult to diagnose correctly, especially preoperatively. We describe four cases of extraskeletal myxoid chondrosarcoma of the extremities diagnosed by a multimodal approach. The cytological examination of fine-needle aspirates showed small and round, mildly pleomorphic cells lying in sheets and cords, but also dispersed within a myxoid and metachromatic intercellular substance. Histological, electron microscopic and immunocytochemical examination also yielded findings compatible with the diagnosis of extraskeletal myxoid chondrosarcoma. Cytogenetic analysis demonstrated a t(9;22)(q22;q12) in two tumours and a t(9;17)(q22;q11) in the third and fourth. The translocation t(9;22)(q22;q12) has been described repeatedly in extraskeletal myxoid chondrosarcoma but never in other tumours; hence, the detection of this pathognomonic chromosome abnormality in short-term cultured cells from fine-needle aspirates verified the diagnosis in two of the cases. The t(9;17)(q22;q11) found in the last two cases probably represents a new cytogenetic subgroup of extraskeletal myxoid chondrosarcoma as it, too, is unknown in other contexts. The multimodal approach taken in these four cases enabled a definite diagnosis of a rare malignant tumour whose cytological and histological features alone are usually not sufficiently distinct to rule out other differential diagnostic possibilities.


Subject(s)
Chondrosarcoma/diagnosis , Chondrosarcoma/genetics , Chromosomes, Human, Pair 17/genetics , Chromosomes, Human, Pair 9/genetics , Muscle Neoplasms/genetics , Translocation, Genetic , Aged , Chondrosarcoma/classification , Chondrosarcoma/ultrastructure , Diagnosis, Differential , Histocytochemistry , Humans , Immunohistochemistry , Karyotyping , Male , Microscopy, Electron , Middle Aged , Muscle Neoplasms/classification , Muscle Neoplasms/diagnosis , Muscle Neoplasms/ultrastructure
17.
Histopathology ; 35(3): 201-8, 1999 Sep.
Article in English | MEDLINE | ID: mdl-10469211

ABSTRACT

AIMS: Extraskeletal myxoid chondrosarcoma is typically a low-to-intermediate grade sarcoma that is associated with a prolonged clinical course. High-grade forms are rare and not well characterized. In this series we report the clinicopathological, immunohistochemical and ultrastructural findings in four cases of high-grade extraskeletal myxoid chondrosarcoma. METHODS AND RESULTS: The patients were three men and one woman (ages 34-73 years) with tumours located in the thigh (two cases), paraspinal soft tissue and perineum. Three patients had metastases, one at 12 weeks, one at 10 months, and one at presentation of recurrent tumour. In the latter case the original tumour was low grade and became high grade when it recurred 3.5 years later. All three patients died of disease. One patient was lost to follow-up. The most striking histological feature in all four tumours was the presence of numerous large epithelioid cells. These cells were arranged in cords within myxoid matrix and in sheets devoid of matrix. Two tumours had areas of conventional extraskeletal myxoid chondrosarcoma intermixed with the high-grade areas. One tumour showed transition to high-grade spindle cell sarcoma. One tumour had cells with rhabdoid features. Immunohistochemically, two tumours focally expressed S100 protein, and one focally expressed EMA. All were negative with cytokeratin, desmin, smooth muscle actin, HMB45, CD31 and CD34. Ultrastructural features in three cases were compatible with chondrosarcoma; one tumour had aggregates of microtubules within rough endoplasmic reticulum, a characteristic feature of this tumour. CONCLUSIONS: High-grade extraskeletal myxoid chondrosaroma is a rare and aggressive soft tissue sarcoma, and should be included in the differential diagnosis of other epithelioid malignancies.


Subject(s)
Chondrosarcoma/pathology , Adult , Aged , Biomarkers, Tumor/metabolism , Biopsy , Chondrosarcoma/metabolism , Chondrosarcoma/secondary , Chondrosarcoma/ultrastructure , Fatal Outcome , Female , Humans , Immunohistochemistry , Male , Microscopy, Electron , Middle Aged , Neoplasm Recurrence, Local
18.
Cancer ; 83(8): 1504-21, 1998 Oct 15.
Article in English | MEDLINE | ID: mdl-9781944

ABSTRACT

BACKGROUND: Skeletal myxoid chondrosarcoma (SMC) is considered to be either a typical chondrosarcoma with prominent myxoid alterations or an altogether unique malignant cartilage tumor. Extraskeletal myxoid chondrosarcoma (EMC) is a relatively rare but well-recognized neoplasm. It was initially thought to be a low grade sarcoma of cartilage derivation and was recently found, in most cases, to contain a reciprocal t(9;22), resulting in a fusion of the EWS and CHN genes. Are SMC and EMC the same entity arising in two different locations, or are they two separate entities? To the authors' knowledge, this study represents the first systematic attempt to answer this question. METHODS: Forty consecutive cases of EMC (20 cases) and SMC (20 cases) were compared by light and electron microscopy, immunohistochemistry, and molecular analysis. The mean clinical follow-up for both groups was 55 months. Histologic criteria for SMC consisted of 95% myxoid matrix, with only minimal hyaline cartilage formation. RESULTS: The gender distribution was identical in both groups (13 males and 7 females). The mean age was 55 years for EMC patients and 45 years for SMC patients. The EMC tumors were predominantly located in the deep soft tissues of the lower extremity (60%) and buttock (20%), and the mean tumor size was 13 cm. SMC was most commonly located in the bones around the hip joint (pelvis 35%; proximal femur 20%) and shoulder (20%); the mean size was 9 cm. Histologic grade in the EMC group correlated with survival (82% of the high grade tumors metastasized). Electron microscopy performed in 8 EMC cases revealed intracisternal microtubules in 3 cases and prominent mitochondria in 5, whereas in 5 SMC cases it revealed only inconspicuous organelles. Molecular analysis for the EWS-CHN fusion RNA resulting from the t(9;22) was performed in 15 cases (9 EMC and 6 SMC) and was detected in 7 of 9 EMC cases and 0 of 6 SMC cases. In one case, the molecular structure of the EWS-CHN fusion RNA was novel. The probability of metastasis was significantly higher (P=0.004) for the EMC group than for the SMC group. CONCLUSIONS: Although similar light microscopic features are noted in EMC and SMC, fundamental differences are noted at the ultrastructural and molecular levels, suggesting that EMC and SMC represent two distinct entities in the chondrosarcoma family of tumors.


