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Increased confidence of diagnosis of Ewing sarcoma using T2-weighted MR images.

To assess whether magnetic resonance imaging could assist in diagnosing Ewing sarcoma, we retrospectively analyzed T1- and T2-weighted images of 24 consecutive solitary lytic bone lesions, including 18 cases of histologically proven Ewing sarcoma, and six aggressive-appearing benign lesions including eosinophilic granuloma and osteomyelitis (3 cases each). Images were obtained using a (1.0T) Siemens GBSII system. No signal intensity differences were noted among the various lesions on T1-weighted images. The observed differences in T2-weighted marrow signal intensities were scored on a 5-point scale (5 = water, 3 = fat, and 1 = muscle) and then histologically correlated. Sixteen of 18 Ewing sarcomas showed homogeneous T2-weighted signal isointense with fat and two were heterogeneous. Signals for all 6 benign lesions were homogeneous and more intense than fat on T2-weighted images. All Ewing sarcomas had associated soft tissue masses whereas, only one benign lesion, an eosinophilic granuloma had a small soft tissue component. In our patient population, a homogeneous intramedullary T2-weighted signal isointense with fat, and the presence of an associated soft tissue mass helped differentiate Ewing sarcoma from benign lytic lesions. The reproducibility of these results requires testing in larger series of patients using a variety of MR imaging equipment of differing field strengths.

Adolescent↗

Myeloradicular features as the initial presentation of sarcomas of childhood.

Sarcomas (chondrosarcoma, Ewing sarcoma, rhabdomyosarcoma, and undifferentiated sarcoma) generally present with nonneurologic symptoms at the onset. Five children with sarcomas who presented with spinal cord compression or radiculopathy as their initial problems are described. These patients appear to be older than those with the more commonly encountered neuroblastoma-related spinal cord compression. Our patients had a favorable neurologic recovery initially, but ultimately succumbed to systemic complications from spread of the sarcoma.

Adolescent↗

Human breast sarcoma and human breast implantation: a time trend analysis based on SEER data (1973-1990).

Since the demonstration in the 1940s of foreign body induction of sarcomas in rodents, the safety of artificial implants in humans has been a matter of concern. In this study, we assess the risk for the development of breast sarcomas in women with silicone breast implants. Our analysis is based on the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) Program database for the years 1973-1990 and on estimates of breast implantation rates from about 1960 onward. We have divided the SEER data into two equal time periods, 1972-1981 and 1982-1990. For each time period, we estimated the average annual number of women in the United States who had received breast implants 10 or more years earlier. This analysis allows for a 10 year latency period for the induction of breast sarcoma. We calculated that the average number of women in the U.S. 10 or more years post breast implantation was 55,000 for the 1973-1981 period and 509,000 for the 1982-1990 period. We then examined the SEER data to observe whether there was a concomitant rise in the female breast sarcoma incidence rates between these two time periods. We found the mean age-adjusted incidence rate of breast sarcomas was 0.13 per 100,000 women for the initial 9-year period, 1973-1981, and 0.12 per 100,000 women for the latter 9-year period, 1981-1990.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Detection and molecular cytogenetic characterization of a novel ring chromosome in a histological variant of Ewing sarcoma.

Ewing sarcoma/peripheral primitive neuro-ectodermal tumor (PNET) is a round-cell sarcoma that may show varying degrees of neuro-ectodermal differentiation. These tumors are identified by a characteristic round-cell morphology and immunohistochemical profile, as well as by specific translocations involving the EWS gene on chromosome 22 and the 3' portion of the E26 transformation-specific family of transcription factors. These translocations result in fusion proteins that act as aberrant transcription factors. The majority of Ewing sarcoma cases are characterized by a balanced t(11;22). Specific chromosomal abnormalities often correlate with distinct morphologic or phenotypic subtypes of tumors and play an important role in prognosis. Here we describe the molecular cytogenetic investigation of a case of Ewing sarcoma in the proximal humerus of a 39-year-old male using COBRA (combined binary ratio labelling) fluorescent in situ hybridization karyotyping, array comparative genomic hybridization, and EWS-gene specific fluorescence in situ hybridization. Multiple chromosomal aberrations were identified, including a der(22)r(20;22), resulting in an amplification of the proximal region of the EWS gene. This is the first time that both translocation and amplification involving the EWS gene and an unidentified gene are described. This case adds to the spectrum of both morphology and genetic rearrangements in Ewing sarcoma, and shows the importance of combined molecular cytogenetic approaches in identifying uncommon rearrangements in sarcomas.

