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PubMed1991

Renal angiomyolipoma with sarcomatous transformation and pulmonary metastases.

We report the case of a 49-year-old woman with a large renal angiomyolipoma that invaded the liver. In some areas, the tumor had the appearance of a typical angiomyolipoma; however, it also had foci where the spindle cells of the lesion showed marked cytologic atypia and mitotic activity, giving it the appearance of a high-grade sarcoma. Immunohistochemical studies demonstrated expression of vimentin, desmin, and muscle-specific actin by the sarcoma cells; these findings were consistent with leiomyosarcoma. A second, small typical angiomyolipoma was also present in the kidney. In addition, the liver exhibited focal nodular hyperplasia. Three weeks after resection of the primary renal tumor, pulmonary metastases were diagnosed by fine-needle aspiration biopsy. This is the first report of a case of angiomyolipoma with sarcomatous transformation and biopsy-proven metastatic disease.

Biopsy, Needle↗

PubMed1974

Tumours of the lung.

Lung tumours are not common in domestic animals; there has not been the increase in epidermoid carcinomas and anaplastic small-cell carcinomas that has occurred in man this century. Adenocarcinoma is the most common type in animals. The biological behaviour of each type of tumour in animals seems to be much the same as in man. The tumours are described histologically, the main categories being: epidermoid carcinoma, anaplastic carcinoma, adenocarcinoma, combined epidermoid and adenocarcinoma, carcinoid tumours, bronchial gland tumours, benign tumours, and sarcomas.

Adenocarcinoma↗

PubMed1987

Deletion mutations in the small t antigen gene alter the tissue specificity of tumors induced by simian virus 40.

Subcutaneous injection of wild-type simian virus 40 into Syrian hamsters normally induces fibrosarcomas at the injection site. We showed that subcutaneous injection of three different small t deletion mutants (dl884, dl883, and dl890) led to the formation of abdominal reticulum cell sarcomas (lymphomas) in about 15% of the animals bearing tumors. The remainder of the tumors were fibrosarcomas occurring with prolonged latencies at the site of injection. We postulated that, in the absence of an active small t protein, which is thought to have cell growth-promoting properties, the mutant virus preferentially transforms rapidly proliferating lymphoid cells.

Animals↗

PubMed1987

Embryonic ultrastructure as a guide in the diagnosis of tumors.

The purpose of this article has been to illustrate the applications and limitations of comparing the ultrastructural morphology of certain poorly differentiated neoplasms with normal human embryonic tissues. The examples used--embryonal rhabdomyosarcoma, Wilms' tumor, and fibrous mesothelioma, in comparison with embryonic mesoderm and its early derivatives--are but a few of the entities that can be investigated in this manner. Ewing's sarcoma was included in the report because of the long-standing and unsolved mystery concerning its histogenesis and because we believe it probably fits into the same category of poorly differentiated mesodermal neoplasms as the other lesions described. However, unlike the other more definite examples of primitive neoplasms manifesting focal markers of secondary mesenchymal differentiation, Ewing's sarcomas exhibit no ultrastructural evidence for myogeneous, nephrogenic, or mesothelial lines of maturation. Nor are there any morphologic indications of ectodermal or endodermal differentiation. The questions arise as to whether the category of Ewing's sarcoma has been perpetuated by so classifying all small-cell neoplasms having no recognizable line of differentiation, and whether this category may include cells of more than one type, that is, cells that are biologically determined to develop along several different pathways. This concept would be one explanation for the occurrence of Ewing's tumors in soft tissue as well as in bone, and we know that the cells contained in somites are ultrastructurally very similar to the least-differentiated cells making up the myotomes and sclerotomes. Apparently, questions such as these cannot be answered by morphologic studies alone. However, a number of other useful diagnostic and academic points of information can be gleaned.

Embryo, Mammalian↗

PubMed1986

Extraskeletal Ewing's sarcoma: first case report in Greece.

The first case of soft tissue Ewing's sarcoma in Greece is presented. The tumour was a circumscribed large mass at the right calf, was radically excised and histologically proved to be small cell malignant neoplasm, performing the characteristic structural and cytological pattern of Ewing's sarcoma. Systematic clinical and radiological examination was negative. Operation was followed by local radiotherapy and systematic chemotherapy and the patient remains disease-free and clinically in perfect health eight months after the operation. The case is presented with special reference to its histological appearance and its treatment.

