Ewing's sarcoma
Ewing's sarcoma is a rare solid malignant tumor that usually affects bone.
Ewing's sarcoma is the second most common type of bone cancer in children and the third most common in adults. Each bone can be of origin, but are most common pelvis and femur affected. As of origin but can also serve soft tissue, ie fat, muscle or connective tissue or tissue of peripheral nerves. The treatment of bone and soft tissue Ewing's sarcoma is based on the same standards. The disease can occur at any age, frequently ill male adolescents aged 12-17 years (sex ratio male: female = 1.5:1. ). In soft tissue sarcomas ill mainly older people. In Germany, each year about 3 out of 1,000,000 children and 1,000,000 2.4 of adolescents aged 15 to 25 years per year on a new Ewing 's sarcoma. The reasons for the emergence of a Ewing 's sarcoma is unknown. Familial occurrence or environmental factors appear to play a role in tumor development. What is interesting is that the Ewing 's sarcoma occurs more frequently in the white population.
Ewing's sarcoma was first described by the American pathologist James Ewing.
Pathology and Molecular Pathology
Ewing's sarcomas are always highly malignant tumors. They belong to the group of small, blue, round cell tumors and must be delimited by special immunohistochemical staining and in particular by molecular pathology of tumors with a similar phenotype, such as rhabdomyosarcoma, lymphoma, small cell osteosarcoma and neuroblastoma. Immunohistochemically, they are characterized by the expression of the product of the MIC2 gene ( CD99 ), so that its detection is an integral part of the routine histopathological evaluation of these tumors. The differentiated Ewing tumors can express neuronal markers such as neuron-specific enolase, S-100, synaptophysin and CD57. Ewing's sarcoma belongs to the primitive neuroectodermal tumor of the family of Ewing's tumors, which are characterized by ews / ets translocations.
Causes
Ewing's sarcoma was the first solid tumor for the tumor-specific balanced translocation could be detected. The translocation affects the EWS gene on chromosome 22 In 85-95 % of patients the EWS gene is fused to an ETS gene on chromosome 11. The result is a T ( 11, 22 ) ( q24, q12 ) with the formation of the fusion protein EWS/FLI1. As the second most common change you will find t (21; 22) ( q22; q12 ) with fusion of EWS and ERG, inv (22). Rarely, a translocation t (7; 22) ( p22; q12 ) detected with fusion of EWS or other EWS fusion partner. More recently, FUS / Ets translocations were detected in patients with Ewing 's sarcoma. Histologically and pathogenetically the Ewing 's sarcoma are related to the primitive neuroectodermal tumors ( PNET ). These entities are therefore grouped together under the term, Ewing 's sarcoma '. Trisomies or Tetrasomien of chromosome 8 or 12 are the most commonly described trisomies in Ewing's sarcoma. Trisomy 8 accounts for 78% of all trisomies and was described in 43 % of all cases studied. In a few cases, an unbalanced translocation (16 ) were t (1, 16 ) and saw losses of 1p36.
Symptoms
Sufferers complain initially about intermittent pain. The pain usually take to load dependent, however, remain at night. The symptoms often occur first in the context of a trivial trauma. The complaints are therefore often initially misinterpreted as growing pains, bone inflammation, or as a result of a sports injury. This often leads to a significant delay in diagnosis. The usually caused by stretching of the periosteum pain follow swelling and redness of the affected area, which are often mistaken for inflammation. If the spine or peripheral nerves involved, deficits can stand in the foreground. With increasing tumor growth may lead to loss of function. Few patients show generalized symptoms such as fever, fatigue and weight loss. These symptoms have usually already been made towards a metastasis of the disease.
Diagnosis
A first and very simple diagnostic measure is the making of a radiograph. The radiograph shows moth -eaten bone destruction, onion- like Periostverkalkung and a Periostsporn ( Codman triangle ). In addition, a computed tomography or magnetic resonance imaging is performed, so that a better determination of the location, size and proximity of the tumor is possible. On suspicion of a Ewing 's sarcoma ultimately ensures a biopsy and the pathological workup, the diagnosis. The biopsy must be performed by physicians who specialize in the operation of sarcomas, as the access path for the subsequent operation must be well chosen in order to avoid unnecessary complications. If the suspected diagnosis confirmed Ewing 's sarcoma, a search for metastases connects. Thus, a bone scan and a CT of the lungs, and a bone marrow biopsy can be performed. In some cases it may also be useful positron emission tomography (PET).
Treatment
The treatment lasts for about a year and comprises chemotherapy, surgery and / or radiation, and possibly a high-dose chemotherapy. There is a standardized treatment protocol in the context of Ewing 2008 study, based on experience of previous studies (eg EURO EWING 99) and against which the patients are Germany are treated equally according to their risk profile. All patients will receive at the beginning of therapy induction chemotherapy. This is very important because thereby the risk of the occurrence of future metastasis is significantly reduced. In addition, the chemotherapy leads to tumor reduction, the subsequent operation easier. Provided are 6 blocks VIDE, so polychemotherapy consisting of vincristine, ifosfamide, doxorubicin, and etoposide. After the surgery closes at. A radical tumor removal is extremely important for the prognosis. The tumor must be surgically resected in healthy subjects. The operation of this rare tumor should be in an experienced center. In addition to the local treatment of the primary tumor and the local treatment of primary metastases the prognosis is crucial. The resulting bone defect is supplied by different reconstruction methods. Possible options are endoprostheses, prostheses or rotation plasty. Patients are classified according to the operation based on various criteria such as the extent of the tumor and the response to induction chemotherapy in three different risk groups R1, R2 and R3 and treated further risk-adapted accordingly.
Forecast
The prognosis of bone and soft tissue Ewing's sarcoma is comparable and depends on the tumor spread at diagnosis, the response to preoperative chemotherapy and the possibility of a radical tumor removal. Statistical figures can not make a statement as to whether the individual patient can be cured or not. Patients who have no visible metastases at diagnosis, can be 65% healed in the long term. Patients with initial metastases have a 5 - year survival rate of 25% on average.
Patients with a relapse of the disease have a 5 - year survival rate of 13% on average. To further improve treatment and prognosis, therapy optimization studies take place. In addition, international research collaborations have established, which set itself the goal of finding new therapeutic targets and biomarkers that allow better risk group classification. Patients who can be cured, are indeed free of tumor, but often not healthy. They often suffer from the direct consequences of therapy, under undesirable side effects, long-term and late effects. In the SAM - Ewing long-term study functional outcomes, quality of life and late side effects are detected the target in a representative sample of Ewing sarcoma Langzeitüberlebendenmit to achieve a derivation of guidelines for improving future osteosarcoma therapy.