Skip to main content
SpringerLink
Log in

Histology

  • Chapter
  • First Online:
Gastrointestinal Stromal Tumor

  • 497 Accesses

Abstract

The discovery of KIT gene mutation in gastrointestinal stromal tumor (GIST) has provided a paradigm shift in the classification, diagnosis, and molecular-targeted therapy of gastrointestinal mesenchymal tumors. According to a recent concept, GIST is considered a spindle or epithelioid cell neoplasm which basically expresses KIT protein and has KIT or platelet-derived growth factor receptor-alpha (PDGFRA) gene mutation. Exceptional cases are immunohistochemically negative or weakly positive for KIT (often with PDGFRA mutation), and minor subset has another gene alteration such as succinate dehydrogenase (SDH), RAS, NF1, or BRAF. There are growing evidences of phenotype–genotype correlations in GIST. Risk stratification based on mitotic counts, tumor size, and rupture is useful for the prognostication and management of patients with GIST. GISTs should be distinguished from various types of neoplasms such as leiomyoma, schwannoma, and inflammatory myofibroblastic tumor, although leiomyosarcoma of the gastrointestinal tract has become a very rare entity in the “KIT” era. Both histopathological procedures and molecular investigations are important for the evolution of diagnosis and treatment of GIST and mimics.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 99.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 129.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Hirota S, Isozaki K, Moriyama Y, et al. Gain-of-function mutations of c-kit in human gastrointestinal stromal tumors. Science. 1998;279:577–80.

    Article  CAS  Google Scholar 

  2. Miettinen M, Lasota J. Gastrointestinal stromal tumors: pathology and prognosis at different sites. Semin Diagn Pathol. 2006;23:70–83.

    Article  Google Scholar 

  3. Fletcher CD, Berman JJ, Corless C, et al. Diagnosis of gastrointestinal stromal tumors: a consensus approach. Hum Pathol. 2002;33:459–65.

    Article  Google Scholar 

  4. Miettinen MM, Corless CL, Debiec-Rychter M, et al. Gastrointestinal stromal tumours. In: Fletcher CDM, Bridge JA, Hogendoorn PCW, Mertens F, editors. WHO classification of tumours of soft tissue and bone. Lyon: IARC Press; 2013. p. 164–7.

    Google Scholar 

  5. Yamamoto H, Oda Y. Gastrointestinal stromal tumor: recent advances in pathology and genetics. Pathol Int. 2015;65:9–18.

    Article  CAS  Google Scholar 

  6. Liegl B, Hornick JL, Corless CL, Fletcher CD. Monoclonal antibody DOG1.1 shows higher sensitivity than KIT in the diagnosis of gastrointestinal stromal tumors, including unusual subtypes. Am J Surg Pathol. 2009;33:437–46.

    Article  Google Scholar 

  7. Lasota J, Miettinen M. KIT and PDGFRA mutations in gastrointestinal stromal tumors (GISTs). Semin Diagn Pathol. 2006;23:91–102.

    Article  Google Scholar 

  8. Corless CL. Gastrointestinal stromal tumors: what do we know now? Mod Pathol. 2014;27(Suppl 1):S1–16.

    Article  CAS  Google Scholar 

  9. Yamamoto H, Oda Y, Kawaguchi K, et al. c-kit and PDGFRA mutations in extragastrointestinal stromal tumor (gastrointestinal stromal tumor of the soft tissue). Am J Surg Pathol. 2004;28:479–88.

    Article  Google Scholar 

  10. Yamamoto H, Kojima A, Nagata S, Tomita Y, Takahashi S, Oda Y. KIT-negative gastrointestinal stromal tumor of the abdominal soft tissue: a clinicopathologic and genetic study of 10 cases. Am J Surg Pathol. 2011;35:1287–95.

    Article  Google Scholar 

  11. Miettinen M, Sobin LH, Lasota J. Gastrointestinal stromal tumors presenting as omental masses – a clinicopathologic analysis of 95 cases. Am J Surg Pathol. 2009;33:1267–75.

