Midenin Gastrointestinal Stromal Tümörleri
Özet
Gastrointestinal stromal tümörler (GİST), gastrointestinal sistemin en yaygın mezenkimal tümörleri olup sıklıkla midenin subseroza veya muskularis propria tabakalarında yerleşir ve Cajal'ın interstisyel hücrelerinden köken alır. Genellikle yaşlı erişkinlerde sporadik olarak gelişen bu neoplazmlar, KIT veya PDGFRA mutasyonları ile karakterizedir; ancak süksinat dehidrojenaz (SDH) eksikliği olan sendromik veya pediatrik vakalar da görülebilir. Tanı sürecinde histopatolojik inceleme ile birlikte CD117 (KIT) ve DOG-1 immünohistokimyasal belirteçleri ve mutasyon analizi kritik rol oynar. Evreleme ve değerlendirmede kontrastlı bilgisayarlı tomografi (BT), MRG ve 18FDG-PET taramalarından yararlanılırken, preoperatif doku örneklemesi için EUS kılavuzluğunda biyopsi tercih edilir. Lokalize primer gastrik GİST'lerin tedavisinde standart yaklaşım, tümör rüptüründen kaçınarak mikroskobik negatif (R0) marj elde etmeyi amaçlayan laparoskopik veya açık cerrahi rezeksiyondur. Tirozin kinaz inhibitörü olan imatinib, yüksek nüks riskine sahip hastalarda üç yıl süreyle adjuvan tedavide kullanıldığı gibi, rezekte edilemeyen, lokal ileri evre veya metastatik hastalıklarda da ilk basamak standart sistemik tedaviyi oluşturur. Nüks riski ise tümör boyutu, mitotik indeks, primer lokalizasyon ve intraoperatif tümör rüptürü durumuna göre belirlenerek hastaların takibi bu doğrultuda yapılandırılır.
Gastrointestinal stromal tumors (GISTs) represent the most common mesenchymal neoplasms of the gastrointestinal tract, predominantly originating from the interstitial cells of Cajal located within the subserosa or muscularis propria of the stomach. Characterized primarily by mutually exclusive activating mutations in KIT or PDGFRA genes, a subset of GISTs can also emerge as syndromic or pediatric variants often driven by succinate dehydrogenase (SDH) deficiency. Accurate diagnosis relies on histopathological morphology combined with immunohistochemical staining for universal markers like CD117 (KIT) and DOG-1, supplemented by mutational profiling. Contrast-enhanced computed tomography (CT), MRI, and 18FDG-PET are standard for staging, while endoscopic ultrasound (EUS)-guided biopsy is preferred for preoperative sampling. Complete surgical resection achieving microscopically negative margins (R0) without tumor rupture remains the primary curative treatment for localized lesions, frequently performed via laparoscopic approaches. The tyrosine kinase inhibitor imatinib has revolutionized GIST management, serving as the standard adjuvant treatment for three years in high-risk patients and as the first-line systemic therapy for advanced, unresectable, or metastatic disease. Risk stratification and subsequent surveillance protocols are determined based on key parameters including tumor size, mitotic index, primary location, and the occurrence of tumor rupture.
Referanslar
Casali PG, Abecassis N, Aro HT et al. Gastrointestinal stromal tumours: ESMO-EURACAN Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2018 Oct 1;29(Suppl 4):iv68-iv78. doi: 10.1093/annonc/mdy095.
Lim KT. Surgical treatment of gastrointestinal stromal tumors of the stomach: current status and future perspective. Transl Gastroenterol Hepatol. 2017 Dec 7;2:104. doi: 10.21037/tgh.2017.12.01. eCollection 2017.
Miettinen M , Lasota J. Gastrointestinal stromal tumors--definition, clinical, histological, immunohistochemical, and molecular genetic features and differential diagnosis. Virchows Arch. 2001 Jan;438(1):1-12. doi: 10.1007/s004280000338.
Ulanja MB, Rishi M, Beutler BD et al. Racial Disparity in Incidence and Survival for Gastrointestinal Stromal Tumors (GISTs): an Analysis of SEER Database. J Racial Ethn Health Disparities. 2019 Oct;6(5):1035-1043. doi: 10.1007/s40615-019-00605-9. Epub 2019 Jun 18.
