A Rare Case of Quadruple Negative GIST with an Unusual Presentation in a Young Female

Abstract

Gastrointestinal stromal tumors (GISTs) are an uncommon malignancy, with origin in the interstitial cells of Cajal located in the myenteric plexus. The incidence is 5000 new cases every year in the US. It is important to determine genetic alterations in GIST. Approximately 90% of GISTs have a gain of function mutation in either the c-KIT protooncogene (which encodes for the receptor tyrosine kinase KIT) accounting for 75%, or the platelet derived growth factor receptor alpha (PDGFRA) protooncogene which accounts for 15%. Only 5-10% constitute Wild Type (WT) GISTs with mutations observed in BRAF, NF1, & SDH. While Imatinib, a Tyrosine Kinase Inhibitor (TKI), is used as adjuvant therapy for most KIT-positive tumors, it cannot be used in TKI-resistant tumors that harbor alternative genetic mutations. We present a rare case of quadruple negative (negative for all aforementioned genes) GIST with a mutation identified as ETV6-NTRK3 fusion. This mutation was first described in a case of rectal quadruple negative WT GIST.