Sarcoma, Alveolar Soft Part
Soft Tissue Neoplasms
Sarcoma
Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
Sarcoma, Clear Cell
Brain metastases in musculoskeletal sarcomas. (1/36)
BACKGROUND: In musculoskeletal sarcomas, brain metastases are rare, but severely affect quality of life. METHODS: All patients with musculoskeletal sarcomas who were treated at our institutions from 1975 to 1997 were reviewed for examples of brain metastasis. RESULTS: Of 480 sarcoma patients, 179 had distant metastases, including 20 patients with brain metastases (4.2%). Alveolar soft part sarcoma (3/4), extraskeletal Ewing's sarcoma (2/8), rhabdomyosarcoma (2/13) and bone Ewing's sarcoma (2/18) tended to metastasize to the brain. All 20 patients had distant or local relapses and 16 of the 20 patients had pulmonary metastases. Three patients underwent surgical treatment and two of them survived over 1 year. Mean survival after diagnosis of brain metastasis was 5.1 months. CONCLUSIONS: Patients with alveolar soft part sarcoma, Ewing's sarcoma, rhabdomyosarcoma and pulmonary metastases have a high risk of brain metastasis. (+info)Human fibroblasts transduced with CD80 or CD86 efficiently trans-costimulate CD4+ and CD8+ T lymphocytes in HLA-restricted reactions: implications for immune augmentation cancer therapy and autoimmunity. (2/36)
Augmenting immunogenicity by genetically modifying tumor cells to express costimulatory molecules has proven to be a promising therapeutic strategy in murine tumor models and is currently under investigation in human clinical trials for metastatic cancer. However, there are significant technical and logistic problems associated with implementing strategies requiring direct gene modification of primary tumor cells. In an effort to circumvent these problems, we are developing a strategy in which the costimulatory signal required for tumor-specific T lymphocyte activation is provided by a genetically modified human fibroblast (trans-costimulation). We have evaluated the efficiency of CD80- and CD86-mediated trans-costimulation in the activation of human CD8+ and CD4+ T lymphocytes in MHC class I- and class II-restricted lymphoproliferation reactions. Our studies demonstrate that the efficiency of CD80- or CD86-mediated trans-costimulation of purified human CD8+ and CD4+ T lymphocytes is comparable to cis-costimulation under defined conditions. Moreover, a dose-response relationship consistent with the predicted two-hit kinetics of the reaction was evident in trans-costimulation reactions in which the ratio of target cells expressing either signal 1 or signal 2 was varied incrementally from 1:10 to 10:1. Importantly, the level of cell-surface CD86 required for trans-costimulation is equivalent to that constitutively expressed by human peripheral blood monocytes. These results may have significant implications for the clinical implementation of this type of cancer immunotherapy and also raise questions about the possibility of trans-costimulating autoreactive T lymphocytes in vivo. (+info)The der(17)t(X;17)(p11;q25) of human alveolar soft part sarcoma fuses the TFE3 transcription factor gene to ASPL, a novel gene at 17q25. (3/36)
Alveolar soft part sarcoma (ASPS) is an unusual tumor with highly characteristic histopathology and ultrastructure, controversial histogenesis, and enigmatic clinical behavior. Recent cytogenetic studies have identified a recurrent der(17) due to a non-reciprocal t(X;17)(p11.2;q25) in this sarcoma. To define the interval containing the Xp11.2 break, we first performed FISH on ASPS cases using YAC probes for OATL1 (Xp11.23) and OATL2 (Xp11.21), and cosmid probes from the intervening genomic region. This localized the breakpoint to a 160 kb interval. The prime candidate within this previously fully sequenced region was TFE3, a transcription factor gene known to be fused to translocation partners on 1 and X in some papillary renal cell carcinomas. Southern blotting using a TFE3 genomic probe identified non-germline bands in several ASPS cases, consistent with rearrangement and possible fusion of TFE3 with a gene on 17q25. Amplification of the 5' portion of cDNAs containing the 3' portion of TFE3 in two different ASPS cases identified a novel sequence, designated ASPL, fused in-frame to TFE3 exon 4 (type 1 fusion) or exon 3 (type 2 fusion). Reverse transcriptase PCR using a forward primer from ASPL and a TFE3 exon 4 reverse primer detected an ASPL-TFE3 fusion transcript in all ASPS cases (12/12: 9 type 1, 3 type 2), establishing the utility of this assay in the diagnosis of ASPS. Using appropriate primers, the reciprocal fusion transcript, TFE3-ASPL, was detected in only one of 12 cases, consistent with the non-reciprocal nature of the translocation in most cases, and supporting ASPL-TFE3 as its oncogenically significant fusion product. ASPL maps to chromosome 17, is ubiquitously expressed, and matches numerous ESTs (Unigene cluster Hs.84128) but no named genes. The ASPL cDNA open reading frame encodes a predicted protein of 476 amino acids that contains within its carboxy-terminal portion of a UBX-like domain that shows significant similarity to predicted proteins of unknown function in several model organisms. The ASPL-TFE3 fusion replaces the N-terminal portion of TFE3 by the fused ASPL sequences, while retaining the TFE3 DNA-binding domain, implicating transcriptional deregulation in the pathogenesis of this tumor, consistent with the biology of several other translocation-associated sarcomas. Oncogene (2001) 20, 48 - 57. (+info)Primary renal neoplasms with the ASPL-TFE3 gene fusion of alveolar soft part sarcoma: a distinctive tumor entity previously included among renal cell carcinomas of children and adolescents. (4/36)
