Small Round Blue Cell Sarcoma Other Than Ewing Sarcoma: What Should an Oncologist Know?

The diagnosis of round cell sarcomas has changed rapidly over the last decade, causing much diagnostic confusion for pathologists and oncologists. The advances in diagnosis are largely due to the advent of next-generation sequencing techniques, which allowed the recognition of novel gene fusions in round cell sarcomas. The new 5th edition of the WHO Classification of Tumors of Soft Tissue and Bone recognizes four subgroups of undifferentiated round cell sarcomas: Ewing sarcoma, CIC-rearranged sarcomas, BCOR-altered sarcomas, and sarcomas with EWSR1-non-ETS fusions, in addition to desmoplastic small round cell tumor. This classification is based on a variety of publications showing that each of these molecular subtypes has unique clinical and prognostic characteristics distinct from Ewing sarcoma, therefore supporting the validity of recognizing these as discrete diagnostic entities. Despite our improved ability to diagnose these new round cell sarcomas, there remains confusion on how best to identify and treat these tumors. However, several key clinicopathologic features can point the physician toward the correct diagnosis. The goal of the following article is to emphasize the key clinical, pathologic, molecular, and prognostic differences between Ewing sarcoma and these non-Ewing round cell malignancies to improve recognition of these rare diseases.