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Clinical presentation, staging, and prognostic factors of the Ewing sarcoma family of tumors

Thomas F DeLaney, MD
Francis J Hornicek, MD, PhD
Section Editors
Alberto S Pappo, MD
Robert Maki, MD, PhD
Raphael E Pollock, MD
Deputy Editor
Diane MF Savarese, MD


Ewing sarcoma (ES) and peripheral primitive neuroectodermal tumor (PNET; previously called peripheral neuroepithelioma) were originally described in the early 1900s as distinct clinicopathologic entities. It became evident that these entities are actually part of a spectrum of neoplastic diseases known as the ES family of tumors (EFT), which also includes extraosseous ES (EES), PNET, malignant small-cell tumor of the thoracopulmonary region (Askin tumor), and atypical ES. Because of their similar histologic and immunohistochemical characteristics, and shared nonrandom chromosomal translocations, these tumors are considered to be derived from a common cell of origin. Although the histogenetic origin has been debated over the years, increasing evidence from immunohistochemical, cytogenetic, and molecular genetic studies supports a mesenchymal progenitor cell origin for all EFT [1]. (See "Epidemiology, pathology, and molecular genetics of the Ewing sarcoma family of tumors".)

The EFT can develop in almost any bone or soft tissue but is most common in the pelvis, axial skeleton, and femur; patients typically present with localized pain and swelling. Although overt metastatic disease is found in fewer than 25 percent at the time of diagnosis, subclinical metastatic disease is presumed to be present in nearly all patients because of the 80 to 90 percent relapse rate in patients undergoing local therapy alone. As a result, systemic chemotherapy has evolved as an important component of treatment [2].

Advances in multidisciplinary management of EFT over the past 30 years have resulted in a marked improvement in survival and a greater likelihood of limb-sparing surgery rather than amputation [3-6] (see "Bone sarcomas: Preoperative evaluation, histologic classification, and principles of surgical management"). In data derived from the Surveillance, Epidemiology, and End Results (SEER) program of the National Cancer Institute, five-year survival rates for patients with ES rose from 36 to 56 percent during the periods 1975 to 1984 and 1985 to 1994 [3]. With modern multidisciplinary treatment, long-term survival can be achieved in 70 to 80 percent of patients presenting with nonmetastatic disease [4,5,7].

Here we will discuss the clinical presentation, diagnosis, and staging of EFT. The epidemiology, pathology, molecular genetics, and treatment of these tumors, principles underlying the performance of a diagnostic bone biopsy, and central (supratentorial) PNET are discussed elsewhere. (See "Epidemiology, pathology, and molecular genetics of the Ewing sarcoma family of tumors" and "Bone tumors: Diagnosis and biopsy techniques" and "Treatment of the Ewing sarcoma family of tumors" and "Radiation therapy for Ewing sarcoma family of tumors" and "Uncommon brain tumors", section on 'CNS embryonal tumor, NOS'.)


Primary sites — The Ewing sarcoma family of tumors (EFT) most often arise in the long bones of the extremities (predominantly the femur but also the tibia, fibula, and humerus) and the bones of the pelvis. The spine, hands, and feet are affected considerably less often [8,9]. In a compilation of data from 975 patients from the European Intergroup Cooperative Ewing Sarcoma Studies (EI-CESS) trials, the distribution of primary sites was as follows [9]:

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Literature review current through: Nov 2017. | This topic last updated: Nov 14, 2016.
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