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PubMed1999

Surgical treatment of primary pulmonary sarcomas.

OBJECTIVE: We sought to identify the long-term prognosis after surgical treatment for primary pulmonary sarcoma. METHODS: Twenty-three patients were retrospectively identified as having been treated surgically for primary pulmonary sarcoma between 1981 and 1996. The records of all patients were reviewed, and the histopathology reexamined by a pathologist. RESULTS: Fifteen patients were male and eight female; their ages ranged from 20 to 78 (mean 51) years. Tumors measured between 0.9 and 12.0 (mean 5.2) cm across the greatest diameter. The histologic diagnoses were malignant fibrous histiocytoma (8, three grade 1 or 2, two grade 3), synovial sarcoma (4), malignant schwannoma (3), leiomyosarcoma (3), and one case each of angiosarcoma, intimal sarcoma, epitheloid hemangioendothelioma, fibrosarcoma and primitive neuroectodermal tumor. Three patients were found to be unresectable. All three underwent radiation and chemotherapy. Lobectomies or bilobectomies were performed in 13 patients including two sleeve resections, one carinal resection, and one chest wall resection. Four patients underwent radical pneumonectomies. Three patients with invasion of the pulmonary artery, pulmonary veins or atrial wall underwent extended resections with the use of cardiopulmonary bypass. In two, a homograft was used to reconstruct the right ventricular outflow tract. Of the resected patients, six had a positive resection margin, and four had at least one positive lymph node in the specimen. Three patients underwent repeat pulmonary resections for recurrences. Eleven patients received postoperative chemotherapy and eight had radiation therapy. Follow-up was available on 22 patients, and ranged from 2 to 183 (mean 48) months; 14 patients are disease free, six died of disease, one died of surgical complications (operative mortality 5%), and two are alive with disease. Actuarial 3- and 5-year survival of the resected patients was 69%. Size and grade were not found to be correlated with significantly increased survival, but completeness of resection was (P<0.05). CONCLUSIONS: Resection of primary pulmonary sarcomas can produce an acceptable survival rate if the resection is complete. Cardiopulmonary bypass can be a useful adjunct when tumors involve a resectable area of the heart or great vessels.

Adult↗

PubMed1977

[Familial cancer syndrome studies in 4 generations of a family].

An account is given of a family from the Canton of Valais suffering from hereditary adenocarcinomatosis. The pedigree extends over four generations; the first three comprised 47 individuals (28 males, 19 females), of whom 21 (16 males and 5 females), i.e. 44.6%, have malignant tumors. Of the 32 people in the fourth generation, only one individual is affected to date (a girl age 21, IV/4). There were 27 tumors in all: 16 adenocarcinomas of the colon, two gastric adenocarcinomas, one duodenal adenocarcinoma, one rectal adenocarcinoma, one papillary carcinoma of the ovary, one osseous sarcoma, one cutaneous fibrosarcoma, a multiform glioblastoma of the basal nuclei of the brain, a basocellular epithelioma, a cerebral metastasis from an adenocarcinoma, the origine of which has not been established, and a tumor invading the biliary tract. Three members of the family had multiple tumors. In three of the patient the colonic adenocarcinoma was accompanied by one or two polyps. The average age at onset for all tumors was 45 years. It was definitely lower in the third than the second generation (anticipation). The transmission was autosomal dominant, with predilection for the male sex (57.1% male and 26.3% female patients). The penetrance was about 80%. Finally, the diagnostic criteria for hereditary adenocarcinoma are discussed and the different familial forms of cancer are reviewed.

Adenocarcinoma↗

PubMed2002

Practical application of molecular genetic testing as an aid to the surgical pathologic diagnosis of sarcomas: a prospective study.

