Ewing sarcoma (Ewing tumor, Ewing’s tumor, tumor of the Ewing family) is a rare malignant tumor of the bone or soft tissue (cartilage and nerves).
Ewing sarcoma is highly malignant tumor, which comprises 1.5% of all childhood malignant tumors. It was described in 1926 by James Ewing. Tumors of the Ewing family include Ewing sarcoma of bone, extraosseous Ewing (EOE) sarcoma, peripheral primitive neuroectodermal tumor (PNET), peripheral neuroepithelioma, atypical Ewing sarcoma and Askin’s tumor. 87% of all the cases of Ewing sarcoma are Ewing sarcoma of the bone. Despite the fact that the bone is affected by the tumor it arises not from the bone tissue, but from the mesenchymal stem cells or the neural crest.
This tumor is more common for children and adolescents from 5 to 15 years. About 10% of Ewing sarcomas develop in persons older than 20 years. Males are more likely to develop the tumor than females with ratio 1.5:1. Annually 2.93 children per 1000000 are diagnosed with Ewing sarcoma. This type of tumor is more common in Caucasians and rare in Asians and African Americans.
Causes and risk factors
It is unknown what causes Ewing sarcoma, there were no reports of family cases of Ewing sarcoma and usually Ewing sarcoma is sporadic.
Ewing sarcoma is caused by the translocation of genetic material between the EWSR1 gene on chromosome 22 and the FLI1 gene on chromosome 11. This is the result of the acquired mutation called somatic. Such change in the genetic material is not inherited and occurs after the conception.
Rarely sarcoma develops secondary to another malignant tumor.
Related: Alveolar rhabdomyosarcoma
Commonly the tumor develops in the long bones of the extremities (especially femurs – 45%, the tibia and humerus), ribs (6%), shoulder blades, the pelvis (20%) and the crest. The long bones are more likely to be affected in the diaphysis (the midpart of the long bone).
Extraosseous/extraskeletal Ewing sarcoma arises from the soft tissues such as cartilages. Peripheral primitive neuroectodermal tumor develops from the nerve tissue, the type of this tumor, which is found in the chest is called Askin’s tumor.
The common symptoms of the tumor include localized pain, stiffness, tenderness and swelling at the affected site that lasts for months. The tumor itself may be palpitated as a somewhat warm mass. Children may also experience fever, fatigue, paralysis and incontinence. The swollen tissues may compress the nerves causing the tingling, numbness or even paralysis. If the tumor develops in the bone pathological fractures may occur.
The tumor usually metastases to the lungs, bone marrow and other bones. The involvement of the bone marrow leads to thrombocytopenia (on the skin petechiae and purpura may be detected) and anemia.
1) Blood test – the common features include increased erythrocyte sedimentation rate (ESR), increased white cell count and anemia, increased C-reactive protein;
2) X-ray examination of the bone show typical “onion peel” appearance due to the elevation of the periosteum, destructive lesions;
3) CT/MRI and PET scan may be helpful to detect metastases and tumors of any size at any site;
4) The radioisotopic bone scan is performed to detect any cancerous lesion;
5) Biopsy (incisional or excisional) is necessary to make a diagnosis. The abnormal cells appear as small, blue cells with increased content of glycogen in the form of granules;
Treatment of Ewing sarcoma requires a combination of chemotherapy, radiotherapy and surgery and usually takes up to 9 months. The surgical measures include:
- amputation of the limb when the cancer affects the nerves and vessels;
- limb-sparing surgery when the removed part of the bone is replaced by a prosthesis or bone graft.
The tumor is highly radiosensitive and shrinks fast once radiotherapy has been started.
Chemotherapeutical agents used in the treatment of Ewing sarcoma include:
- Actinomycin D;
Commonly chemotherapy is administered as a course of 2 regimens:
1 – vinctristine + doxorubicin + cyclophosphamide;
2- ifosfamide + etoposide.
The younger the affected person is the better outcome may be expected. The absence of the metastases, localized tumor in the distal extremities part is more favorable as well.