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PubMed1976

[Morphological studies on cellfree induced sarcomas in syrian hamster (author's transl)].

Morphological studies on sarcomas induced in syrian hamsters by cellfree transmission are described. The tumour tissue for the cellfree preparations stemmed from a sarcoma, containing C-particles. Basically, three histological groups have been distinguished: 1. neoplasms of the peripheral nerve-sheath, 2. undifferentiated sarcomas, and 3. liposarcomas. Furthermore, a rhabdomyosarcoma, an angiosarcoma and, in a heterotransfection on rat, an osteosarcoma have been established. The great majority of tumours could be transmitted by cellfree preparations. To this neoplasms belong the undifferentiated histological structure.

Animals↗

PubMed1999

Prognostic factors for the outcome of chemotherapy in advanced soft tissue sarcoma: an analysis of 2,185 patients treated with anthracycline-containing first-line regimens--a European Organization for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group Study.

PURPOSE: A total of 2,185 patients with advanced soft tissue sarcomas who had been treated in seven clinical trials investigating the use of doxorubicin- or epirubicin-containing regimens as first-line chemotherapy were studied in this prognostic-factor analysis. PATIENTS AND METHODS: Overall survival time (median, 51 weeks) and response to chemotherapy (26% complete response or partial response) were the two end points. The cofactors were sex; age; performance status; prior therapies; the presence of locoregional or recurrent disease; lung, liver, and bone metastases at the time of entry onto the trial; long time period between the initial diagnosis of sarcoma and entry onto the study; and histologic type and grade. RESULTS: Univariate analyses showed (a) a significant, favorable influence of good performance status, young age, and absence of liver metastases on both survival time and response rate, (b) a significant, favorable influence of low histopathologic disease grade on survival time, despite a significantly lower response rate, (c) increased survival time for patients with a long time period between the initial diagnosis of sarcoma and entry onto the study, despite equivalent response rates, and (d) increased survival time with liposarcoma or synovial sarcoma, a decreased survival time with malignant fibrous histiocytoma, a lower response rate with leiomyosarcoma, and a higher response rate with liposarcoma (P < .05 for all log-rank and chi2 tests). The Cox model selected good performance status (P < .0001), absence of liver metastases (P = .0001), low histopathologic grade (P = .0002), long time lapse since initial diagnosis (P = .0004), and young age (P = .0045) as favorable prognostic factors of survival time. The logistic model selected absence of liver metastases (P < .0001), young age (P = .0024), high histopathologic grade (P = .0051), and liposarcoma (P = .0065) as favorable prognostic factors of response rate. CONCLUSION: This analysis demonstrates that for advanced soft tissue sarcoma, response to chemotherapy is not predicted by the same factors as is overall survival time. This needs to be taken into account in the interpretation of trials assessing the value of new agents for this disease on the basis of response to treatment.

Adult↗

PubMed1995

Soft tissue sarcomas that mimic benign lesions.

Although it is well known that a variety of benign mesenchymal neoplasms and reactive proliferations may mimic sarcomas, the fact that some types of sarcoma commonly are misinterpreted as benign is less widely appreciated. This review considers five such lesions in soft tissue: low grade fibromyxoid sarcoma, low grade myxofibrosarcoma (myxoid "MFH"), well differentiated liposarcoma (atypical lipoma), epithelioid sarcoma, and so-called inflammatory fibrosarcoma. Principal reasons for their underrecognition are their generally bland cytology, often relative hypocellularity, and indolent clinical course. Common to several of these lesions, however, is a tendency for histological and hence biological progression in local recurrences, underlining the importance of accurate diagnosis and adequate treatment of the primary lesion. This review considers the principal clinicopathologic features, differential diagnosis and (where appropriate) nosologic status of this treacherous group of neoplasms.

Connective Tissue↗

PubMed2006

Cytogenetic and molecular genetic findings in dedifferentiated liposarcoma with neural-like whorling pattern and metaplastic bone formation.

Dedifferentiated liposarcoma, a subtype of liposarcoma, is characterized by juxtaposition of well-differentiated liposarcoma with a nonadipocytic sarcoma. A peculiar form of dedifferentiated liposarcoma has been described, characterized by a nonlipogenic component with a neural-like whorling pattern of growth and metaplastic bone formation. We report the cytogenetic and molecular genetic findings of this peculiar form of dedifferentiation in a retroperitoneal tumor found in a 58-year-old woman. The neoplasm had the typical histologic findings and a complex karyotype characterized by several numeric and structural chromosome abnormalities, including the presence of ring and giant rod chromosomes. Molecular genetic studies found high levels of amplification of the MDM2 oncogene, consistent with the amplification of the 12q14 chromosome band, a cytogenetic abnormality commonly found in these tumors. These findings indicate that, despite its unique and peculiar morphologic features, this unusual type of dedifferentiated liposarcoma shares many of the cytogenetic and molecular genetic abnormalities found in other forms of dedifferentiation. However, the specific cytogenetic and molecular determinants of these peculiar morphologic findings remain unknown.