The strong correlation of specific reciprocal translocations with individual tumor types and the demonstration that polymerase chain reaction (PCR)-based methods can detect translocations in tissue samples have stimulated interest in the role of molecular genetic testing in diagnostic surgical pathology. To evaluate the clinical utility of PCR-based molecular analysis of soft tissue neoplasms in routine surgical pathology, 131 consecutive soft tissue tumors submitted for molecular genetic testing at a tertiary care teaching hospital were prospectively analyzed over a 36-month period. RT-PCR was used to test tumor RNA for fusion transcripts characteristic of malignant round cell tumors (including Ewing sarcoma/primitive neuroectodermal tumor, desmoplastic small round cell tumor, and alveolar rhabdomyosarcoma), spindle cell tumors (including synovial sarcoma and congenital fibrosarcoma), and fatty tumors (myxoid liposarcoma). DNA sequence analysis was used to confirm the identity of all PCR products, and the PCR results were compared with the histopathologic diagnosis. We found that sufficient RNA for RT-PCR-based testing was recovered from 96% of the 131 cases and the percentage of tumors that tested positive for the associated characteristic fusion transcript was in general agreement with those reported in the literature. DNA sequence analysis of PCR products identified both variant transcripts and spurious PCR products, underscoring the value of product confirmation steps when testing formalin-fixed, paraffin-embedded tissue. Only in rare cases did testing yield a genetic result that was discordant with the histopathologic diagnosis. We conclude that PCR-based testing is a useful adjunct for the diagnosis of malignant small round cell tumors, spindle cell tumors, and other miscellaneous neoplasms in routine surgical pathology practice.

Base Sequence↗

PubMed1988

Computer classification of experimental brain tumors in mice.

The purpose of this study was to develop a mathematical model which would be easy to use and which could provide an objective classification of experimental brain tumors. 250 brain tumors (glioblastomas, astrocytomas, astroblastomas, oligodendrogliomas, ependymomas, fibrosarcomas and giant cell sarcomas), induced in mice, were studied. In every case the same 50 histological characteristics were analyzed. For astroblastomas, oligodendrogliomas and ependymomas the diagnosis given by the neuropathologist and that given by the computer corresponded in 100% of the cases. However, some fibrosarcomas and giant cell sarcomas were not grouped in the same diagnostic category by the computer as that assigned by the neuropathologist. Thus an overall efficiency of 94.35% was obtained. This simple and efficient system of classification allows for further statistical analyses and makes it possible to correlate the results presented by different authors, thus providing for unity in all those works concerned with experimental neurooncology.

Animals↗

PubMed2002

P53 expression is a factor for prognostic assessment in breast sarcoma.

The present study was undertaken with the aim of evaluating the clinical and anatomopathological findings, emphasizing expression of the protein p53 as possible prognostic markers, in patients with breast sarcoma. p53 immunohistochemical expression was determined in archival paraffin embedded tissue blocks of 30 breast sarcoma patients, (19 fibrosarcomas, nine malignant fibrohistiocytomas and two liposarcomas) treated at the Hospital do Cancer AC Camargo, São Paulo, Brazil from 1955 to 1990. Immunopositivity was present in 50% of the cases. The survival of the patients was compared with the above parameters. Median follow up time was 113 months. The 5 years specific survival rates were 55.1% for patients with a positive expression of p53 contrariwise to 92.3% of specific survival found in p53 negative patients (p = 0.04). Positive expression of p53 was found in 3/4 (75%) of the patients with local recurrence and in 7/9 (77%) of patients with metastatic disease. No significant correlation between survival and clinicopathologic features (age, menopausal status, tumor size, stage and histological type), was found. A slight positive correlation between high grade and poor outcome was observed, 89% of the metastatic cases being classified as high grade (p = 0.02, by one sided Fisher's exact test). When we have compared, independently, survival probability curves between p53 positive/negative expression and each category of clinicopathologic features a worse prognosis was observed when p53 was positive in patients older than 50 years (p = 0.01), in tumors larger than 5 cm (p = 0.02), within the malignant fibrous histiocytoma subtype (p = 0.01) and in tumors classified as high grade (p = 0.07). In conclusion p53 expression seems to be a useful prognostic marker for this type of tumor.

Adult↗

PubMed1995

Normalization of tumor-induced increases in hepatic amino acid transport after surgical resection.