The unbalanced translocation, der(17)t(X;17)(p11.2;q25), is characteristic of alveolar soft part sarcoma (ASPS). We have recently shown that this translocation fuses the TFE3 transcription factor gene at Xp11.2 to ASPL, a novel gene at 17q25. We describe herein eight morphologically distinctive renal tumors occurring in young people that bear the identical ASPL-TFE3 fusion transcript as ASPS, with the distinction that the t(X;17) translocation is cytogenetically balanced in these renal tumors. A relationship between these renal tumors and ASPS was initially suggested by the cytogenetic finding of a balanced t(X;17)(p11.2;q25) in two of the cases, and the ASPL-TFE3 fusion transcripts were then confirmed by reverse transcriptase-polymerase chain reaction. The morphology of these eight ASPL-TFE3 fusion-positive renal tumors, although overlapping in some aspects that of classic ASPS, more closely resembles renal cell carcinoma (RCC), which was the a priori diagnosis in all cases. These tumors demonstrate nested and pseudopapillary patterns of growth, psammomatous calcifications, and epithelioid cells with abundant clear cytoplasm and well-defined cell borders. By immunohistochemistry, four tumors were negative for all epithelial markers tested, whereas four were focally positive for cytokeratin and two were reactive for epithelial membrane antigen (EMA) (one diffusely, one focally). Electron microscopy of six tumors demonstrated a combination of ASPS-like features (dense granules in four cases, rhomboid crystals in two cases) and epithelial features (cell junctions in six cases, microvilli and true glandular lumens in three cases). Overall, although seven of eight tumors demonstrated at least focal epithelial features by electron microscopy or immunohistochemistry, the degree and extent of epithelial differentiation was notably less than expected for typical RCC. We confirmed the balanced nature of the t(X;17) translocation by fluorescence in situ hybridization in all seven renal tumors thus analyzed, which contrasts sharply with the unbalanced nature of the translocation in ASPS. In summary, a subset of tumors previously considered to be RCC in young people are in fact genetically related to ASPS, although their distinctive morphological and genetic features justify their classification as a distinctive neoplastic entity. Finally, the finding of distinctive tumors being associated with balanced and unbalanced forms of the same translocation is to our knowledge, unprecedented. (+info)Pancreatic metastasis of alveolar soft-part sarcoma: a case report and review of the literature. (5/36)
Alveolar soft-part sarcoma is a rare tumour. Patients commonly present with distant metastases both at the time of diagnosis and late in the course of disease. We present a case of pancreatic metastasis, occurring more than six years after diagnosis. Treatment consisted in subtotal pancreatoduodenectomy with pylorus resection. Both specific patterns of relapse and treatment opportunities of this uncommon feature are discussed. (+info)Pulmonary metastases of alveolar soft-part sarcoma: CT findings in three patients. (6/36)
Alveolar soft-part sarcoma is a rare soft tissue sarcoma of young adults with unknown histogenesis, and the organ most frequently involved in metastasis is the lung. We report the CT findings of three patients of pulmonary metastases of alveolar soft-part sarcoma, which manifested as clearly enhanced pulmonary nodules or masses. On enhanced scans, some of the masses were seen to contain dilated and tortuous intratumoral vessels. (+info)Highly vascular pelvic tumor causing high-output heart failure because of massive arteriovenous shunting: a case report. (7/36)
A 53-year-old Japanese woman underwent investigation of her heart murmur. A continuous abdominal bruit was heard. Blood gas analysis and chest X-ray showed congestive heart failure. Enhanced computed tomography of the pelvis showed a 10 x 4 cm hypervascular tumor in the retroperitoneal space. Cardiac catheterization disclosed a cardiac output of 13.2 L/min and a step-up of oxygen at the right common iliac vein. Abdominal aortic angiography showed an extremely vascular pelvic tumor and rapid filling of the inferior vena cava. This is a rare case of a highly vascular pelvic tumor causing high-output heart failure because of th massive arteriovenous shunting. (+info)Alveolar soft-part sarcoma of the tongue. (8/36)
Alveolar soft-part sarcoma is a rare, aggressive malignancy of uncertain histologic origin with a propensity for vascular invasion and distant metastasis. This neoplasm may mimic benign vascular neoplasms or malformations but careful evaluation of the unique imaging features on CT scans, MR images, and angiograms lead to the correct diagnosis. We present a case of alveolar soft-part sarcoma of the tongue and emphasize its radiologic and clinical features. (+info)Alveolar Soft Part Sarcoma (ASPS) is a rare type of sarcoma, which is a cancer that develops in the body's connective or supportive tissues such as muscles, tendons, ligaments, cartilage, nerves, and blood vessels. ASPS typically arises in deep soft tissues, often in the legs or arms, but can also occur in other parts of the body like the head and neck region.
