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Low-grade fibrosarcoma of the proximal humerus.

We present the clinical, radiographical and pathological features of low-grade fibrosarcoma of the left proximal humerus in a 23-year-old man in whom it was necessary to distinguish the tumor from desmoplastic fibroma, malignant fibrous histiocytoma and intramedullary well-differentiated osteosarcoma. The patient presented with a 10-day history of pain in his left upper arm sustained when trying to break his fall with his left hand when slipping in the street. Plain radiography revealed an expanding multilobular osteolytic lesion from the proximal metaphysis to the diaphysis of his left humerus, accompanied by a pathological fracture at the distal portion of the lesion. Open biopsy of the lesion was performed twice; however, a conclusive diagnosis could not be obtained. The patient underwent wide excision and prosthetic replacement of the left proximal humerus. Histologically, the resected tumor was composed of both cellular areas and hypocellular areas. Cellular areas revealed a proliferation of bundles of uniform fibroblastic spindle-shaped cells with minimal cellular atypia, mixed with abundant intercellular collagenization. Mitotic figures were occasionally seen. Hypocellular areas showed myxoid features with loose bundles of collagen fibers. The patient demonstrates no evidence of disease 42 months after surgery. It is important to detect the scant atypical cells for the differential diagnosis of low-grade fibrosarcoma and desmoplastic fibroma of bone.

Adult↗

Ovarian fibrosarcoma with long-term survival: a case report.

Primary ovarian fibrosarcoma is an exceedingly rare malignant ovarian stromal tumor which has a poor prognosis. We report here a 46-year-old woman who suffered from irregular vaginal bleeding for 2 months. She received hysterectomy and salpingo-oophorectomy due to a provisional diagnosis of uterine and ovarian tumors. At surgery, an 8-cm ovarian solid multilobular tumor was found. Frozen section examination revealed an ovarian fibrosarcoma. She then underwent staging procedures including intraperitoneal washing, cytology, and pelvic and para-aortic lymph node sampling. Final pathologic examination revealed that the tumor exhibited densely packed spindle cells in storiform configuration with obvious increased mitotic activity. In addition, the flow cytometric study showed marked elevated percentage of tumor cells in the S phase (13.1%). After surgery, the patient received six courses of combination chemotherapy with epirubicin, ifosfamide, and dacarbazine (DTIC). The patient stood the treatment well and is free from disease 6 years later.

Antineoplastic Combined Chemotherapy Protocols↗

Congenital infantile fibrosarcoma.

Infantile fibrosarcoma is a rare tumour in the paediatric age group. It occurs mainly in children below the age of 5 years. About 200 cases have been reported in the literature so far, very few of them in new-borns. We present here a case of infantile fibrosarcoma in a 27-day-old baby.

Arm↗

[Observations in two cases of primary fibrosarcoma of the lung (author's transl)].

Two cases of primary fibrosarcoma of the lung are reported. The different clinical findings as well as the different courses in both patients reveal problems in diagnosis and treatment of this rare pulmonary lesion. The diagnostic aspects are given and discussed with regards to bronchial carcinoma. It is believed that lobectomy is the rational treatment of primary fibrosarcoma although pneumonectomy must be considered in the indifferentiated typ. The doubtful prognosis requires an exact postoperative follow up in order to have the change of early surgical treatment or irradiation if metastasis or recurrence of the tumor occurs.

Adult↗

Congenital fibrosarcoma of the jejunum in a premature infant with meconium peritonitis.

We report an unusual case of perforation of a congenital fibrosarcoma of the jejunum in utero and secondary meconium peritonitis. Prenatal ultrasound showed polyhydramnios and fetal ascites from 25 gestational weeks in the absence of other fetal congenital anomalies. A 2200 g baby girl was born at 34 weeks gestation, presenting with severe generalized edema and respiratory distress immediately after birth. Plain radiography revealed progressive abdominal distension and pneumoperitoneum. The baby subsequently underwent surgery at the age of one day. A perforation of the upper jejunum, which had resulted in meconium peritonitis, was discovered intraoperatively and the perforated section of the intestine was resected and anastomosed successfully. The postoperative course was uneventful. Pathological examination confirmed that the perforation was caused by rupture of a congenital fibrosarcoma originating from the jejunum. Rupture of a malignant tumor is an extremely rare cause of peritonitis in the fetus and neonate.

Female↗

Primary tracheal fibrosarcoma in a child: a case of tracheal resection under ECMO support.

We report a case of severe airway obstruction due to endotracheal fibrosarcoma in a 3-year-old boy. Successful tracheal resection and reconstruction was performed under extracorporeal membrane oxygenation support. A solid, elastic hard tumor with a smooth surface was attached by a tiny stalk structure to the membranous part of the lower trachea. Histological findings of the tumor were consistent with infantile fibrosarcoma, showing proliferation of spindle cells forming interlacing patterns.