BACKGROUND: The liver of the host with cancer requires increased amounts of amino acids to support the synthesis of glucose and key defense proteins. To study the effect of the growing tumor on hepatic amino acid uptake, the authors measured hepatic transport activity in tumor-bearing rats and in rats at various times after tumor resection. METHODS: Fischer-344 rats were implanted subcutaneously with methylcholanthrene-induced fibrosarcoma cells (MCA sarcoma). When the tumors reached 10% of body weight, hepatic amino acid transport activity was assayed or the animals underwent surgical removal of the tumor. In animals that underwent tumor excision, livers were removed at 1, 3, or 5 days post-resection, and hepatic plasma membrane vesicles (HPMVs) were prepared. Nontumor-bearing pair-fed rats undergoing sham implantation or sham resection served as controls. System N (glutamine), System A (MeAIB), and System y+ (arginine) transport activity were assayed, which allowed the authors to compare differences in tumor-induced rates of transport and the influence of resection on transport activity. RESULTS: System A transport activity was unaltered by tumor growth. In contrast, the presence of the growing tumor increased arginine and glutamine uptake by the liver. Hepatic glutamine transport remained elevated for 5 days after tumor resection, although by postoperative day 5 there was a trend toward normalization. In contrast, arginine transport remained increased by twofold onpost-resection day 1 and had normalized by postoperative day 3. The enhanced arginine transport was a result of an increase in maximal transport velocity (Vmax) rather than a change in carrier affinity. CONCLUSIONS: Increases in hepatic amino acid transport normalize within several days of tumor resection, indicating a key role for the tumor in the induction of this response. The observation that hepatic glutamine transport activity remains augmented after tumor resection longer than any other transporter studied suggests a key role for this amino acid in overall hepatic nitrogen metabolism and may partially explain the persistent glutamine depletion that is characteristic of the tumor-bearing host.

Amino Acids↗

PubMed1997

Solitary fibrous tumor. A cytologic-histologic study with clinical, radiologic, and immunohistochemical correlations.

BACKGROUND: Solitary fibrous tumors (SFT) are rare neoplasms that most commonly involve the pleura, mediastinum, and lung. They are believed to be submesothelial in origin. Histologically, they are characterized by fibroblast-like cells and connective tissue in varying proportions. The "patternless pattern" and the hemangiopericytoma-like pattern are the most common arrangements. The majority of SFTs have been immunoreactive for CD34. Very little has been reported regarding the cytologic findings in these tumors. METHODS: The authors reviewed the radiographic findings and studied fine-needle aspiration biopsies performed on seven patients with SFT of the pleura, and examined subsequent histologic material. The cell blocks or smears of all cases were stained with a monoclonal antibody to CD34. RESULTS: The cytologic preparations showed varying degrees of cellularity. Smears were comprised of spindled cells in a bloody background with small amounts of collagen. The three malignant tumors had a greater number of cells, both dispersed and in clusters, with nuclear pleomorphism and prominent nucleoli. The cell blocks characteristically showed varying degrees of cellularity with thickened blood vessels and a hemangiopericytoma-like pattern. The cells from the four benign tumors tended to be smaller in size and grouped in more cohesive clusters than the malignant ones. CD34 stained the spindle tumor cells in the cell blocks or smears from five cases; one malignant and one benign case failed to stain. The corresponding histologic samples from these cases demonstrated the same CD34 staining pattern in all cases except one. CONCLUSIONS: The differential diagnosis of SFT includes neurogenic tumors, mesotheliomas, sarcomatoid carcinoma, synovial sarcoma, hemangiopericytoma, and fibrosarcoma. CD34, when present, may prove equally helpful as a positive marker in cytology and in histologic preparations in the differential diagnosis of SFT.

Adult↗

PubMed1982

Transformation of MMC-E epithelial cells by acute 3611-MSV: inhibition of collagen synthesis and induction of novel polypeptides.

Mouse embryo epithelial cells MMC-E were transformed by novel fibrosarcoma-inducing murine sarcoma virus 3611-MSV. The cells were analyzed for the production and deposition of pericellular glycoproteins by immunofluorescence and by radioactive metabolic and cell surface labeling techniques followed by analysis in polyacrylamide gels and fluorography. The pericellular fibronectin matrix was lost, but unlike in virus-transformed fibroblastic cells, the production of fibronectin was not affected. The major differences detected were decrease in collagen production and initiation of synthesis of two major glycoproteins with Mr 58,000 and 60,000. Cell surface carbohydrate labeling indicated that after 3611-MSV transformation the cells expressed Mr 100,000 and 68,000 polypeptides. The present and previous results show that viral transformation of epithelial cells induces different transformed phenotypes that are associated with distinct alterations in pericellular glycoproteins.

