Gastrointestinal stromal tumors (GIST) were recognized as a specific entity in the late 1980s based on clinical, histopathological and immunohistochemical features and were thought to be derived from smooth muscle cells given the spindle cell appearance at light microscopy. In 1998, Hirota and colleagues achieved a significant breakthrough by demonstrating a near-universal expression of the transmembrane KIT receptor tyrosine kinase (c-KIT, CD 117, stem cell growth factor receptor) on the surface of GIST, while other spindle cell tumours are typically c-KIT negative. Currently, GIST are thought to arise from pacemakers cells, the interstitial cells of Cajal, as both express c-KIT protein.
Ground-breaking understanding of molecular mechanisms involved in molecular pathophysiology of GIST has led to improved overall survival of patients by targeting specific cellular signalling pathways. The practicing general surgeon will need an understanding of the specific diagnostic and therapeutic options for these patients. The treatment of metastatic GIST patients with oral inhibitor molecule of KIT has improved median survival from 18 months to over 5 years. This has led to a growing cohort of patients surviving GIST over many years who will be managed in general surgical practice.
This is a preview of subscription content, log in to check access.
Cameron S. Long-term adjuvant treatment of gastrointestinal stromal tumors (GIST) with imatinib-a comment and reflection on the PERSIST-5 study. Transl Gastroenterol Hepatol. 2018;3:16.CrossRefGoogle Scholar
Cavnar MJDRP. The management of gastrointestinal stromal tumors. In: Cameron JLCAM, editor. Current surgical therapy. 12th ed. Philadelphia, PA: Elsevier; 2017. p. 104.Google Scholar
Corless CL, Ballman KV, Antonescu CR, Kolesnikova V, Maki RG, Pisters PW, et al. Pathologic and molecular features correlate with long-term outcome after adjuvant therapy of resected primary GI stromal tumor: the ACOSOG Z9001 trial. J Clin Oncol. 2014;32(15):1563–70.CrossRefGoogle Scholar
DeMatteo RP, Ballman KV, Antonescu CR, Corless C, Kolesnikova V, von Mehren M, et al. Long-term results of adjuvant imatinib mesylate in localized, high-risk, primary gastrointestinal stromal tumor: ACOSOG Z9000 (Alliance) intergroup phase 2 trial. Ann Surg. 2013;258(3):422–9.CrossRefGoogle Scholar
Fairweather M, Balachandran VP, Li GZ, Bertagnolli MM, Antonescu C, Tap W, et al. Cytoreductive surgery for metastatic gastrointestinal stromal tumors treated with tyrosine kinase inhibitors: a 2-institutional analysis. Ann Surg. 2018;268(2):296–302.CrossRefGoogle Scholar
Gold JS, Dematteo RP. Combined surgical and molecular therapy: the gastrointestinal stromal tumor model. Ann Surg. 2006;244(2):176–84.CrossRefGoogle Scholar
Guller U, Tarantino I, Cerny T, Schmied BM, Warschkow R. Population-based SEER trend analysis of overall and cancer-specific survival in 5138 patients with gastrointestinal stromal tumor. BMC Cancer. 2015;15:557.CrossRefGoogle Scholar
Hirota S, Isozaki K, Moriyama Y, Hashimoto K, Nishida T, Ishiguro S, et al. Gain-of-function mutations of c-kit in human gastrointestinal stromal tumors. Science. 1998;279(5350):577–80.CrossRefGoogle Scholar
Joensuu H, DeMatteo RP. The management of gastrointestinal stromal tumors: a model for targeted and multidisciplinary therapy of malignancy. Annu Rev Med. 2012;63:247–58.CrossRefGoogle Scholar
Joensuu H, Roberts PJ, Sarlomo-Rikala M, Andersson LC, Tervahartiala P, Tuveson D, et al. Effect of the tyrosine kinase inhibitor STI571 in a patient with a metastatic gastrointestinal stromal tumor. N Engl J Med. 2001;344(14):1052–6.CrossRefGoogle Scholar
Kim MY, Jung HY, Choi KD, Song HJ, Lee JH, Kim DH, et al. Natural history of asymptomatic small gastric subepithelial tumors. J Clin Gastroenterol. 2011;45(4):330–6.CrossRefGoogle Scholar
Maynard MA, Marino-Enriquez A, Fletcher JA, Dorfman DM, Raut CP, Yassa L, et al. Thyroid hormone inactivation in gastrointestinal stromal tumors. N Engl J Med. 2014;370(14):1327–34.CrossRefGoogle Scholar
Miettinen M, Lasota J. Histopathology of gastrointestinal stromal tumor. J Surg Oncol. 2011;104(8):865–73.CrossRefGoogle Scholar
Miettinen M. Gastrointestinal stromal tumors. An immunohistochemical study of cellular differentiation. Am J Clin Pathol. 1988;89(5):601–10.CrossRefGoogle Scholar
Miettinen MLJ. Gastrointestinal stromal tumors: pathology and prognosis at different sites. Semin Diagn Pathol. 2006;23(2):70–83.CrossRefGoogle Scholar
Nilsson B, Bumming P, Meis-Kindblom JM, Oden A, Dortok A, Gustavsson B, et al. Gastrointestinal stromal tumors: the incidence, prevalence, clinical course, and prognostication in the preimatinib mesylate era—a population-based study in western Sweden. Cancer. 2005;103(4):821–9.CrossRefGoogle Scholar