Synovial sarcoma
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| ICD-O: | 9040/3-9043/3 |
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Contents |
[edit] Introduction
Synovial sarcoma is a rare soft-tissue sarcoma defined by the presence of a unique translocation, t(X;18)(q11.2;p11.2). It usually occurs adjacent to joints in the limbs and was originally thought to arise from synovium; however, synovial sarcoma is a misnomer and the tissue of origin is unknown. Accordingly, primary synovial sarcomas have been documented in most human tissues and organs, including brain, prostate and heart. Synovial sarcoma arises most commonly in adolescents and young adults compared to other age groups. Diagnosis is based on histology and there are three major histologic subtypes: monophasic (consisting on sheets of spindle cells), biphasic (spindle cells admixed with areas of epithelial differentiation) and poorly differentiated. Immunohistochemical techniques can help, however the gold standard for diagnosing synovial sarcoma is detection of t(X;18) by cytogenetics, FISH or RT-PCR. Despite treatment prognosis is generally poor, with approximately 50% of patients dying from local reccurrence or metastasis within 10 years.
[edit] Causes
Synovial sarcoma is defined by the presence of the SYT-SSX fusion gene, the result of a translocation event between the SYT gene on chromosome 18 and one of 3 SSX genes (SSX1, SSX2 and SSX4) on chromosome X and the diagnosis of synovial sarcoma, typically made based on histology, is confirmed by the presence of t(X;18). The SYT-SSX fusion protein that results from this translocation brings together the transcriptional activating domain of SYT and the transcriptional repressor domains of SSX. SYT-SSX is thus thought to underlie synovial sarcoma pathogenesis through dysregulation of gene expression; accordingly, gene expression studies have identified a pattern of gene expression typical of synovial sarcoma. The exact function(s) of the fusion protein remain unclear; however, recent research has offered some insight into synovial sarcoma development. The genes identified in expression studies resemble those activated in developemnt of the neural crest, an area of the vertebrate embryo that eventually gives rise to various tissues, including nerves and cartilage. SYT-SSX has be shown to interact with transcriptional regulators involved in cell differentiation and proliferation. Interestingly, when instered into non-synovial sarcoma cell lines, SYT-SSX has been shown to be tumorigenic in some but not others, suggesting that SYT-SSX oncogenesis occurs only in an approriate cellular context. Further investigation of the molecular mechanisms underlying SYT-SSX function will likely lead to not only a better understanding of this disease but improved diagnostic and treatment tools for this tumor.
[edit] Symptoms
General symptoms related to maligancies are reported (fatigue, fever, etc.) however synovial sarcoma uaually presents with an otherwsie asymptomatic swelling or mass. Pain/discomfort or inhibition/loss of function in the area of the tumor may also be reported. Symptoms related to metastases are usually site-specific and related to mass effects. The diagnosis of synovial sarcoma is made by histology, immunohistochemistry and, if necessary/possible, demonstration of t(X;18).
[edit] Treatment
Treatment usually involves:
- Surgery, to remove the tumor and a safety margin of healthy tissue. This is the mainstay of synovial sarcoma treatment and is curative in approximately 20-70% of patients, depending on the particular study being quoted.
- Conventional chemotherapy, (for example, Doxorubicin hydrochloride and Ifosfamide), to reduce the number of remaining microscopic cancer cells. The benefit of chemotherapy in synovial sarcoma to overall survival remains unclear, although a recent study has shown that survival of patients with advanced, poorly differentiated disease marginally improves with doxorubicin/ifosfamide treatment.
- Radiotherapy to reduce the chance of local recurrence. The benefit of radiotherapy in this disease is less clear than for chemotherapy.
Recent laboratory-based studies have identified a number of potential systemic therapies that may prove more effecacious than conventional chemotherapy and improve survival, however the rarity of this tumor makes clinical trial organization difficult and validation of these experimental therapeutics will likely be long in coming.
[edit] Scans to undertaken before, during, and after treatment
Various scanning techniques can be used to further localise and identify this cancer:
During treatment, the patient may have Bone Density Scans, to measure the impact of the chemotherapy on the skeleton.