Adult↗

Significant growth suppression of synovial sarcomas by the histone deacetylase inhibitor FK228 in vitro and in vivo.

About 97% of synovial sarcomas harbor the SYT-SSX fusion gene by chromosomal translocation. We found that the histone deacetylase (HDAC) inhibitor FK228 significantly suppressed the growth of synovial sarcoma cells as compared with that of osteosarcoma. The 50% growth inhibition IC50 value we obtained for FK228 was 0.02-0.2 nM, and it indicates that its suppression effect on synovial sarcoma cells is the highest of any of the HDAC inhibitors yet reported. It was not likely that the growth suppression of FK228 depends on the doubling time of these cells. Introduction of SYT-SSX cDNA into HEK293 cells enhanced the sensitivity of the cells for FK228. Immunostaining of the FK228-treated cells using an anti-acetyl-histone H3 antibody showed that FK228 inhibits deacetylation of histone. In a mice assay, the growth of synovial sarcoma cells was markedly inhibited by FK228 treatment, and the invasion of tumors into surrounding tissues was suppressed. These results suggest that FK228 may be useful in developing therapeutic strategies to treat synovial sarcoma.

Animals↗

[Radiation-induced sarcomas after breast cancer: experience of Institute Curie and review of literature].

Adjuvant radiotherapy to the breast plays a significant role in preventing local failure in women treated for early stage breast cancer. This fact is supported by multiple clinical trials demonstrating that adjuvant radiotherapy decreases the risk of local recurrence and increases the rate of breast preservation, and actually the rules of adjuvant breast irradiation are clearly established. Sarcomas are a rare but recognized complication of radiation therapy for breast carcinoma, and are associated with poor prognosis. The first case of a bone sarcoma after radiation therapy of breast cancer was described by Beck in 1922. In 1948, Cahan et al. defined the criteria for diagnosis of radiation-induced sarcoma. Since then, some studies have reported the incidence of radiation-induced sarcoma after radiotherapy for different cancers. This article reports and discusses the incidence, management and treatment outcome of radiation-induced sarcomas occurring after radiotherapy for breast cancer in our institute. The incidence, histology, latency of appearance, genesis, their treatment and the prognostic factors of these rare tumors are discussed and the literature is reviewed.

Adult↗

[Surgery of limb and trunk wall soft tissue sarcoma].

UNLABELLED: For this review of surgery in soft tissue sarcoma, we reviewed literature and added our personal experience. In front of a soft tissue tumour, the major objective is to think it could be a sarcoma. Diagnosis actually is made by core needle biopsies, but sometimes a surgical biopsy is needed. Surgical resection is better defined since ten years and distinguishes resection R0 (in sano), R1 (microscopic residual disease) and R2 (macroscopic residual disease). Quality of resection is determined collegially by confrontation of surgical and pathological reports according recommendations of the French Sarcoma Group (FSG). The risk of local recurrence depends on resection-type and tumour grade. With the help of the surgical classification from FSG, local prognosis is better understood and treatment can be adapted to individual tumours. In experienced hands, local recurrence can be pushed down to near 10 against 20% formerly. Severe complications after sarcoma surgery occur in 14% of cases. Functional outcome studies have benefited from new scoring systems, which complete each other. Isolated limb perfusion is a method that could save limbs in some desperate situations. CONCLUSION: Due to rarity and treatment specifications, soft tissue sarcoma should be treated in specialised centres.

Extremities↗

Expression profiling of EWS/FLI identifies NKX2.2 as a critical target gene in Ewing's sarcoma.

Our understanding of Ewing's sarcoma development mediated by the EWS/FLI fusion protein has been limited by a lack of knowledge regarding the tumor cell of origin. To circumvent this, we analyzed the function of EWS/FLI in Ewing's sarcoma itself. By combining retroviral-mediated RNA interference with reexpression studies, we show that ongoing EWS/FLI expression is required for the tumorigenic phenotype of Ewing's sarcoma. We used this system to define the full complement of EWS/FLI-regulated genes in Ewing's sarcoma. Functional analysis revealed that NKX2.2 is an EWS/FLI-regulated gene that is necessary for oncogenic transformation in this tumor. Thus, we developed a highly validated transcriptional profile for the EWS/FLI fusion protein and identified a critical target gene in Ewing's sarcoma development.

