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PubMed1983

Mesenchymal chondrosarcoma. A clinicopathologic analysis of 35 patients with emphasis on treatment.

Almost a quarter of a century has passed since mesenchymal chondrosarcoma, a rare, insufficiently studied and still poorly understood cartilage neoplasm has been described. Based on 35 cases diagnosed and treated at this Cancer Center, this study found 20 males and 15 females with an average age of 26 years (range, 6-70 years). All but five of the tumors arose in the skeleton in the femur, humerus, and ilium in five cases each, while the os calcis (a rare site for any other osseous tumor) gave rise to this tumor in four instances. Pain was the cardinal symptom in 27 patients. The lesional size varied from 4 to 18 cm (average, 9.5 cm). Histologic examination revealed nine of the tumors to be of the small cell undifferentiated types while the others were of the "hemangiopericytomatoid" variant. According to this subclassification, patients with the small cell type of lesions responded to combination chemotherapy and irradiation, as usually do other small cell sarcomas. The addition of surgical resection may be of value especially in the patients with the hemangiopericytomatoid variant. Preliminary results in the treatment of five such patients with evaluable disease suggest that this combined treatment approach is encouraging. Follow-up analysis of all patients revealed a 37.9 months median survival, and 28% to be alive at ten years.

Adolescent↗
PubMed1976

Generalized urticaria to cyclophosphamide: Type I hypersensitivity to an immunosuppressive agent.

A 6-yr-old white boy, Patient L. B., who was receiving cyclophosphamide (CY) for chemotherapy of a localized undifferentiated small cell sarcoma of the chest wall, developed generalized urticaria on three separate occasions immediately after CY administration. Serum samples were obtained 2 and 5 wk after the patient's last reaction and were examined for reaginic activity to the drug. Homocytotropic antibody activity to CY was found in the 2-wk postreaction sample by Prausnitz-Küstner type passive transfer skin testing to chimpanzees. This homocytotropic antibody was found to be of the IgE type, by means of an in vitro double-antibody coprecipitation assay measuring binding of free 14C-CY by specific immunoglobulin E and G fractions. Sera from 3 CY-treated patients who did not have adverse reactions to the drug and 6 normal, age-matched volunteers were used as control samples for the coprecipitation assay. None of the 3 CY-treated control patients had significant binding of 14C-CY by IgE when compared to normal individuals. However, it was found that all CY-treated patients had significant binding of 14C-CY by their IgG fraction when compared to normal subjects.

Binding Sites, Antibody↗
PubMed1997

The clinical role of molecular genetics in soft tissue tumor pathology.

Cytogenetic and molecular analysis of soft tissue tumors has yielded a wealth of information over the past decade. Some of the genetic aberrations that have been identified appear to be fairly specific for individual tumor types. It is because of this specificity that these findings harbor the promise to become useful as diagnostic and/or prognostic markers. Technical advances that allow the application of cytogenetic and molecular techniques to archival material have been crucial in this respect. Molecular genetics has already become an integral part of the work-up of some tumors, e.g., small cell sarcomas of childhood, which demonstrate fairly characteristic translocations, often involving the Ewing's sarcoma gene. Some genetic abnormalities have become established as prognostic markers, such as the deletion of the short arm of chromosome 1 for neuroblastomas. Soft tissue tumor pathology has also benefitted from major advances in identifying genes that are critical in mesenchymal differentiation or cell cycle control. MyoD is a good example of a such a gene, that has become useful as a diagnostic tool in rhabdomyosarcomas. Beyond potential practical applications of cytogenetic and molecular analyses in the diagnosis of these tumors, we also review their impact on several philosophical concepts concerning soft tissue neoplasia.

Child↗
PubMed1991

Correlation between retinoblastoma gene expression and differentiation in human testicular tumors.

Inactivation of the retinoblastoma gene (RB gene) is associated with the development of several human malignancies including retinoblastomas, some osteo- and soft tissue sarcomas, small cell lung cancer, and possibly breast and bladder cancers. To our knowledge, this gene has not been evaluated in human germ-cell malignancies. In this study 67 primary testicular germ-cell tumors and 4 testicular non-germ-cell malignancies were examined to determine the prevalence and nature of RB gene alterations. Decreased expression of RB gene mRNA was found in all testicular germ-cell tumors (both seminomas and nonseminomas) examined. The RB protein could not be detected by immunohistochemical analysis in the undifferentiated cells of any germ-cell tumors whereas the differentiated malignant cells present in 14/15 teratocarcinomas expressed the protein. No gross alterations of the RB gene were found at DNA level in any of the examined specimens. This and the presence of the RB protein in the more differentiated tumor cells of teratocarcinomas suggest that changes in transcript levels rather than mutation(s) of the gene may be responsible for the absent or decreased RB expression in human germ-cell tumors. To date studies on the mechanism of RB regulation have demonstrated that it occurs at the protein level by phosphorylation of the p105 gene product. The findings presented here indicate that additional regulation might occur at the transcript level.

