{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T19:05:13Z","timestamp":1792695913847,"version":"4.5.0"},"reference-count":60,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,11,19]],"date-time":"2024-11-19T00:00:00Z","timestamp":1731974400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:p>Gastrointestinal stromal tumors (GISTs) arise from the interstitial cells of Cajal, predominantly affecting the stomach and small intestine, with rare occurrences in the duodenum, rectum, and extraintestinal sites. Histologically, GISTs can present as spindle cells, epithelioid cells, or mixed morphologies, with immunohistochemical staining revealing expression of KIT (CD117) and discovered on GIST 1 (DOG1). Approximately 80% of GISTs harbor activating mutations in KIT or platelet derived growth factor receptor \u03b1 (PDGFRA), which influence their clinical behavior and treatment response. SDH-deficient GISTs, associated with syndromes such as Carney triad and Carney\u2013Stratakis syndrome, represent a distinct subgroup with unique characteristics and management challenges. The standard treatment includes surgery and imatinib for metastatic cases; however, resistance to tyrosine kinase inhibitors remains a significant hurdle, especially in pediatric and wildtype GISTs. This highlights the need for advanced therapeutic strategies and emphasizes the importance of molecular profiling in guiding treatment decisions and improving outcomes for GIST patients.<\/jats:p>","DOI":"10.3389\/fonc.2024.1487467","type":"journal-article","created":{"date-parts":[[2024,11,19]],"date-time":"2024-11-19T05:10:33Z","timestamp":1731993033000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":12,"title":["Pathologic diagnosis and molecular features of gastrointestinal stromal tumors: a mini-review"],"prefix":"10.3389","volume":"14","author":[{"given":"Younghoon","family":"Kim","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sung Hak","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,11,19]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1007\/s00423-005-0005-5","article-title":"Gastrointestinal stromal tumours: A regular origin in the muscularis propria, but an extremely diverse gross presentation. A review of 200 cases to critically re-evaluate the concept of so-called extra-gastrointestinal stromal tumours","volume":"391","author":"Agaimy","year":"2006","journal-title":"Langenbecks Arch Surg"},{"key":"B2","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1053\/j.semdp.2006.09.001","article-title":"Gastrointestinal stromal tumors: pathology and prognosis at different sites","volume":"23","author":"Miettinen","year":"2006","journal-title":"Semin Diagn Pathol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.4137\/CMO.S9180","article-title":"Primary extra-gastrointestinal stromal tumor of retroperitoneum","volume":"6","author":"Casella","year":"2012","journal-title":"Clin Med Insights Oncol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2023.1033598","article-title":"Primary extra-gastrointestinal stromal tumor of retroperitoneum: clinicopathologic characteristics and prognosis of six cases","volume":"13","author":"Lin","year":"2023","journal-title":"Front Oncol"},{"key":"B5","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1016\/j.canep.2015.10.031","article-title":"Global epidemiology of gastrointestinal stromal tumours (Gist): A systematic review of population-based cohort studies","volume":"40","author":"Soreide","year":"2016","journal-title":"Cancer Epidemiol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.5858\/arpa.2018-0370-RS","article-title":"Succinate dehydrogenase-deficient gastrointestinal stromal tumors","volume":"144","author":"Ibrahim","year":"2020","journal-title":"Arch Pathol Lab Med"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/s0959-8049(02)80602-5","article-title":"Pathology and diagnostic criteria of gastrointestinal stromal tumors (Gists): A review","author":"Miettinen","year":"2002","journal-title":"Eur J Cancer"},{"key":"B8","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s004280000338","article-title":"Gastrointestinal stromal tumors\u2013definition, clinical, histological, immunohistochemical, and molecular genetic features and differential diagnosis","volume":"438","author":"Miettinen","year":"2001","journal-title":"Virchows Arch"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/j.prp.2013.12.008","article-title":"Dedifferentiated gastrointestinal stromal tumor arising de novo from the small intestine","volume":"210","author":"Choi","year":"2014","journal-title":"Pathol Res Pract"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0b013e31826c1761","article-title":"Dedifferentiation in gastrointestinal stromal tumor to an anaplastic kit-negative phenotype: A diagnostic