Association Between Gastrointestinal Stromal Tumors and Other Malignancies: It Is Only a Matter of Time ? A Case Series and an Overview of Systematic Reviews

Abstract

Purpose

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.

Methods

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.

Results

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.

Conclusion

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.

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References

  1. 1.

    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.

    Article  PubMed  Google Scholar 

  2. 2.

    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.

    Article  PubMed  Google Scholar 

  3. 3.

    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.

    Article  PubMed  Google Scholar 

  4. 4.

    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.

    CAS  Article  PubMed  Google Scholar 

  5. 5.

    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.

    Article  PubMed  Google Scholar 

  6. 6.

    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.

    Article  PubMed  Google Scholar 

  7. 7.

    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.

    Article  PubMed  Google Scholar 

  8. 8.

    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.

    PubMed  Google Scholar 

  9. 9.

    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.

    Article  PubMed  Google Scholar 

  10. 10.

    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.

    Article  PubMed  Google Scholar 

  11. 11.

    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.

    Article  PubMed  Google Scholar 

  12. 12.

    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.

    Article  PubMed  Google Scholar 

  13. 13.

    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.

    Article  PubMed  Google Scholar 

  14. 14.

    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.

    Article  PubMed  PubMed Central  Google Scholar 

  15. 15.

    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.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  16. 16.

    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.

    Article  PubMed  PubMed Central  Google Scholar 

  17. 17.

    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.

    CAS  Article  PubMed  Google Scholar 

  18. 18.

    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.

    Article  PubMed  PubMed Central  Google Scholar 

  19. 19.

    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.

    Article  PubMed  Google Scholar 

  20. 20.

    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.

    Article  PubMed  Google Scholar 

  21. 21.

    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.

    Article  PubMed  PubMed Central  Google Scholar 

  22. 22.

    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.

    Article  Google Scholar 

  23. 23.

    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.

    Article  Google Scholar 

  24. 24.

    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.

    PubMed  Google Scholar 

  25. 25.

    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.

    Article  PubMed  Google Scholar 

  26. 26.

    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.

    Article  PubMed  Google Scholar 

  27. 27.

    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.

    CAS  Article  PubMed  Google Scholar 

  28. 28.

    The US National Cancer Institute’s Surveillance Epidemiology and End Results (SEER) Database. https://seer.cancer.gov. Online Accessed 14 Aug 2019.

  29. 29.

    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.

    Article  PubMed  PubMed Central  Google Scholar 

  30. 30.

    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.

    Article  PubMed  PubMed Central  Google Scholar 

  31. 31.

    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.

    Article  PubMed  Google Scholar 

  32. 32.

    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.

    Article  PubMed  Google Scholar 

  33. 33.

    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.

    CAS  Article  PubMed  Google Scholar 

  34. 34.

    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.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  35. 35.

    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.

    Article  PubMed  Google Scholar 

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Authors

Contributions

Mauro Podda: Study conception and design, literature search, acquisition, interpretation, and analysis of data; drafting and critically revising the article for important intellectual content; and final approval of the version to be published. Giulia Ferraro: Study conception and design, literature search, acquisition, interpretation, and analysis of data; drafting and critically revising the article for important intellectual content; and final approval of the version to be published. Salomone Di Saverio: Interpretation and analysis of data; drafting and critically revising the article for important intellectual content; and final approval of the version to be published. Alessandro Cois: Interpretation and analysis of data; critically revising the article for important intellectual content; and final approval of the version to be published. Oreste Nardello: Interpretation and analysis of data; critically revising the article for important intellectual content; and final approval of the version to be published. Gaetano Poillucci: Interpretation and analysis of data; critically revising the article for important intellectual content; and final approval of the version to be published. Marco Vito Marino: Interpretation and analysis of data; critically revising the article for important intellectual content; and final approval of the version to be published. Adolfo Pisanu: Study conception and design, literature search, interpretation and analysis of data; drafting and critically revising the article for important intellectual content; and final approval of the version to be published.

Corresponding author

Correspondence to Mauro Podda.

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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.

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An informed consent for enabling the sharing of research data was obtained from all individual patients included in the study.

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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

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Keywords

  • Gastrointestinal stromal tumors
  • Associated neoplasms
  • Synchronous malignancies
  • Secondary primary tumors
  • Overview of systematic reviews