Bone and Bones↗

PubMed2007

Cytogenetic and molecular cytogenetic findings in dedifferentiated liposarcoma with neural-like whorling pattern and metaplastic bone formation.

Dedifferentiated liposarcoma is a subtype of liposarcoma characterized by juxtaposition of well-differentiated liposarcoma with a nonadipocytic sarcoma. A peculiar form of dedifferentiated liposarcoma has been described, characterized by a nonlipogenic component with a neural-like whorling pattern of growth and metaplastic bone formation. We report the cytogenetic and molecular genetic findings of this peculiar form of dedifferentiation in a retroperitoneal tumor found in a 58-year-old female. The neoplasm had typical histologic findings and a complex karyotype characterized by several numeric and structural chromosomal abnormalities, including the presence of ring and giant rod chromosomes. Molecular cytogenetic studies found high levels of amplification of the MDM2 oncogene, consistent with the amplification of the 12q14 chromosome band, a cytogenetic abnormality commonly found in these tumors. These findings indicate that, despite its unique and peculiar morphologic features, this unusual type of dedifferentiated liposarcoma shares many of the cytogenetic features and molecular genetic abnormalities found in other forms of dedifferentiation. The specific cytogenetics and molecular determinants of these peculiar morphologic findings, however, remain unknown.

Bone and Bones↗

PubMed1997

Liposarcoma: a review of current diagnosis and management.

Liposarcoma is an uncommon sarcoma. Its presentation can be deceptive, varying from innocuous to frank malignancy. Liposarcoma behaves differently from other sarcomas. This article highlights the key prognostic factors of liposarcoma, based on current literature, and suggests a plan of management.

Female↗

PubMedDate not supplied

[Retroperitoneal tumors: a case of liposarcoma].

The Authors report a case of retroperitoneal sarcoma, in the histological subtype "liposarcoma", occasionally diagnosed in a 57 year old woman, who presented aspecific symptoms, characterized by dry cough, vomiting and chest pain. Chest TC showed a neoplasm of the retroperitoneum, close to liver, right colon, duodenum and right kidney. The arteriography of the right renal artery showed a neovascolarization inside the mass. A surgical resection was performed. The histological examination confirmed the diagnosis of liposarcoma. Liposarcomas account for 30% of the retroperitoneal soft tissue sarcomas; symptoms and diagnosis are late and the surgical resection of primary neoplasm, metastases and local recurrences representing the only therapeutic choice.

Female↗

PubMed2006

NR0B1 is required for the oncogenic phenotype mediated by EWS/FLI in Ewing's sarcoma.

A number of solid tumors, such as alveolar rhabdomyosarcoma, synovial sarcoma, and myxoid liposarcoma, are associated with recurrent translocation events that encode fusion proteins. Ewing's sarcoma is a pediatric tumor that serves as a prototype for this tumor class. Ewing's sarcomas usually harbor the (11;22)(q24;q12) translocation. The t(11;22) encodes the EWS/FLI fusion oncoprotein. EWS/FLI functions as an aberrant transcription factor, but the key target genes that are involved in oncogenesis are largely unknown. Although some target genes have been defined, many of these have been identified in heterologous model systems with uncertain relevance to the human disease. To understand the function of EWS/FLI and its targets in a more clinically relevant system, we used retroviral-mediated RNAi to "knock-down" the fusion protein in patient-derived Ewing's sarcoma cell lines. By combining transcriptional profiling data from three of these lines, we identified a conserved transcriptional response to EWS/FLI. The gene that was most reproducibly up-regulated by EWS/FLI was NR0B1. NR0B1 is a developmentally important orphan nuclear receptor with no previously defined role in oncogenesis. We validated NR0B1 as an EWS/FLI-dysregulated gene and confirmed its expression in primary human tumor samples. Functional studies revealed that ongoing NR0B1 expression is required for the transformed phenotype of Ewing's sarcoma. These studies define a new role for NR0B1 in oncogenic transformation and emphasize the utility of analyzing the function of EWS/FLI in Ewing's sarcoma cells.

