Fine needle aspiration in myxoid tumors of the soft tissues

Myxoid tumors of soft tissues constitute a histogenetically heterogeneous group of lesions, both benign and malignant, that show an overproduction of mucopolysaccharide substances. A correlative fine needle aspiration (FNA) cytologic and histologic study was performed on 16 such cases (3 intramuscular myxomas, 2 lipoblastomas, 6 myxoid liposarcomas, 4 myxoid malignant fibrous histocytomas [MFHs] and 1 extraskeletal myxoid chondrosarcoma), with electron microscopic examination of the aspirate in 4 cases. FNA of all tumors produced a gelatinous material. Smears from all but one of the tumors had a granular myxoid background substance that stained blue to blue-red with the Diff-Quik stain; the exception was the extraskeletal myxoid chondrosarcoma, whose smears stained intensely blue-red to red. On light microscopy, only lipomatous tumors had distinctive cells with diagnostic value: the lipoblasts. Although the arrangement of lipoblasts in lipoblastomas differed somewhat from that found in myxoid liposarcomas, clinical data were important for making a definitive diagnosis. Intramuscular myxomas generally showed a low cellularity composed of fibroblastlike cells with no cytologic atypia. Myxoid MFHs were composed of fibroblastlike cells and macrophagelike cells; the elongated cells with slight-to-moderate nuclear atypia predominated in tumors of low-grade malignancy, while polygonal or round cells with one or more nuclei and marked nuclear atypia predominated in high-grade tumors. Although extraskeletal myxoid chondrosarcoma was mainly differentiated from low-grade myxoid MFH by its metachromatic matrix, ultrastructural studies showed the distinctive distended cisternae with microtubular aggregates in the extraskeletal myxoid chondrosarcoma, thus contributing to the definitive diagnosis.     

Logistic regression analysis of low grade spindle cell lesions. A cytologic study

OBJECTIVE: To identify key diagnostic cytologic criteria for various low grade spindle cell lesions. STUDY DESIGN: We reviewed 20 synovial sarcomas, 18 benign neural tumors, 10 reparative lesions, 24 other benign and 27 additional malignant low grade spindle cell lesions. All specimens were coded as to the presence or absence of the following variables: high cellularity, tissue fragments, tissue culture appearance, epithelial fragments, vessel fragments, vascular arcades, fibrillar ground substance, myxoid background, microcystic areas, parallel arrangement of nuclei, naked nuclei, single cells, binucleate cells, multinucleate cells, long filamentous cells, short spindle cells, stellate cells, lipoblasts, nuclear pleomorphism, nuclei with pointed ends, comma/fishhook nuclei, cigar-shaped nuclei, ovoid/round nuclei, small nucleoli, large nucleoli, mitotic figures, intranuclear vacuoles and background histiocytes. A logistic regression analysis was performed to identify the variables predictive of malignant lesions, specifically synovial sarcomas, benign neural tumors and reparative lesions. RESULTS: Statistical analysis selected high cellularity, short spindle cells, small nucleoli and absence of tissue culture appearance as the main criteria for malignant neoplasms. Tissue fragments and high cellularity were selected as the primary criteria and absence of long filamentous cells and of myxoid background as the secondary criteria for synovial sarcomas. It selected fibrillar ground substance and absence of ovoid/round nuclei as the key criteria for benign neural tumors. The presence of a tissue culture appearance was the major criterion for reparative lesions. CONCLUSION: There are many previously described cytologic criteria, but we found that when subjected to statistical analysis, only a few features were significant in the evaluation of low grade spindle cell lesions.     

Cytologic features of a primary myxoid malignant fibrous histiocytoma arising in the uterus: a case report.

BACKGROUND: Primary malignant fibrous histiocytoma (MFH) of the uterus is extremely rare. The 10 cases reported in the literature all involved the pleomorphic variant, and to the best of our knowledge, the myxoid variant has not been reported before. We describe the cytologic findings of primary uterine myxoid MFH in relation to the myxoid component, potentially leading to an incorrect diagnosis. CASE: A 68-year-old woman presented with a primary uterine tumor. Endometrial cytology showed numerous loosely arranged, spindle-shaped fibroblastlike cells; atypical histiocytelike cells; and giant cells with a necrotic background. The overall cytologic picture was of a degenerated pleomorphic leiomyosarcoma with an inconclusive diagnosis. A diagnosis of myxoid MFH was established after electron microscopic and immunohistochemical studies of the primary tumor and tumor transplanted, as primary cultured cells, in nude mice. The patient underwent an exploratory laparotomy and died of tumor progression 38 days after the initial consultation, without treatment. CONCLUSION: Because of overlapping cytologic features among uterine sarcomas with myxoid stroma, it is important to recognize the histiocytic lineage of tumor cells by immunohistochemistry and electron microscopy in various presentations of fresh samples.     