Animals↗

Sarcomas of the head and neck. Results from the treatment of 25 patients.

AIMS: Head and neck sarcomas comprise a heterogenous and biologically diverse group of rare neoplasms. In an effort to clarify some of the obscure clinical behavior of head and neck sarcomas, we present our experience and review the relevant literature. METHODS: Retrospective analysis of patients with histologically proven head and neck sarcomas treated in a tertiary Hospital Department between 1992 and 2002. RESULTS: During this period, 25 patients with head and neck sarcomas were registered. Follow-up ranged from 8 to 144 months. Twenty-three patients were treated with surgery as the primary modality; 14 were treated by surgery alone. Clear margins were obtained in all of them and local control was achieved in 12/13. The 2- and 5-year survival rates for the entire group were 80 and 40%, respectively. Mean overall survival time of our patients was 62 months (median 52 months). CONCLUSIONS: Surgical treatment remains the cornerstone of therapeutic management of head and neck sarcomas.

Adolescent↗

Histopathological outcome of 597 isolated soft tissue tumors suspected of soft tissue sarcoma: a single-center 12-year experience.

BACKGROUND: The aim of this present report was to analyze the patients referred to us with the presumptive diagnosis of soft tissue sarcoma (STS). METHODS: We reviewed all patients referred to us with suspected soft tissue sarcoma (STS) of the extremities or trunk over a 12-year period. RESULTS: We treated 597 patients with soft tissue tumors. Open biopsy revealed soft tissue sarcoma in 318 cases, benign mesenchymal tumor in 124 cases and isolated metastases (ISTM) from carcinomas in 98 patients; other pathologies were found in 57 patients. The primary carcinomas were lung cancer in 26 patients, breast cancer in 19 patients, renal carcinoma in 16 patients, carcinoma of the esophagus in 12 patients, colonic carcinoma in 5 patients, thyroid gland cancer in 6 patients, and in 14 patients carcinoma of unknown primary was diagnosed. CONCLUSIONS: In our collective with soft tissue tumor, 50% of the patients had the diagnosis of soft tissue sarcoma, 20% presented with a metastasis of carcinoma and 20% had a benign tumor. Referring to our results, in patients with the presumptive diagnosis of soft tissue sarcomas, soft tissue metastasis of a primary carcinoma was unexpectedly common, indicating that greater consideration should be given to this differential diagnosis.

Adolescent↗

Prognostic factors and outcome in women with uterine sarcoma.

OBJECTIVES: A retrospective analysis of patients with uterine sarcoma was undertaken to assess prognostic factors and treatment related outcomes. PATIENTS AND METHODS: Ninety-four patients (median age: 60years, range: 20-93years) with a histologically verified uterine sarcoma treated at the McGill University Health Centre (MUHC) between 1989 and 2004 were identified from the tumor registry and pathology database. RESULTS: Twenty-eight patients had an endometrial stromal sarcoma (ESS), 30 had a leiomyosarcoma (LMS), and 36 had mixed muellerian tumors (MMT). According to FIGO classification, Stage I, II, III, and IV tumors were identified in 49, 7, 20, and 18 patients, respectively. At the time of analysis, 55.5% of patients (52/94) were dead due to progressive sarcoma disease; 8.5% of the patients (8/94) were alive with disease recurrence, and 36.2% (34/94) were alive without disease recurrence, with a median survival of 35months. Univariate analysis demonstrated a statistically significant association between overall survival and histology in favor of patients with ESS (p<0.001). Analyzing each of the histological subtypes separately, adjuvant treatment with chemotherapy and/or hormonal treatment had no demonstrable impact on overall survival. In multivariate analysis age and advanced stage, remained a significant predictor for overall survival in patients with LMS and MMT, but not in patients with ESS. Regarding adjuvant treatment, radiotherapy had a significant impact on overall survival only in patients with MMT (p=0.002). CONCLUSIONS: In patients with uterine sarcoma, in comparison to LMS and MMT, ESS tends to present as a less aggressive disease with a favorable outcome. Furthermore, reflected by an improved overall survival after radiotherapy only in patients with MMT, it seems to be mandatory to differentiate between these histological subtypes.

Adult↗

Undifferentiated sarcoma of the pulmonary artery mimicking pulmonary thromboembolic disease.