Blotting, Southern↗
PubMed1989

Steroid hormone receptors in meningiomas of Chinese patients.

Meningioma is a hormone-related intracranial tumor. Brain tumor samples were collected from 32 Chinese patients, 20 of whom had meningiomas. Estrogen receptors were present in 6 of 17 meningiomas, 1 hemangioblastoma, 1 gemistocytic astrocytoma, and 1 neurilemoma. Of the 26 samples assayed for progesterone receptors, measurable bindings were found in 14 of 17 meningiomas, 1 of 2 astrocytomas, 1 malignant lymphoma, 1 hemangioblastoma, 1 ganglioglioma, 1 glioblastoma multiforme, 1 anaplastic ependymoma, 1 small cell sarcoma, and 1 neurilemoma. Androgen receptors were found in 8 of 19 meningiomas, but not in the 11 other brain tumors examined. Measurable glucocorticoid receptors were found in 15 of 19 meningiomas, 1 malignant lymphoma, 1 hemangioblastoma, 2 craniopharyngiomas, 1 neurilemoma, 1 of 2 glioblastomas, and 1 of 2 astrocytomas. Of the 10 samples examined for tyrosine aminotransferase activity, measurable enzyme activity was found in 7 of the 8 meningiomas, but not in the single hemangioblastoma nor in the single craniopharyngioma. In accordance with other published studies, the results from this study also suggest that the growth of meningiomas may be regulated by hormones, and that the role steroid hormones and their receptors play in the meningioma is worthy of further investigation.

Adult↗
PubMed1967

Adenovirus tumorigenesis: role of the viral genome in determining tumor morphology.

Adenovirus type 12 transforms the fibroblastic BHK21 (baby hamster kidney) cell line into rounded or cuboidal cells that give rise in hamsters to undifferentiated small cell sarcomas indistinguishable from those induced in newborn hamsters by inoculation of the virus itself. In contrast. cells from this line transformed by polyoma virus retain their fibroblastic morphology and induce fibrosarcomas in hamsters. This suggests that the morphology of tumors induced by the adenovirus-transformed cells from this line may be determined by the viral genome and that such mechanism may also explain the remarkably uniform microscopic appearance which seems to characterize tumors induced in hamsters by direct inoculation of adenovirus type 12.

Adenoviridae↗
PubMed1985

Integrated imaging of hepatic tumors in childhood. Part I: Malignant lesions (primary and metastatic).

Both the prognosis and treatment of hepatic tumors in children depend upon the histological diagnosis and the extent of disease. Recent advances in imaging techniques permit characterization of specific tumors and differentiation from other intrahepatic processes. An integrated imaging protocol involving a combination of ultrasound, computed tomography, and scintigraphy often provides a high degree of accuracy. Patterns derived from 40 cases of hepatoblastoma, hepatocellular carcinoma, rhabdomyosarcoma, monotypic small-cell sarcoma, and metastatic tumors are discussed and an algorithm for evaluation of hepatic tumors in children is presented.

Adolescent↗
PubMed1975

Rhabdomyosarcoma in childhood.

Fifty-four rhabdomyosarcomas in children affected mainly the pelvis and scrotum, 22 cases, head and neck, 19, and limbs and limb girdles, 11. Rhabdomyosarcomas of the female genital tract occurred only in children under 2 years, and those in the lower eyelid presented in the first year of life. A leiomyosarcoma-like appearance, and an undifferentiated small cell sarcoma sometimes mimicking Ewing's tumour, were patterns giving rise to diagnostic difficulty. Many fine gradations from undifferentiated embryonal to almost purely differentiated "pleomorphic" examples, made microscopic classification arbitrary. However, the histological pattern had no bearing on prognosis in children in this series. Of the 46 cases adequately followed, 43 are dead. Two of the 3 long-term survivors had paratesticular tumours.

Adolescent↗
PubMed2002

Biricodar. Vertex Pharmaceuticals.

Vertex is developing biricodar as a chemosensitizing agent designed to restore the effectiveness of chemotherapeutic agents in tumor multidrug resistance. By November 1998, phase II trials had commenced for biricodar, in combination with chemotherapy, for five common cancer indications: breast, ovarian, soft-tissue sarcomas, small cell lung cancer and prostate cancer. Phase II trials were ongoing in January 2002. By March 2000, Vertex was the sole developer of biricodar, as an agreement made in 1996 with BioChem Pharma (now Shire Pharmaceuticals), for the development and marketing of biricodar in Canada was terminated. Biricodar is the free base compound, which also has a citrate salt analog known as VX-710-3. Vertex has published three patents, WO-09615101, WO-09636630 and WO-09736869, disclosing derivatives of biricodar that are claimed for the treatment of multidrug resistant protein and P-glycoprotein-mediated multidrug resistant tumors. In January 2002, a Banc of America analyst report forecast that biricodar had a 30% chance of reaching the market with a launch date in the second half of 2005, with peak sales estimated at $250 million.