pitfall: morphologic and molecular characterization of 8 cases occurring either de novo or after imatinib therapy","volume":"37","author":"Antonescu","year":"2013","journal-title":"Am J Surg Pathol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1038\/s41379-021-00949-w","article-title":"Gastrointestinal stromal tumors (Gists) arising in uncommon locations: clinicopathologic features and risk assessment of esophageal, colonic, and appendiceal gists","volume":"35","author":"Hu","year":"2022","journal-title":"Mod Pathol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1038\/modpathol.3880210","article-title":"Immunohistochemical spectrum of gists at different sites and their differential diagnosis with a reference to cd117 (Kit)","volume":"13","author":"Miettinen","year":"2000","journal-title":"Mod Pathol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.5858\/arpa.2011-0022-RA","article-title":"Gastrointestinal stromal tumor: advances in diagnosis and management","volume":"135","author":"Patil","year":"2011","journal-title":"Arch Pathol Lab Med"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2004.05.140","article-title":"Biology of gastrointestinal stromal tumors","volume":"22","author":"Corless","year":"2004","journal-title":"J Clin Oncol"},{"key":"B15","doi-asserted-by":"publisher","first-page":"27","DOI":"10.21037\/tgh.2018.04.01","article-title":"Differential diagnosis of gastrointestinal stromal tumor by histopathology and immunohistochemistry","volume":"3","author":"Hirota","year":"2018","journal-title":"Transl Gastroenterol Hepatol"},{"key":"B16","doi-asserted-by":"publisher","first-page":"646","DOI":"10.3390\/genes14030646","article-title":"Sdha germline mutations in sdh-deficient gists: A current update","volume":"14","author":"Schipani","year":"2023","journal-title":"Genes (Basel)"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1080\/00365521.2016.1251607","article-title":"Cytohistological and immunohistochemical characteristics of spindle-shaped mesenchymal neoplasms occurring in the gastrointestinal tract","volume":"52","author":"Ieni","year":"2017","journal-title":"Scand J Gastroenterol"},{"key":"B18","doi-asserted-by":"publisher","first-page":"194","DOI":"10.3390\/diagnostics11020194","article-title":"Update on molecular genetics of gastrointestinal stromal tumors","volume":"11","author":"Brcic","year":"2021","journal-title":"Diagnostics (Basel)"},{"key":"B19","article-title":"Gastrointestinal stromal tumor with chondroid differentiation","volume":"29","author":"Pulcini","year":"2009","journal-title":"Anticancer Res"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(11)70299-6","article-title":"Risk of recurrence of gastrointestinal stromal tumour after surgery: an analysis of pooled population-based cohorts","volume":"13","author":"Joensuu","year":"2012","journal-title":"Lancet Oncol"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejso.2018.12.014","article-title":"A new nomogram for recurrence-free survival prediction of gastrointestinal stromal tumors: comparison with current risk classification methods","volume":"45","author":"Chen","year":"2019","journal-title":"Eur J Surg Oncol"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1245\/s10434-007-9633-z","article-title":"Surgically managed gastrointestinal stromal tumors: A comparative and prognostic analysis","volume":"15","author":"Hassan","year":"2008","journal-title":"Ann Surg Oncol"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1016\/j.humpath.2008.06.025","article-title":"Risk stratification of patients diagnosed with gastrointestinal stromal tumor","volume":"39","author":"Joensuu","year":"2008","journal-title":"Hum Pathol"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1097\/MCG.0b013e31821f8bf6","article-title":"Predictors of recurrence after resection of small gastric gastrointestinal stromal tumors of 5 cm or less","volume":"46","author":"Kim","year":"2012","journal-title":"J Clin Gastroenterol"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1016\/j.tranon.2020.100812","article-title":"Prognostic indicators for gastrointestinal stromal tumors: A review","volume":"13","author":"Zhang","year":"2020","journal-title":"Transl Oncol"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1053\/j.semdp.2015.02.017","article-title":"Genotyping and immunohistochemistry of gastrointestinal stromal tumors: an update","volume":"32","author":"Rubin","year":"2015","journal-title":"Semin Diagn Pathol"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.6004\/jnccn.2017.0057","article-title":"The call of \u201cthe wild\u201d-type gist: it\u2019s time for domestication","volume":"15","author":"Alkhuziem","year":"2017","journal-title":"J Natl Compr Canc Netw"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.16014","article-title":"Genetic