Ewing's sarcoma

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Classification according to ICD-10
C40 Malignant neoplasm of the bone and articular cartilage of the extremities
C41 Malignant neoplasm of bone and articular cartilage in other and unspecified locations
ICD-10 online (WHO version 2019)
X-ray of Ewing's sarcoma of the tibia (shin) in a child
Metastatic Ewing sarcoma cells
Histopathological picture

The Ewing's sarcoma is a rare solid malignant tumor , the most bone attacks.

Ewing's sarcoma is the second most common type of bone cancer in children and the third most common in adults. Any bone can be the site of origin, but the pelvis and thigh bones are most commonly affected. Soft tissue , that is, fat , muscle or connective tissue or tissue of peripheral nerves can also serve as the place of origin . Treatment of bone and soft tissue Ewing sarcomas follows the same standards. The disease can occur at any age; male adolescents between the ages of 12 and 17 years often become ill (male: female gender ratio = 1.5: 1). It is mostly older people who develop soft tissue sarcomas. In Germany, around 3 out of 1,000,000 children and 2.4 out of 1,000,000 adolescents between the ages of 15 and 25 develop Ewing's sarcoma every year. The causes of Ewing sarcoma are unknown. Family accumulation or environmental influences do not seem to play a role in tumor development. It is interesting, however, that Ewing's sarcoma occurs more frequently in the white population.

Ewing's sarcoma was first described by the US pathologist James Ewing .

Pathology and molecular pathology

Ewing's sarcomas are always highly malignant tumors . They belong to the group of small, blue and round cell tumors and must be differentiated from tumors with a similar phenotype, such as rhabdomyosarcoma , lymphoma , small cell osteosarcoma or neuroblastoma , by means of special immunohistochemical staining and, in particular, by molecular pathological examinations . 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 assessment of these tumors. The differentiated Ewing tumors can express neuronal markers such as neuron-specific enolase, S-100, CD57 and synaptophysin. Ewing's sarcoma, along with the primitive neuroectodermal tumor, belongs to the family of Ewing tumors, which are characterized by ews / ets translocations.

causes

Ewing's sarcoma was the first solid tumor for which a tumor-specific balanced translocation could be demonstrated. The translocation affects the EWS gene on chromosome 22. The EWS gene is fused with an ETS gene on chromosome 11 in 85 to 95% of patients. A t (11; 22) (q24; q12) results with the formation of the EWS / FLI1 fusion protein. The second most frequent change is t (21; 22) (q22; q12) with the fusion of EWS and ERG, inv (22). A translocation t (7; 22) (p22; q12) with fusion of EWS or other EWS fusion partners can rarely be detected. Recently, FUS / Ets translocations have also been detected in patients with Ewing's sarcoma. EWS-ETS fusion oncoproteins interact in the genome with repetitive nucleotide sequences (GGAA microsatellites), which can contribute to the development and course of the disease. Pathohistologically and pathogenetically, Ewing's sarcomas are related to primitive neuroectodermal tumors (PNET). These entities are therefore also summarized under the term 'Ewing's sarcoma'. Trisomies or tetrasomies of chromosome 8 or 12 are the most commonly described trisomies in Ewing's sarcoma. Trisomy 8 accounts for 78% of all trisomies and has been described in 43% of all cases examined. In a few cases, an unbalanced translocation of (16) t (1; 16) and losses of 1p36 were seen.

Symptoms

Those affected initially complain of intermittent pain. The pain usually increases with exercise, but persists at night. Symptoms often first appear in connection with a trivial trauma. The symptoms are therefore often initially misinterpreted as growing pains , bone inflammation or as a result of a sports injury. This often leads to a considerable delay in diagnosis. The pain, which is usually caused by stretching the periosteum , is followed by swelling and reddening of the affected region, which are often misinterpreted as inflammation. If the spine or peripheral nerves are involved, failure symptoms can be in the foreground. With increasing tumor growth, there may be functional losses. Few patients show general symptoms such as fever, fatigue and weight loss. These symptoms usually indicate that the disease has already metastasized .

diagnosis

A first and very simple diagnostic measure is to take an X-ray . The X-ray shows moth-eaten bone destruction, onion skin-like calcification of the periosteum and a periosteal spur (Codman triangle). In addition, a computed tomography or magnetic resonance tomography is carried out so that a better determination of the position, size and neighborhood of the tumor is possible. If Ewing's sarcoma is suspected, a sample biopsy and its pathological processing ultimately confirms the diagnosis. The biopsy must be carried out by doctors who specialize in the operation of sarcomas, as the access route for the subsequent operation must be chosen appropriately in order to avoid unnecessary complications. If the suspected diagnosis of Ewing's sarcoma is confirmed, a search for metastases follows. Thus, a bone scan and a CT of the lungs, and a bone marrow biopsy performed. In individual cases, positron emission tomography (PET) can also be useful.