Animals↗

PubMed1989

[Unusual sarcomas of the breast. Report of 3 cases].

Non phylloides sarcomas of the breast are infrequent malignant tumors that can be identified only at histologic examination since clinical presentation may not differ from the more frequent phylloides type. In addition to fibrosarcoma, leiomyosarcoma, rhabdomyosarcoma, angiosarcoma and liposarcoma, the stromal sarcoma of the breast has been recently identified. We report 3 such cases with heterologous components of osteosarcoma, chondrosarcoma and liposarcoma. A third case with an anti-sarcoma appearing post radiotherapy for breast carcinoma is also reported.

Adult↗

PubMed2003

[Dedifferentiated liposarcoma of spermatic cord: degeneration of lipoma previously resected].

Spermatic cord sarcomas are rare tumours. Dedifferentiated liposarcoma accounts for only 10% of all spermatic cord sarcomas. These are usually large-sized tumours histologically characterised for being well-differentiated liposarcomas with some high grade sarcoma areas. Volume, location, mass homogeneity as well as presence of pelvic and retroperitoneal adenopathies are reported by CT and ultrasound techniques. These are useful for post-treatment follow-up. This paper presents one spermatic cord, dedifferentiated liposarcoma from which lipomas from the same spermatic cord had been previously removed in three occasions. We believe this is a degeneration of the earlier resected lipoma. Management is by extended inguinal radical orchiectomy. Value of adjuvant radio- and chemotherapy is uncertain. Post-surgery local relapses are common, and haematogenous and pelvic nodes metastasis likely. Survival at 5 and 10 years is 75% and 63% respectively.

Genital Neoplasms, Male↗

PubMed1982

Bone marrow involvement in adult soft tissue sarcomas.

Bone marrow biopsy was performed as part of the initial assessment in 74 patients with soft tissue sarcoma. Infiltration of the marrow by tumour was present in four cases, all from the group of 56 patients who had other evidence of metastatic disease, giving an overall incidence of 7%. The histological subtypes were pleomorphic rhabdomyosarcoma, angiosarcoma, synovial sarcoma and myxoid liposarcoma, of which the first three were high-grade tumours. Although it was not possible to determine whether response to chemotherapy was influenced by marrow involvement, haematological toxicity seemed excessive.

Adolescent↗

PubMed1992

[Increasing frequency of soft tissue sarcomas in The Netherlands].

Recent data from literature show an increase in incidence and mortality due to soft tissue sarcoma (STS). In the Netherlands age-standardised mortality rates of soft tissue sarcoma (STS) over the period 1950-1988 show a more than fivefold increase. Males predominate over females by a factor of 1.17. Age-adjusted hospital admission rates in 1980-1988 show an increase by a factor of 1.36. The mean estimated incidence is 4.74 per 100,000 person years over a three-year period (1988-1990). The most prevalent histological types in that period were leiomyosarcoma (20.1%), malignant fibrous histiocytoma (16.2%), Kaposi's sarcoma (13.9%) and liposarcoma (13.8%). The distribution of the different histological types changes in time. The increasing incidence of Kaposi's sarcoma is due to the increasing prevalence of AIDS. Hospital admission rates for STS increased from 0.67% of admission rates for all malignant neoplasms in 1970, to 0.96% in 1988. Further epidemiological studies are needed to elucidate the increase of STS throughout the world.

Adolescent↗

PubMed1975

Soft tissue sarcomas.

One hundred fifty-five adult patients with "operable" soft part sarcomas including rhabdomyosarcoma, liposarcoma, leiomyosarcoma and fibrosarcoma of the trunk and extremities are reviewed. Local recurrences of 93% and 60% occurred after local and wide excisions of the primary tumor. In this series of patients, amputation was the most efficient procedure for controlling the primary site. The absolute 5 and 10-year survival rates for all groups of tumors were 50% and 26%. Development of a second primary tumor of a different cell type occurred in 9% of the patients. Local recurrence, single distant metastasis, and/or second primary tumors should be considered potentially curable and appropriate surgical and/or radiation therapy carried out.

Abdomen↗

PubMed2001

Metalloproteinase expression and prognosis in soft tissue sarcomas.