progression in gastrointestinal stromal tumors: mechanisms and molecular interventions","volume":"8","author":"Li","year":"2017","journal-title":"Oncotarget"},{"key":"B29","doi-asserted-by":"publisher","first-page":"679","DOI":"10.3390\/cancers11050679","article-title":"Clinical diagnosis of gastrointestinal stromal tumor (Gist): from the molecular genetic point of view","volume":"11","author":"Wu","year":"2019","journal-title":"Cancers (Basel)"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1309\/AJCPPCKGA2QGBJ1R","article-title":"Braf mutation status in gastrointestinal stromal tumors","volume":"133","author":"Hostein","year":"2010","journal-title":"Am J Clin Pathol"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-16-0152","article-title":"Quadruple-negative gist is a sentinel for unrecognized neurofibromatosis type 1 syndrome","volume":"23","author":"Gasparotto","year":"2017","journal-title":"Clin Cancer Res"},{"key":"B32","doi-asserted-by":"publisher","first-page":"290","DOI":"10.1038\/nrc3911","article-title":"A rasopathy gene commonly mutated in cancer: the neurofibromatosis type 1 tumour suppressor","volume":"15","author":"Ratner","year":"2015","journal-title":"Nat Rev Cancer"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(13)60106-3","article-title":"Gastrointestinal stromal tumour","volume":"382","author":"Joensuu","year":"2013","journal-title":"Lancet"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms14674","article-title":"Max inactivation is an early event in gist development that regulates P16 and cell proliferation","volume":"8","author":"Schaefer","year":"2017","journal-title":"Nat Commun"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2974","article-title":"Dystrophin is a tumor suppressor in human cancers with myogenic programs","volume":"46","author":"Wang","year":"2014","journal-title":"Nat Genet"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1038\/1209","article-title":"Familial gastrointestinal stromal tumours with germline mutation of the kit gene","volume":"19","author":"Nishida","year":"1998","journal-title":"Nat Genet"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdr127","article-title":"Prognostic value of kit\/pdgfra mutations in gastrointestinal stromal tumours (Gist): polish clinical gist registry experience","volume":"23","author":"Wozniak","year":"2012","journal-title":"Ann Oncol"},{"key":"B38","doi-asserted-by":"publisher","first-page":"174","DOI":"10.3892\/ol.2021.12435","article-title":"Mutational characteristics of gastrointestinal stromal tumors: A single-center analysis of 302 patients","volume":"21","author":"Liang","year":"2021","journal-title":"Oncol Lett"},{"key":"B39","article-title":"Association of kit exon 9 mutations with nongastric primary site and aggressive behavior: kit mutation analysis and clinical correlates of 120 gastrointestinal stromal tumors","volume":"9","author":"Antonescu","year":"2003","journal-title":"Clin Cancer Res"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.3390\/gidisord6040059","article-title":"Unraveling gastric and small intestine gastrointestinal stromal tumors: A review of our current knowledge","volume":"6","author":"Eskitzis","year":"2024","journal-title":"Gastrointestinal Disord"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1038\/modpathol.2008.2","article-title":"Clinicopathologic profile of gastrointestinal stromal tumors (Gists) with primary kit exon 13 or exon 17 mutations: A multicenter study on 54 cases","volume":"21","author":"Lasota","year":"2008","journal-title":"Mod Pathol"},{"key":"B42","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1016\/j.ejca.2017.02.007","article-title":"Clinical characteristics and treatment outcome in a large multicentre observational cohort of pdgfra exon 18 mutated gastrointestinal stromal tumour patients","volume":"76","author":"Farag","year":"2017","journal-title":"Eur J Cancer"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2014.57.4970","article-title":"Kit and pdgfra mutations and the risk of gi stromal tumor recurrence","volume":"33","author":"Joensuu","year":"2015","journal-title":"J Clin Oncol"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1016\/j.humpath.2013.10.025","article-title":"High-resolution melting analysis is a sensitive diagnostic tool to detect imatinib-resistant and imatinib-sensitive pdgfra exon 18 mutations in gastrointestinal stromal tumors","volume":"45","author":"Kunstlinger","year":"2014","journal-title":"Hum Pathol"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1111\/pin.12431","article-title":"Wild type\u201d Gist: clinicopathological features and clinical practice","volume":"66","author":"Wada","year":"2016","journal-title":"Pathol Int"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1002\/gcc.22991","article-title":"Gastrointestinal