Antineoplastic Agents↗
PubMed1986

The in vitro growth, heterotransplantation, and differentiation of a human rhabdomyosarcoma cell line.

A human rhabdomyosarcoma (RMS) cell line was established from a case of childhood small cell sarcoma, which in vivo showed no evidence of differentiation, but which demonstrated myogenic differentiation in tissue culture. In a serum-free culture medium, the tumor cells demonstrated continuous growth without ultrastructural or biochemical evidence of differentiation. Heterotransplanted RMS cells gave rise to tumors in nude mice which also showed no myogenic differentiation. However, RMS cells grown in the presence of either retinoic acid (5 microns), phorbol ester (1 nM), prostaglandin E1 (10 ng/ml), or 2% fetal calf serum gave rise to myotubes with a biochemical shift in the creatine kinase isoenzyme pattern from the embryonic to the mature skeletal muscle form. The karyotype of the RMS cells revealed a translocation of Chromosomes 2 and 13, which may represent a nonrandom aberration unique to this morphologic subtype. In addition, the RMS cells gave evidence for gene amplification in the form of double minute chromosomes. This human RMS cell line provides a valuable in vitro system for study of myogenesis and factors which induce differentiation.

Cell Differentiation↗
PubMedDate not supplied

[Definition of the T parameter in nasosinusal neoplasms: a CT-MR comparison].

This study was aimed at investigating the value of CT and MRI in the staging of sinonasal tumors. The authors report 22 cases of sinonasal tumors: 7 squamous cell carcinomas, 4 adenoid-cystic carcinomas, 1 mucoepidermoid carcinoma, 6 adenocarcinomas, 1 esthesioneuroblastoma, 1 osteosarcoma, 1 small-cell sarcoma and finally 1 non-Hodgkin lymphoma. No significant differences were observed between CT and MR staging: 2 T2 and 15 T4 lesions were diagnosed in the maxillary sinuses and 3 stage-II and 1 stage-III lesions in the naso-ethmoidal region. Tumor spread was similar in 20/22 cases: MRI excluded the involvement of maxillary and sphenoid sinuses in 2 cases. CT was superior in the assessment of bone destruction particularly at the base of the skull, but MRI better demonstrated intracranial spread. MRI detailed the intraorbital muscles and, in the infratemporal fossa, the pterygoid muscles better than CT. High agreement was observed between CT and histology in 5/7 cases and between MRI and histology in 6/7 cases undergoing craniofacial resection. Seventeen of 22 cases had low to intermediate signal intensity on T1-weighted, PD and T2-weighted MR images. Signal was hyperintense in 5 cases: 1 adenocarcinoma with mucinous features, 3 adenoid-cystic carcinomas and 1 esthesioneuroblastoma. In agreement with literature data, this study confirms CT as the examination of choice in staging sinonasal tumors: nonetheless, MRI yields valuable information in the cases with tumor spread to the muscles and soft tissues.

Adult↗
PubMed2002

Prognostic significance of grading and staging systems using MIB-1 score in adult patients with soft tissue sarcoma of the extremities and trunk.

BACKGROUND: The predictive value of histologic grading and staging systems for overall survival in different types of adult soft tissue sarcoma of the extremities and trunk is unclear. METHODS: Histologic slides from 193 patients with primary tumors were reviewed for diagnosis, and Ki-67 (MIB-1) immunostaining was performed for grading in all patients. Univariate and multivariate analyses were conducted to analyze the results from patients with soft tissue sarcomas as a group and among the six main histologic categories: malignant fibrous histiocytoma (n = 49 patients), liposarcoma (n = 48 patients), synovial sarcoma (n = 30 patients), spindle cell sarcoma (n = 24 patients), small round cell sarcoma (n = 15 patients), and others (n = 27 patients). The median follow-up was 50 months. RESULTS: Univariate analysis of soft tissue sarcomas showed that tumor size and depth, histologic type, MIB-1 score, grades based on three criteria (tumor differentiation/histologic type, necrosis, and either mitosis or MIB-1 score) and disease stage, as assessed by tumor size, depth, and grade, were associated with overall survival. Among these variables, grading and staging systems using the MIB-1 score had better predictive value compared with the MIB-1 score and standard grading and staging models in the main histologic categories. Because survival curves for the different tumor grades and stages showed similar trends between the different histologic types, multivariate analysis was conducted adjusting for age, gender, disease site, surgical margin, tumor size and depth, grade, stage, and histologic type. Consequently, Grade 3 emerged as the most significant adverse prognostic factor. Additional adverse prognostic factors were Stage III, Grade 2, a histologic type of spindle cell sarcoma, and patient age > 50 years at the time of presentation. The histologic type liposarcoma was identified as a favorable prognostic factor. CONCLUSIONS: The current results indicate that grading and staging systems using the MIB-1 score are very strong prognostic factors in patients with the main histologic types of soft tissue sarcoma. Specific assessment of histologic type should be carried out before deciding on treatment strategies.