Bronchial brushing cytology features of primary malignant fibrous histiocytoma of the lung. A case report

BACKGROUND: Malignant fibrous histiocytoma (MFH) of the lung is rare. Early diagnosis is very important because of its poor prognosis. Long-term survivors of pulmonary MFH are patients who had surgical resection. When the patient can undergo surgery after a prompt diagnosis, the prognosis improves more than with other therapy. However, it is not easy to establish the diagnosis of thoracic MFH. In general, the small fragments from bronchial or percutaneous transthoracic fine needle aspiration (FNA) biopsies are inadequate for cytologic or pathologic analysis. Bronchial brushing cytology is greatly superior to FNA cytology because one can obtain a large amount of cells. Therefore, bronchial brushing cytology may play a useful role in diagnosis when endobronchial involvement is found. CASE: A 65-year-old female was admitted with a cough, yellow sputum and exertional dyspnea. A chest roentgenogram showed a 12 x 12-cm mass in the left lung field. Bronchial brushing cytology revealed many fibroblastlike, histiocytelike, bizarre and multinucleated giant cells in a background of necrosis. Atypical mitotic figures were also found. The cytologic findings strongly suggested MFH. Although the pathologic findings from FNA biopsy showed storiform clusters structured by pleomorphic, fibroblastlike cells with bizarre nuclei and mitotic figures, the material was too small to diagnose it definitively. Six months later the patient died. An autopsy confirmed the diagnosis of MFH: the typical storiform clusters were composed of many fibroblastlike and histiocytelike cells that were positive for CD68 (PGM1) antibody. CONCLUSION: Bronchial brushing cytology may be a useful method for early, definitive diagnosis of MFH. The presence of pleomorphic, spindle-shaped fibroblastlike and histiocytelike cells with the clusters showing a storiform pattern may permit the diagnosis of MFH.     

Cytopathologic aspects of pulmonary metastasis of malignant fibrous histiocytoma, myxoid variant: fine needle aspiration biopsy of a case

The cytopathologic findings of a fine needle aspiration biopsy of pulmonary metastasis of a malignant fibrous histiocytoma, myxoid variant, are documented. Isolated and irregular loose clusters or bundles of spindle cells and pleomorphic multinucleated giant cells were found. No signet-ring lipoblastlike cells were identified. The cytologic findings were similar to the histology of the primary tumor removed from the patient's leg 18 months previously.     

Postradiation pleomorphic malignant fibrous histiocytoma of the breast

A case of primary malignant fibrous histiocytoma (MFH) of the breast occurring two years after surgical excision and radiation therapy for a carcinoma of the left breast is reported. Fine needle aspiration was positive for malignant cells, consistent with a pleomorphic sarcoma. Cytologic examination revealed giant cells with marked pleomorphism. Some cells showed single large nuclei with cytoplasmic vacuoles while others revealed multinucleation with foamy cytoplasm, phagocytosed erythrocytes and cellular debris. These findings are considered useful in the cytologic diagnosis of the pleomorphic variant of MFH.     

Fine needle aspiration and touch imprint cytology of a malignant fibrous histiocytoma of the spermatic cord. Case report