Animals↗

PubMed2002

Connective tissue tumors.

Connective tissue consists of collagen, elastic fibers and ground substances produced by fibrocytes. These cells are usually spindle-shaped with slender nuclei and bipolar cytoplasmic extensions. Apart from labeling for vimentin and variable reactivity for factor XIIIa and CD34, fibrocytes are immunonegative. Electron microscopy reveals prominent endoplasmic reticulum, but is otherwise indistinct. Lesions with fibrocytic differentiation can be divided into five categories: scars, keloids, dermatofibromas, nodular fasciitis, and superficial fibromatoses are inflammatory lesions. Thereby, dermatofibromas and their subcutaneous/deep soft tissue counterpart nodular fasciitis can present with a wide variety of clinicopathologic variants which may be misinterpreted as malignancies. Prurigo nodularis, chondrodermatitis nodularis helicis, acanthoma fissuratum, and knuckle pads are hyperplasias; fibroma molle, fibrous papules, connective tissue nevi, and elastofibroma are hamartomas; and fibroma of tendon sheath, pleomorphic fibroma, and giant cell tumor of tendon sheath are benign neoplasms. Deep fibromatoses, dermatofibrosarcoma protuberans, giant cell fibroblastoma, giant cell angiofibroma, hyalinizing spindle cell tumor with giant rosettes, solitary fibrous tumor, myxofibrosarcoma, low-grade fibromyxoid sarcoma, acral myxoinflammatory fibroblastic sarcoma, and classical fibrosarcoma, are malignant neoplasms, that is fibrosarcomas of variable malignant potential. Lesions dominated by myocytes/ myofibroblasts, e.g. cutaneous myofibroma/infantile myofibromatosis, or by macrophages, e.g. xanthogranulomas, are not part of this chapter.

Humans↗

PubMed1984

Gamma-irradiation facilitates the expression of adoptive immunity against established tumors by eliminating suppressor T cells.

It was found that sublethal (550 rad) whole-body gamma-irradiation of mice bearing established immunogenic tumors enabled tumor-sensitized spleen cells infused intravenously 1 h later to cause complete tumor regression in all mice. In contrast, gamma-irradiation alone caused only a temporary halt in tumor growth, and immune cells gave practically no therapeutic effect at all. This result was obtained with the SA1 sarcoma, Meth A fibrosarcoma, P815 mastocytoma, and P388 lymphoma. Additional experiments with the Meth A fibrosarcoma revealed that the spleen cells from tumor-immune donors that caused tumor regression in gamma-irradiated recipients were T cells, as evidenced by their functional elimination by treatment with anti-Thy-1.2 antibody and complement. It was shown next that adoptive T-cell-mediated regression of tumors in gamma-irradiated recipients was inhibited by an intravenous infusion of spleen cells from donors with established tumors, but not by spleen cells from normal donors. The spleen cells that suppressed the expression of adoptive immunity were functionally eliminated by treatment with anti-Thy-1.2 antibody and complement. Moreover, they were destroyed by exposing the tumor-bearing donors to 500 rad of gamma-radiation 24 h before harvesting their spleen cells. The results are consistent with the interpretation that gamma-radiation facilitates the expression of adoptive T-cell-mediated immunity against established tumors by eliminating a population of tumor-induced suppressor T cells from the tumor-bearing recipient.

Animals↗

PubMed1983

Leiomyosarcoma in bone: primary or secondary? A case report and review of the literature.

Our case demonstrates how metastases may be present and symptomatic long before they produce sufficient osseous changes to render the lesions radiologically detectable. A case of leiomyosarcoma arising in the uterus and initially presenting as a femoral lesion is presented. It required an intensive review of the case history and of the previous pathology in order to identify the primary site in the uterus. In the literature nine cases of metastatic leiomyosarcoma presenting initially in bone are reviewed. Ten additional cases from the literature showed bone metastases as the first site of recurrence. When this is assessed together with some 14 cases of primary leiomyosarcomas reported arising in bone, one is impressed that this is an uncommon tumour in bone either as a primary or secondary. In all patients in whom a leiomyosarcoma is histologically proven in bone, all primary sites should be specifically and categorically excluded before the lesion is accepted as an osseous primary. This should include special stains for myofibrils and electron microscopy if at all possible, in order to differentiate such tumours from other sarcomas such as fibrosarcoma. This applies especially to patients with uterine lesions that have been previously treated, even if they have been regarded as benign initially. All previous pathology and in particular hysterectomy specimens should be carefully reviewed. The need to specifically identify a leiomyosarcoma as a primary lies in the different modalities of treatment used: aggressive ablative surgery for primary lesions as opposed to radiation and chemotherapy for metastatic disease.

