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PubMed1999

Amplification and overexpression of the hepatocyte growth factor receptor (HGFR/MET) in rat DMBA sarcomas.

In the present study subcutaneous fibrosarcomas were induced by the carcinogen 7,12-dimethylbenz(a)anthracene (DMBA) in rats from F1 generation cross breedings of two different inbred strains. Comparative genomic hybridization (CGH) analysis, which allows detection of DNA sequence copy changes, was applied to one of the tumors and it was found that there were increased copy numbers of sequences at chromosome 4q12-q21 in this tumor. We have previously determined that the loci for the hepatocyte growth factor (Hgf) and hepatocyte growth factor receptor (Hgfr/Met), a protooncogene, are situated in this particular chromosome region. Using probes for the two genes in FISH (fluorescence in situ hybridization) and in Southern blots we found that the Hgfr/Met gene was amplified in five of the 19 sarcomas studied, and that the Hgf gene was coamplified in two of them. Northern and Western blots and tyrosine phosphorylation analysis showed that the HGF receptor was overexpressed and functional in all five tumors, as well as in two additional tumors. In summary, both amplification and overexpression of the Hgfr/Met gene was found in about 25% of DMBA-induced experimental rat sarcomas, and HGF receptor overexpression alone was seen in two additional tumors. Possibly this reflects an involvement in paracrine or autocrine stimulation of growth and invasiveness by HGF. Our finding could provide a rodent model system to increased knowledge about causality and therapy, which may be applicable to the sizeable fraction of human musculoskeletal tumors displaying MET overexpression.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1994

Resection of primary hepatic malignant fibrous histiocytoma, fibrosarcoma, and leiomyosarcoma.

Four patients had resection for primary hepatic sarcoma: one with malignant fibrous histiocytoma (MFH), two with poorly differentiated fibrosarcoma, and one with leiomyosarcoma. Age ranged from 40 to 69 years. One patient had a cousin and a grandmother who had died of hepatic tumors. At presentation, all patients had pain; one had tumor rupture, and one had mental changes and hypoglycemia. None had hepatitis or cirrhosis. Results of laboratory evaluation were nonspecific, including normal carcinoembryonic antigen and alpha-fetoprotein levels. Computed tomography showed hypodense masses with enhancement. Angiography showed a hypervascular mass in three patients and an avascular mass in the patient with MFH. Despite large tumors (8 to 32 cm), portal and hepatic veins were not invaded. The pattern of vascularization and lack of venous invasion helps differentiate primary hepatic sarcomas from hepatocellular carcinoma, especially in noncirrhotic patients. All patients had extensive hepatic resections, with one operative death. Immunohistochemical stains of the tumors were positive for vimentin but negative for epithelial markers, differentiating these lesions from other hepatic tumors. The patient with MFH died with recurrence at 10 1/2 months. The patient with the ruptured fibrosarcoma had a second resection and chemotherapy, but died with recurrence at 3 years. The patient with the leiomyosarcoma had a second resection and was disease free at 4 years. Resection of primary hepatic sarcoma is warranted, with potential survival measured in years.

Adult↗
PubMed1984

Diagnosis of soft tissue sarcomas.

Based on a review of 752 cases coded as soft tissue sarcomas, histologic features were analyzed for a differential diagnosis, dividing the sarcomas in the first diagnostic step into purely descriptive groups, regardless of biologic behavior: spindle cell, small cell, pleomorphic and myxoid varieties. The tumor categories mainly discussed in order were fibrosarcoma, leiomyosarcoma, malignant schwannoma, synovial sarcoma, malignant fibrous histiocytoma, embryonal and alveolar rhabdomyosarcoma, malignant neuroepithelioma , extraskeletal Ewing's sarcoma, and myxoid and other types of liposarcoma. The discussion was focused on the problems we were facing often in the histologic diagnosis of these tumors, emphasizing in particular those microscopic features which were helpful in differential diagnosis. Principal clinical features, important for an accurate diagnosis, were added to the histopathologic considerations in each item, together with prognosis of all these Japanese patients, regardless of the stages. Other benign and malignant lesions confused occasionally with the soft tissue sarcomas were also listed. With the aid of electron microscopy and immunohistochemistry, sometimes each differentiating feature can be identified but these methods are not always contributory to a diagnosis. Routine light microscopy with or without standard histochemical techniques remains essential to avoid pitfalls when attempting to diagnose the tumor.