stromal tumors with braf gene fusions. A report of two cases showing low or absent kit expression resulting in diagnostic pitfalls","volume":"60","author":"Torrence","year":"2021","journal-title":"Genes Chromosomes Cancer"},{"key":"B47","doi-asserted-by":"publisher","first-page":"105","DOI":"10.3390\/cancers15010105","article-title":"Gists with ntrk gene fusions: A clinicopathological, immunophenotypic, and molecular study","volume":"15","author":"Cao","year":"2022","journal-title":"Cancers (Basel)"},{"key":"B48","doi-asserted-by":"publisher","first-page":"10244","DOI":"10.1038\/s41598-019-46124-9","article-title":"Sdhc epi-mutation testing in gastrointestinal stromal tumours and related tumours in clinical practice","volume":"9","author":"Casey","year":"2019","journal-title":"Sci Rep"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2014.05.033","article-title":"Succinate dehydrogenase deficient gastrointestinal stromal tumors (Gists) - a review","volume":"53","author":"Miettinen","year":"2014","journal-title":"Int J Biochem Cell Biol"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2021.680609","article-title":"Carney triad, carney-stratakis syndrome, 3pas and other tumors due to sdh deficiency","volume":"12","author":"Pitsava","year":"2021","journal-title":"Front Endocrinol (Lausanne)"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1016\/j.radcr.2020.08.002","article-title":"Carney-stratakis syndrome: A dyad of familial paraganglioma and gastrointestinal stromal tumor","volume":"15","author":"Recht","year":"2020","journal-title":"Radiol Case Rep"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1245\/ASO.2004.09.011","article-title":"Surgery and imatinib in the management of gist: emerging approaches to adjuvant and neoadjuvant therapy","volume":"11","author":"Eisenberg","year":"2004","journal-title":"Ann Surg Oncol"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1097\/00000658-200001000-00008","article-title":"Two hundred gastrointestinal stromal tumors: recurrence patterns and prognostic factors for survival","volume":"231","author":"DeMatteo","year":"2000","journal-title":"Ann Surg"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1186\/s13045-020-01026-6","article-title":"The management of metastatic gist: current standard and investigational therapeutics","volume":"14","author":"Kelly","year":"2021","journal-title":"J Hematol Oncol"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2022.978885","article-title":"A Systematic Review and Network Meta-Analysis of the Efficacy and Safety of Third-Line and over Third-Line Therapy after Imatinib and Tki Resistance in Advanced Gastrointestinal Stromal Tumor","volume":"13","author":"Xiao","year":"2022","journal-title":"Front Pharmacol"},{"key":"B56","doi-asserted-by":"publisher","first-page":"9519","DOI":"10.1038\/s41598-017-09132-1","article-title":"Treatment patterns, efficacy and toxicity of regorafenib in gastrointestinal stromal tumour patients","volume":"7","author":"Schvartsman","year":"2017","journal-title":"Sci Rep"},{"key":"B57","doi-asserted-by":"publisher","first-page":"4989","DOI":"10.3390\/cancers14204989","article-title":"Latest advances in the management of pediatric gastrointestinal stromal tumors","volume":"14","author":"Andrzejewska","year":"2022","journal-title":"Cancers (Basel)"},{"key":"B58","doi-asserted-by":"publisher","first-page":"216","DOI":"10.3390\/cancers15010216","article-title":"Exploring the dynamic crosstalk between the immune system and genetics in gastrointestinal stromal tumors","volume":"15","author":"Dimino","year":"2022","journal-title":"Cancers (Basel)"},{"key":"B59","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1080\/14728214.2021.1896704","article-title":"Emerging drugs for the treatment of gastrointestinal stromal tumors","volume":"26","author":"Pilco-Janeta","year":"2021","journal-title":"Expert Opin Emerg Drugs"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.3390\/curroncol30010034","article-title":"Gastrointestinal stromal tumours (Gist) of the rectum: A systematic review and meta-analysis","volume":"30","author":"Khan","year":"2022","journal-title":"Curr Oncol"}],"container-title":["Frontiers in Oncology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2024.1487467\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,11,19]],"date-time":"2024-11-19T05:10:36Z","timestamp":1731993036000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2024.1487467\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,19]]},"references-count":60,"alternative-id":["10.3389\/fonc.2024.1487467"],"URL":"https:\/\/doi.org\/10.3389\/fonc.2024.1487467","relation":{},"ISSN":["2234-943X"],"issn-type":[{"value":"2234-943X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11,19]]},"article-number":"1487467"}}