NF1 Mutated Gastrointestinal Stromal Tumors With Coamplification of MDM2 and MYC

We report a unique case of a 57-year-old man with a gastrointestinal stromal tumor (GIST) that developed a high-grade phenotype and additional genetic alterations in the subsequent recurrence. Histologically, the initial resected tumor showed a typical morphology with uniform spindle-shaped cells arranged in fascicular and whorling patterns. However, based on large tumor size and mitotic activity it was designated as high risk. Tumor cells were immunoreactive for CD117 and DOG1. Mutational analysis identified no KIT or PDGFRA hotspot mutations. Next-generation sequencing (NGS) further demonstrated an NF1 mutation (c.1466A>G) without KIT or PDGFRA mutations. In contrast, the recurrent tumor displayed a higher-grade morphology. Tumor cells were positive for MDM2, while showing decreased expression for CD117 and DOG1. NGS and molecular assays detected no KIT or PDGFRA mutations, but confirmed the NF1 mutation (c.1466A>G). In addition, NGS identified MDM2 and MYC amplification. This is the first report describing an NF1-mutant GIST harboring coamplification of MDM2 and MYC and associated with a higher-grade tumor progression.