ASPS is called "alveolar" because the cancer cells sometimes form structures that look like the air sacs (alveoli) found in the lungs. The term "soft part" indicates that this type of sarcoma usually arises in the soft tissues of the body.
Histologically, ASPS is characterized by the presence of distinctive organoid nests or alveolar structures composed of large polygonal cells with eosinophilic cytoplasm and distinct cell borders. The nuclei are round to oval, with finely dispersed chromatin and prominent nucleoli. Immunohistochemically, ASPS cells typically express TFE3, a transcription factor that can be used in the diagnosis of this tumor type.
ASPS tends to grow slowly but can metastasize (spread) to other parts of the body, such as the lungs, brain, and bones. It primarily affects adolescents and young adults, with a slight female predominance. Treatment usually involves surgical resection, radiation therapy, and/or systemic treatment like targeted therapy or chemotherapy. The prognosis for ASPS is variable, depending on factors such as the tumor's size, location, and extent of metastasis at diagnosis.
Soft tissue neoplasms refer to abnormal growths or tumors that develop in the soft tissues of the body. Soft tissues include muscles, tendons, ligaments, fascia, nerves, blood vessels, fat, and synovial membranes (the thin layer of cells that line joints and tendons). Neoplasms can be benign (non-cancerous) or malignant (cancerous), and their behavior and potential for spread depend on the specific type of neoplasm.
Benign soft tissue neoplasms are typically slow-growing, well-circumscribed, and rarely spread to other parts of the body. They can often be removed surgically with a low risk of recurrence. Examples of benign soft tissue neoplasms include lipomas (fat tumors), schwannomas (nerve sheath tumors), and hemangiomas (blood vessel tumors).
Malignant soft tissue neoplasms, on the other hand, can grow rapidly, invade surrounding tissues, and may metastasize (spread) to distant parts of the body. They are often more difficult to treat than benign neoplasms and require a multidisciplinary approach, including surgery, radiation therapy, and chemotherapy. Examples of malignant soft tissue neoplasms include sarcomas, such as rhabdomyosarcoma (arising from skeletal muscle), leiomyosarcoma (arising from smooth muscle), and angiosarcoma (arising from blood vessels).
It is important to note that soft tissue neoplasms can occur in any part of the body, and their diagnosis and treatment require a thorough evaluation by a healthcare professional with expertise in this area.
Sarcoma is a type of cancer that develops from certain types of connective tissue (such as muscle, fat, fibrous tissue, blood vessels, or nerves) found throughout the body. It can occur in any part of the body, but it most commonly occurs in the arms, legs, chest, and abdomen.
Sarcomas are classified into two main groups: bone sarcomas and soft tissue sarcomas. Bone sarcomas develop in the bones, while soft tissue sarcomas develop in the soft tissues of the body, such as muscles, tendons, ligaments, fat, blood vessels, and nerves.
Sarcomas can be further classified into many subtypes based on their specific characteristics, such as the type of tissue they originate from, their genetic makeup, and their appearance under a microscope. The different subtypes of sarcoma have varying symptoms, prognoses, and treatment options.
Overall, sarcomas are relatively rare cancers, accounting for less than 1% of all cancer diagnoses in the United States each year. However, they can be aggressive and may require intensive treatment, such as surgery, radiation therapy, and chemotherapy.
Basic Helix-Loop-Helix (bHLH) Leucine Zipper Transcription Factors are a type of transcription factors that share a common structural feature consisting of two amphipathic α-helices connected by a loop. The bHLH domain is involved in DNA binding and dimerization, while the leucine zipper motif mediates further stabilization of the dimer. These transcription factors play crucial roles in various biological processes such as cell fate determination, proliferation, differentiation, and apoptosis. They bind to specific DNA sequences called E-box motifs, which are CANNTG nucleotide sequences, often found in the promoter or enhancer regions of their target genes.
Sarcoma, clear cell, is a rare type of cancer that arises from certain types of connective tissue in the body. It is called "clear cell" because the cancer cells have a clear appearance when viewed under a microscope due to the presence of lipids or glycogen within the cytoplasm.
Clear cell sarcoma can occur in various parts of the body, but it most commonly affects the soft tissues of the extremities, such as the legs and arms. It is an aggressive cancer that tends to spread to other parts of the body, including the lungs, lymph nodes, and bones.
Clear cell sarcoma typically occurs in young adults, with a median age at diagnosis of around 30 years old. The exact cause of this type of sarcoma is not known, but it has been linked to genetic mutations involving the EWSR1 gene. Treatment for clear cell sarcoma usually involves surgery to remove the tumor, followed by radiation therapy and/or chemotherapy to kill any remaining cancer cells. Despite treatment, the prognosis for patients with clear cell sarcoma is generally poor, with a five-year survival rate of around 50%.