    Article  Google Scholar 

  12. Yamamoto H, Miyamoto Y, Nishihara Y, et al. Primary gastrointestinal stromal tumor of the liver with PDGFRA gene mutation. Hum Pathol. 2010;41:605–9.

    Article  CAS  Google Scholar 

  13. Long KB, Butrynski JE, Blank SD, et al. Primary extragastrointestinal stromal tumor of the pleura: report of a unique case with genetic confirmation. Am J Surg Pathol. 2010;34:907–12.

    Article  Google Scholar 

  14. Sakurai S, Hishima T, Takazawa Y, et al. Gastrointestinal stromal tumors and KIT-positive mesenchymal cells in the omentum. Pathol Int. 2001;51:524–31.

    Article  CAS  Google Scholar 

  15. Doyle LA, Hornick JL. Gastrointestinal stromal tumours: from KIT to succinate dehydrogenase. Histopathology. 2014;64:53–67.

    Article  Google Scholar 

  16. Miettinen M, Wang ZF, Sarlomo-Rikala M, Osuch C, Rutkowski P, Lasota J. Succinate dehydrogenase-deficient GISTs: a clinicopathologic, immunohistochemical, and molecular genetic study of 66 gastric GISTs with predilection to young age. Am J Surg Pathol. 2011;35:1712–21.

    Article  Google Scholar 

  17. 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;2:922–8.

    Article  Google Scholar 

  18. Janeway KA, Kim SY, Lodish M, et al. Defects in succinate dehydrogenase in gastrointestinal stromal tumors lacking KIT and PDGFRA mutations. Proc Natl Acad Sci U S A. 2011;108:314–8.

    Article  CAS  Google Scholar 

  19. Andersson J, Bümming P, Meis-Kindblom JM, et al. Gastrointestinal stromal tumors with KIT exon 11 deletions are associated with poor prognosis. Gastroenterology. 2006;130:1573–81.

    Article  CAS  Google Scholar 

  20. Heinrich MC, Corless CL, Demetri GD, et al. Kinase mutations and imatinib response in patients with metastatic gastrointestinal stromal tumor. J Clin Oncol. 2003;21:4342–9.

    Article  CAS  Google Scholar 

  21. Antonescu CR. The GIST paradigm: lessons for other kinase-driven cancers. J Pathol. 2011;223:251–61.

    Article  CAS  Google Scholar 

  22. 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.

    Article  Google Scholar 

  23. Rege TA, Wagner AJ, Corless CL, Heinrich MC, Hornick JL. “Pediatric-type” gastrointestinal stromal tumors in adults: distinctive histology predicts genotype and clinical behavior. Am J Surg Pathol. 2011;35:495–504.

    Article  Google Scholar 

  24. Dwight T, Benn DE, Clarkson A, et al. Loss of SDHA expression identifies SDHA mutations in succinate dehydrogenase-deficient gastrointestinal stromal tumors. Am J Surg Pathol. 2013;37:226–33.

    Article  Google Scholar 

  25. Pantaleo MA, Astolfi A, Urbini M, et al. Analysis of all subunits, SDHA, SDHB, SDHC, SDHD, of the succinate dehydrogenase complex in KIT/PDGFRA wild-type GIST. Eur J Hum Genet. 2014;22:32–9.

    Article  CAS  Google Scholar 

  26. Mason EF, Hornick JL. Conventional risk stratification fails to predict progression of succinate dehydrogenase-deficient gastrointestinal stromal tumors: a clinicopathologic study of 76 cases. Am J Surg Pathol. 2016;40:1616–21.

    Article  Google Scholar 

  27. Carney JA, Sheps SG, Go VL, Gordon H. The triad of gastric leiomyosarcoma, functioning extra-adrenal paraganglioma and pulmonary chondroma. N Engl J Med. 1977;296:1517–8.

    Article  CAS  Google Scholar 

  28. Carney JA, Stratakis CA. Familial paraganglioma and gastric stromal sarcoma: a new syndrome distinct from the Carney triad. Am J Med Genet. 2002;108:132–9.

