Gastrointestinal stromal tumors (GISTs): SEAP–SEOM consensus on pathologic and molecular diagnosis
Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms of the digestive tract, with an incidence of 1.1 cases/100,000 inhabitants/year. A group of experts from the Spanish Society of Pathology and the Spanish Society of Oncology met to discuss a brief update on GISTs and agree on aspects relating to the pathological and molecular diagnosis of these tumors. GISTs are generally solitary, well-circumscribed lesions of variable size (<10 mm–35 cm) that may present with intra- or extra-luminal parietal growth or a mixed-type (hourglass) growth pattern. Histologically, they are unencapsulated neoplasms displaying expansive growth and spindle-shaped (70%), epithelioid (20%), or mixed cellularity (10%). Mitotic activity is generally moderate or low and should be evaluated only in areas with high cellularity or higher mitotic frequency. The great majority of GISTs harbour mutually exclusive activating mutations in genes coding for the type III receptor tyrosine kinases KIT and PDGFRA; less commonly, GISTs have also been reported to display mutations elsewhere, including BRAF and NF1 and SDH-complex genes. The method most widely used to detect KIT and PDGFRA mutations is amplification of the exons involved by polymerase chain reaction followed by direct sequencing (Sanger method) of these amplification products. Molecular analyses should always specify the type of analysis performed, the region or mutations evaluated, and the sensitivity of the detection method employed.
KeywordsGastrointestinal stromal tumor GIST Pathologic diagnosis Molecular diagnosis Consensus
The authors would like to thank Fernando Rico-Villademoros (COCIENTE SL, Madrid, Spain) for editorial assistance in the preparation of this manuscript. SEOM and SEAP are grateful for financial support for this project in the form of unrestricted Grants from Bayer and Pfizer.
Compliance with ethical standards
Conflict of interest
The authors declare that, when writing and revising the text, they did not know the names of the pharmaceutical companies that provided financial support for this project, so this support has not influenced the content of this article.
The manuscript does not contain clinical studies or patient data
- 2.Golden T, Stout AP. Smooth muscle tumors of the gastrointestinal tract and retroperitoneal tissues. Surg Gynecol Obstet. 1941;73:784–810.Google Scholar
- 14.Blanke CD, Demetri GD, von Mehren M, Heinrich MC, Eisenberg B, Fletcher JA, et al. Long-term results from a randomized phase II trial of standard- versus higher-dose imatinib mesylate for patients with unresectable or metastatic gastrointestinal stromal tumors expressing KIT. J Clin Oncol. 2008;26:620–5.CrossRefPubMedGoogle Scholar
- 17.Otto C, Agaimy A, Braun A, Radecke J, Hoeppner J, Illerhaus G, et al. Multifocal gastric gastrointestinal stromal tumors (GISTs) with lymph node metastases in children and young adults: a comparative clinical and histomorphological study of three cases including a new case of Carney triad. Diagn Pathol. 2011;6:52.CrossRefPubMedPubMedCentralGoogle Scholar
- 19.Kalkmann J, Zeile M, Antoch G, Berger F, Diederich S, Dinter D, et al. Consensus report on the radiological management of patients with gastrointestinal stromal tumours (GIST): recommendations of the German GIST Imaging Working Group. Cancer Imaging. 2012;12:126–35.CrossRefPubMedPubMedCentralGoogle Scholar
- 26.Sobin LH, Gospodarowicz MK, Wittekind C, International Union against Cancer. TNM classification of malignant tumours. Chichester, Hoboken: Wiley-Blackwell; 2010.Google Scholar
- 28.Diaz Delgado M, Hernandez Amate A, Pereira Gallardo S, Jaramillo S, Virizuela Echaburu JA, Gonzalez-Campora RJ. Gastrointestinal stromal tumors: morphological, immunohistochemical and molecular changes associated with kinase inhibitor therapy. Pathol Oncol Res. 2011;17:455–61.CrossRefPubMedGoogle Scholar
- 35.Lasota J, Wang Z, Kim SY, Helman L, Miettinen M. Expression of the receptor for type i insulin-like growth factor (IGF1R) in gastrointestinal stromal tumors: an immunohistochemical study of 1078 cases with diagnostic and therapeutic implications. Am J Surg Pathol. 2013;37:114–9.CrossRefPubMedPubMedCentralGoogle Scholar
- 39.Doyle LA, Nelson D, Heinrich MC, Corless CL, Hornick JL. Loss of succinate dehydrogenase subunit B (SDHB) expression is limited to a distinctive subset of gastric wild-type gastrointestinal stromal tumours: a comprehensive genotype-phenotype correlation study. Histopathology. 2012;61:801–9.CrossRefPubMedGoogle Scholar
- 50.Demetri GD, von Mehren M, Antonescu CR, DeMatteo RP, Ganjoo KN, Maki RG, et al. NCCN Task Force report: update on the management of patients with gastrointestinal stromal tumors. Natl Compr Cancer Netw. 2010;8(Suppl 2):S1–41.Google Scholar
- 51.Martin J, Poveda A, Llombart-Bosch A, Ramos R, Lopez-Guerrero JA, Garcia del Muro J, et al. Deletions affecting codons 557-558 of the c-KIT gene indicate a poor prognosis in patients with completely resected gastrointestinal stromal tumors: a study by the Spanish Group for Sarcoma Research (GEIS). J Clin Oncol. 2005;23:6190–8.CrossRefPubMedGoogle Scholar
- 53.Martin-Broto J, Gutierrez A, Garcia-del-Muro X, Lopez-Guerrero JA, Martinez-Trufero J, de Sande LM, et al. Prognostic time dependence of deletions affecting codons 557 and/or 558 of KIT gene for relapse-free survival (RFS) in localized GIST: a Spanish Group for Sarcoma Research (GEIS) Study. Ann Oncol. 2010;21:1552–7.CrossRefPubMedGoogle Scholar
- 56.Casali PG, Le Cesne A, Poveda Velasco A, Kotasek D, Rutkowski P, Hohenberger P, et al. Time to definitive failure to the first tyrosine kinase inhibitor in localized GI stromal tumors treated with imatinib as an adjuvant: a European Organisation for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group Intergroup Randomized Trial in Collaboration With the Australasian Gastro-Intestinal Trials Group, UNICANCER, French Sarcoma Group, Italian Sarcoma Group, and Spanish Group for Research on Sarcomas. J Clin Oncol. 2015;33:4276–83.CrossRefPubMedGoogle Scholar
- 57.Wozniak A, Rutkowski P, Schoffski P, Ray-Coquard I, Hostein I, Schildhaus HU, et al. Tumor genotype is an independent prognostic factor in primary gastrointestinal stromal tumors of gastric origin: a European multicenter analysis based on ConticaGIST. Clin Cancer Res. 2014;20:6105–16.CrossRefPubMedGoogle Scholar
- 59.Blanke CD, Rankin C, Demetri GD, Ryan CW, von Mehren M, Benjamin RS, et al. Phase III randomized, intergroup trial assessing imatinib mesylate at two dose levels in patients with unresectable or metastatic gastrointestinal stromal tumors expressing the kit receptor tyrosine kinase: S0033. J Clin Oncol. 2008;26:626–32.CrossRefPubMedGoogle Scholar
- 62.Demetri GD, Reichardt P, Kang YK, Blay JY, Rutkowski P, Gelderblom H, et al. Efficacy and safety of regorafenib for advanced gastrointestinal stromal tumours after failure of imatinib and sunitinib (GRID): an international, multicentre, randomised, placebo-controlled, phase 3 trial. Lancet. 2013;381:295–302.CrossRefPubMedGoogle Scholar