Adult↗

PubMed2000

Progress in the diagnosis and treatment of rhabdomyosarcoma and related soft tissue sarcomas.

Advances in the diagnosis and treatment of rhabdomyosarcoma and related soft tissue sarcomas continue in the Intergroup Rhabdomyosarcoma Study Group (IRSG) and European cooperative groups. The use of molecular biology techniques in soft tissue sarcomas are redefining the classic pathology of these small blue cell tumors. Improvements in imaging, radiotherapy, and surgery, in part, deserve credit for the better survival seen in all cooperative trials. These advances confound the interpretation of consecutively run chemotherapy trials using historical comparisons. The IRSG has reported improvement in the prognosis of both nonmetastatic and metastatic embryonal rhabdomyosarcoma as attributable to three, three-drug regimens that use cyclophosphamide at 2.2 g/m2 in either maintenance or induction and maintenance therapy. Patients of any age with metastatic, nonembryonal, and those over 10 years of age with metastatic embryonal rhabdomyosarcoma continue to have a poor prognosis, which even megatherapy has failed to change. The doublet of ifosfamide and etoposide in combination with vincristine, actinomycin D, and cyclophosphamide at 2.2 g/m2 achieved a remarkable 3-year survival of 58% in patients with metastatic rhabdomyosarcoma and undifferentiated soft tissue sarcoma. The topoisomerase I inhibitor, topotecan, has recently been found by the IRSG to have a 57% overall response rate in patients with metastatic alveolar rhabdomyosarcoma. Topotecan has completed testing with cyclophosphamide in a phase II window study in newly diagnosed patients with metastatic disease and has been incorporated into a randomized trial in intermediate risk patients in IRSG-V. Molecular studies in IRSG-V will be applied in the detection of occult bone marrow metastases and the evaluation of resection margins at initial and second-look surgery. Long-term follow-up will be required in patients with gross residual sarcoma randomized to conventional and hyperfractionated radiotherapy in IRSG-IV to assess late effects. Although older patients with unfavorable histology and metastatic disease continue to have a poor prognosis, the overall 5-year survival of children and adolescents with nonmetastatic and metastatic rhabdomyosarcoma is approaching 80%. As molecular discoveries advance the diagnosis and detection of rhabdomyosarcoma, it is hoped that the futuristic molecular based treatment strategies in development and early testing will further improve survival in high-risk patients with metastatic soft tissue sarcoma.

Adolescent↗

PubMed1998

Primary cutaneous Ewing's sarcoma: immunophenotypic and molecular cytogenetic evaluation of five cases.

Cutaneous small blue cell tumors are relatively uncommon and include primary lesions of either adnexal or neuroendocrine differentiation, as well as metastatic disease. Extraosseous Ewing's sarcoma/malignant primitive neuroectodermal tumor (MPNET) rarely may occur as a primary, superficially based neoplasm in children and young adults. We describe a series of five cases of Ewing's sarcoma/malignant primitive neuroectodermal tumor occurring as a primary cutaneous malignancy supported diagnostically both by immunohistochemical stains and fluorescence in situ hybridization (FISH). All five cases occurred as a solitary dermal nodule and were located in the lower extremities (3 cases), the axilla (1 case), and the flank (1 case). Three of the cases were clinically polypoid. Four of the five patients were female, and age at presentation ranged form 8 to 50 years of age (median, 18 years). All five tumors consisted of nodular proliferations of monomorphous, small blue cells with round, vesicular nuclei, and scant to moderate cytoplasm that were uniformly immunoreactive for the CD99 cell surface glycoprotein in a characteristic membranous pattern. Fluorescence in situ hybridization analysis of paraffin-embedded tissue revealed that three of four tumors were positive for a chromosomal translocation involving the EWS locus at 22q12, seen in more than 90% of cases of Ewing's sarcoma/malignant primitive neuroectodermal tumor. One case was not analyzable. All five patients were treated using local excision, and two patients additionally received postoperative chemotherapy and radiotherapy. Clinical follow-up is available in three cases (median duration, 33 months) and to date none has shown evidence of either local recurrence or metastasis. Because similar cases reported in the literature have likewise had favorable clinical courses after excision, primary cutaneous Ewing's sarcoma/malignant primitive neuroectodermal tumor may represent a clinically favorable subset of this otherwise highly aggressive neoplasm.