Bone Neoplasms↗

PubMed2005

Dedifferentiated liposarcoma of the oral cavity with angiosarcomatous dedifferentiation.

We report a unique case of a 42-year-old woman with a dedifferentiated liposarcoma of the soft tissue of the oral cavity with angiosarcomatous dedifferentiation. Liposarcomas compromising the head and neck region are very unusual, and most of the cases in oral cavity show a well-differentiated pattern. Dedifferentiation in liposarcomas occurs in about 10% of the cases and, when it occurs, the dedifferentiated areas usually resemble high-grade fibrosarcoma or pleomorphic sarcoma. Divergent differentiation might also occur. To the best of our knowledge, there are only nine cases of dedifferentiated liposarcoma of the oral cavity, none of which show an angiosarcomatous dedifferentiation.

Adult↗

PubMed1994

31P MRS to monitor the induction of tumor hypoxia by the modification of the oxygen affinity of hemoglobin using BW 589C.

PURPOSE: BW 589C induces severe tumor hypoxia by modifying the affinity of oxyhemoglobin, causing a left shift of the oxygen-hemoglobin dissociation curve. 31P magnetic resonance spectra (MRS) was used to monitor the effects of BW 589C on tumor energy metabolism in three experimental tumor models. METHODS AND MATERIALS: HT-29 colon xenograft, murine transplantable RIF-1 fibrosarcoma and KHT sarcoma were studied in unanesthetised mice. 31P MR spectra were acquired on a 4.7 Tesla magnet before administering oral BW 589C (250 mg/kg) and after 3, 6, and 24 h. Samples of tail vein blood were then taken for 2,3 DPG levels for RIF-1 and HT-29 tumors. RESULTS: Doubling of inorganic phosphorus (Pi) to total phosphorus was observed 5-6 h after BW 589C for all three tumor types. Although the left shift due to BW 589C persists at 24 h, the level of Pi to total phosphorus returned to baseline with no significant difference from control values for the RIF-1 and HT-29 tumors. These results suggest that there was cellular metabolic adaptation to the reduction of oxygen delivery by BW 589C. This does not appear to involve 2,3 DPG as there was no significant alteration in tumor levels. The death of hypoxic cells may, also, have contributed to the recovery of Pi to total phosphorus. CONCLUSION: The efficacy of bioreductive drugs can be enhanced by increasing the severity of tumor hypoxia. 31P MRS in conjunction with other techniques for assessing the intratumor environment could play an important role in planning cancer therapy.

Animals↗

PubMed1975

Hypercoagulability in childhood cancer.

Thirty-two children with solid tumors (lymphangioma, fibrosarcoma, hepatocarcinoma, osteogenic sarcoma, rhabdomyosarcoma, lymphosarcoma, mesenchymoma, hepatoma, Ewing's sarcoma, reticulum cell sarcoma, neuroblastoma, Hodgkin's disease, and brain tumors) were studied for alterations in coagulation by means of platelet counts, platelet aggregation, thrombelastogram, procoagulant and antigenic factor VIII, fibrin split products, and antithrombin III level. Results indicated hypercoagulability as shown by abnormally short thrombelastograms and elevated factor VIII levels and platelet counts in approximately one-half of the group. With the exception of increased fibrin split products in a third of the patients, little laboratory or clinical evidence for disseminated intravascular coagulation was seen. Hypercoagulability, as noted in adult carcinoma patients, can also occur in childhood sarcoma patients.

Adolescent↗

PubMed1977

Nucleic acid sequences of primate type C viruses in normal and neoplastic human tissues.