Airway Obstruction↗

Expression of antigenic crossreactivity to RD114 p 30 protein in a human fibrosarcoma cell line.

An antigen crossreacting with the 30,000-molecular-weight protein (p30) of the feline endogenous oncornavirus (RD114) was detected in a well-characterized human fibrosarcoma cell line, HT1080, by indirect immunofluorescence. Three antisera against RD114 p30 gave similar positive results, while two antisera prepared against simian sarcoma virus p30, one antiserum prepared against murine leukemia virus p30, and one antiserum prepared against feline leukemia virus p30 gave no immunofluorescence. The reactivity observed with the antiserum against RD114 p30 was detected in 10-40% of the cells at early passages and was no longer expressed by the forty-first subculture. The reactivity could be removed by adsorption of the antiserum with RD114-infected dog or human cells, but not by uninfected cells or by cells infected with an antigenically unrelated oncornavirus, feline leukemia virus. Neither complete virus particles nor reverse transcriptase (RNA-dependent DNA nucleotidyltransferase) activity was detected in the culture. These experiments suggest that the fibrosarcoma cell line is expressing an antigen related to the p30 protein of RD114 baboon endogenous virus group of oncornaviruses without producing complete virions.

Animals↗

Correlation of patterns of anchorage-independent growth with in vivo behavior of cells from a murine fibrosarcoma.

The pattern of in vitro anchorage-independent growth of tumor cells from the murine UV-2237 fibrosarcoma correlated with their ability to produce experimental metastasis in vivo. When seeded into 0.3% Noble agar semisolid medium, cells of metastatic clones developed into larger tumor colonies at a faster rate than did cells of clones with low metastatic potential. Furthermore, when tumor cells were plated into 0.6% Noble agar, colony development by cells of low metastatic potential clones was almost completely restricted. Tumor cells from the heterogeneous parent UV-2237 fibrosarcoma were plated into dishes containing 0.6% agar semisolid medium. In separate experiments, 16 colonies were isolated 2 weeks thereafter and were established as individual cell lines in monolayer cultures. All of these cell lines produced experimental metastases as determined by in vivo lung colony assay. The data suggest that anchorage-independent growth of UV-2237 tumor cells in 0.6% Noble agar semisolid medium is selective and permits the isolation of metastatic subpopulations.

Agar↗

Relation of cell surface antigens on methylcholanthrene-induced fibrosarcomas to immunoglobulin heavy chain complex variable region-linked T cell interaction molecules.

For optimal activation, T suppressor cells must receive a signal froma specialized inducer cell. The activating signal is delivered by a molecular complex that is composed, in part, of polymorphic gene products that are controlled by the immunoglobulin heavy chain complex (Igh) and that map to the variable region (Igh-V) of the complex. Consequently, if suppressor/inducer cells and their acceptor cells do not share Igh-V-encoded polymorphisms, the inducer molecules fail to activate the suppressor cells. Other polymorphic gene products (those that act as transplantation antigens on methylcholanthrene-induced fibrosarcomas) have been shown to be encoded by a gene(s) that maps to the same general region of chromosome 12 as does the Igh complex. Therefore, we tested the hypothesis that polymorphic gene products expressed by the T suppressor/inducer cell and its biologically active product were related to the transplantation antigens on these fibrosarcomas. We have found that isoantisera directed to a number of BALB/c methylcholanthrene-induced tumors block the induction of T suppressor cells but they do so only if the inducer or acceptor T cell (or both) expresses BALB/c Igh-linked polymorphisms. All other BALB/c gene products are irrelevant. These findings suggest that "transformation related antigens" on some sarcoma cells are variants of, or are otherwise related to, the cell interaction molecules that T cell subsets use to communicate with one another under normal circumstances. Furthermore, the findings that (a) multiple methylcholanthrene-induced tumors express serologically related antigens (as well as the unique ones that have been previously demonstrated by transplantation tests) and (b) these serologically related antigens can be found on Igh-V-controlled T cell communication molecules raise the intriguing possibility that, like certain viruses, methylcholanthrene reacts with specific regions of cellular DNA that either directly or indirectly regulate the expression of other specific genes (in this particular case the genes that encode the T cell communication molecules).

Animals↗

Molecular characterization of novel H-2 class I molecules expressed by a C3H UV-induced fibrosarcoma.