BACKGROUND: No cytologic reports on spermatic cord sarcomas have been published. CASE: A 64-year-old man presented with a slowly growing, painless, left spermatic cord enlargement. Fine needle aspiration (FNA) obtained < 1 mL of bloody fluid consisting of solitary, mark-edly anaplastic and pleomorphic tumor giant cells occasionally arranged in small fragments. Rare atypical spindle cells could be observed. Some reactive lymphocytes were observed intermingled with tumor cells. Immunohistochemistry displayed vimentin reactivity and negativity for keratins and leukocytic common antigen. The specimen removed showed a well-circumscribed, 30-mm, yellowish solid tumor. Touch imprints displayed pleomorphic tumor cells showing intense anisonucleosis; a moderate amount of clear, sometimes microvacuolated cytoplasm; and tissue fragments with a storiform pattern. Histologic examination revealed microscopic and immunohistochemical features of malignant fibrous histiocytoma (MFH) arising in soft tissues of the spermatic cord. CONCLUSION: FNA of a spermatic cord lesion may reveal a pleomorphic sarcoma. A pleomorphic appearance together with some spindle elements and compatible immunocytochemistry could help diagnose spermatic cord MFH. This is one of the few reports dealing with FNA cytology of paratesticular tumors and the first report, to the best of our knowledge, showing the cytologic characteristics of a case of spermatic cord MFH.     

Osteoclastomalike anaplastic carcinoma of the thyroid. Diagnosis by fine needle aspiration cytology

Fine needle aspiration (FNA) of a neck mass yielded cytologic specimens containing two cell populations: multinucleated giant cells and smaller, round-to-oval, undifferentiated malignant cells. The giant cells were frequently so numerous as to obscure the other cells. The FNA cytodiagnosis of a rare anaplastic thyroid carcinoma containing osteoclastic giant cells was substantiated by the subsequent exploratory surgery and biopsy specimen. Immunohistochemical staining suggested a dual origin of the two cell populations.     

Cytoarchitectural findings in the diagnosis of primary soft tissue tumors

OBJECTIVE: To review the major cytologic and architectural criteria in the diagnosis of primary soft tissue tumors, highlighting the importance of clinical correlation and the value of ancillary methods. STUDY DESIGN: Given the variety and complexity of clinicopathologic entities, the initial approach is based on pattern analysis. Six basic categories are established as a function of cell shape, stromal characteristics and resemblance to normal tissue. RESULTS: First, in myxoid-rich matrix tumors, special attention should be paid to lipoblasts, ganglion type, stellate cells and metachromatic fibrillar matrix. Second, in round cell tumors the following cytoarchitectural findings are of special interest: atypical rhabdomyoblasts, atypical lipoblasts, neuroblast rosettes, cytoplasmic glycogen, melanin pigment, islets of mature cartilage, hyaline cytoplasmic inclusions and fragments of connective tissue closely associated with round cells. Third, in spindle tumors the most important cytoarchitectural findings are: biphasic cellularity; elongated, buckled or wavy, tapered nuclei; nuclear palisades; straight, elongated, blunt-ended nuclei; melanotic pigment; storiform pattern; tissue fragments with collagen fibers or degenerated elastin; intracytoplasmic hyaline globules; and scattered spindle cells in a background of red blood cells. Fourth, in pleomorphic tumors specific typing is often difficult, if not impossible, since cells display few or no differential features. Fifth, in epithelial like cell tumors the cytologic findings of major diagnostic interest are: melanin deposits, crystalline inclusions, intracytoplasmic lumina, anisonucleosis and nuclear cytoplasmic inclusions. Last, in maturelike cell tumors, the architectural pattern resembles that of mature tissues. CONCLUSION: Although cytologic analysis of primary soft tissue tumors is hampered by the paucity of diagnostic findings, the establishment of clinicocytologic correlations, taking into account architectural patterns, cytologic details and clinical characteristics of the lesion, allows precise diagnosis of a significant number of tumors. Application of new techniques (immunocytochemistry, electron microscopy and cytogenetics) to cytologic aspirates has prompted a substantial reduction in the number of doubtful clinicocytologic diagnoses and considerably broadened the diagnostic spectrum.     

Malignant melanoma of the cervix. Report of a case

A malignant melanoma of the cervix, a rare neoplasm, was found to have an unusual cytologic pattern, similar to that of a leiomyosarcoma. A biopsy sample was diagnosed as cervical malignant melanoma of the spindle cell type. Some neoplastic cells in the tissue contained melanin pigment, whereas none of the abnormal cells in the cervical scrapes, except for an abnormal giant cell, had visible cytoplasmic pigment. The abnormal cells in the cervical scrape specimen were spindle-shaped, as were their nuclei, which is why the cytologic pattern was interpreted as that of a leiomyosarcoma. Evidence from this and previously reported cases shows that malignant melanoma must be considered as a possible source of exfoliated abnormal nonpigmented spindle-shaped cells in a cervicovaginal cell sample.     