Adolescent↗

PubMed2006

Bevacizumab: an angiogenesis inhibitor for the treatment of solid malignancies.

BACKGROUND: Bevacizumab is a recombinant humanized monoclonal antibody that was approved by the US Food and Drug Administration (FDA) in February 2004 for use as part of combination therapy with fluorouracil-based regimens for metastatic colorectal cancer (mCRC). OBJECTIVES: This article reviews the mechanism of action, clinical pharmacology, and pharmacodynamic and pharmacokinetic properties of bevacizumab. It summarizes data on the clinical efficacy and tolerability of bevacizumab from Phase II/III trials in mCRC, breast cancer, non-small-cell lung cancer, and renal cell carcinoma and preliminary data from investigational studies in pancreatic cancer and soft-tissue sarcomas. The dosing and administration of bevacizumab also are discussed. METHODS: A comprehensive search of the English-language literature indexed on MEDLINE (1966-April 2006) was performed using the terms Avastin, bevacizumab, vascular endothelial growth factor, angiogenesis, and bevacizumab plus colorectal cancer, breast cancer, non-small-cell lung cancer, pancreatic cancer, and renal cell carcinoma. Published abstracts from American Society of Clinical Oncology annual meetings from 2002 to 2006, FDA submission documents, and the product information for bevacizumab also were reviewed. Pertinent review articles, preclinical studies, and editorials and all published Phase II/III clinical trials were selected for review. The reference lists of identified articles were examined for additional publications. RESULTS: Bevacizumab exhibits linear pharmacokinetics in the dose range between 0.3 and 10 mg/kg q2-3wk and steady state, which is reached in approximately 100 days. The estimated t(1/2) of bevacizumab is approximately 20 days. After correction for body weight, clearance and V(d) are reported to be a respective 26% and 22% higher in men than in women. Statistical analyses have not been performed, however, and the clinical impact of these gender differences has not been assessed. No dose adjustment is currently recommended based on age, sex, or renal function. Bevacizumab has been reported to result in changes in exposure to concomitant chemotherapy, although formal drug-interaction studies have not been performed. Surrogate markers of disease progression or treatment response to bevacizumab have been studied, but no significant correlations with any outcome measure have been found. When combined with standard chemotherapy regimens, bevacizumab has been associated with significant improvements compared with chemotherapy alone in the efficacy end points of overall survival, progression-free survival, and response rates in patients with mCRC (all, P < 0.05). Based on these findings, bevacizumab is considered a first-line option for this disease. Combination bevacizumab regimens have been associated with clinical activity in breast cancer, non-small-cell lung cancer, renal cell carcinoma, pancreatic cancer, and soft-tissue sarcoma. The observed toxicities of bevacizumab include hypertension, proteinuria, mild to moderate hemorrhage, wound healing complications, and thromboembolic events. A bevacizumab dose of 5 mg/kg q2wk has been established as effective and well tolerated in the setting of mCRC. A variety of dosing schemes have been investigated in other solid neoplasms, but no consensus has been reached on the optimal bevacizumab regimen. CONCLUSIONS: Bevacizumab is effective and generally well tolerated as first-line therapy for mCRC. The results from clinical studies of bevacizumab as a single agent or as part of combination regimens for breast cancer, non-small-cell lung cancer, renal cell carcinoma, and other solid malignancies have been promising. The most effective regimens for various malignancies and predictive markers of treatment response have not been fully determined. Combining bevacizumab with chemotherapy or other novel targeted agents appears to be a rational approach that may enhance efficacy while limiting the traditional nonselective toxicities.

Angiogenesis Inhibitors↗

PubMed1999

Documentation of EWS gene rearrangements by fluorescence in-situ hybridization (FISH) in frozen sections of Ewing's sarcoma-peripheral primitive neuroectodermal tumor.

