Gastrointestinal Stromal Tumor Disease Background

Introduction

Gastrointestinal stromal tumors (GIST) are morphologically spindle cell, epithelioid, or occasionally pleomorphic mesenchymal tumors of the gastrointestinal tract. 

Epidemiology

Gastrointestinal stromal tumors are the most common mesenchymal tumors originating from the gastrointestinal tract. These tumors are notably rare with high variations in reported incidence, from 0.4-2 cases per 100,000 per year. The incidence of gastrointestinal stromal tumors is highly variable based on geographic location. The highest incidence rates of gastrointestinal stromal tumors were seen in Hong Kong, Shanghai, Taiwan, Korea, and Norway with around 19-22 cases per million population per year. While the lowest rates were seen in the province of Shanxi of China with around 4.3 cases per million population per year, as well as in the Czech Republic and Slovakia with around 5.2 cases per million population per year. However, the exact prevalence of gastrointestinal stromal tumors is not known as many cases remain silent throughout their life and may be higher than is currently observed.  

Gastrointestinal stromal tumors occur at any age, but most cases are seen later in life, with a median age of diagnosis of around 60-69 years of age. Occurrence in children is very rare and presents a distinct subset than those found. With regards to sex, gastrointestinal stromal tumors have higher incidence in males. 

Pathophysiology

Most gastrointestinal stromal tumors (70%) are benign, associated with activating mutations in the tyrosine kinase receptor KIT and/or the platelet-derived growth factor receptor-α (PDGFRA). Overexpression or activation of tyrosine kinase leads to hyperplasia involving the cells from the lineage of the interstitial cells of Cajal (ICC), and subsequently, gastrointestinal stromal tumor formation. Approximately 80% of gastrointestinal stromal tumors have a mutation in the gene encoding the KIT receptor tyrosine kinase, while 5-10% have a mutation in the gene encoding PDGFRA receptor tyrosine kinase. PDGFRA exon 18 mutations are common in gastric gastrointestinal stromal tumors. For the rest of the gastrointestinal stromal tumors, they do not have detectable KIT or PDGFRA gene mutations, and constitute a distinct subset called wild-type gastrointestinal stromal. Wild-type gastrointestinal stromal tumors, which makes up 90% of pediatric gastrointestinal stromal tumors, represent a heterogenous group that suffer from mutations in BRAF, NRAS, and SDH to name a few.  

Gastrointestinal stromal tumors usually occur in the stomach (60%) or the small intestines (30%) with the liver and/or the peritoneal surfaces being the most common sites of metastasis. In <5% of cases, gastrointestinal stromal tumors are located outside the GI tract, most commonly in the mesentery or omentum.