Updates on WHO classification for small round cell tumors: Ewing sarcoma vs. everything else

Carina A Dehner; Alexander J Lazar; John S A Chrisinger

doi:10.1016/j.humpath.2024.01.007

Updates on WHO classification for small round cell tumors: Ewing sarcoma vs. everything else

Hum Pathol. 2024 May:147:101-113. doi: 10.1016/j.humpath.2024.01.007. Epub 2024 Jan 26.

Authors

Carina A Dehner¹, Alexander J Lazar², John S A Chrisinger³

Affiliations

¹ Department of Anatomic Pathology and Laboratory Medicine, Indiana University, 635 Barnhill Drive, Indianapolis, IN, 46202, USA. Electronic address: cadehner@iu.edu.
² Department of Pathology, University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030, USA; Department of Genomic Medicine, University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030, USA. Electronic address: alazar@mdanderson.org.
³ Department of Pathology and Immunology, Division of Anatomic and Molecular Pathology, Washington University School of Medicine, 660 S. Euclid Ave, St. Louis, MO, 63110, USA. Electronic address: jschrisi@wustl.edu.

PMID: 38280658
DOI: 10.1016/j.humpath.2024.01.007

Abstract

The WHO Classification of Soft Tissue and Bone Tumours currently recognizes four categories of undifferentiated small round cell sarcoma: Ewing sarcoma, round cell sarcoma with EWSR1-non-ETS fusions including NFATc2 and PATZ1, CIC-rearranged sarcoma, and sarcoma with BCOR genetic alterations. These neoplasms frequently pose significant diagnostic challenges due to rarity and overlapping morphologic and immunohistochemical findings. Further, molecular testing, with accompanying pitfalls, may be needed to establish a definitive diagnosis. This review summarizes the clinical, histologic, immunohistochemical, and molecular features of these neoplasms. In addition, differential diagnosis and areas of uncertainty and ongoing investigation are discussed.

Keywords: BCOR; CIC; Ewing sarcoma; Ewing-like; NFATc2; PATZ1; Review; Round cell.

Publication types

Review

MeSH terms

Biomarkers, Tumor* / analysis
Biomarkers, Tumor* / genetics
Bone Neoplasms* / classification
Bone Neoplasms* / genetics
Bone Neoplasms* / pathology
Diagnosis, Differential
Gene Rearrangement
Genetic Predisposition to Disease
Humans
Immunohistochemistry
Oncogene Proteins, Fusion / genetics
Phenotype
Predictive Value of Tests
Proto-Oncogene Proteins / genetics
RNA-Binding Protein EWS / genetics
Repressor Proteins / genetics
Sarcoma, Ewing* / chemistry
Sarcoma, Ewing* / classification
Sarcoma, Ewing* / genetics
Sarcoma, Ewing* / pathology
Sarcoma, Small Cell* / classification
Sarcoma, Small Cell* / genetics
Sarcoma, Small Cell* / pathology
Soft Tissue Neoplasms / classification
Soft Tissue Neoplasms / genetics
Soft Tissue Neoplasms / pathology
World Health Organization*

Substances

Biomarkers, Tumor
BCOR protein, human
EWSR1 protein, human
RNA-Binding Protein EWS
Repressor Proteins
Proto-Oncogene Proteins
Oncogene Proteins, Fusion