Gastrointestinal stromal tumors: review on morphology, diagnosis and management

Gastrointestinal stromal tumors (GISTs) are the most frequent mesenchymal tumors of the gastrointestinal tract. Major advances in their definition and classification and the understanding of their molecular mechanisms have recently been made. These advances have become a model of targeted therapy in oncology. The diagnosis of GISTs relies on histological arguments--proliferation of spindle-shaped cells in 70% of cases, of epithelioid cells in 20%, histological variants are rare--, and on immunohistochemical arguments--expression of CD117 in 95%, usually associated with CD34 expression in 70% of cases. Most GISTs are associated with molecular abnormalities in low target genes: KIT and PDGFRA. The differential diagnosis of GISTs includes the other mesenchymal tumors of the gastrointestinal tract, such as leiomyomas, leiomyosarcomas, schwannomas and intra-abdominal fibromatosis. The evaluation of the prognosis is essential and is based on a simple algorithm using two histoprognostic parameters, tumor size and mitotic index. The treatment of localized GISTs is surgical resection and that of advanced or unresecable GISTs is based on the use of targeted therapy, imatinib, which is a pharmacological antagonist of the c-kit protein. Proper understanding and utilization of the diagnostic criteria and classification of GISTs by pathologists are essential for good patient management.