Undifferentiated sarcoma: does it exist? A clinicopathologic study of 7 pediatric cases and review of literature

Undifferentiated sarcomas are primitive mesenchymal tumors that cannot be classified among standardized histopathologic entities. Whether they represent a homogeneous group with common histogenesis and clinical behavior or comprise a variety of tumors able to differentiate along specific maturative lineages is still debated. To identify prognostic and histogenetic markers, we analyzed 7 undifferentiated sarcomas (4 in the trunk and 3 in the extremities). Mean patient age was 7.5 years, and mean follow-up was 18 months. Two clinicopathologic subtypes emerged from this study. Four primitive mesenchymal undifferentiated sarcomas arose mainly on the trunk and very proximal extremities, had an aggressive clinical course with poor outcome (3 deaths from disease, 1 with persistent disease), and displayed sheets of oval cells, with bland nuclei. Three spindle cell undifferentiated sarcomas arose on the extremities, had a favorable outcome, and showed elongated spindle cells with areas of primitive fibrosarcoma. All were negative for epithelial membrane antigen, cytokeratins, CD34, smooth muscle actin, desmin, Myf4, and HMB45 and showed nuclear staining for INI. Focal staining for S100 and CD99 was found in 3 and 4, respectively. Among stem cell markers, CD117 was positive in 3 cases (1 primitive, 2 spindle), nestin in 5 cases (4 primitive, 1 spindle), and CD105-stained tumor cells lining newly formed vascular spaces in 4 cases (1 primitive, 3 spindle). Survivin was weakly expressed in 6 cases and reflected low levels of mRNA (median survivin/GAPDH ratio, 1.096). Cytogenetic analysis revealed nonspecific translocations in 3 tumors. No translocations associated with Ewing sarcoma, synovial sarcoma, or alveolar rhabdomyosarcoma were found. In summary, primitive undifferentiated sarcomas occur in the trunk, behave aggressively, and express nestin. Spindle cell undifferentiated sarcomas occur in extremities, have a favorable outcome, resemble fibrosarcomas, and have similarly low survivin levels and display CD105-positive vascular spaces, which may represent an early hemangiopericytomatous pattern.     

Peripheral-type benzodiazepine receptor (PBR) and PBR drug ligands in fibroblast and fibrosarcoma cell proliferation: role of ERK, c-Jun and ligand-activated PBR-independent pathways

Peripheral-type benzodiazepine receptor (PBR) is a 18-kDa high-affinity drug and cholesterol binding protein, that has been implicated in several physiological processes, such as cholesterol transport and mitochondrial respiration. Specific PBR ligands regulate cell proliferation, although their action is controversial and probably cell-type specific. The aim of the present study was to examine the expression of PBR in cells of mesenchymal origin, i.e. human fibroblasts and fibrosarcoma cells, as well as its role in the regulation of their proliferation. Both mesenchymal cell types express high levels of PBR, localized exclusively in mitochondria. PBR-specific drug ligands, the isoquinoline carboxamide PK 11195 and the benzodiazepine Ro5-4864, at relative high concentrations (10(-4)M), exert a strong inhibitory effect on cell proliferation by arresting the cells at the G0/G1 phase of the cell cycle, while no apoptotic cell death was observed. In normal fibroblasts, this inhibition was correlated with a decrease in the activation of the cell cycle markers ERK and c-Jun. PBR knockdown by RNA inhibition did not affect the proliferation of either cell type and did not influence the inhibitory effect of PK 11195 and Ro5-4864 on cell growth. These data suggest that in fibroblasts and fibrosarcoma cells PBR drug ligands inhibit cell proliferation in a PBR-independent manner. These results are in contrast to data reported on cells of epithelial origin, suggesting that the origin of the cells is crucial in defining the role of PBR in their proliferation, and raise caution in the commonly made assumption that PBR mediates cell functions affected by PBR drug ligands.     