BACKGROUND: Degradation of extracellular matrix by tumor-associated proteases can promote cell invasion and metastasis. This study assessed the prognostic role of MMP2, MMP9 metalloproteinases, and of the metalloproteinase inhibitor TIMP2, related to disease-free survival (DFS), in soft tissue sarcoma (STS) patients. MATERIALS AND METHODS: Level and distribution of MMP2, MMP9, and TIMP2 expression were evaluated on 73 biopsies by immunohistochemistry and immunoblotting. Biopsies included 29 liposarcomas, 29 synovial sarcomas, and 15 malignant peripheral nerve sheath tumors (MPNST). Association between DFS and overall survival with different variables was assessed. RESULTS: In terms of DFS, increased MMP2 reactivity and lack of TIMP2 expression were significant for poor prognosis in all samples (P = 0.0005 and P = 0.006 respectively). MMP2 correlated to histologic grade (P = 0.005). Lack of TIMP2 expression was a poor prognostic factor for DFS in synovial sarcoma (P = 0.009), while MMP2 and MMP9 correlated with metastasis (P = 0.008 and P = 0.005, respectively) and grade (P = 0.001 and P = 0.04 respectively) in liposarcoma. CONCLUSIONS: These prognostic markers that influence growth and spread of tumor cells might be useful to define tumor aggressiveness and risk of the metastasic event.

Adolescent↗

PubMed1995

Molecular and immunohistochemical p53 status in liposarcoma and malignant fibrous histiocytoma: identification of seven new mutations for soft tissue sarcomas.

BACKGROUND: p53 mutations are the most frequently observed tumor-related genetic changes. Mutational analysis concerns mostly carcinomas and is not comprehensive for soft tissue sarcomas. Among soft tissue sarcomas, malignant fibrous histiocytoma (MFH) and liposarcoma represent the most frequent tumor types. Most of the few identified mutations for soft tissue sarcomas are localized in the core domain of p53. A correlation between p53 positive immunoreactivity, missense mutations, and a poor prognosis is generally assumed. However, the character of p53 mutations and their functional importance for the clinical process is still unknown. METHODS: Sixty-two soft tissue sarcoma samples were investigated for the presence of p53 mutations and for p53 immunoreactivity. Exons 4-9 of the p53 gene were amplified from genomic DNA with the polymerase chain reaction. A prescreen for mutations was performed by nonradioactive single strand conformation polymorphism analysis; striking cases were sequenced directly. For an evaluation of the immunohistochemical status, five p53 antibodies were used. RESULTS: In 10 tumor samples 7 new p53 mutations and one polymorphism were identified. Mutations were detected for five liposarcomas (four patients) and four MFHs (three patients). Of the seven mutations, three were missense point mutations, three were deletions, and one was a complex conversion. All mutations but one were localized in the core domain of p53. Of 62 tumor samples, 56% (14 of 32 liposarcomas and 21 of 30 MFHs) were positive for p53 immunostaining. CONCLUSIONS: The mutations identified in the core domain affect codons that are structurally or functionally involved in DNA binding. A relation between p53 positive immunoreactivity and a poor prognosis, but not with an exclusively high tumor grade, is evident. p53 mutations in soft tissue sarcomas have a similar spectrum to those in carcinomas.

Histiocytoma, Benign Fibrous↗

PubMed1996

Myxoid/round cell liposarcoma of the extremities. A clinicopathologic study of 29 cases with particular attention to extent of round cell liposarcoma.

Round cell liposarcoma, a high-grade sarcoma, is a poorly differentiated form of myxoid liposarcoma, which is low grade. It is not known, however, how much of a round cell component within an otherwise typical myxoid liposarcoma results in a neoplasm that behaves as a high-grade sarcoma. Twenty-nine cases of myxoid liposarcoma of the extremities with or without a component of round cell liposarcoma were studied to semiquantitate the amount of round cell component needed to adversely affect prognosis. An estimate of the percent of necrosis, round cell liposarcoma, myxoid liposarcoma, and transitional areas was obtained for each slide on all cases. Transitional areas were defined as those that displayed an increased cellularity compared with typical myxoid liposarcoma, but in which the cells remained spindled, did not have overlapping nuclear borders, and retained an easily discernible plexiform vascular pattern. The amount of necrosis was subtracted from the total material available for evaluation, and a composite estimate of the percent of round cell, myxoid, and transitional areas was obtained. Two tumors were located on the upper extremity, 27 on the lower extremity; tumor size ranged frm 3 to 30 cm (median, 14 cm). All 29 tumors had a myxoid component, with a range from 12 to 100% (median, 73%). The range of transitional component for all 29 tumors was 0 to 88% (median, 11%). Twenty-one tumors had transitional areas (range, 4-88%). The range of round cell component for all 29 tumors was 0 to 58% (median, 0%). Twelve tumors had round cell areas (range, 1-58%). Seventeen patients are either alive without disease, or died from unrelated causes at 24-202 months (median, 96 months). Twelve patients are either alive with metastases or died of disease at 10 to 180 months (median, 53 months). Patients with > 5% round cell component in their initial tumor had a statistically significant higher rate of metastasis or death due to disease than those with < or = 5% round cell liposarcoma (p = 0.05). In addition, patients with myxoid liposarcoma with transitional areas did not fare worse than those with myxoid liposarcoma alone. In conclusion, we found that a round cell component of > 5% portends a higher risk of metastasis or death from disease. Furthermore, transitional areas alone do not appear to alter the prognosis of myxoid liposarcoma. Thus, only those areas that are unequivocally round cell liposarcoma should be designated as high grade.