treatment

The treatment takes about a year and consists of chemotherapy , surgery and / or radiation and, if necessary, high-dose chemotherapy . There is a standardized treatment protocol as part of the Ewing 2008 study, which is based on the experience of previous studies (e.g. EURO EWING 99) and on the basis of which patients are treated equally throughout Germany according to their risk profile. All patients receive induction chemotherapy at the start of therapy. This is very important as it significantly reduces the risk of later metastases. In addition, the chemotherapy leads to a tumor reduction, which simplifies the subsequent operation. 6 VIDE blocks are planned, i.e. a polychemotherapy consisting of vincristine , ifosfamide , doxorubicin and etoposide . This is followed by the operation. Radical tumor removal is extremely important for the prognosis. The tumor must be surgically resected in a healthy state. The operation of this rare tumor must be done in an experienced center. In addition to local therapy of the primary tumor, local therapy of primary metastases is also decisive for the prognosis. The resulting bone defect is treated using different reconstruction methods. Possible options are endoprostheses, prostheses or reversal plastics. After the operation, the patients are divided into three different risk groups R1, R2 and R3 on the basis of various criteria, such as the extent of the tumor and the response to induction chemotherapy, and further treatment is appropriately risk-adapted.

forecast

The prognosis for bone and soft tissue Ewing sarcomas is comparable and depends on the extent of the tumor at the time of diagnosis, the response to preoperative chemotherapy and the possibility of radical tumor removal. Statistical figures cannot make a statement about whether the individual patient can be cured or not. 65% of the patients who have no visible metastases at the time of diagnosis can be cured in the long term. Patients with initial metastases have an average 5-year survival rate of 25%.

Patients with disease relapse have an average 5-year survival rate of 13%. Therapy optimization studies are being conducted to further improve treatment and prognosis. In addition, international research alliances have been set up with the aim of finding new therapeutic target structures and biomarkers that allow better classification of risk groups. Patients who can be cured are tumor-free, but often not healthy. They often suffer from the direct consequences of therapy, from undesirable side effects, long-term and late-stage damage. In the SAM Ewing long-term study, functional results, quality of life and late side effects are recorded in a representative sample of Ewing sarcoma long-term survivors with the aim of deriving guidelines for improving future bone sarcoma therapy.

Web links

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  1. ↑ Böcker et al .: Pathology. 5th edition. Munich 2012, p. 875f.
  2. ↑ Thomas GP Grünewald, Florencia Cidre-Aranaz, Didier Surdez, Eleni M. Tomazou, Enrique de Álava: Ewing sarcoma . In: Nature Reviews Disease Primers . tape 4 , no. 1 , July 5, 2018, ISSN  2056-676X , doi : 10.1038 / s41572-018-0003-x ( nature.com [accessed July 7, 2018]).
  3. ↑ IM Ambros, PF Ambros, S. Strehl et al .: MIC2 is a specific marker for Ewing's sarcoma and peripheral primitive neuroectodermal tumors. Evidence for a common histogenesis of Ewing's sarcoma and peripheral primitive neuroectodermal tumors from MIC2 expression and specific chromosome aberration. In: Cancer . 1991 Apr 1; ​​67 (7), pp. 1886-1893.
  4. ↑ A. Llombart-Bosch, C. Carda, A. Peydro-Olaya et al .: Soft tissue Ewings` sarcoma. Characterization in established cultures and xenografts with evidence of a neuroectodermic phenotype. In: Cancer. 1990 Dec 15; 66 (12), pp. 2589-2601.
  5. ^ O. Delattre et al .: The Ewing family of tumors - a subgroup of small-round-cell tumors defined by specific chimeric transcripts. In: New England Journal of Medicine . (1994); 331, pp. 294-299.
  6. ↑ U. Dirksen, H. Juergens: Approaching Ewing sarcoma. In: Future Oncology . 2010; 6, pp. 1155-1162.
  7. ↑ T. Berg, AH Kalsaas, J. Buechner et al .: Ewing sarcoma-peripheral neuroectodermal tumor of the kidney with a FUS-ERG fusion transcript. In: Cancer Genet Cytogenet. 2009 Oct; 194 (1), pp. 53-57. doi: 10.1016 / j.cancergencyto.2009.06.002 .
  8. ^ Thomas GP Grünewald, Virginie Bernard, Pascale Gilardi-Hebenstreit, Virginie Raynal, Didier Surdez: Chimeric EWSR1-FLI1 regulates the Ewing sarcoma susceptibility gene EGR2 via a GGAA microsatellite . In: Nature Genetics . tape 47 , no. 9 , September 2015, ISSN  1546-1718 , p. 1073-1078 , doi : 10.1038 / ng.3363 , PMID 26214589 .
  9. ^ Julian Musa, Florencia Cidre-Aranaz, Marie-Ming Aynaud, Martin F. Orth, Maximilian ML Knott: Cooperation of cancer drivers with regulatory germline variants shapes clinical outcomes . In: Nature Communications . tape 10 , no. 1 , September 11, 2019, ISSN  2041-1723 , p. 4128 , doi : 10.1038 / s41467-019-12071-2 , PMID 31511524 .
  10. ↑ P. Roberts, S. Burchill, S. Brownhill: Ploidy and karyotype complexity are powerful prognostic indicators in the Ewing's sarcoma family of tumors: A study by the United Kingdom Cancer Cytogenetics and the Children's Cancer and Leukemia Group. In: Genes, Chromosomes & Cancer . Volume 47, Issue 3, March 2008, pp. 207-220.
  11. ^ J. Haeusler, A. Ranft, T. Boelling et al .: The value of local treatment in patients with primary, disseminated, multifocal Ewing sarcoma (PDMES). In: Cancer. 2010; 116, pp. 443-450.
  12. ↑ kinderkrebsinfo.de
  13. ^ M. Stahl, A. Ranft, M. Paulussen et al .: Risk of recurrence an Survival after relapse in patients with Ewing Sarcoma. In: Pediatric Blood & Cancer . 2011; 57, pp. 549-553.