Søreide K, Sandvik OM, Søreide JA et al. Global epidemiology of gastrointestinal stromal tumours (GIST): A systematic review of population-based cohort studies. Cancer Epidemiol. 2016 Feb;40:39-46. doi: 10.1016/j.canep.2015.10.031. Epub 2015 Nov 24.
Ma GL, Murphy JD, Martinez ME et al. Epidemiology of gastrointestinal stromal tumors in the era of histology codes: results of a population-based study Cancer Epidemiol Biomarkers Prev. 2015 Jan;24(1):298-302. doi: 10.1158/1055-9965.EPI-14-1002. Epub 2014 Oct 2.
Landi B, Blay JY, Bonvalot S. Gastrointestinal stromal tumours (GISTs): French Intergroup Clinical Practice Guidelines for diagnosis, treatments and follow-up (SNFGE, FFCD, GERCOR, UNICANCER, SFCD, SFED, SFRO). Dig Liver Dis. 2019 Sep;51(9):1223-1231. doi: 10.1016/j.dld.2019.07.006. Epub 2019 Aug 3.
Uptodate (2021). Clinical presentation, diagnosis, and prognosis of gastrointestinal stromal tumors This topic last updated: May 24, 2021. (01.08.2021 tarihinde https://www.uptodate.com/contents/clinical-presentation-diagnosis-and-prognosis-of-gastrointestinal-stromal-tumors?search=gist&source=search_result&selectedTitle=1~93&usage_type=default&display_rank=1adresinden ulaşılmıştır.)
Hirota S, Isozaki K, Moriyama Y et al. Gain-of-function mutations of c-kit in human gastrointestinal stromal tumors. Science. 1998 Jan 23;279(5350):577-80. doi: 10.1126/science.279.5350.577.
Besmer P, Murphy JE, George PC et al. A new acute transforming feline retrovirus and relationship of its oncogene v-kit with the protein kinase gene family. Nature. 1986 Apr 3-9;320(6061):415-21. doi: 10.1038/320415a0.
Fletcher CD, Berman JJ, Corless C et al. Diagnosis of gastrointestinal stromal tumors: a consensus approach Int J Surg Pathol. 2002 Apr;10(2):81-9. doi: 10.1177/106689690201000201.
Coe TM, Fero KE, Fanta PT, et al. PopulationBased Epidemiology and Mortality of Small Malignant Gastrointestinal Stromal Tumors in the USA. J Gastrointest Surg. 2016 Jun;20(6):1132-40. doi: 10.1007/s11605-016-3134-y. Epub 2016 Mar 29.
National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology: GIST. https://www.nccn.org/professionals/physician_gls/pdf/gist.pdf (Accessed on January 29, 2020).
Eriksson M, Reichardt P, Sundby Hall K, et al. Needle biopsy through the abdominal wall for the diagnosis of gastrointestinal stromal tumour - Does it increase the risk for tumour cell seeding and recurrence? Eur J Cancer. 2016 May;59:128-133. doi: 10.1016/j.ejca.2016.02.021.
Tateishi U, Hasegawa T, Satake M et al. Gastrointestinal stromal tumor. Correlation of computed tomography findings with tumor grade and mortality. J Comput Assist Tomogr. Sep-Oct 2003;27(5):792-8. doi: 10.1097/00004728-200309000-00018.
Parab TM, DeRogatis MJ, Boaz AM, et al. Gastrointestinal stromal tumors: a comprehensive review. J Gastrointest Oncol. 2019 Feb;10(1):144-154. doi: 10.21037/jgo.2018.08.20.
Kim SJ, Lee SW. Performance of F-18 FDG PET/CT for predicting malignant potential of gastrointestinal stromal tumors: A systematic review and meta-analysis. J Gastroenterol Hepatol. 2018 Mar;33(3):576-582. doi: 10.1111/jgh.14015.
Fujimoto Y, Nakanishi Y, Yoshimura K, et al. Clinicopathologic study of primary malignant gastrointestinal stromal tumor of the stomach, with special reference to prognostic factors: analysis of results in 140 surgically resected patients. Gastric Cancer. 2003;6(1):39-48. doi: 10.1007/s101200300005.
Kim IH, Kim IH, Kwak SG, et al. Gastrointestinal stromal tumors (GISTs) of the stomach: a multicenter, retrospective study of curatively resected gastric GISTs. Ann Surg Treat Res. 2014 Dec;87(6):298-303. doi: 10.4174/astr.2014.87.6.298. Epub 2014 Nov 28.