    Article  Google Scholar 

  29. Stratakis CA, Carney JA. The triad of paragangliomas, gastric stromal tumours and pulmonary chondromas (Carney triad), and the dyad of paragangliomas and gastric stromal sarcomas (Carney-Stratakis syndrome): molecular genetics and clinical implications. J Intern Med. 2009;266:43–52.

    Article  CAS  Google Scholar 

  30. Antonescu CR. Gastrointestinal stromal tumor (GIST) pathogenesis, familial GIST, and animal models. Semin Diagn Pathol. 2006;23:63–9.

    Article  Google Scholar 

  31. Patil DT, Rubin BP. Gastrointestinal stromal tumor: advances in diagnosis and management. Arch Pathol Lab Med. 2011;135:1298–310.

    Article  CAS  Google Scholar 

  32. Miettinen M, Fetsch JF, Sobin LH, Lasota J. Gastrointestinal stromal tumors in patients with neurofibromatosis 1: a clinicopathologic and molecular genetic study of 45 cases. Am J Surg Pathol. 2006;30:90–6.

    Article  Google Scholar 

  33. Pantaleo MA, Nannini M, Corless CL, Heinrich MC. Quadruple wild-type (WT) GIST: defining the subset of GIST that lacks abnormalities of KIT, PDGFRA, SDH, or RAS signaling pathways. Cancer Med. 2015;4:101–3.

    Article  CAS  Google Scholar 

  34. Joensuu H. Risk stratification of patients diagnosed with gastrointestinal stromal tumor. Hum Pathol. 2008;39:1411–9.

    Article  Google Scholar 

  35. Joensuu H, Vehtari A, Riihimäki J, et al. Risk of recurrence of gastrointestinal stromal tumour after surgery: an analysis of pooled population-based cohorts. Lancet Oncol. 2012;13:265–74.

    Article  Google Scholar 

  36. ESMO/European Sarcoma Network Working Group. Gastrointestinal stromal tumours: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2014;25(Suppl 3):iii21–6.

    Article  Google Scholar 

  37. Agaimy A, Haller F, Gunawan B, Wünsch PH, Füzesi L. Distinct biphasic histomorphological pattern in gastrointestinal stromal tumours (GISTs) with common primary mutations but divergent molecular cytogenetic progression. Histopathology. 2009;54:295–302.

    Article  Google Scholar 

  38. Yamamoto H, Kojima A, Miyasaka Y, et al. Prognostic impact of blood vessel invasion in gastrointestinal stromal tumor of the stomach. Hum Pathol. 2010;41:1422–30.

    Article  Google Scholar 

  39. Antonescu CR, Romeo S, Zhang L, et al. 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. Am J Surg Pathol. 2013;37:385–92.

    Article  Google Scholar 

  40. Choi H, Charnsangavej C, Faria SC, et al. Correlation of computed tomography and positron emission tomography in patients with metastatic gastrointestinal stromal tumor treated at a single institution with imatinib mesylate: proposal of new computed tomography response criteria. J Clin Oncol. 2007;25:1753–9.

    Article  Google Scholar 

  41. Antonescu CR, Besmer P, Guo T, et al. Acquired resistance to imatinib in gastrointestinal stromal tumor occurs through secondary gene mutation. Clin Cancer Res. 2005;11:4182–90.

    Article  CAS  Google Scholar 

  42. Miettinen M, Sarlomo-Rikala M, Sobin LH, Lasota J. Esophageal stromal tumors: a clinicopathologic, immunohistochemical, and molecular genetic study of 17 cases and comparison with esophageal leiomyomas and leiomyosarcomas. Am J Surg Pathol. 2000;24:211–22.

    Article  CAS  Google Scholar 

  43. Miettinen M, Kopczynski J, Makhlouf HR, et al. Gastrointestinal stromal tumors, intramural leiomyomas, and leiomyosarcomas in the duodenum: a clinicopathologic, immunohistochemical, and molecular genetic study of 167 cases. Am J Surg Pathol. 2003;27:625–41.

    Article  Google Scholar 

  44. Deshpande A, Nelson D, Corless CL, et al. Leiomyoma of the gastrointestinal tract with interstitial cells of Cajal: a mimic of gastrointestinal stromal tumor. Am J Surg Pathol. 2014;38:72–7.