Two novel class I-like molecules expressed on tumor 1591, a C3H UV-induced fibrosarcoma, are biochemically characterized using two-dimensional gel electrophoresis, a cross-blocking RIA, and tryptic peptide mapping. One novel molecule that reacts with CP28, a syngeneic tumor-specific monoclonal antibody, appears mosaic because it possesses characteristics of both Kk and Dk class I molecules. The second molecule is closely related but not identical to the bona fide Ld molecule expressed on BALB/c spleen. Thus 1591 expresses at least two novel class I molecules and is vigorously rejected by normal C3H mice, while a variant tumor derived from 1591, termed AS7, does not express these two class I molecules although it still expresses Kk and Dk. The significance of these observations to the immunobiology and genetics of the UV-induced fibrosarcoma system is discussed. Speculations on the role that the major histocompatibility complex may play in the immunosurveillance of neoplasms are also presented.

Animals↗

Transcription factor EGR-1 suppresses the growth and transformation of human HT-1080 fibrosarcoma cells by induction of transforming growth factor beta 1.

The early growth response 1 (EGR-1) gene product is a transcription factor with role in differentiation and growth. We have previously shown that expression of exogenous EGR-1 in various human tumor cells unexpectedly and markedly reduces growth and tumorigenicity and, conversely, that suppression of endogenous Egr-1 expression by antisense RNA eliminates protein expression, enhances growth, and promotes phenotypic transformation. However, the mechanism of these effects remained unknown. The promoter of human transforming growth factor beta 1 (TGF-beta 1) contains two GC-rich EGR-1 binding sites. We show that expression of EGR-1 in human HT-1080 fibrosarcoma cells uses increased secretion of biologically active TGF-beta 1 in direct proportion (rPearson = 0.96) to the amount of EGR-1 expressed and addition of recombinant human TGF-beta 1 is strongly growth-suppressive for these cells. Addition of monoclonal anti-TGF-beta 1 antibodies to EGR-1-expressing HT-1080 cells completely reverses the growth inhibitory effects of EGR-1. Reporter constructs bearing the EGR-1 binding segment of the TGF-beta 1 promoter was activated 4- to 6-fold relative to a control reporter in either HT-1080 cells that stably expressed or parental cells cotransfected with an EGR-1 expression vector. Expression of delta EGR-1, a mutant that cannot interact with the corepressors, nerve growth factor-activated factor binding proteins NAB1 and NAB2, due to deletion of the repressor domain, exhibited enhanced transactivation of 2- to 3.5-fold over that of wild-type EGR-1 showing that the reporter construct reflected the appropriate in vivo regulatory context. The EGR-1-stimulated transactivation was inhibited by expression of the Wilms tumor suppressor, a known specific DNA-binding competitor. These results indicate that EGR-1 suppresses growth of human HT-1080 fibrosarcoma cells by induction of TGF-beta 1.

Binding Sites↗

Induction of early growth response-1 gene expression by calmodulin antagonist trifluoperazine through the activation of Elk-1 in human fibrosarcoma HT1080 cells.

The early growth response gene-1 (Egr-1) is a transcription factor that plays an important role in cell growth and differentiation. It has been known that Egr-1 expression is down-regulated in many types of tumor tissues, including human fibrosarcoma HT1080 cells, and introduction of the Egr-1 gene into HT1080 cells inhibits cell growth and tumorigenic potential. Trifluoperazine (TFP), a phenothiazine class calmodulin antagonist, is known to inhibit DNA synthesis and cell proliferation and potentially important in antitumor activities. To understand the regulatory mechanism of Egr-1, we investigated the effect of TFP on expression of Egr-1 in HT1080 cells. Herein, we report that Egr-1 expression was increased by TFP in synergy with serum at the transcriptional level. Both the Ca(2+)/calmodulin-dependent protein kinase II inhibitor KN62 and the calcineurin inhibitor cyclosporin A enhanced TFP-dependent increase of Egr-1, suggesting that the Ca(2+)/calmodulindependent pathway plays a role in regulation of Egr-1 expression in HT1080 cells. The TFP-stimulated increase of the Egr-1 protein was preferentially inhibited by the MEK-specific inhibitor PD98059. In addition, activation of human Egr-1 promoter and the transcriptional activation of the ternary complex factor Elk-1 induced by TFP were inhibited both by pretreatment of PD98059 and by expression of the dominant-negative RasN17. These results indicate that the Ras/MEK/Erk/Elk-1 pathway is necessary for TFP-induced Egr-1 expression. We propose that the calmodulin antagonist TFP stimulates Egr-1 gene expression by modulating Ras/MEK/Erk and activation of the Elk-1 pathway in human fibrosarcoma HT1080 cells.

Calmodulin↗

Primary fibrosarcoma and malignant fibrous histiocytoma of bone--a comparative ultrastructural study: evidence of a spectrum of fibroblastic differentiation.

