Dedifferentiated gastrointestinal stromal tumor: Recent advances

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal lesions of the gastrointestinal tract. A small minority of GISTs exhibit morphologic and phenotypic changes and differentiate into an unusual phenotype through the process of dedifferentiation. Dedifferentiation can occur either de novo or after prolonged treatment with imatinib, a selective tyrosine kinase inhibitor. GISTs can present with various morphologies including rhabdomyosarcoma, angiosarcoma, or undifferentiated pleomorphic sarcoma. The unusual histologic and immunohistochemical characteristics of these tumors can be diagnostically challenging. Therefore, it is essential that the pathologists recognize GISTs with unusual morphology and be aware of the dedifferentiation process. This review aims to provide an overview of the morphologic and molecular features of dedifferentiated GISTs. Additionally, we discuss diagnostic dilemmas and recent immunohistochemical markers that are useful in distinguishing dedifferentiated GISTs from other gastrointestinal tumors. •We highlight the molecular alterations underlying GIST dedifferentiation.•We discuss critical morphologic and molecular markers supporting dedifferentiated GIST diagnosis.•Protein kinase C theta (PKC θ) and carbonic anhydrase II (CAII) are new, useful biomarkers in GIST diagnosis.•We discuss pitfalls and diagnostic challenges that pathologists can encounter in routine practice.