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Surgical Management of Germline Gastrointestinal Stromal Tumor

  • Gastrointestinal Oncology
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

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.

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Acknowledgment

The investigators were supported by NIH grants R01 CA102613 and T32 CA251063, the David Foundation, Betsy Levine-Brown and Marc Brown, and the GIST Cancer Research Fund (RPD).

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Author notes

  1. Hyunjee V. Kwak and Katherine J. Tardy have contributed equally to this work.

Authors and Affiliations

  1. Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

    Hyunjee V. Kwak MD, Katherine J. Tardy MD & Ronald P. DeMatteo MD

  2. Department of Pathology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

    Andrew Allbee MD, PhD & Kristen Stashek MD

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  1. Hyunjee V. Kwak MD
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Correspondence to Ronald P. DeMatteo MD.

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Hyunjee V. Kwak, Katherine J. Tardy, Andrew Allbee, Kristen Stashek, and Ronald P. DeMatteo declare no conflicts of interest.

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Kwak, H.V., Tardy, K.J., Allbee, A. et al. Surgical Management of Germline Gastrointestinal Stromal Tumor. Ann Surg Oncol 30, 4966–4974 (2023). https://doi.org/10.1245/s10434-023-13519-y

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