Chondrosarcoma↗
PubMed2003

Calponin and h-caldesmon expression in synovial sarcoma; the use of calponin in diagnosis.

AIMS: To assess the frequency of expression and potential diagnostic utility of calponin and caldesmon in synovial sarcomas. METHODS AND RESULTS: Immunohistochemistry with antibodies to calponin and h-caldesmon was undertaken in paraffin sections from 50 synovial sarcomas (19 biphasic and 31 monophasic, of which one biphasic and eight monophasic tumours had poorly differentiated areas), 10 each of malignant peripheral nerve sheath tumour (MPNST), solitary fibrous tumour (SFT), dermatofibrosarcoma (DFSP), Ewing's sarcoma (ES/PNET), and neuroblastoma, eight alveolar rhabdomyosarcomas, five adult fibrosarcomas and five carcinosarcomas. Nine of 19 biphasic synovial sarcomas were positive for calponin in spindle and glandular areas, nine in spindle cells only, and one in glands only. All monophasic synovial sarcomas and poorly differentiated areas expressed calponin; in monophasic tumours this was focally (29% of cases), moderately (39%), or diffusely (32%) positive and the poorly differentiated areas were usually moderately or diffusely positive. Four synovial sarcomas showed focal reactivity for h-caldesmon. Calponin was found in 4/10 MPNST, 7/10 SFT, 4/10 DFSP, 3/5 fibrosarcomas and the spindle component of the carcinosarcomas. H-caldesmon was weakly positive in 1/10 MPNST, 4/10 SFT, 0/10 DFSP, 0/5 fibrosarcomas and 1/5 carcinosarcomas (glands only). Both markers were negative in the other small round cell tumours. CONCLUSIONS: Calponin can be used as an additional marker for synovial sarcoma. Its absence argues against the diagnosis. The presence of calponin might be useful in distinguishing poorly differentiated synovial sarcoma from other small round cell tumours. H-caldesmon is not helpful in diagnosis of synovial sarcoma.

Biomarkers, Tumor↗
PubMed1983

Carcinogenesis tests of nickel arsenides, nickel antimonide, and nickel telluride in rats.

Carcinogenicity of nickel arsenides (NiAs, Ni11As8, Ni5As2, NiAsS), nickel antimonide (NiSb), and nickel telluride (NiTe) was tested by IM administration to male Fischer rats (14 mg Ni/rat). Three negative control groups received similar IM injections of glycerol vehicle, ferronickel alloy (NiFe), or nickel titanate (NiTiO3); two positive control groups received nickel oxide (NiO) or ferronickel sulfide (Ni4FeS4) at equivalent dosages (14 mg Ni/rat). Within 2 years, the incidences of sarcomas at the injection site were: 0/20 (0%) in NiAs-treated rats, 8/16 (50%) in Ni11As8-treated rats; 17/20 (85%) in Ni5As2-treated rats; 14/16 (85%) in NiAsS-treated rats; 17/29 (59%) in NiSb-treated rats; and 14/26 (54%) in NiTe-treated rats. No local sarcomas occurred in the negative control groups, including 40 glycerol-treated rats, 16 NiFe-treated rats, and 20 NiTiO3-treated rats; in the positive control groups, local sarcomas occurred in 14/15 (93%) of NiO-treated rats and 15/15 (100%) of Ni4FeS4-treated rats. The 99 sarcomas that were induced by the various nickel compounds included 67 rhabdomyosarcomas, 11 fibrosarcomas, 15 osteosarcomas, 1 fibrous histiocytic sarcoma, and 5 undifferentiated sarcomas; metastases were found in 57 sarcoma-bearing rats. This study demonstrates that Ni11As8, Ni5As2, NiAsS, NiSb, and NiTe are carcinogenic for rats. Since Ni11As8, Ni5As2, and NiAsS are likely to be formed during oil shale retorting, environmental contamination by nickel arsenides in spent shale products could conceivably pose a carcinogenic hazard if large-scale production of petroleum from oil share is established.

Animals↗
PubMed2001

Fibrosarcoma in pediatric patients: results of the Italian Cooperative Group studies (1979-1995).

