WHO Classification of Small Round Cell Sarcomas: Context, Challenges and Molecular Tools

In 2020, the differential diagnoses for “small round blue cell tumors” expanded to include new official entities described by the World Health Organization (WHO). Specifically, the WHO editorial board now recognizes novel subtypes of undifferentiated small round cell sarcomas, defined by specific molecular alterations. These undifferentiated round cell sarcomas were previously referred to as “Ewing-like sarcomas.” We now know this group includes tumors with distinct diagnostic and clinical features. Namely, round cell sarcomas with EWSR1–non-ETS fusions show unexpected and unusual morphologic and immunophenotypic patterns. CIC-rearranged sarcomas are critically important to recognize because they can occur at any age, arise in any location and are uniquely, extremely aggressive. Sarcomas with BCOR genetic alterations are the rarest of the undifferentiated round cell sarcomas and can present with deceptively low-grade appearances. Although this field continues to evolve, there are now molecular/genomic tools available in clinical laboratories to accurately diagnose these entities. Importantly for providers, the National Comprehensive Cancer Network (NCCN) clinical guidelines for bone and soft tissue tumors include recommendations for comprehensive genomic profiling of suspected Ewing sarcomas if conventional assays such as FISH, PCR, and/or cytogenetics is negative. This is a logical recommendation given the diversity of genetic alterations, the limitations of conventional assays and the distinct, as well as emerging, types of round cell sarcomas.

Originally published on December 6, 2022

Lecture Presenter

Allie H. Grossmann, MD, PhD Associate Professor of Pathology University of Utah School of Medicine Medical Director, Anatomic Pathology and Molecular Oncology ARUP Laboratories

Dr. Allie H. Grossmann is the medical director of anatomic pathology and molecular oncology at ARUP Laboratories and an associate professor at the University of Utah School of Medicine. She graduated from Oregon Health Science University with her doctorate and medical degrees. She then completed an anatomic pathology residency, molecular medicine fellowship, and a molecular genetic pathology fellowship at the University of Utah School of Medicine. Dr. Grossmann is certified by the American Board of Pathology in molecular genetic pathology and anatomic pathology. She is the recipient of the Harry J. Lloyd Charitable Trust Career Development award, the NCI K08 Mentored Clinical Scientist award, and the American Cancer Society Research Scholars Grant. Her research interests include mechanisms of tumorigenesis, metastasis, and the development of targeted and immunotherapies for cancer treatment.

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Objectives

After this presentation, participants will be able to:

• Describe the unique clinical, morphologic, immunophenotypic, and molecular features of undifferentiated round cell sarcomas
• Define and distinguish the various types of undifferentiated round cell sarcomas

Sponsored by:

University of Utah School of Medicine, Department of Pathology, and ARUP Laboratories