    Article  Google Scholar 

  45. Heidet L, Boye E, Cai Y, et al. Somatic deletion of the 5′ ends of both the COL4A5 and COL4A6 genes in a sporadic leiomyoma of the esophagus. Am J Pathol. 1998;152:673–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  46. Yamamoto H, Handa M, Tobo T, et al. Clinicopathological features of primary leiomyosarcoma of the gastrointestinal tract following recognition of gastrointestinal stromal tumours. Histopathology. 2013;63:194–207.

    Article  Google Scholar 

  47. Miettinen M, Sobin LH, Lasota J. True smooth muscle tumors of the small intestine: a clinicopathologic, immunohistochemical, and molecular genetic study of 25 cases. Am J Surg Pathol. 2009;33:430–6.

    Article  Google Scholar 

  48. Lasota J, Wasag B, Dansonka-Mieszkowska A, et al. Evaluation of NF2 and NF1 tumor suppressor genes in distinctive gastrointestinal nerve sheath tumors traditionally diagnosed as benign schwannomas: a study of 20 cases. Lab Investig. 2003;83:1361–71.

    Article  CAS  Google Scholar 

  49. Yamamoto H, Kohashi K, Tsuneyoshi M, Oda Y. Heterozygosity loss at 22q and lack of INI1 gene mutation in gastrointestinal stromal tumor. Pathobiology. 2011;78:132–9.

    Article  CAS  Google Scholar 

  50. Gleason BC, Hornick JL. Inflammatory myofibroblastic tumours: where are we now? J Clin Pathol. 2008;61:428–37.

    Article  CAS  Google Scholar 

  51. Coffin CM, Fletcher JA. Inflammatory myofibroblastic tumor. In: Fletcher CDM, Bridge JA, Hogendoorn PCW, Mertens F, editors. WHO classification of tumours of soft tissue and bone. Lyon: IARC Press; 2013. p. 83–4.

    Google Scholar 

  52. Mano H. ALKoma: a cancer subtype with a shared target. Cancer Discov. 2012;2:495–502.

    Article  CAS  Google Scholar 

  53. Yamamoto H, Yoshida A, Taguchi K, et al. ALK, ROS1 and NTRK3 gene rearrangements in inflammatory myofibroblastic tumours. Histopathology. 2016;69:72–83.

    Article  Google Scholar 

  54. Goldblum JR, Fletcher JA. Desmoid-type fibromatosis. In: Fletcher CDM, Bridge JA, Hogendoorn PCW, Mertens F, editors. WHO classification of tumours of soft tissue and bone. Lyon: IARC Press; 2013. p. 72–3.

    Google Scholar 

  55. Lucas DR, Al-Abbadi M, Tabaczka P, et al. c-Kit expression in desmoid fibromatosis. Comparative immunohistochemical evaluation of two commercial antibodies. Am J Clin Pathol. 2003;119:339–45.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pathology, Kyushu University Hospital, Fukuoka, Japan

    Hidetaka Yamamoto

  2. Department of Anatomic Pathology, Kyushu University Graduate School of Medicine, Fukuoka, Japan

    Hidetaka Yamamoto

Authors
  1. Hidetaka Yamamoto
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hidetaka Yamamoto .

Editor information

Editors and Affiliations

  1. Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Osaka, Japan

    Yukinori Kurokawa

  2. Department of Cancer Chemotherapy, Hokkaido University Hospital Cancer Center, Sapporo, Hokkaido, Japan

    Yoshito Komatsu

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer Nature Singapore Pte Ltd.

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Yamamoto, H. (2019). Histology. In: Kurokawa, Y., Komatsu, Y. (eds) Gastrointestinal Stromal Tumor. Springer, Singapore. https://doi.org/10.1007/978-981-13-3206-7_2

Download citation

  • DOI: https://doi.org/10.1007/978-981-13-3206-7_2

  • Published:

  • Publisher Name: Springer, Singapore

  • Print ISBN: 978-981-13-3205-0

  • Online ISBN: 978-981-13-3206-7

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation