Little is known about the sporadic coincidence of gastrointestinal stromal tumors (GISTs) with second primary tumors (SPTs). The aim of this study is to clarify if there is a clinicopathologic correlation responsible for the synchronous or metachronous occurrence of SPTs in GIST patients.
We carried out a single-center, retrospective analysis on patients with GISTs surgically treated at our institution from January 2019 to June 2019. Two groups of patients were identified: isolated GIST (group A) and GIST associated with SPT (group B). A meta-review was conducted with the aim to examine the published systematic reviews that included studies assessing the SPT risk in GIST patients.
Thirty-nine patients were surgically treated for GIST during the study period, with seven (17.9%) of them having other SPTs. SPTs were most frequent in the colon. Group A patients had a lower mean age at initial diagnosis (56.8 ± 15.2 vs. 73.4 ± 16.6, P = 0.012). No statistically significant difference was found between the two groups in terms of tumor location, mitotic index, Ki-67 expression, risk classification, and imatinib therapy. The overview showed that the cumulative prevalence rate of SPTs ranged from 9.3 to 18.0%. SPTs were more frequent in the gastrointestinal tract (37.9–95.0%), followed by the genitourinary tract.
GIST patients under our care experienced a 17.9% overall risk of developing SPTs with different histology. When comparing patients with isolated GIST and patients with GIST and SPT, age was the only variable significantly related to the development of other neoplasms. However, the potential non-random association and causal relationship between GISTs and SPTs remain to be investigated.
This is a preview of subscription content, access via your institution.
Buy single article
Instant access to the full article PDF.
Tax calculation will be finalised during checkout.
Subscribe to journal
Immediate online access to all issues from 2019. Subscription will auto renew annually.
Tax calculation will be finalised during checkout.
Mazzola P, Spitale A, Banfi S, Mazzucchelli L, Frattini M, Bordoni A. Epidemiology and molecular biology of gastrointestinal stromal tumors (GISTs): a population-based study in the South of Switzerland, 1999-2005. Histol Histopathol. 2008;23:1379–86. https://doi.org/10.14670/HH-23.1379.
Miettinen M, Lasota J, Sobin LH. Gastrointestinal stromal tumors of the stomach in children and young adults: a clinicopathologic, immunohistochemical, and molecular genetic study of 44 cases with long-term follow-up and review of the literature. Am J Surg Pathol. 2005;29:1373–81. https://doi.org/10.1097/01.pas.0000172190.79552.8b.
Søreide K, Sandvik OM, Søreide JA, Giljaca V, Jureckova A, Bulusu VR. Global epidemiology of gastrointestinal stromal tumours (GIST): a systematic review of population-based cohort studies. Cancer Epidemiol. 2016;40:39–46. https://doi.org/10.1016/j.canep.2015.10.031.
Miettinen M, Lasota J. Gastrointestinal stromal tumors—definition, clinical, histological, immunohistochemical, and molecular genetic features and differential diagnosis. Virchows Arch. 2001;438:1–12. https://doi.org/10.1007/s004280000338.
Miettinen M, Majidi M, Lasota J. Pathology and diagnostic criteria of gastrointestinal stromal tumors (GISTs): a review. Eur J Cancer. 2002;38(Suppl 5):S39–51. https://doi.org/10.1016/S0959-8049(02)80602-5.
Tran T, Davila JA, El-Serag HB. The epidemiology of malignant gastrointestinal stromal tumors: an analysis of 1,458 cases from 1992 to 2000. Am J Gastroenterol. 2005;100:162–8. https://doi.org/10.1111/j.1572-0241.2005.40709.x.
Agaimy A, Wünsch PH, Sobin LH, Lasota J, Miettinen M. Occurrence of other malignancies in patients with gastrointestinal stromal tumors. Semin Diagn Pathol. 2006;23:120–9. https://doi.org/10.1053/j.semdp.2006.09.004.
Machado-Aranda D, Malamet M, Chang YJ, Jacobs MJ, Ferguson L, Silapaswan S, et al. Prevalence and management of gastrointestinal stromal tumors. Am Surg. 2009;75:55–60.
Dematteo RP, Gold JS, Saran L, Gönen M, Liau KH, Maki RG, et al. Tumor mitotic rate, size, and location independently predict recurrence after resection of primary gastrointestinal stromal tumor (GIST). Cancer. 2008;112:608–15. https://doi.org/10.1002/cncr.23199.
Nilsson B, Bümming P, Meis-Kindblom JM, Odén 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;103:821–9. https://doi.org/10.1002/cncr.20862.
Fernández JA, Olivares V, Gómez-Ruiz AJ, Ferri B, Frutos MD, Soria T, et al. Additional malignancies in patients with gastrointestinal stromal tumors (GIST): incidence, pathology and prognosis according to a time of occurrence-based classification. Clin Transl Oncol. 2019;21:646–55. https://doi.org/10.1007/s12094-018-1966-5.
Liszka Ł, Zielińska-Pajak E, Pajak J, Gołka D, Huszno J. Coexistence of gastrointestinal stromal tumors with other neoplasms. J Gastroenterol. 2007;42:641–9. https://doi.org/10.1007/s00535-007-2082-4.
Gonçalves R, Linhares E, Albagli R, Valadão M, Vilhena B, Romano S, et al. Occurrence of other tumors in patients with GIST. Surg Oncol. 2010;19:e140–3. https://doi.org/10.1016/j.suronc.2010.06.004.
Mendonca SJ, Sanchez A, Blum KA, Ghanaat M, Kashan MY, Benfante N, et al. The association of renal cell carcinoma with gastrointestinal stromal tumors. J Surg Oncol. 2018;117:1716–20. https://doi.org/10.1002/jso.25080.
Kramer K, Wolf S, Mayer B, Schmidt SA, Agaimy A, Henne-Bruns D, et al. Frequence, spectrum and prognostic impact of additional malignancies in patients with gastrointestinal stromal tumors. Neoplasia. 2015;17:134–40. https://doi.org/10.1016/j.neo.2014.12.001.
Du J, Shen N, He HS, Fu XL, Wang JZ, Mao CZ. Synchronous gastrointestinal cancer and gastrointestinal stromal tumors: a single-institution experience. World J Surg Oncol. 2016;14:130. https://doi.org/10.1186/s12957-016-0882-9.
Giuliani J, Bonetti A. The occurrence of gastrointestinal stromal tumors and second malignancies. J Gastrointest Cancer. 2015;46:408–12. https://doi.org/10.1007/s12029-015-9759-3.
Hechtman JF, DeMatteo R, Nafa K, Chi P, Arcila ME, Dogan S, et al. Additional primary malignancies in patients with gastrointestinal stromal tumor (GIST): a clinicopathologic study of 260 patients with molecular analysis and review of the literature. Ann Surg Oncol. 2015;22:2633–9. https://doi.org/10.1245/s10434-014-4332-z.
Catena F, Di Battista M, Ansaloni L, Pantaleo M, Fusaroli P, Di Scioscio V, et al. Microscopic margins of resection influence primary gastrointestinal stromal tumor survival. Onkologie. 2012;35:645–8. https://doi.org/10.1159/000343585.
Miettinen M, Lasota J. Gastrointestinal stromal tumors: pathology and prognosis at different sites. Semin Diagn Pathol. 2006;23(2):70–83. https://doi.org/10.1053/j.semdp.2006.09.001.
Kung J, Chiappelli F, Cajulis OO, Avezova R, Kossan G, Chew L, et al. From systematic reviews to clinical recommendations for evidence-based health care: validation of revised assessment of multiple systematic reviews (R-AMSTAR) for grading of clinical relevance. Open Dent J. 2010;4:84–91. https://doi.org/10.2174/1874210601004020084.
Fernández Hernández JÁ, Olivares Ripoll V, Parrilla Paricio P. Asociación de tumores del estroma gastrointestinal con otros tumores primarios. Propuesta de una nueva clasificación. Med Clín. 2016;147:405–9. https://doi.org/10.1016/j.medcli.2016.06.006.
Núñez-Martín R, Cubedo Cervera R, Provencio Pulla M. Gastrointestinal stromal tumour and second tumours: a literature review. Med Clin (Barc). 2017;149:345–50. https://doi.org/10.1016/j.medcli.2017.06.010.
Diamantis A, Bouliaris K, Christodoulidis G, Vasdeki D, Perivoliotis K, Tepetes K. Gastrointestinal stromal tumors and synchronous intra-abdominal malignancies: review of the literature. J BUON. 2018;23:1573–9.
Petrelli F, Tomasello G, Barni S, Varricchio A, Costanzo A, Rampulla V, et al. Risk of second primary tumors in GIST survivors: a systematic review and meta-analysis. Surg Oncol. 2019;29:64–70. https://doi.org/10.1016/j.suronc.2019.03.001.
Giuliani J, Marzola M, Indelli M, Aliberti C, Sartori S, Lanza G, et al. Gastrointestinal stromal tumors and other malignancies: a case series. J Gastrointest Cancer. 2012;43:634–7. https://doi.org/10.1007/s12029-012-9371-8.
Maiorana A, Fante R, Maria Cesinaro A, Adriana Fano R. Synchronous occurrence of epithelial and stromal tumors in the stomach: a report of 6 cases. Arch Pathol Lab Med. 2000;124:682–6. https://doi.org/10.1043/0003-9985(2000)124%3C0682:SOOEAS%3E2.0.CO;2.
The US National Cancer Institute’s Surveillance Epidemiology and End Results (SEER) Database. https://seer.cancer.gov. Online Accessed 14 Aug 2019.
Wronski M, Ziarkiewicz-Wroblewska B, Gornicka B, Cebulski W, Slodkowski M, Wasiutynski A, et al. Synchronous occurrence of gastrointestinal stromal tumors and other primary gastrointestinal neoplasms. World J Gastroenterol. 2006;12:5360–2. https://doi.org/10.3748/wjg.v12.i33.5360.
Lin M, Lin JX, Huang CM, Zheng CH, Li P, Xie JW, et al. Prognostic analysis of gastric gastrointestinal stromal tumor with synchronous gastric cancer. World J Surg Oncol. 2014;12:25. https://doi.org/10.1186/1477-7819-12-25.
Vassos N, Agaimy A, Hohenberger W, Croner RS. Coexistence of gastrointestinal stromal tumours (GIST) and malignant neoplasms of different origin: prognostic implications. Int J Surg. 2014;12:371–7. https://doi.org/10.1016/j.ijsu.2014.03.004.
Ferreira SS, Werutsky G, Toneto MG, Alves JM, Piantá CD, Breunig RC, et al. Synchronous gastrointestinal stromal tumors (GIST) and other primary cancers: case series of a single institution experience. Int J Surg. 2010;8:314–7. https://doi.org/10.1016/j.ijsu.2010.03.008.
Ponti G, Luppi G, Martorana D, Rossi G, Losi L, Bertolini F, et al. Gastrointestinal stromal tumor and other primary metachronous or synchronous neoplasms as a suspicion criterion for syndromic setting. Oncol Rep. 2010;23:437–44. https://doi.org/10.3892/or_00000653.
Kanda T. Criminal or bystander: imatinib and second primary malignancy in GIST patients. Chin J Cancer Res. 2013;25:490–2. https://doi.org/10.3978/j.issn.1000-9604.2013.10.15.
Kaffes A, Hughes L, Hollinshead J, Katelaris P. Synchronous primary adenocarcinoma, mucosa-associated lymphoid tissue lymphoma and a stromal tumor in a Helicobacter pylori-infected stomach. J Gastroenterol Hepatol. 2002;17:1033–6. https://doi.org/10.1046/j.1440-1746.2002.02649.x.
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors
Conflicts of Interest
The authors declare that they have no conflict of interest.
All procedures performed in this study were in accordance with the ethical standards of the 1964 Helsinki declaration and its later amendments or comparable ethical standards. This study was conducted after the approval of the Institutional Ethics Review Board of the Azienda Ospedaliero-Universitaria di Cagliari, Cagliari University Hospital “D. Casula,” Cagliari, Italy.
An informed consent for enabling the sharing of research data was obtained from all individual patients included in the study.
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
About this article
Cite this article
Podda, M., Ferraro, G., Di Saverio, S. et al. Association Between Gastrointestinal Stromal Tumors and Other Malignancies: It Is Only a Matter of Time ? A Case Series and an Overview of Systematic Reviews. J Gastrointest Canc 51, 914–924 (2020). https://doi.org/10.1007/s12029-019-00324-8
- Gastrointestinal stromal tumors
- Associated neoplasms
- Synchronous malignancies
- Secondary primary tumors
- Overview of systematic reviews