Adolescent↗
PubMed1964

RETICULUM CELL SARCOMA OF THE SMALL BOWEL AND STEATORRHOEA.

This series presents further evidence for an association between reticulosis of the intestine and steatorrhoea. Although some patients have a definite past history of gluten enteropathy, it seems likely that in certain patients the reticulosis itself is the primary cause of the steatorrhoea.

Ascorbic Acid↗
PubMed1993

Small round and spindle cell sarcoma with neuronal differentiation and oncocyte-like features of the thoracic wall: a case report with histological, immunohistochemical and ultrastructural examinations.

A case of small round and spindle cell sarcoma with neuronal differentiation and oncocyte-like features is presented. The tumor was encountered in a 32 year old Japanese woman with an initial presentation of palpable tumor in the left lateral region of the thorax. The resected tumor was a partially well encapsulated whitish medullary one and consisted of small round and spindle tumor cells, together with so-called rhabdoid cells in the small round cell area. Although pseudorosettes were often observed, true rosette formation could not be detected anywhere. Ultrastructurally, despite a histologic variety of tumor cells, most tumor cells possessed numerous mitochondria, some of which occasionally contained abnormal filamentous or crystalloid structures. Various amounts of microfilaments were present in most tumor cells and microtubules were present in a few. A minority of small round cells possessed a small number of neurosecretory granules, especially in short cytoplasmic processes. A positive immunoreaction for neuron specific enolase was found by immunohistochemical examination in several small round tumor cells and for neurofilaments in lesser numbers. Despite the lack of S-100 protein, MB2 was detected in both small round and spindle cells. On the basis of these findings, the tumor of the present case corresponds to malignant peripheral nerve sheath tumor with neuronal differentiation and oncocytic features.

Adult↗
PubMed2000

Small-cell variant of synovial sarcoma: fine-needle aspiration with ancillary features and potential diagnostic pitfalls.

We report a small-cell variant of synovial sarcoma examined by fine-needle aspiration (FNA) biopsy. The patient is a 23-yr-old female who had a synovial sarcoma involving the left infratemporal region, diagnosed at 7 yr of age, followed by a metastatic lesion involving the lung and chest wall 16 yr later. The chest wall metastases was sampled by FNA biopsy. The aspirate consisted of numerous, small, round cells with very high nuclear-to-cytoplasmic ratios. The cytomorphologic features could potentially be confused with other pediatric small round cell tumors. Ancillary studies demonstrated positive staining of the neoplastic cells for cytokeratin, epithelial membrane antigen (EMA), and CD99. The differential diagnosis of other small round cell tumors that may be mistaken for the small-cell variant of synovial sarcoma are presented. We believe that this is the first FNA report detailing the cytologic and ancillary features of the small-cell variant of synovial sarcoma.

Adult↗
PubMed2005

Alternating sequential chemotherapy with high-dose ifosfamide and doxorubicin/cyclophosphamide for adult non-small round cell soft tissue sarcomas.

Doxorubicin and ifosfamide are the two most active agents used to treat soft tissue sarcomas. However, because of their overlapping side effects, concurrent administration to achieve optimal doses of each agent is difficult. We therefore conducted a Phase II trial to investigate the efficacy and feasibility of a novel alternating sequential chemotherapy regimen consisting of high dose ifosfamide and doxorubicin/cyclophosphamide in advanced adult non-small round cell soft tissue sarcomas. Adult patients with non-small round cell soft tissue sarcomas were enrolled. The treatment consisted of four sequential courses of chemotherapy that was planned for every 3 weeks. Cycles 1 and 3 consisted of ifosfamide (14 g/m(2)), and cycles 2 and 4 consisted of doxorubicin (60 mg/m(2)) and cyclophosphamide (1200 mg/m(2)). Forty-two patients (median age 47 years) were enrolled. Of the 36 assessable patients, 1 complete response and 16 partial responses were observed, for a response rate of 47.2%. Responses were observed in 57% of patients who had received no previous chemotherapy and 13% of those who had previously undergone chemotherapy. Grade 3-4 neutropenia was observed during 70% of all cycles. Sequential administration of high-dose ifosfamide and doxorubicin/cyclophosphamide has promising activity with manageable side effects in patients with advanced adult non-small round cell soft tissue sarcomas.

Adult↗