Primary pulmonary artery sarcoma is an uncommon tumor. Mandelstamm in 1923 was the first to describe the disease in an autopsy. Since then, less than 200 cases were reported. The incidence is 0.001-0.03%, they are always highly malignant sarcoma, and women are involved twice as often as men. The presentation is often cough, dyspnea, and chest pain, and patients are usually diagnosed as suffering from pulmonary emboli, and primary tumor of the pulmonary artery is not usually considered in the differential diagnosis. The diagnosis of pulmonary artery sarcoma is made of the "clot" resected during pulmonary artery thrombendarterectomy. Our suggestion is that in patients with unilateral pulmonary artery occlusive disease, no evidence of positive hypercoagulability tests, and no history of thromboembolism, a high suspicion of pulmonary artery sarcoma should be kept in mind, and an angiographic-guided biopsy from the intra-arterial occlusive material should be considered. The treatment is surgery. The survival without operation is less than 2 months. Some patients were treated with adjuvant chemotherapy. We report on a woman with undifferentiated sarcoma of the pulmonary artery, mimicking chronic pulmonary artery emboli. This case illustrates the need to consider malignancy in the differential diagnosis of patients having pulmonary emboli.

Aged↗

Surgical management of sarcomas.

Nearly all bone and soft tissue sarcomas will require surgical management. Early consultation with a surgeon who is experienced in sarcomas, before a biopsy is performed, will avoid potential errors that may complicate subsequent surgery. Advances in imaging, neoadjuvant therapies, and reconstructive techniques have improved the ability to resect adequately most bone and soft tissue sarcomas. The use of oncologic and functional outcomes assessment tools facilitates the development of improved treatments for sarcoma patients. Results from major centers reveal that most patients who have a nonmetastatic bone or soft tissue sarcoma will survive 5 years after surgery when combined with either chemotherapy or radiation.

Humans↗

Prognostic factors and expression of p53 and mdm-2 in uterine sarcomas.

OBJECTIVES: To evaluate the clinicopathologic prognostic factors of uterine sarcoma, and determine whether overexpression of p53 and mdm-2 proteins correlate with overall survival and prognostic factors. METHODS: Thirty specimens from 43 patients with uterine sarcoma were available for slide review and evaluated by immunohistochemistry at Yonsei and Ajou University Medical Centers for the expression of p53 and mdm-2. RESULTS: Overall survival was found to correlate to histologic type of uterine sarcoma, surgical stage, tumor grade, and mitotic index. Whereas 63% of the sarcomas expressed p53, with a significant correlation to overall survival, 60% expressed mdm-2, with a significant correlation to the mitotic index but not to overall survival. CONCLUSION: Histologic type, surgical stage, tumor grade, mitotic index, and p53 expression were prognostic factors of the overall survival of patients with uterine sarcoma.

Adult↗

Angiogenesis and Ewing sarcoma--relationship to pulmonary metastasis and survival.

BACKGROUND/PURPOSE: Intratumoral angiogenesis quantified by microvessel density (MVD) has been shown to be a strong prognostic indicator in a number of malignant tumors. Its association with prognosis in Ewing sarcoma has not been previously studied. The aim of our study was to investigate the relationship between angiogenesis and clinical outcome in Ewing sarcoma. METHODS: Twenty-seven patients with Ewing sarcoma were included in a retrospective immunohistochemical study. Sections from diagnostic biopsies were immunostained using anti-von Willebrand factor antibody and microvessels were counted at 400x magnification on three microscopic fields per patient. Microvessel density was correlated with overall and disease-free survival as a continuous variable using univariate regression analysis and as a dichotomous variable by Kaplan-Meier and log-rank analysis. Correlation between clinicopathologic variables and the degree of angiogenesis was tested using chi(2) test. RESULTS: Increasing MVD was not confirmed to be a poor prognostic factor in univariate analysis. Also, statistically significant difference was not found in overall survival or disease-free survival between patients with high (>31.6 vessels per field) and low (<or=31.6 vessels per field) microvessel counts. Finally, there was no difference regarding the metastatic rate between patients with high and low microvessel counts. CONCLUSIONS: Our results did not confirm increasing angiogenesis quantified by MVD to be predictive of prognosis or pulmonary metastasis in Ewing sarcoma. The diffuse pattern of distribution of microvessels found in Ewing sarcoma may be responsible for the observed lack of prognostic significance of angiogenesis. Future work is required to assess the prognostic importance of MVD in this disease.

Adolescent↗

Cost-effectiveness of pulmonary resection and systemic chemotherapy in the management of metastatic soft tissue sarcoma: a combined analysis from the University of Texas M. D. Anderson and Memorial Sloan-Kettering Cancer Centers.