Subject(s)
Bone Neoplasms/pathology , Chondrosarcoma/pathology , Nerve Tissue Proteins , Soft Tissue Neoplasms/pathology , Adolescent , Adult , Aged , Aged, 80 and over , Bone Neoplasms/genetics , Bone Neoplasms/ultrastructure , Buttocks/pathology , Cartilage/ultrastructure , Chondrosarcoma/genetics , Chondrosarcoma/ultrastructure , Chromosomes, Human, Pair 22/genetics , Chromosomes, Human, Pair 9/genetics , DNA-Binding Proteins/genetics , Female , Femoral Neoplasms/genetics , Femoral Neoplasms/pathology , Femoral Neoplasms/ultrastructure , Follow-Up Studies , Heterogeneous-Nuclear Ribonucleoproteins , Humans , Hyalin/ultrastructure , Immunohistochemistry , Leg , Male , Microscopy, Electron , Middle Aged , Neoplasm Proteins/genetics , Nuclear Proteins/genetics , Pelvic Bones/pathology , RNA-Binding Protein EWS , RNA-Binding Proteins/genetics , Receptors, Steroid , Receptors, Thyroid Hormone , Retrospective Studies , Ribonucleoproteins/genetics , Shoulder/pathology , Soft Tissue Neoplasms/genetics , Soft Tissue Neoplasms/ultrastructure , Survival Rate , Translocation, Genetic , Zinc Fingers/genetics
19.
Int J Cancer ; 77(6): 854-9, 1998 Sep 11.
Article in English | MEDLINE | ID: mdl-9714054

ABSTRACT

A new human chondrosarcoma cell line, OUMS-27, was established. Monolayer cultures consisted of elongated polygonal cells with a doubling time of 41 hr and a plating efficiency of 2.1%. After reaching confluence, the cells continued to slowly proliferate and formed nodule-like structures, which showed metachromasia when stained with toluidine blue, indicating the presence of proteoglycan. The cells in the nodules were round to polygonal in shape, multilayered and surrounded by abundant extracellular matrix. Types I, II and III collagens were identified by Northern blotting and immunostaining. The cells formed colonies (0.1%) in 0.3% soft-agar medium 3 weeks after inoculation. Inoculation of cells into athymic mice resulted in the formation of tumors at the injection site, resembling the original chondrosarcoma. These results demonstrated that OUMS-27 cells expressed a differentiated chondrocytic phenotype. Moreover, OUMS-27 cells had p53-gene mutation. Thus, the OUMS-27 cell line can provide a useful model not only for studies on human chondrocyte but also for basic studies on the diagnosis, treatment and etiology of human chondrosarcoma.


Subject(s)
Bone Neoplasms/ultrastructure , Chondrocytes/cytology , Chondrocytes/ultrastructure , Chondrosarcoma/ultrastructure , Cell Differentiation , Genes, p53/genetics , Humans , Karyotyping , Mutation , Phenotype , Tumor Cells, Cultured/ultrastructure
20.
Otolaryngol Clin North Am ; 30(2): 251-68, 1997 Apr.
Article in English | MEDLINE | ID: mdl-9052669

ABSTRACT

Conventional squamous cell carcinoma is the most common type of laryngeal cancer. Nevertheless, it is important to be cognizant of the less common laryngeal malignancies because of their distinctive clinical behavior and the concomitant implications for therapy. Additionally, it would be useful to identify pathologic prognostic factors in laryngeal squamous cell carcinoma that would allow optimal individualization of therapy. The histopathology of various laryngeal malignancies and various putative pathologic prognosticators in laryngeal squamous cell carcinoma are reviewed.


Subject(s)
Carcinoma, Squamous Cell/pathology , Laryngeal Neoplasms/pathology , Carcinoma, Neuroendocrine/genetics , Carcinoma, Neuroendocrine/pathology , Carcinoma, Neuroendocrine/ultrastructure , Carcinoma, Squamous Cell/genetics , Carcinoma, Squamous Cell/ultrastructure , Chondrosarcoma/genetics , Chondrosarcoma/pathology , Chondrosarcoma/ultrastructure , Flow Cytometry , Humans , Laryngeal Neoplasms/genetics , Neoplasm Staging , Ploidies , Prognosis
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