Prompt and accurate diagnosis of small round cell tumors warrants ancillary studies. Recently, two-color fluorescence in-situ hybridization (FISH) using probes for specific gene rearrangements has gained wide acceptance. EWS gene rearrangements, present in essentially 100% of Ewing's Sarcoma/peripheral primitive neuroectodermal tumor, were evaluated by FISH on frozen sections (FS) of tumor biopsies from 10 patients, plus a negative control, and in seven other malignant neoplasms of childhood. 4mu FS were hybridized overnight, using a single EWS gene-specific probe spanning the EWS breakpoint. We identified EWS rearrangements in 8 of 10 cases (80%) of Ewing's Sarcoma/pPNET. There are no known false positives in diploid or near-diploid tumors, or in any of the non-EWS tumors tested; the uncommon false negative can be confirmed by RT-PCR. Hyperdiploid cases with multiple copies of chromosome 22 may be better evaluated by two-color FISH. This is the first use on FS biopsy material of a single probe for EWS, capable of detecting all known EWS rearrangements, in ES and other tumors. Utilization of this ancillary technique on FS for ES/pPNET and other tumors with distinctive chromosomal translocation is highly specific, reliable, expeditious (24-36 hours) and cost-effective.

Chromosomes, Human, Pair 11↗

PubMed2005

Kaposi's sarcoma-associated herpesvirus expresses an array of viral microRNAs in latently infected cells.

MicroRNAs (miRNAs) are an endogenously encoded class of small RNAs that have been proposed to function as key posttranscriptional regulators of gene expression in a range of eukaryotic species, including humans. The small size of miRNA precursors makes them potentially ideal for use by viruses as inhibitors of host cell defense pathways. Here, we demonstrate that the pathogenic human herpesvirus Kaposi's sarcoma-associated herpesvirus (KSHV) encodes an array of 11 distinct miRNAs, all of which are expressed at readily detectable levels in latently KSHV infected cells. Individual KSHV miRNAs were expressed at up to 2,200 copies per cell. The KSHV miRNAs are expressed from what appears to be a single genetic locus that largely coincides with an approximately 4-kb noncoding sequence located between the KSHV v-cyclin and K12/Kaposin genes, both of which are also expressed in latently infected cells. Computer analysis of potential mRNA targets for these viral miRNAs identified a number of interesting candidate genes, including several mRNAs previously shown to be down-regulated in KSHV-infected cells. We hypothesize that these viral miRNAs play a critical role in the establishment and/or maintenance of KSHV latent infection in vivo and, hence, in KSHV-induced oncogenesis.

Base Sequence↗

PubMedDate not supplied

Identification of types and primary sites of malignant tumors by examination of exfoliated tumor cells in serous fluids. Comparison with the diagnostic accuracy on small histologic biopsies.

The accuracy of identification of tumor type and primary site of malignant tumors by examination of exfoliated tumor cells was cytologically studied in 448 malignant effusions from 366 patients for whom the primary tumor site had been confirmed by histology. Ninety-seven corresponding small biopsies from metastases were separately reviewed histopathologically. In four fluids, the cells were too scanty or too poorly preserved for tumor typing. The cytologic tumor typing was performed with nearly 100% accuracy in the remaining 444 fluids, except for those of intermediate-cell anaplastic carcinomas (0 of 3) and poorly differentiated squamous (epidermoid) carcinomas (1 of 5). Adenocarcinoma was correctly identified in 98% of 285 fluids, large-cell carcinoma in 97% of 108 fluids, oat-cell carcinoma in 94% of 16 fluids, well-differentiated (keratinizing) squamous carcinoma in 100% of 3 fluids, malignant lymphoma in 100% of 22 fluids and sarcoma in 100% of 2 fluids. The criteria and the failures are discussed at length. In the investigation of the accuracy of cytologic and histologic diagnoses with respect to the primary tumor site, tumors with variable sites of origin (sarcomas and lymphomas) and those with usually singular sites of origin (e.g., small-cell anaplastic carcinoma of the lung) were excluded, leaving 387 cytologic and 83 histologic specimens available for review. The breast as a primary site was correctly identified in 70% of both the cytologic and histologic specimens; the primary cytodiagnostic criteria included a uniform cell pattern, finely granular chromatin, dense cytoplasm and cell balls with smooth borders. Ovarian primaries were correctly identified in 70% of the fluids and 83% of the biopsy samples on the basis of very irregular clusters of large pleomorphic tumor cells, large nucleoli and psammoma bodies. Lung primaries, identified in 50% of the fluids and 29% of the biopsy samples, showed quite variable cell patterns, most often including large pleomorphic cells with or without mucus formation and prominent multinucleation. Gastric cancers of the diffuse type were accurately identified in 52% of the corresponding fluids, which showed mainly isolated cells with dense cytoplasmic rims, occasional signet-ring cells, "embryo-shaped" nuclei, marked hyperchromasia and densely granular chromatin.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenocarcinoma↗