BACKGROUND AND OBJECTIVES: Fibrosarcoma is a rare soft tissue sarcoma (STS) that has two peaks of incidence in pediatric patients: one in infants and young children (infantile fibrosarcoma), another in older children ("adult type" fibrosarcoma). The purpose of this study was to describe the clinical features and the treatment results in patients affected by fibrosarcoma enrolled in two consecutive studies run by the STS-Italian Cooperative Group (ICG) between 1979 and 1995. PATIENTS AND METHODS: Twenty-five evaluable patients were grouped according the intergroup rhabdomyosarcoma staging (IRS) system: 12 Gr I, 5 Gr II, 8 Gr III. The cut-off point between the two forms was considered the age of 2 years: 14 patients were affected by infantile and 11 by adult type of fibrosarcoma. The therapeutic guidelines were not strict and not different for the two forms: patients with initial macroscopic excision (Gr I-II) were given IVA or VAC; Gr III had VAC or VAIA and subsequent excision, if feasible. Radiation therapy (RT) was delivered in patients > 3 years with microscopic (42 Gy) and macroscopic (54 Gy) residuals. RESULTS: Thirteen patients are alive without evidence of disease: 10 in first complete remission (CR), 7 Gr I, 1 Gr II, 2 Gr III, 3 in second CR after local relapse (LR) (2 Gr I, 1 Gr II). Two Gr I patients are alive with metastatic relapse. Nine patients died: six of progressive disease (PD) (three Gr II, three Gr III), two because of a second tumor (one Gr I, one Gr III) and one because of other causes (Gr III). One Gr III patient was lost at follow up, 2 years from diagnosis. The 10 years overall survival (OS) is 67.4% and the progression-free survival (PFS) is 52.2%. The OS for patients < 2 years is 78.6% (11 of 14), versus 51% for patients > 2 years (5 of 11). CONCLUSIONS: The complete excision at diagnosis was the treatment of choice and was related to the best outcome. Microscopical residuals were difficult to treat with chemo-radiotherapy in both forms of fibrosarcoma. Neoadjuvant chemotherapy (CT) obtained a partial remission (PR) only in three of eight cases, while no conclusions concerning the efficacy of CT for infantile forms are possible. Patients < 2 years had a better outcome than the older ones: most of them had a tumor on extremities which was excised at diagnosis.

Adolescent↗
PubMed2000

[Congenital fibrosarcoma. Diagnostic-therapeutic implications].

Most of the soft tissue sarcomas of childhood other than rabdomyosarcoma, have as final diagnosis fibrosarcoma, specially in the first months of life. Overlapping features between infantile myofibromatosis and congenital fibrosarcoma, hemangiopericytoma and fibrohistiocytoma have seen noted. Five patients with congenital fibrosarcoma were operated since 1991. Anatomical sites included lower limb, hand and forearm, and three of them had previous diagnoses of hemangiopericytoma, fibrohistiocytoma and myofibromatosis, with provocated non radical surgery and reoperation. The postoperative course was satisfactory and all are live one to eight years later. In our experience accurate histological diagnosis must be achieved to perform radical surgery on these cases.

Fibrosarcoma↗
PubMed1981

Postradiation sarcoma of bone: review of 78 Mayo Clinic cases.

Postradiation sarcoma of bone is an uncommon but serious sequela of radiation therapy. Seventy-eight Mayo Clinic patients have been treated for sarcomas arising in irradiated bones. They received their initial radiotherapy for a wide variety of nonneoplastic and neoplastic conditions, both benign and malignant. Thirty-five sarcomas arose in bone that was normal at the time of radiotherapy, and 43 arose in irradiated preexisting osseous lesions. The latent period between radiotherapy and diagnosis of sarcoma averaged 14.3 years. Ninety percent of the postradiation sarcomas were either osteosarcomas or fibrosarcomas; chondrosarcoma, malignant (fibrous) histiocytoma, malignant lymphoma, Ewing's tumor, and metastasizing chondroblastoma also occurred. Prompt radical surgery, when feasible, is usually the treatment of choice for the sarcoma. About 30% of patients with sarcomas of the extremities or craniofacial bones survived 5 years without recurrence; there were no disease-free survivors among patients with tumors of the vertebral column, pelvis, or shoulder girdle. The low risk of sarcoma following radiotherapy for the treatment of cancer should not be a contraindication to its use in these patients; however, radiation therapy for benign bone tumors should be reserved for lesions that are not amenable to surgical treatment. An unusual case is also reported herein in which a fibrosarcoma was discovered in the humerus of a patient who had received radiotherapy 55 years previously for a verified osteosarcoma in the same site.

