Figure 1

The complexity of KIT ^WT / PDGFRA ^WT GIST molecular biology. KIT ^WT/PDGFRA ^WT GIST could be firstly divided two main group according to the SDHB immunohistochemical status: SDHB ^IHC+ (including NF1-mutated GIST and sporadic KIT ^WT/PDGFRA ^WT GIST with or without KRAS/BRAF mutations) and SDHB ^IHC- or SDH-deficient GIST. The latter could be further divided according to the SDHA immunohistochemical status: SDHB ^IHC-/SDHA ^IHC- GIST (pediatric type or young adult GIST characterized by germline or somatic inactivating SDHA mutations) and SDHB ^IHC/SDHA ^IHC+ GIST (including Carney-Stratakis Syndrome-related GIST, characterized by germline or somatic inactivating SDHB, −C, −D mutations, Carney Triad-related GIST that lack SDHx mutations, and sporadic KIT ^WT/PDGFRA ^WT GIST, characterized by germline or somatic inactivating SDHB, −C, −D mutations and SDHA mutations, reported in only three cases [15]. In red the subset of KIT ^WT/PDGFRA ^WT GIST referred to as quadruple ^WT GIST (KIT ^WT/PDGFRA ^WT/SDH ^WT/RAS-P ^WT), that represent the subject of this study.