Cytologic criteria of cystic papillary carcinoma of the thyroid

OBJECTIVE: To establish differential cytologic criteria between benign and malignant thyroid cysts. STUDY DESIGN: The study was a retrospective, transverse, analytic, comparative one of 3 groups of patients with nonfunctional thyroid nodules subjected to fine needle aspiration biopsy (FNAB) and surgical resection of the lesions, with histologic study as the diagnostic gold standard. Fifteen cases of cystic papillary carcinomas (group 1) with initial false negative diagnoses, 42 goiters accompanied by cystic degeneration (group 2) and 15 noncystic papillary carcinomas (group 3) were studied. Independent variables were age and sex; dependent variables were the presence of tridimensional fragments, papillae, anisonucleosis, nuclear bars, pseudoinclusions, powdery chromatin, cytoplasmic vacuoles, metaplastic cytoplasm, psammoma bodies, autolysis, multinucleated giant cells, spindle cells, colloid, monolayered laminae and macrophages in FNAB specimens. Statistical analysis was performed by central tendency measures and the chi 2 test. RESULTS: The chi 2 test revealed a statistically significant difference between group 2 and the groups with papillary carcinoma based on the presence of tridimensional fragments, anisonucleosis, nuclear bars, pseudoinclusions, powdery chromatin, cytoplasmic vacuoles, metaplastic cytoplasm and autolysis. CONCLUSION: The above cytologic characteristics must be searched for systematically in the FNAB of every cystic lesion of the thyroid to rule out the presence of cystic papillary thyroid carcinoma and to decrease the rate of false negative results.     

Two cases of spontaneous malignant fibrous histiocytoma in Wistar rats

Spontaneous malignant fibrous histiocytoma (MFH) of subcutaneous tissues was found in 2 Wistar rats of a 18-month-old male and a 21-month-old female. These tumors consisted of spindle, oval, myxoid and giant cells. In the female rat, a similar histological pattern was found in the metastatic tumor nodules in the lung and liver. In the electron microscopy, four differentiated cells of fibroblast-like, histiocyte-like, giant and undifferentiated cells were identified in these tumors. Spontaneous MFH of Wistar rats in the present study was quite similar to those reported in rats of other strains.     

Cytologic findings in primary malignant carcinoid tumor of the cervix. Including immunohistochemistry and electron microscopy performed on cervical smears

The cytologic findings in a primary malignant carcinoid tumor of the cervix are presented. In addition to the presence in the smears of cells suggestive of squamous carcinoma and adenocarcinoma, which led to an initial diagnosis of adenosquamous carcinoma, there were multinucleated giant cells with prominent, reddish nucleoli, finely granular chromatin and grayish-blue to eosinophilic cytoplasm, as well as smaller pleomorphic cells, against a tumor-diathesis type of background. Immunocytochemistry performed on the cervical smears showed the presence of serotonin, and ultrastructural analysis revealed abundant intracytoplasmic, membrane-bound granules in malignant cells, thus confirming the diagnosis of a carcinoid tumor.     

Aspiration cytology of heterotopic ossification. A case report.

Heterotopic ossification (myositis ossificans) is usually a posttraumatic reactive process involving new bone formation. This nonneoplastic process can be clinically and radiologically confused with osteosarcoma. A case of heterotopic ossification is reported in which cytologic material was obtained from a partially calcified thigh mass from a 17-year-old, athletic male. Aspiration cytology revealed numerous osteoclastic giant cells containing multiple plump nuclei. These cells were admixed in a benign-appearing stromal background composed of mature fibroblasts and were typified by elongated spindle cells. A small incisional biopsy showed new bone formation, osteoclasts, osteoblasts and fibroblasts consistent with maturing heterotopic ossification. Heterotopic ossification may be distinguished cytologically from osteosarcoma by the presence of numerous uniform benign stromal cells composed of mature fibroblasts and osteoclastic giant cells. The differential diagnosis may be more difficult in the early stages of this reactive and proliferative process. Adequate sampling of suspected heterotopic ossification by aspiration cytology may avoid surgery in a selected group of patients.     