PubMedDate not supplied

[Prognosis in Ewing sarcoma patients with initial pathological fractures of the primary tumor site].

In this retrospective analysis, data of 52 patients with Ewing's sarcoma or PNET with a pathological fracture in the area of the primary tumor were evaluated. All patients were treated according to the trials CESS 81, CESS 86 P, CESS 86, CESS 91 P and EICESS 92 of the German Society of Pediatric Oncology and Haematology (GPOH). At the date of evaluation (15. September 1994) all patients had completed treatment and had been under observation for at least one year following diagnosis. The median follow-up time was 28 months. 22 patients were female, 30 male. The median age was 12 years. 75% of primary tumors had a volume of > or = 100 ml. 30 patients presented with fractures in proximal, 12 in central and 10 in distal parts of the skeleton. 10 patients had primary metastases. The histological definition was Ewing's sarcoma (including atypical Ewing's sarcoma) in 43 patients, PNET in 8 and small-cell osteosarcoma in 1 patient. For local therapy the patients underwent surgery, definitive radiotherapy or a combination of both. The percentage of primary metastases in the group of the patients with pathological fractures is comparable to the whole reference group. The present analysis focuses on those patients with pathological fractures who had no metastases at diagnosis. The relapse-free survival of patients with a pathological fracture and no primary metastases is 58%, the overall survival 65%. These rates are similar to those of the reference group of protocol patients without pathological fractures at diagnosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1999

[Ten-year experience with intraoperative radiotherapy].

An analysis of the end results of combined treatment for stage III non-small cell lung cancer, stage III gastric cancer and soft-tissue sarcoma has been carried out. Radical surgery was supplemented with intraoperative radiation therapy (IORT) with a single dose of 10-20 Gy. The radiation source was an original small-size betatron installed in the operating room. IORT did not interfere with wound healing nor did it involve increase in postoperative lethality. The 5-year survival rates for lung cancer patients who received IORT or surgery alone were 34.1 and 24.4%, respectively. The same indices for gastric cancer in IORT patients were 34.2% while in surgical cases--21.7%. Two-year non-relapse survival in patients with soft-tissue sarcomas showed a rise due to reduced recurrence incidence in irradiated areas.

Adult↗

PubMed1990

[Chemotherapy of highly malignant thyroid tumors].

In a prospective phase II study 15 patients suffering from anaplastic thyroid carcinoma or thyroid sarcoma were treated by surgery and chemotherapy. Chemotherapy varied according to age of the patient and histological subtype of the tumour. The following regimen was used: 100 mg/m2 BSA CDDP, 20 mg/m2 mitoxantrone and 1.5 mg/m2 vincristine. 10 patients responded to chemotherapy, 4 of whom had a complete response. Responders showed a longer mean and median survival time (20.8 months versus 4.5 ms, 15.5 ms vs. 3.8 ms, respectively) than non-responders. In the group responding to chemotherapy no evidence of metachronous metastases was found. Local recurrence was absent only in the patients showing a complete response. Anaplastic carcinomas with areas of differentiated thyroid carcinoma and small cell carcinomas (after exclusion of malignant lymphoma of the thyroid) showed a higher response rate to chemotherapy than spindle or giant cell carcinoma or thyroid sarcoma.

Aged↗

PubMed2005

Synovial sarcoma with radiological appearances of primitive neuroectodermal tumour/Ewing sarcoma: differentiation by molecular genetic studies.