Adolescent↗

PubMed2006

Expression of the FUS-CHOP fusion protein in primary mesenchymal progenitor cells gives rise to a model of myxoid liposarcoma.

A subset of sarcomas is associated with specific chromosomal translocations that give rise to fusion genes believed to participate in transformation and oncogenesis. Identification of the primary cell environment that provides permissiveness for the oncogenic potential of these fusion genes is essential to understand sarcoma pathogenesis. We have recently shown that expression of the EWS-FLI-1 fusion protein in primary mesenchymal progenitor cells (MPCs) suffices to develop Ewing's sarcoma-like tumors in mice. Because most sarcomas bearing unique chromosomal translocations are believed to originate from common progenitor cells, and because MPCs populate most organs, we expressed the sarcoma-associated fusion proteins FUS/TLS-CHOP, EWS-ATF1, and SYT-SSX1 in MPCs and tested the tumorigenic potential of these cells in vivo. Whereas expression of EWS-ATF1 and SYT-SSX1 failed to transform MPCs, FUS-CHOP-expressing cells formed tumors resembling human myxoid liposarcoma. Transcription profile analysis of these tumors revealed induction of transcripts known to be associated with myxoid liposarcoma and novel candidate genes, including PDGFA, whose expression was confirmed in human tumor samples. MPC(FUS-CHOP) and the previously described MPC(EWS-FLI-1) tumors displayed distinct transcription profiles, consistent with the different target gene repertoires of their respective fusion proteins. Unexpectedly, a set of genes implicated in cell survival and adhesion displayed similar behavior in the two tumors, suggesting events that may be common to primary MPC transformation. Taken together, our observations suggest that expression of FUS-CHOP may be the initiating event in myxoid liposarcoma pathogenesis, and that MPCs may constitute one cell type from which these tumors originate.

Animals↗

PubMed2003

Overexpression of the Wilms' tumor gene WT1 in human bone and soft-tissue sarcomas.

The expression levels of the Wilms' tumor gene WT1 were examined in 36 cases of various types of human bone and soft-tissue sarcomas using quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR). They included 12 malignant fibrous histiocytomas (MFH), 3 malignant peripheral nerve sheath tumors (MPNST), 6 synovial sarcomas (SyS), 4 myxoid liposarcomas (MyLS), one angiosarcoma (AGS), one clear cell sarcoma (CCS), and 9 osteosarcomas (OS). Eleven (92%) of 12 MFH, 2 (67%) of 3 MPNST, all (100%) of 6 SyS, 2 (50%) of 4 MyLS, one AGS, one CCS, and 5 (56%) of 9 OS cases overexpressed WT1 in the range of 1.4 x 10(-3)-3.9 x 10(-1) levels (WT1 expression level in K562 leukemic cells was defined as 1.0). Thus, 28 (78%) out of 36 various types of human bone and soft-tissue sarcomas overexpressed the WT1 gene. Immunohistochemical analysis showed positive staining for WT1 protein in all of 4 cases (one case each of MFH, MyLS, AGS and OS) with WT1 gene overexpression detected by RT-PCR analysis, demonstrating clearly that WT1 was expressed at the protein level in various types of human bone and soft-tissue sarcomas. The direct sequencing analysis of the WT1 genomic DNA showed no mutations in any of 10 exons of the WT1 gene in 8 different sarcoma samples (3 MFH, one SyS, one MyLS, one AGS, and 2 OS). The present study demonstrates that various types of human bone and soft-tissue sarcomas frequently overexpress the wild-type WT1 gene, suggesting an important role of the wild-type WT1 gene in tumorigenesis of various types of human bone and soft-tissue sarcomas.

Adult↗