Abstract
Ewing’s sarcoma (ES), also known as mesenchymal primitive neuroectodermal tumor
(PNET), is a malignant round blue cell tumor (MRBCT) with a varying degree of neuronal differentiation.
PNET arises from the primitive nerve cells of the central nervous system (CNS) but may
also occur in the bones of the extremities, pelvis, vertebral column, and chest wall. Extraskeletal
ES/PNET may affect the various soft tissues, including those of the pelvis, paraspinal region, and
thoracopulmonary region.
Histopathological differentiation between ES, PNET, and other related sarcomas is often difficult.
On light microscopy, the same histopathological appearance of ES has been termed PNET, Askin-
Rosay (A-R) tumor, and malignant neuroepithelioma by various other authors. The immunohistochemical
distinction is also difficult due to poor tissue differentiation and low intake of the various
specific immunohistochemical markers. The most frequent translocation is t (11; 22) (q24; q12), resulting
in the EWSR1-FLI1 fusion gene detected in nearly 90% of cases and is considered the hallmark
of the diagnosis of ES, PNET, atypical ES, and A-R tumor. Therefore, ES, atypical ES,
PNET, and A-R tumor are currently regarded as one entity grouped together under the Ewing Family
Tumor (EFT) and are treated in an identical way. EFT represents only about 3% of all pediatric
malignancies. The annual incidence is between 2 and 5 cases per million children per year. The
peak prevalence of the tumor is between the ages of 10 and 15 years. The incidence is higher in
males than in females, with a ratio of 1.3:1.
Newer groups of MRBCT that have great similarities to EFT are being recently described. These tumors,
atypical EFT and Ewing’s like Sarcomas (ELS), bear similarities to EFT but have basic morphological
and molecular differences. Optimal treatment requires the use of adjuvant and new-adjuvant
chemotherapy (CTR), radical surgical resection and/or involves field radiotherapy (RT). The
reported disease-free survival (DFS) and overall survival (OS) range between 45-80% and 36-71%,
respectively. The overall prognosis for the metastatic and recurrent disease remains poor. The use
of newer conventional and targeted medications, improved RT delivery, and surgical techniques
may further improve the outcomes. The past few years have seen advances in genomics-based sarcoma
diagnosis and targeted therapies. In this comprehensive review article, we provide a detailed
report of EFT and discuss the various clinical aspects and the recent advances used in the diagnosis
and treatment.