Synovial sarcoma (SS) arises in soft tissues but may invade adjacent bone. We describe a case of SS presenting as aggressive lysis of the proximal ulna, the imaging of which suggested a primary bone lesion. Needle biopsy showed a "small round blue cell tumour", and a primitive neuroectodermal tumour (PNET)/Ewing sarcoma was suggested on the basis of the imaging appearances. The definitive diagnosis of synovial sarcoma was made following molecular genetic studies, which demonstrated a fusion product incorporating the genes SYT and SSX1. The importance of correct diagnosis to guide appropriate management, and, therefore, the necessity for molecular genetic studies, is discussed.

Adult↗

PubMed2005

[Sarcomas of the small intestine].

Sarcomas of the small intestine are rare, clearly differentiated, malignant, mesenchymatous tumours that can be of smooth muscle, Schwann cell or fibroblastic origin. From a clinical point of view, the pain and abdominal mass are the 2 types of symptoms that frequently reveal the disease. In rare cases, sarcomas of the small intestine are manifested by an acute complication. No imaging method can clearly confirm the diagnosis. Before immunohistochemistry, differential diagnosis was made on undifferentiated mesenchymatous "stromal" tumours, which are also rare. Exeresis must be complete and without perforation of the tumour because of the risk of locoregional relapse. The benefits provided by chemotherapy and radiotherapy are limited because of the low mitotic activity of the tumour cells and its weak vascularisation. Long-term survival is limited by poor prognosis criteria: high grade malignancy, size greater than 5 cm, tumour extension, perforation of the tumour, quality of surgical resection and histological type.

Diagnostic Imaging↗

PubMedDate not supplied

Bone marrow metastasis in Ewing's sarcoma and peripheral primitive neuroectodermal tumor: An immunohistochemical study.

Bone marrow metastases from small round cell tumors can present diagnostic difficulties. In this study, we assessed the value of immunohistochemistry, using two monoclonal antibodies to CD99, for the diagnosis of metastatic disease in bone marrow trephine specimens from patients with Ewing's sarcoma or primitive neuroectodermal tumor (PNET). The proportions of specimens showing metastases were 10.3% with routine staining and 20.7% with immunohistochemistry. The specimens that were negative on conventional light microscopy and positive with immunohistochemistry all showed other abnormalities. The results do not support the routine use of immunohistochemistry in specimens that are normal by conventional light microscopy, but indicate that useful information may be gained in cases where marrow histology is obscured by fibrosis, necrosis, or distortion artefact. Neither of the two antibodies tested was superior for this purpose.

12E7 Antigen↗

PubMed2000

Myogenin is a specific marker for rhabdomyosarcoma: an immunohistochemical study in paraffin-embedded tissues.

Myogenin belongs to a group of myogenic regulatory proteins whose expression determines commitment and differentiation of primitive mesenchymal cells into skeletal muscle. The expression of myogenin has been demonstrated to be extremely specific for rhabdomyoblastic differentiation, which makes it a useful marker in the differential diagnosis of rhabdomyosarcomas (RMS) from other malignant small round cell tumors of childhood. Commercially available antibodies capable of detecting myogenin in routinely processed formalin-fixed paraffin-embedded (FFPE) tissue are now available. In this study, we evaluated myogenin expression using the monoclonal myf-4 antibody (Novocastra Labs) on FFPE in a large number of pediatric tumors in order to define the clinical utility of this marker. A total of 119 tumors were studied. These included 48 alveolar RMS (ARMS), 20 embryonal RMS (ERMS), one spindle cell RMS, 16 Ewing's sarcomas (ES), six nephroblastomas, two ectomesenchymomas, seven precursor hematopoietic neoplasms, five olfactory neuroblastomas, three neuroblastomas, six desmoplastic small round cell tumors, and five rhabdoid tumors. Distinct nuclear staining for myogenin was noted in all 69 RMS. Notably, the number of positive tumor cells differed between the ARMS and ERMS. In ARMS, the majority of tumor cells (75 to 100%) were positive, in contrast to ERMS, in which the positivity ranged from rare + to 25% in all but three tumors. Additionally, myogenin positivity was seen in two of two ectomesenchymomas and in two nephroblastomas with myogenous differentiation. All other tumors were clearly negative. Our results indicate that staining for myogenin is an extremely reliable and specific marker for rhabdomyoblastic differentiation. It gives consistent and easily interpretable results in routinely fixed tissues.

Biomarkers, Tumor↗