First described by James Ewing, New York pathologist, in 1926, this is one of the two common bone tumours occurring in young people, with a peak age of incidence of 15-18 years. It occurs with an annual incidence of 0.6 per million in most populations but is extremely rare in non-Caucasians.
Aetiology is unknown and is not generally associated with cancer 'syndromes'. Any bone in the body can be affected, with 55% in the axial skeleton and 45% in the limbs. Within the long bones, the tumour tends to be more centrally situated in the diaphysis rather than at the ends of the bone.
Clinical presentation is usually with a painful swelling that may be warm and/or red. Those occurring in central sites may present with severe pain, signs of abdominal organ or urinary tract compression, or nerve compression from those arising in the vertebral bodies. About 10% present with a hot, swollen bone, along with a substantial fever, and in this situation osteomyelitis is part of the differential diagnosis.
♦ X-ray—destructive, osteolytic lesions
—elevation of periosteum —onion skin appearance
♦ Aspiration biopsy rarely sufficient
♦ Open biopsy—send to laboratory fresh
♦ Histology—small, blue, round cell tumour
—glycogen within cells (PAS, neural markers positive - S - 100, vimentin, NSE)
♦ Cyogenetics—1(11,:22) translocation
—EWS/FL11 gene rearrangement
♦ Subtypes—typical Ewing's sarcoma
—atypical Ewing's sarcoma
—primitive neuroectodermal tumour ofbone (PNET) In practical terms, treatment and outcome are identical for all three subtypes. Other pre-treatment investigations that can be helpful are:
♦ Full blood count
♦ Alkaline phosphatase
♦ Plasma creatinine
Prior to therapy, a test of renal function (e.g. Cr51EDTA) and cardiac function (e.g. echocardiogram) should be undertaken. The most important prognostic factor is the presence of metastases at diagnosis and, in order to ascertain such lesions, it is important to undertake an isotope bone scan, a CT of the lungs, and a bone marrow aspirate/ trephine from a bone not affected by the primary tumour.
The basic treatment plan is similar for all patients—but chemotherapy ^ definitive treatment of primary ^ chemotherapy ^ follow-up—needs to be individualized depending on the site of the primary tumour and the presence of metastatic disease. This is a rare tumour and should be treated in a specialist centre.
There are six drugs that have substantial proven activity in this disease:
♦ Actinomycin D
While there is some controversy as to whether maximally tolerable doses of cyclophosphamide are inferior to ifosfamide, the latter is usually used.
Surgery and/or radiotherapy may be used. Surgery should be considered in all cases and if it is possible to remove the tumour without undue mutilation, then it is the treatment of choice. Surgical developments mean that there are few bones in the body which are not amenable to surgery. Complete removal is recommended but if it is incomplete, radiotherapy should be given in addition. The latter should be given to the whole bone, but the most distant epiphysis may be spared in tumours arising at the end of the long bone.
Lung metastases should be treated with conventional chemotherapy as detailed, with whole-lung irradiation to any residual disease. However, those with bony metastases have a dismal prognosis and it may be worth considering megatherapy after conventional induction treatment. Either melphalan, busulphan, or TBI, or a combination, may be used as a conditioning regime.
The major prognostic factors are metastases at presentation and site and volume of the tumour. For those with small tumours (<100 cc), usually in the long bones, over 80% can be cured. Pelvic tumours and those with lung metastases have a 30% chance of survival. With conventional therapy, the majority of those with bone metastases die. Ewing's tumour may relapse up to 10 or more years after diagnosis.
Cardiac and nephrotoxic late effects, as a result of chemotherapy, may occur, but these are not disease-specific. Second primary tumours, most often osteosarcomas, may occur in the irradiation field, and the late effects of major endoprosthetic surgery can be substantial.
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