In Vitro Proliferation of Fibrosarcoma Cells Depends on Intact Functions of Lipoxygenases and Cytochrome P-450-Monooxygenase

Proliferation of mouse fibrosarcoma cells G:5:113 was studied in vitro after affecting particular pathways of arachidonic acid metabolism by selected inhibitors. After 48 hours of cultivation with nonspecific lipoxygenase inhibitors, nordihydroguaiaretic acid (NDGA) and esculetin; a specific 12-lipoxygenase inhibitor, baicalein; and inhibitor of five-lipoxygenase activating protein, MK-886, markedly suppressed the number of cells and induced significant changes in cell cycle distribution in a dose-dependent manner. While proadifen, an inhibitor of cytochrome P-450-monooxygenase, applied in low concentrations, increased the cell number, at higher concentrations, it inhibited cell proliferation and significantly changed the cell cycle. Cyclooxygenase inhibitors, ibuprofen, flurbiprofen, and diclofenac suppressed cell numbers only moderately without any changes in the cell cycle. The occurrence of apoptosis was not significant for any of the selected drugs in comparison with untreated control cells. Moreover, not even one of the drugs caused the specific cleavage of poly (ADP-ribose) polymerase to the 89-kDa fragment, however, a decrease in total amount of this protein was observed after treatment with NDGA and esculetin. We conclude that the proliferation ability of fibrosarcoma cells G:5:113 in vitro depends on intact functions of 5-lipoxygenase, 12-lipoxygenase, and cytochrome P-450-monooxygenases, and that the effects of inhibitors do not include regulation of apoptosis.     

Hyalinizing spindle cell tumor with giant rosettes and low-grade fibromyxoid sarcoma: an immunohistochemical and ultrastructural comparative investigation

Hyalinizing spindle cell tumor with giant rosettes (HSCTGR) and low-grade fibromyxoid sarcoma (LGFMS) are 2 variants of fibrosarcoma, which share several clinicopathologic features. This study compares the light microscopic, immunohistochemical, and ultrastructural features of 2 examples of HSCTGR and 3 of LGFMS to determine the degree of overlap of these 2 tumors. HSCTGR were composed of bland spindle cells within hyalinized to myxoid stroma. Scattered throughout the lesions were characteristic rosette-like structures, formed by a central collagenous core surrounded by spindled neoplastic cells. LGFMS consisted of a mixture of fibrous and myxoid areas, composed of fibroblast-like cells arranged in a swirling, whorled growth pattern. Immunohistochemical analysis showed diffuse positivity for vimentin in all cases, while few scattered tumor cells stained for CD57, CD34, factor XIIIA, and actin. The extracellular matrix showed intense positivity for type IV collagen, laminin, and fibronectin, with the exception of myxoid areas of LGFMS and the central core of the giant rosettes in HSCTGR. Ultrastructurally, both tumor types were composed of cells with the features of fibroblasts, embedded in a collagenous stroma with irregular deposits of amorphous basal lamina-like substance. In conclusion, HSCTGR and LGFMS share similar immunophenotypic and ultrastructural features, and together with other fibrosing fibrosarcomas, like sclerosing epithelioid fibrosarcoma, may constitute a subset of fibrosarcomas formed by fibroblasts capable of producing large amounts of basal lamina-like material.     

雷公藤内酯醇对纤维肉瘤HT-1080细胞表达基质金属蛋白酶的影响

目的研究雷公藤内酯醇（TL）对人纤维肉瘤HT-1080细胞表达基质金属蛋白酶（MMP）-2和-9的影响。方法以终浓度分别为6、12和18nM的TL处理HT-1080细胞72h，未加药物处理细胞为对照组，RT—PCR检测MMP-2和-9mRNA表达，明胶酶谱实验检测MMP-2和-9的活性。结果与对照组比较，18nMTL处理HT-1080细胞72h后，MMP-9的mRNA表达及活性明显下调，但MMP-2的表达及活性无明显变化。结论TL抑制纤维肉瘤HT-1080细胞表达MMP-9。     

Malignant Fibrosarcoma with Features of Myxoma

Left atrial tumor, diagnosed as myxoma at first investigation, was later demonstrated to be a malignant fibrosarcoma with myxoid change. Myxoma should be diagnosed and managed carefully because of its wide range of histopathologic features.     

