{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T19:01:06Z","timestamp":1788462066064,"version":"build-2803163510"},"reference-count":121,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,6,10]],"date-time":"2025-06-10T00:00:00Z","timestamp":1749513600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background\/Objectives: The present investigation quantifies the striking predisposition for small intestinal GISTs in NF-1 patients, examining both multifocal and solitary tumor patterns while establishing critical epidemiological comparisons with the general population. By elucidating these distinct clinical and biological profiles, the study aims to transform the understanding of NF1-associated tumorigenesis and optimize patient surveillance strategies. Methods: This systematic review and meta-analysis was conducted in strict accordance with PRISMA guidelines, the gold-standard framework for minimizing bias and maximizing reproducibility in evidence synthesis. Prospectively registered in PROSPERO, the study employed a PICO framework to evaluate interventions, outcomes, and comparisons. Results: This systematic review and meta-analysis reveals a profound oncogenic propensity for small intestinal GISTs in NF-1 patients, demonstrating markedly increased prevalence relative to population baselines. The tumors display characteristic presentation and histological profiles, with a distribution of 54% multifocal lesions, 41% solitary SI-GIST, and 5% solitary duodenal GIST cases, demonstrating the diverse clinical manifestations of NF-1-associated tumors. These compelling findings not only redefine the epidemiological landscape of NF1-associated malignancies but also underscore extraordinary disease susceptibility, far surpassing previous estimates and sporadic occurrence rates in the general population. Conclusions: The distinct clinical patterns and high frequency of these tumors among NF-1 patients provide important insights into GIST development while underscoring the need for heightened clinical suspicion, particularly in patients manifesting gastrointestinal hemorrhage. These findings highlight the unique challenges in managing these cases\u2014including diagnostic limitations and therapeutic constraints\u2014underscoring the imperative for multidisciplinary therapeutic frameworks for detection, monitoring and treatment in this high-risk population.<\/jats:p>","DOI":"10.3390\/cancers17121934","type":"journal-article","created":{"date-parts":[[2025,6,10]],"date-time":"2025-06-10T09:59:14Z","timestamp":1749549554000},"page":"1934","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Multifocal Gastrointestinal Stromal Tumors (GISTs) of the Small Intestine in Patients with Neurofibromatosis Type 1 (NF-1): Meta-Analysis and Systematic Review of the Literature"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-9771-8995","authenticated-orcid":false,"given":"Stylianos","family":"Mantalovas","sequence":"first","affiliation":[{"name":"3rd Surgical 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Department, AHEPA University Hospital of Thessaloniki, School of Medicine, Aristotle University of Thessaloniki, 1st St. Kiriakidi Street, 54621 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-7630-4253","authenticated-orcid":false,"given":"Panagiota","family":"Roulia","sequence":"additional","affiliation":[{"name":"3rd Surgical Department, AHEPA University Hospital of Thessaloniki, School of Medicine, Aristotle University of Thessaloniki, 1st St. Kiriakidi Street, 54621 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8571-371X","authenticated-orcid":false,"given":"Stavros","family":"Savvakis","sequence":"additional","affiliation":[{"name":"3rd Surgical Department, AHEPA University Hospital of Thessaloniki, School of Medicine, Aristotle University of Thessaloniki, 1st St. Kiriakidi Street, 54621 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georgios","family":"Anthimidis","sequence":"additional","affiliation":[{"name":"3rd Surgical Department, AHEPA University Hospital of Thessaloniki, School of Medicine, Aristotle University of Thessaloniki, 1st St. Kiriakidi Street, 54621 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Konstantinos","family":"Papadopoulos","sequence":"additional","affiliation":[{"name":"3rd Surgical Department, AHEPA University Hospital of Thessaloniki, School of Medicine, Aristotle University of Thessaloniki, 1st St. Kiriakidi Street, 54621 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-2298-9333","authenticated-orcid":false,"given":"Vasiliki","family":"Magra","sequence":"additional","affiliation":[{"name":"3rd Surgical Department, AHEPA University Hospital of Thessaloniki, School of Medicine, Aristotle University of Thessaloniki, 1st St. Kiriakidi Street, 54621 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5849-5515","authenticated-orcid":false,"given":"Nikolaos","family":"Varsamis","sequence":"additional","affiliation":[{"name":"3rd Surgical Department, AHEPA University Hospital of Thessaloniki, School of Medicine, Aristotle University of Thessaloniki, 1st St. Kiriakidi Street, 54621 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoforos S.","family":"Kosmidis","sequence":"additional","affiliation":[{"name":"3rd Surgical Department, AHEPA University Hospital of Thessaloniki, School of Medicine, Aristotle University of Thessaloniki, 1st St. Kiriakidi Street, 54621 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isaak","family":"Kesisoglou","sequence":"additional","affiliation":[{"name":"3rd Surgical Department, AHEPA University Hospital of 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