Surgical Management of Germline Gastrointestinal Stromal Tumor

Gastrointestinal stromal tumor (GIST) is the most common human sarcoma and usually results from a sporadic mutation in KIT or, less frequently, platelet-derived growth factor alpha (PDGFRA). Rarely, a germline mutation in the KIT, PDGFRA, succinate dehydrogenase (SDH), or neurofibromatosis 1 (NF1) gene is responsible for GIST. These tumors are found in the stomach (PDGFRA and SDH), small bowel (NF1), or a combination of both (KIT). There is a need to improve care for these patients regarding genetic testing, screening, and surveillance. Since most GISTs due to a germline mutation do not respond to tyrosine kinase inhibitors, the role of surgery is critical, especially when considering germline gastric GIST. However, in contrast to the established recommendation for prophylactic total gastrectomy in cadherin 1 (CDH1) mutation carriers once they reach adulthood, there are no formal guidelines as to the timing or extent of surgical resection for patients who are either carriers of a germline GIST mutation causing gastric GIST or have already developed gastric GIST(s). Surgeons must balance treating what is often multicentric, yet initially indolent disease with the chance of cure and the complications associated with total gastrectomy. Here, we consider the major issues in performing surgery in patients with germline GIST and illustrate the principles with a previously unreported patient harboring a germline KIT 579 deletion.