Unravelling undifferentiated soft tissue sarcomas: insights from genomics

Undifferentiated pleomorphic sarcoma now falls under the broader rubric of undifferentiated soft tissue sarcoma (USTS) in the 2020 World Health Organization classification of bone and soft tissue tumours. These rare cancers remain a diagnosis of exclusion, and show genomic complexity manifesting as extreme forms of aneuploidy and genetic rearrangement. This review covers some of the recent advances in the diagnosis and treatment of USTS based on genomic sequencing, cancer evolution and heterogeneity studies, and immunotherapy. We highlight the critical role that pathologists have to play in the diagnosis and treatment of patients with USTS, viewed through the lens of the hallmarks of cancer.