Adolescent↗
PubMed1981

Bioassay of metals for carcinogenesis: whole animals.

Metals have been evaluated as potential carcinogens by administering pure elements or compounds by a large variety of routes. These include mixing the agent in the food, dissolving the test compound in the drinking water, or administering the material by gavage. The respiratory tract routes tested include inhalation, intratracheal instillation, the direct injection of particulates into the pleural cavity, or the implantation of hooks by surgical intervention. The parenteral routes used were intravenous injection, intraperitoneal injection, subcutaneous implantation, as well as intrafemoral and intramuscular injection. This latter route is the most commonly used. There are major objections to the subcutaneous implantations route, and data generated from these experiments are difficult to interpret for the foreign body reaction may give rise also to fibrosarcomas. This then is a nonspecific reaction. Exotic routes tested include intrarenal, intratesticular, and intracranial injections. The endpoints of the carcinogenic reactions are, in the main, sarcomas of certain types with fibrosarcomas predominating. Rhabdomyosarcomas are the next most frequent cancer found, and squamous cell carcinoma may account for less than 2% of the cancers reported. Much more research is necessary to clarify the nature of metal carcinogenesis. Dose-response information is almost nonexistent; the divided dose problem has not been studied adequately, and very little information is available on interspecies reactions. More work is needed to help interpret the mechanism of action.

Administration, Oral↗
PubMed1983

[Pathology of the most common malignant soft tissue tumors].

The present article provides an overview on the main pathological criteria of the most frequent malignant soft tissue tumors. Although these malignancies are only rarely observed and amount only to approximately 1% of all malignancies, their exact morphological analysis is of importance, because different therapeutical consequences may be drawn depending on the kind of the tumor and its grade of malignancy. Also, the prognosis of soft tissue sarcomas is extremely variable but is related to the morphology. Therefore, soft tissue sarcomas should be investigated very individually. Proper information of the pathologist by the clinician of each given case is necessary for a proper histological evaluation of biopsies that must be representative. It is recommended, whenever possible to excise the total of the tumor. With regard to these aspects liposarcomas, malignant fibrous histiocytomas, rhabdomyosarcomas, leiomyosarcomas, synovial sarcomas, malignant mesenchymomas, angiosarcomas, and fibrosarcomas are discussed, and their essential properties are reported.

Fibrosarcoma↗
PubMed2002

Pineal sarcoma.

We report a case of fibrosarcoma arising in the pineal of a 36-year-old female patient. She died at the age 43 following biopsy, radiation therapy, tumor resection, chemotherapy, and stereotactic radiosurgery. Light microscopic study of all tissues obtained, including immunohistochemistry and electron microscopy of surgically resected tumor and autopsied tissue revealed a slowly progressing primary fibrosarcoma.

Adult↗
PubMed2001

In utero ultrasound detection of a large fetal sarcoma of the back.

A congenital fibrosarcoma, a very rare soft-tissue tumor of infancy, was suspected on prenatal ultrasound at 23 weeks' gestation. On sonography, a large soft tissue growth on the left side of the fetal back, measuring 53 x 65 x 22 mm, was observed. The diagnosis was further validated by magnetic resonance imaging. Delivery by Cesarian section occurred at 31 weeks of gestation, due to fetal distress. The baby underwent an unusual embolization of the tumor-feeding arteries and an operation at the age of 1 month to remove the tumor. The pathological and cytogenetic examinations were consistent with the diagnosis of a fibrosarcoma.

Adult↗
PubMed1991

[Bone tumor and ABO blood type].

During a period of 31 years, from January 1958 through 1988, a total of 449 operations had been performed on the in-patients whose blood type was recorded. There were 111 osteogenic sarcoma, 28 synovioma, 75 metastatic bone tumor, 172 giant cell tumor of bone, 14 fibrosarcoma, 28 chondrosarcoma, 11 Ewing's sarcoma, 10 chondrosarcoma, and 10 chordoma. The distribution of ABO blood type in these patients was processed statistically and compared with that of 268,794 normal blood donors registered in Shanghai, 1988. The analysis showed that people with blood type A were prone to develop synovioma and metastatic bone tumor but not osteogenic sarcoma. The authors tried to explain the above observation on basis of ABH blood type-substances and tried to make predictions by changes in trace elements in the bone tumor. Further implications on genetics and immunology is attempted.

ABO Blood-Group System↗