Establishment and characterization of a cell line, HS-Os-1 derived from an osteoblastic type of human osteosarcoma

A new human cell line, HS-Os-1, derived from a case of osteoblastic osteosarcoma arising in the humerus of an 11-year-old girl was established. Light microscopically, HS-Os-1 cells growing in a monolayer (in vitro) were pleomorphic, intermingled with a few multinucleated giant ones, and positive with alkaline phosphatase reaction. In the transplanted tumors in athymic nude mice (in vivo), atypical spindle or polygonal cells densely proliferated with prominent osteoid formation and even calcification. HS-Os-1 cells, both in vitro and in vivo, were mostly positive for vimentin and a few for S-100 protein. Ultrastructurally, HS-Os-1 cells in vitro and in vivo also revealed essentially the same features as the eccentrically located, euchromatin-rich nuclei with prominent nucleoli, a lot of well-developed, irregularly-dilated rough endoplasmic reticula, polysomes and microfilaments in the cytoplasm. Namely, HS-Os-1 cells fully expressed and possessed morphological characteristics as osteoblastic nature during the cultivation and heterotransplantation. This cell line, therefore, proved to be extremely useful to search for human osteosarcomas.     

Cytologic features of ovarian tumors of low malignant potential in peritoneal fluids

The distinction of ovarian tumors of low malignant potential (OTLMP) from invasive ovarian carcinomas has significant therapeutic and prognostic implications. This study was undertaken to define the cytologic features of OTLMP in peritoneal fluids and to compare them with the cytologic features of invasive carcinomas. Peritoneal fluids from 13 patients with OTLMP and 10 patients with invasive ovarian carcinoma contained neoplastic cells and were reviewed with attention to papillary fragment morphology, cellular pleomorphism and cytoplasmic and nuclear characteristics. Cytologic preparations from patients with OTLMP contained large, cohesive papillary fragments with smooth borders. The neoplastic cells were relatively small and uniform, with high nuclear-cytoplasmic (N/C) ratios (greater than 1:2), few intracytoplasmic vacuoles and inconspicuous nucleoli. Mitotic figures were rare. Peritoneal fluids from patients with invasive ovarian carcinoma contained smaller discohesive papillary fragments with irregular borders. The neoplastic cells were relatively large and pleomorphic, with low N/C ratios (less than or equal to 1:2), abundant intracytoplasmic vacuoles and prominent nucleoli; most preparations contained many single cells and mitotic figures.     

Malignant fibrous histiocytoma,giant cell type,of the breast mimicking metaplastic carcinoma. A case report

BACKGROUND: We report a case of malignant fibrous histiocytoma, giant cell type (MFHGC), of the breast. A review of the literature failed to reveal cytology-based reports on this entity. The cytologic similarity of breast MFHGC on fine needle aspiration biopsy (FNAB) to other malignant breast neoplasms, including carcinoma with osteoclastlike giant cells, metaplastic carcinoma and breast sarcomas, as well as benign reactive processes, makes the recognition of this tumor challenging. CASE: A 72-year-old woman presented with a 5-month history of an enlarging breast mass. FNAB of the mass showed a hypercellular smear composed of cohesive, branching clusters of spindle cells with ovoid, focally hyperchromatic nuclei and inconspicuous nucleoli. Interspersed osteoclastlike giant cells, some associated with clusters of spindle cells, were uniformly seen throughout the smear. The background was hemorrhagic, with cellular debris and occasional spindle cells and lymphocytes. No ductal epithelial or myoepithelial cells were seen. An incisional biopsy was performed, followed by radical mastectomy. The histologic examination was diagnostic of MFHGC. The diagnosis was supported by immunohistochemical and electron microscopic studies. CONCLUSION: MFHGC, also called primary giant cell tumor of soft tissues, is composed of a mixture of histiocytes, fibroblasts and bland-appearing osteoclastlike giant cells with a multinodular growth pattern. Although MFHGC rarely occurs in the breast and the definitive diagnosis is difficult based on cytology alone, the diagnosis can be considered when a cytologic examination reveals a hypercellular, spindle cell smear with osteoclastlike giant cells in the absence of ductal epithelial or myoepithelial cells.     

Cystosarcoma phyllodes. Diagnosis by fine needle aspiration cytology.