Fibrosarcoma in bizarre parosteal osteochondromatous proliferation

Bizarre parosteal osteochondromatous proliferation (BPOP) is a rare benign lesion predominantly involving the small bones of the hands and feet. Malignant transformation in BPOP has not been documented in the English literature. This report presents the coexistence of fibrosarcoma with BPOP in the right distal fibula of an 18-year-old woman. Received: 18 April 2000 Revision requested: 2 June 2000 Revision received: 23 June 2000 Accepted: 28 June 2000     

鼻腔硬化性上皮样纤维肉瘤

硬化性上皮样纤维肉瘤（sclerosing epithelioid fibrosarcoma,SEF）是一种罕见的好发于软组织的肿瘤由Meis-kindblom等在1995年首次报道,原发于鼻腔的SEF未见报道。2008年3月我科收治1例鼻腔SEF的患者,现对其临床表现、病理特征、诊断等进行初步分析。     

Transduction of murine and human tumors using recombinant adenovirus vectors

Background: Most cytokine-based cancer gene therapy clinical trials have used labor-intensive, retrovirus-mediated strategies resulting in unpredictable gene expression. Recombinant AdV vectors were evaluated for easier, more reproducible gene transfer into 12 human melanoma, 2 murine fibrosarcomas, and 8 other tumor cell lines. Methods: AdV vectors contained a reporter (Escherichia coli β-galactosidase or firefly luciferase) or cytokine gene (human interleukin-2 [IL-2] or IL-7). Transduction efficiencies and expression levels were assessed by histochemical staining, flow cytometry, polymerase chain reaction, fluorometry, and enzyme-linked immunosorbent assay. Tumorigenicity was determined by subcutaneous injection of cells into syngeneic mice. Results: All cell lines studied were transduced with AdV. Most cell lines exhibited 100% transduction efficiencies (by flow cytometry) at multiplicities of infection (MOI) ε10. Gene expression correlated linearly with MOI, but a cytopathic effect was observed at MOI >100 with all vectors. Nanogram gene expression levels were routinely achieved. Irradiation (30 Gy) minimally affected expression levels. Tumorigenicity of AdV-IL-2-transduced fibrosarcoma cells in mice was inversely related to IL-2 production. A majority of mice that rejected their tumor challenge were immune to tumor rechallenge. Conclusions: E1-deleted AdV vectors may prove useful in generating tumor vaccines ex vivo with high, transient cytokine expression levels. Results of this study were presented in part at the 45th Annual Meeting of The Society of Surgical Oncology, Boston, Massachusetts, March 23–26, 1995.     

Familial risk for soft tissue tumors: a nation-wide epidemiological study from Sweden

Purpose Reliable data on familial risks are important for clinical counseling and cancer genetics. However, population-based studies on familial soft tissue tumors are limited, which we will examine. Methods Adjusted standardized incidence ratios (SIRs), calculated from the nation-wide Swedish Family Cancer Database, were used to measure the familial risk. Results There were 17 offspring-parent pairs with concordant soft tissue tumuors, the SIR was increased but not significant. Offspring soft tissue tumors were associated with paternal prostate and endocrine gland tumors and Hodgkin’s disease. Offspring myxosarcoma was associated with paternal endocrine gland tumors. Offspring fibrosarcoma was associated with parental stomach cancer and liposarcoma was associated with parental bladder cancer and maternal breast cancer. Leiomyosarcoma was associated with maternal breast cancer. The associations of myxosarcoma with melanoma and liposarcoma with non-Hodgkin’s lymphoma were noted among siblings. Conclusions The present study showed that familial clustering of soft tissue tumors was limited to specific subtypes. Because of multiple comparisons, some of observed associations may be negative. Aggregation of melanoma and myxosarcoma among siblings may suggest Werner syndrome. A very small proportion of soft tissue sarcomas may be explained by Li–Fraumeni syndrome. Other novel associations, such as offspring liposarcoma with parental bladder cancer, and liposarcoma and non-Hodgkin’s lyhphoma among siblings, may be related to other unidentified familial diseases.