Wild-type GIST: a comprehensive review

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract. The vast majority demonstrates mutually exclusive KIT or PDGFRA gain-of-function mutations. KIT or PDGFRA mutation is an early event in GIST pathogenesis and development, and has led to the introduction of KIT and PDGFRA kinase inhibitors in GIST, which has tremendously changed survival of patients suffering from this disease. Approximately 85 % of pediatric GISTs and 10–15 % of adult GISTs are devoid of mutations in the KIT and PDGFRA genes and are referred to as wild-type GISTs (WT-GIST). Over the past years, it has been shown that WT-GISTs are profoundly different from mutant GIST with regard to their clinical behavior as well as their molecular profile, and are now considered a separate pathological entity. Based on their significant molecular and clinical heterogeneity, WT-GISTs should be considered a group of diseases rather than a single disease entity. The following short review will exclusively focus on WT-GISTs, a group of tumors traditionally divided into a syndromic and a nonsyndromic (sporadic) subgroup. In addition, immunohistochemical expression of succinate dehydrogenase B (SDHB) has recently been introduced to subtype WT-GISTs into an SDHB-positive (proficient) from SDHB-negative (deficient) group.