As primary bone fibrosarcoma (FS) and malignant fibrous histiocytoma (MFH) have similar clinical, radiographic, or survival manifestations, ultrastructural and immunohistochemical studies were undertaken to determine the differentiation pathways of constituent malignant cells. Twelve cases of primary intraosseous FS and MFH were selected for this ultrastructural comparative study and were analyzed for fibroblastic or modified fibroblastic differentiation. There were 4 FS cases and 8 MFH cases, of which 5 were storiform-pleomorphic, 2 were giant cell, and 1 was myxoid type. All FS consisted of spindle fibroblasts with a prominent rough endoplasmic reticulum and Golgi apparatus, variable amounts of vimentin intermediate filaments, and extracellular collagen fibrils. The MFH were composed of a mixture of spindle and pleomorphic fibroblasts (8/8), histiofibroblasts (4/8), and myofibroblasts (3/8). Variable numbers of undifferentiated cells were found in both tumors. In conclusion, fibroblastic differentiation and collagen production was noted in all cases. The often pleomorphic histiofibroblasts present in some MFH cases most likely represent "modified fibroblasts," similar to myofibroblasts. These findings support the hypothesis that the fibroblast and its variants are the predominant cell types found in these tumors, suggesting that the diagnostic entity MFH should be classified as a pleomorphic fibrosarcoma.

Adolescent↗

Fibrosarcoma mimicking plasmacytoma or carcinoma: an ultrastructural study of 4 cases.

Because the fibroblast has a remarkable capability of phenotypic modulations, reflected in both morphologic and immunohistochemical (IHC) changes, ultrastructural studies are mandatory to identify the variants of fibroblasts. Myofibroblasts or histiofibroblasts are such examples, demonstrating chimeric ultrastructural features of fibroblastic cells in common with smooth muscle cells or with histiocytes, respectively. The presence of epithelioid fibroblastic cells sharing morphologic features with epithelial or plasma cells has not been yet characterized. The authors identified 4 cases of fibrosarcomas (FS) characterized by an unusual phenotype and associated with peculiar ultrastructural findings. The electron microscopic (EM) findings were correlated with the histologic appearance and immunoprofile. All tumors were located in the extremities, 3 in soft tissues and 1 in the bone. By light microscopy 2 cases were composed predominantly by round uniform cells with a striking plasmacytoid appearance. One case mimicked carcinoma, composed predominantly by epithelioid cells and scattered giant tumor cells. The fourth case showed a mixture of plasmacytoid-like and epithelioid cells. By IHC, tumor cells were positive for vimentin and in 2 cases also for epithelial membrane antigen. Kappa/lambda light chain and cytokeratins markers were negative. By EM all 4 tumors showed in addition to classic features of fibroblasts, unusual epithelial-type features, such as secretory granules of "neurosecretory-type" (3 cases), rudimentary cell junctions (3 cases), microvilli (2 cases), and lumen-like structures (1 case). One plasmacytoid-type tumor showed finely granular extracellular deposits. The study describe 4 examples of fibrosarcomas with unusual features at the ultrastructural level, which are associated microscopically with a peculiar phenotype, mimicking plasmacytoma or carcinoma. These findings broaden the spectrum of fibroblastic cell variants in neoplasia.

Adult↗

Fibrosarcoma of the brachial plexus presenting in childhood.

We report a case of malignant fibrosarcoma involving the brachial plexus presenting in childhood. Primary malignant tumours of the brachial plexus are rare entities. In particular, fibrosarcoma of the brachial plexus occurring in a child has not been previously reported. Dilemmas in resolving the management and long-term consequences of this condition are discussed.

Arm↗

Infantile fibrosarcoma associated with urticaria pigmentosa.

The authors report the case of an infant with urticaria pigmentosa who developed infantile fibrosarcoma. The tumor was successfully resected but the skin lesions have persisted. This is the first report of a fibrosarcoma in association with urticaria pigmentosa. A brief review is presented of the available medical literature on associations of solid tumors with mastocytosis.

Fibrosarcoma↗

Response of a rodent fibrosarcoma to photodynamic therapy using 5-aminolaevulinic acid or polyhaematoporphyrin.

The effects of 5-aminolaevulinic acid (ALA)-based photodynamic therapy (PDT) on the growth of an intradermal rat fibrosarcoma have been determined following topical, intravenous, or intratumour application of ALA. The pattern of tumour growth was identical following each type of therapy and we conclude that the efficacy of ALA-PDT is independent of the route of drug administration, at least in this tumour system. We have also compared the efficacy of interstitial ALA-based PDT with similar therapy using a conventional photosensitizer, polyhaematoporphyrin (PHP). ALA-PDT was less effective than PHP-based therapy at inhibiting the growth of a subcutaneous rat fibrosarcoma at light doses over 300 J. It is suggested that protoporphyrin IX photo-bleaching may limit the effectiveness of treatment, whilst the more bleach-resistant PHP may continue to be effective at higher light doses.

Aminolevulinic Acid↗

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.

Animals↗