BACKGROUND: We sought to determine the cost-effectiveness of different treatment strategies for patients with pulmonary metastases from soft tissue sarcoma. METHODS: We constructed a decision tree to model the outcomes of 4 treatment strategies for patients with pulmonary metastases from soft tissue sarcoma: pulmonary resection, systemic chemotherapy, pulmonary resection and systemic chemotherapy, and no treatment. Data from 1124 patients with pulmonary metastases from soft tissue sarcoma were used to estimate disease-specific survival for pulmonary resection and no treatment. Outcomes of systemic chemotherapy and pulmonary resection and of systemic chemotherapy were estimated by assuming a 12-month improvement in disease-specific survival with chemotherapy; this was done on the basis of the widely held but unproven assumption that chemotherapy provides a survival benefit in patients with metastatic soft tissue sarcoma. Direct costs were examined for a series of patients who underwent protocol-based pulmonary resection or doxorubicin/ifosfamide-based chemotherapy. RESULTS: The mean cost of pulmonary resection was 20,339 dollars per patient; the mean cost of 6 cycles of chemotherapy was 99,033 dollars. Compared with no treatment and assuming a 12-month survival advantage with chemotherapy, the incremental cost-effectiveness ratio was 14,357 dollars per life-year gained for pulmonary resection, 104,210 dollars per life-year gained for systemic chemotherapy, and 51,159 dollars per life-year gained for pulmonary resection and systemic chemotherapy. Compared with pulmonary resection, the incremental cost-effectiveness ratio of pulmonary resection and systemic chemotherapy was 108,036 dollars per life-year gained. Sensitivity analyses showed that certain patient and tumor features, as well as the assumed benefit of chemotherapy, affected cost-effectiveness. CONCLUSIONS: For patients with pulmonary metastases from soft tissue sarcoma who were surgical candidates, pulmonary resection was the most cost-effective treatment strategy evaluated. Even with favorable assumptions regarding its clinical benefit, systemic chemotherapy alone, compared with no treatment, was not a cost-effective treatment strategy for these patients.

Antineoplastic Agents↗

Soft tissue sarcomas may present with deep vein thrombosis.

PURPOSE: To bring attention to our observation that soft tissue sarcomas may present initially as deep venous thromboses (DVTs). METHOD: A query of our health system database (1996 to 2004) for patients diagnosed with soft tissue sarcomas and DVTs was undertaken. Patient medical records were reviewed to select those patients whose DVT occurred before the diagnosis of their tumor. Patient demographics, tumor classification, presentation, and outcome were noted. RESULTS: Six of 19 patients were identified (four men, two women; aged 41 to 85 years). All tumors occurred in the lower extremities. All DVTs occurred in the same extremity as the tumor. Pathology specimens indicated four different types of sarcomas. In five cases, sarcoma diagnosis was delayed as treatment of the DVT occurred. In one, a mass was seen on the initial venous duplex screen. Four are deceased, one remains in treatment, and one was lost to follow-up. The average length of follow-up was 10 months. CONCLUSION: Soft tissue sarcomas can initially present as, or even be misdiagnosed as, DVT. Given a delay in diagnosis adversely affects prognosis, it is important that physicians be vigilante for associated tumors when evaluating for suspected DVT.

Adult↗

Absence of amplification of HER-2/neu (c-erbB-2) gene in Ewing's sarcoma: a real-time polymerase chain reaction method.

Amplification and overexpression of the HER-2/neu (c-erbB-2) oncogene have been observed in many cancers and are associated with a poor prognosis particularly in breast cancer. The human epidermal growth factor (HER)-2 receptor has recently been implicated in Ewing's sarcoma tumor cell line growth and chemosensitivity. The present study evaluates the amplification of HER-2/neu gene in paraffin sections from 42 cases of Ewing's sarcoma by a real-time quantitative polymerase reaction method using LightCycler system (Roche diagnostics, GmbH Mannheim, Germany). The relative copy number of HER-2/neu versus beta-globin was calculated at the crossing point. The mean calculated copy number in these cases of Ewing's sarcoma and normal controls was 26.43 and 26.93, respectively. The p value was 0.215 (p<0.05). Our results demonstrated an absence of HER-2/neu oncogene amplification in Ewing's sarcomas, and we suggest that HER-2/neu is not a biologically or therapeutically important pathway in Ewing's sarcoma.

Beta-Globulins↗