Virchows Archiv

, Volume 456, Issue 2, pp 111–127

Gastrointestinal stromal tumors

Authors

  • Bernadette Liegl-Atzwanger
    • Department of PathologyBrigham and Women’s Hospital and Harvard Medical School
    • Department of PathologyMedical University of Graz
  • Jonathan A. Fletcher
    • Department of PathologyBrigham and Women’s Hospital and Harvard Medical School
    • Department of PathologyBrigham and Women’s Hospital and Harvard Medical School
    • Department of PathologyBrigham and Women’s Hospital
Review and Perspective

DOI: 10.1007/s00428-010-0891-y

Cite this article as:
Liegl-Atzwanger, B., Fletcher, J.A. & Fletcher, C.D.M. Virchows Arch (2010) 456: 111. doi:10.1007/s00428-010-0891-y

Abstract

Gastrointestinal stromal tumors (GISTs) have emerged from being poorly defined, treatment-resistant tumors to a well-recognized, well-understood, and treatable tumor entity within only one decade. The understanding of GIST biology has made this tumor a paradigm for molecularly targeted therapy in solid tumors and provides informative insights into the advantages and limitations of so-called targeted therapeutics. Approximately 85% of GISTs harbor activating mutations in KIT or the homologous receptor tyrosine kinase PDGFRA gene. These mutations are an early event in GIST development and the oncoproteins serve as a target for the small molecule tyrosine kinase inhibitors imatinib and sunitinib. The existing and emerging treatment options demand exact morphologic classification and risk assessment. Although, KIT (CD117) immunohistochemistry is a reliable diagnostic tool in the diagnosis of GIST, KIT-negative GISTs, GISTs showing unusual morphology as well as GISTs which progress during or after treatment with imatinib/sunitinib can be a challenge for pathologists and clinicians. This review focuses on GIST pathogenesis, morphologic evaluation, promising new immunohistochemical markers, risk assessment, the role of molecular analysis, and the increasing problem of secondary imatinib resistance and its mechanisms.

Keywords

Gastrointestinal stromal tumor GIST Imatinib Sunitinib Tyrosine kinase inhibitors Resistance KIT PDGFRA

Copyright information

© Springer-Verlag 2010