Recurrent gastrointestinal stromal tumor with c-KIT double exon mutations: A rare case report

Gastrointestinal stromal tumors (GISTs) represent the most common mesenchymal neoplasms of the gastrointestinal tract and are typically associated with activating mutations in the kinase insert domain receptor (c-KIT) or platelet-derived growth factor receptor alpha. The advent of targeted therapies, such as imatinib, has substantially improved clinical outcomes; however, primary double-mutant GISTs present significant therapeutic challenges. We report the case of a 51-year-old man who presented with a 2-week history of left upper abdominal pain and melena. Contrast-enhanced abdominal computed tomography revealed a mass in the pelvic region of the small intestine. Histopathological analysis demonstrated a spindle cell morphology with a high mitotic index. Immunohistochemical staining was positive for CD117, CD34, and Dog-1, confirming the diagnosis of a high-risk small intestinal GIST. At the time of diagnosis, genetic testing was not performed, and the patient was initiated on imatinib therapy. After 5 years of treatment, the patient developed clinical resistance. First-generation sequencing identified concurrent mutations in c-KIT exons 11 (V560D) and exon 17 (N822K), implicating these double mutations in acquired imatinib resistance. This case underscores the clinical significance of double mutations in GIST, the limitations of first-line therapy in such contexts, and the importance of early genetic profiling to inform personalized treatment strategies.