The cytologic features of 10 benign, 2 borderline and 5 malignant phyllodes tumors were studied, and an attempt was made to correlate the cytologic findings with corresponding histologic categories. Seventy-five percent of the benign and borderline tumors were interpreted as benign cystosarcoma phyllodes on fine needle aspiration cytology. Eighty percent of the malignant phyllodes tumors were identified as malignant lesions cytologically. The cytologic features assessed were the epithelial:stromal ratio and morphology of the stromal component, including the degree of atypia, mitotic activity, capillary vessels traversing the stromal fragments, presence of foamy macrophages, histiocytic giant cells and bipolar naked nuclei. A diagnosis of phyllodes tumor was suggested cytologically by the presence of both epithelial and stromal elements; the stroma was present as cellular "phyllodes fragments" and isolated mesenchymal cells. The parameters suggesting malignancy were extreme paucity or absence of epithelial elements and stromal cells in diffuse sheets and clusters less cohesive than normal, with marked stromal atypia and mitotic activity.     

Low grade fibromyxoid sarcoma: report of a case with fine needle aspiration cytology and histologic correlation

BACKGROUND: Low grade fibromyxoid sarcoma has been fully described histologically; however, the fine needle aspiration (FNA) cytologic findings are scantily defined, and the distinction from other benign and malignant soft tissue tumors can be difficult. CASE: We examined FNA cytologic material from a slowly growing, large chest wall mass in a 28-year-old woman. The surgical specimen was processed for routine histology and immunohistochemical studies. The cytologic smears were adequately cellular, showing spindly cells with uniform, elongated nuclei; small, inconspicuous nucleoli; and scanty, wispy cytoplasm associated with myxoid material. No significant nuclear pleomorphism or mitoses were noted. The excised tumor was well circumscribed, focally infiltrating the surrounding muscles. The cut surface was variable, featuring fibrous, solid, fleshy and myxoid areas. Microscopically, the solid, fibrous areas displayed increased cellularity with storiform, intersecting and parallel patterns. In the myxoid areas the cells grew in a haphazard fashion and appeared floating in abundant mucoid matrix associated with a capillary vascular network similar to the chicken-wire pattern seen in cases of myxoid liposarcoma. The tumor cells were spindly, with fusiform, uniform nuclei. Focal, moderate nuclear pleomorphism was noted. The mitotic index was low. The tumor cells were positive for vimentin, alpha-1-antitrypsin and lysozyme and negative for S-100, actin, desmin and CD34. CONCLUSION: Although low grade fibromyxoid sarcoma is a rare neoplasm, it should be recognized and distinguished from other soft tissue tumors because of its low malignant potential. The definitive FNA cytologic diagnosis can be challenging but is possible if the tumor is adequately sampled, with multiple passes from different areas. Clinical and radiologic correlations are of great help. All spindle cell tumors with myxoid changes, such as myxoid liposarcoma, myxofibrosarcoma, cellular myxoma, myxoid leiomyosarcoma and peripheral nerve sheath tumors, should be considered in the differential diagnosis. In contrast to the cytologic features, the histologic findings are characteristic and well established.     

Cysteine proteinases in chondrosarcomas

The aim of the present study was to define the role of cathepsins B, H, K, L and S in the pathogenesis of human chondrosarcomas. For this purpose 40 tumour samples obtained from 12 patients with the diagnosis of conventional chondrosarcoma were systematically investigated for the expression of cathepsin mRNAs by Northern hybridisation, and for immunohistochemical localisation of the proteins. Northern analysis demonstrated the highest levels of cathepsins B and L in a recurring grade 1 chondrosarcoma, and in a grade 3 chondrosarcoma and in fibrous histiocytomas. Increased expression of cathepsin K mRNA was seen in seven chondrosarcomas, as well as in control tumours; fibrous histiocytomas, osteosarcomas, enchondromas and a giant cell tumour of bone. Cathepsin L was immunolocalised within the large chondrocytes, while cathepsin K was predominantly localised in large multinucleated osteoclastic cells and in some hypertrophic chondrocytes. These results suggest that chondrosarcoma can be included in the growing list of tumours, where cathepsins may well be involved in tumour progression. The simultaneous upregulation of cathepsins B and L, together with matrix metalloproteinase-13, and the association of cathepsin K with negative prognostic parameters suggests that an aggressive biological behaviour of chondrosarcoma may be related to the synthesis of cysteine proteinases and activation of other proteolytic enzymes. If this turns out to be the case, cathepsin inhibitors could provide the much needed adjuvant therapy for chondrosarcomas.