Recent reports on the isolation of type C viruses from human cells have generated considerable controversy because of the close relationship of the viruses to the type C viruses of subhuman primates. These findings have been interpreted as evidence for contamination despite the repeated isolation of some type C viruses from separate clinical specimens or from separate frozen primary cell stocks of the same donor. Our laboratory has described a type C virus which is released from the HEL-12 strain of normal human embryonic lung fibroblasts. The HEL-12 virus is related immunologically to simian sarcoma (woolly monkey fibrosarcoma) virus (SiSV) and the endogenous type C viruses of baboons and domestic cats. To demonstrate that the HEL-12 virus is not an adventitious contaminant, fresh human tissues were examined for antigenic cross-reactivity with HEL-12 virus antigens. Some patients with myelogenous leukemia contain circulating immunoglobulins which specifically inhibit the reverse transcriptases of HEL-12 virus and primate type C viruses. In addition, the glomerular immune complexes in patients with systemic lupus erythematosus contain antigens related to HEL-12 virus proteins. Using the techniques of molecular hybridisation, we demonstrate here that HEL-12 cells contain proviral DNA sequences before antigen expression or spontaneous virus release can be detected. We also present evidence for the existence of nucleic acid sequences homologous to HEL-12 viral RNA in the DNAs from certain cancer patients.

Animals↗

PubMed1986

"Replacement" of COOH-terminal truncation of v-fms with c-fms sequences markedly reduces transformation potential.

Protooncogenes when transduced by retroviruses may undergo structural modifications that render their gene products oncogenic. The c-fms gene encodes a transmembrane protein with tyrosine kinase activity that is very similar or identical to the receptor for the monocyte-macrophage colony-stimulating factor. Its transforming homologue (v-fms) in the Susan McDonough strain feline sarcoma virus causes fibrosarcomas in cats. Molecular cloning and sequence analysis of the cDNA that encodes the cytoplasmic domain of the human c-fms gene shows that the product of the transduced viral homologue, v-fms, is truncated at the COOH-terminal end. The COOH-terminal 40 amino acids of the c-fms gene product are replaced in the v-fms gene product by 11 amino acids encoded by the retroviral genome. Hybrid v-fms/c-fms genes, in which either the entire cytoplasmic domain or the COOH-terminal coding sequences of the v-fms gene were replaced by the corresponding segments of the c-fms gene, had a reduced ability to transform fibroblasts despite a high level of encoded protein on the cell surface. These data indicate that the COOH-terminal modifications contribute to the transforming potential of the v-fms viral oncogene product.

Amino Acid Sequence↗

PubMed1998

Neoplasms with neural differentiation: a review. Part II: Malignant neoplasms.

Malignant peripheral nerve sheath tumors (MPNSTs) encompass a wide and unusual group of neoplasms with features of neural differentiation. They most commonly present as spindle cell neoplasms and it can be difficult to differentiate them from other spindle cell neoplasms such as leiomyosarcomas, fibrosarcomas and synovial sarcomas. Strict criteria need to be applied in order to make the diagnosis of MPNSTs. Helpful features include contiguity with a nerve or an association with von Recklinghausen disease. The use of immunohistochemical stains may also help to confirm the diagnosis. Markers such as S-100 protein, neurofilament, epithelial membrane antigen and Leu-7 (CD57) are frequently used to assess neural differentiation in these neoplasms. In addition to the spindle cell pattern, MPNSTs may also display an epithelioid pattern. Rarely, other elements may be seen including glands in the so-called glandular MPNST or muscle in triton tumors. In more unusual cases cartilage, adipose tissue and even bone are present. Also included in the group of MPNSTs are the peripheral neuroepithelial tumor, neurotropic or desmoplastic melanomas and malignant granular cell tumors. MPNSTs are highly aggressive tumors and should be treated accordingly.

Adult↗

PubMed1981

Carcinosarcoma of the skin. Case report and review.

A carcinosarcoma of the skin in a 74-year-old man is reported. The epithelial element consisted of a highly anaplastic basal cell carcinoma with focal keratinization. The mesenchymal component included elements of fibrosarcoma, chondrosarcoma, osteogenic sarcoma, and synovial sarcoma. This is, to our knowledge, the second reported case of carcinosarcoma arising in the skin.

Aged↗