Gastrointestinal Stromal Tumors: A Guide to the Diagnosis

Gastrointestinal stromal tumors (GISTs) have emerged from being a poorly understood and therapeutically refractory sarcoma to a tumor whose biology has not only provided insight into a mechanism of oncogenesis but has also led to a rational basis for therapy. Most GISTs are characterized by KIT protein (CD117) expression and constitutive activating mutations in either the c-kit or platelet-derived growth factor receptor α genes. This information can now be obtained from routine formalin-fixed and paraffin-embedded tissue. Because the correct diagnosis is the key to successful treatment of this tumor, it is incumbent on the pathologist to be familiar with the various gross and histologic patterns shown by these tumors. GISTs range from small incidental stromal nodules to large cystic and solid tumor masses. GISTs show a variety of microscopic patterns and therefore several other tumors enter the differential diagnosis. Fortunately, with an understanding of GIST histology, and with the proper use of immunohistochemistry and molecular analysis, a correct diagnosis can usually be made. In addition to the correct diagnosis, several key attributes of the tumor need to be determined because they provide the basis for proper clinical management. This article summarizes the gross, microscopic, and molecular findings of GISTs, and discusses the differential diagnosis and key attributes of this interesting group of neoplasms.