Karakousis GC, Singer S, Zheng J, et al. Laparoscopic versus open gastric resections for primary gastrointestinal stromal tumors (GISTs): a size-matched comparison. Ann Surg Oncol. 2011 Jun;18(6):1599-605. doi: 10.1245/s10434-010-1517-y. Epub 2011 Jan 5.
Huang CM, Chen QF, Lin JX, et al. Can laparoscopic surgery be applied in gastric gastrointestinal stromal tumors located in unfavorable sites? A study based on the NCCN guidelines. Medicine (Baltimore). 2017 Apr;96(14):e6535. doi: 10.1097/MD.0000000000006535.
Joensuu H, Eriksson M, Sundby Hall K, et al. Radiotherapy for GIST progressing during or after tyrosine kinase inhibitor therapy: a prospective study. J ClinOncol 2016;34:244–50.
Fletcher CDM, Berman J, Corless C, et al. Diagnosis of gastrointestinal stromaltumours: a consensus approach. Hum Pathol. 2002 May;33(5):459-65. doi: 10.1053/hupa.2002.123545.
Miettinen M, Lasota J. Gastrointestinal stromal tumours: pathology and prog-nosis at different sites. Semin Diagn Pathol. 2006 May;23(2):70-83. doi: 10.1053/j.semdp.2006.09.001.
Joensuu H. Risk stratification of patients diagnosed with gastrointestinal stromal tumour. Hum Pathol. 2008 Oct;39(10):1411-9. doi: 10.1016/j.humpath.2008.06.025.
Joensuu H, Vehtari A, Riihimäki J, et al. Risk of recurrence of gastrointestinalstromal tumour after surgery: an analysis of pooled population-based cohorts. Lancet Oncol. 2012 Mar;13(3):265-74. doi: 10.1016/S1470-2045(11)70299-6.
Miettinen M, Sobin LH, Lasota J. Gastrointestinal stromal tumors of the stomach: a clinicopathologic, immunohistochemical, and molecular genetic study of 1765 cases with long-term follow-up. Am J Surg Pathol. 2005 Jan;29(1):52-68. doi: 10.1097/01.pas.0000146010.92933.de.
Miettinen M, Makhlouf H, Sobin LH et al. Gastrointestinal stromal tumors of the jejunum and ileum: a clinicopathologic, immunohistochemical, and molecular genetic study of 906 cases before imatinib with long-term follow-up. Am J Surg Pathol. 2006 Apr;30(4):477-89. doi: 10.1097/00000478-200604000-00008.
Kukar M, Kapil A, Papenfuss W, et al. Gastrointestinal stromal tumors (GISTs) at uncommon locations: a large population based analysis. J Surg Oncol. 2015 May;111(6):696-701. doi: 10.1002/jso.23873. Epub 2015 Jan 5.
Taniguchi M, Nishida T, Hirota S, et al. Effect of c-kit mutation on prognosis of gastrointestinal stromal tumors. Cancer Res. 1999 Sep 1;59(17):4297-300.
Burkill GJ, Badran M, Al-Muderis O, et al. Malignant gastrointestinal stromal tumor: distribution, imaging features, and pattern of metastatic spread. Radiology. 2003 Feb;226(2):527-32. doi: 10.1148/radiol.2262011880.
Güller U, Tarantino I, Cerny T, et al. Population-based SEER trend analysis of overall and cancer-specific survival in 5138 patients with gastrointestinal stromal tumor. BMC Cancer. 2015 Jul 30;15:557. doi: 10.1186/s12885-015-1554-9.
Boikos SA, Pappo AS, Killian JK, et al. Molecular Subtypes of KIT/PDGFRA Wild-Type Gastrointestinal Stromal Tumors: A Report From the National Institutes of Health Gastrointestinal Stromal Tumor Clinic. JAMA Oncol. 2016 Jul 1;2(7):922-8. doi: 10.1001/jamaoncol.2016.0256.
Joensuu H, Rutkowski P, Nishida T, et al. KIT and PDGFRA mutations and the risk of GI stromal tumor recurrence. J Clin Oncol. 2015 Feb 20;33(6):634-42. doi: 10.1200/JCO.2014.57.4970. Epub 2015 Jan 20.
