Evaluation of Benign Submucosal Tumors

  • Sanjay SalgadoEmail author
  • Marvin Ryou


Foregut submucosal tumors are intramural lesions of the gastrointestinal tract arising from beneath the histologic epithelium. Benign submucosal tumors consist of a variety of lesions, which can be subdivided into benign neoplasms, potentially malignant SMTs, and nonneoplastic masses – each with its own etiology, characteristic radiologic appearance, and tissue architecture. This chapter focuses on the diagnostic evaluation of these lesions, including immunohistochemical composition, preferred imaging, endoscopic ultrasonography findings, and initial management.


Submucosal tumors Endoscopic ultrasound Gastrointestinal stromal tumor Leiomyoma Schwannoma Lipoma Carcinoid Glomus tumor Granular cell tumors Duplication cyst Brunner gland hamartoma 


  1. 1.
    Abraham SC, Krasinskas AM, Hofstetter WL, et al. “Seedling” mesenchymal tumors (gastrointestinal stromal tumors and leiomyomas) are common incidental tumors of the esophagogastric junction. Am J Surg Pathol. 2007;31:1629–35. Scholar
  2. 2.
    Aoyama K, Kamio T, Hirano A, et al. Granular cell tumors: a report of six cases. World J Surg Oncol. 2012;10:204. Scholar
  3. 3.
    Chen K-B, Chen L. Glomus tumor in the stomach: a case report and review of the literature. Oncol Lett. 2014;7:1790–2. Scholar
  4. 4.
    Chou FF, Eng HL, Sheen-Chen SM. Smooth muscle tumors of the gastrointestinal tract: analysis of prognostic factors. Surgery. 1996;119:171–7.CrossRefGoogle Scholar
  5. 5.
    Davis GB, Blanchard DK, Hatch GF, et al. Tumors of the stomach. World J Surg. 2000;24:412–20.CrossRefGoogle Scholar
  6. 6.
    de la Serna-Higuera C, Pérez-Miranda M, Díez-Redondo P, et al. EUS-guided single-incision needle-knife biopsy: description and results of a new method for tissue sampling of subepithelial GI tumors (with video). Gastrointest Endosc. 2011;74:672–6. Scholar
  7. 7.
    DeWitt J, Emerson RE, Sherman S, et al. Endoscopic ultrasound-guided Trucut biopsy of gastrointestinal mesenchymal tumor. Surg Endosc. 2011;25:2192–202. Scholar
  8. 8.
    Eloubeidi MA, Cohn M, Cerfolio RJ, et al. Endoscopic ultrasound-guided fine-needle aspiration in the diagnosis of foregut duplication cysts: the value of demonstrating detached ciliary tufts in cyst fluid. Cancer. 2004;102:253–8. Scholar
  9. 9.
    Fanburg-Smith JC, Meis-Kindblom JM, Fante R, Kindblom LG. Malignant granular cell tumor of soft tissue: diagnostic criteria and clinicopathologic correlation. Am J Surg Pathol. 1998;22:779–94.CrossRefGoogle Scholar
  10. 10.
    Fletcher JA, Rubin BP. KIT mutations in GIST. Curr Opin Genet Dev. 2007;17:3–7. Scholar
  11. 11.
    Folpe AL, Fanburg-Smith JC, Miettinen M, Weiss SW. Atypical and malignant glomus tumors: analysis of 52 cases, with a proposal for the reclassification of glomus tumors. Am J Surg Pathol. 2001;25:1–12.CrossRefGoogle Scholar
  12. 12.
    Fujimaki E, Nakamura S, Sugai T, Takeda Y. Brunner’s gland adenoma with a focus of p53-positive atypical glands. J Gastroenterol. 2000;35:155–8.CrossRefGoogle Scholar
  13. 13.
    Gayed I, Vu T, Iyer R, et al. The role of 18F-FDG PET in staging and early prediction of response to therapy of recurrent gastrointestinal stromal tumors. J Nucl Med Off Publ Soc Nucl Med. 2004;45:17–21.Google Scholar
  14. 14.
    Godwin JD. Carcinoid tumors. An analysis of 2,837 cases. Cancer. 1975;36:560–9.CrossRefGoogle Scholar
  15. 15.
    Goh BKP, Chow PKH, Kesavan S, et al. Intraabdominal schwannomas: a single institution experience. J Gastrointest Surg Off J Soc Surg Aliment Tract. 2008;12:756–60. Scholar
  16. 16.
    Hedenbro JL, Ekelund M, Wetterberg P. Endoscopic diagnosis of submucosal gastric lesions. The results after routine endoscopy. Surg Endosc. 1991;5:20–3.CrossRefGoogle Scholar
  17. 17.
    Heinrich MC, Corless CL, Duensing A, et al. PDGFRA activating mutations in gastrointestinal stromal tumors. Science. 2003;299:708–10. Scholar
  18. 18.
    Hizawa K, Iwai K, Esaki M, et al. Endosonographic features of Brunner’s gland hamartomas which were subsequently resected endoscopically. Endoscopy. 2002;34:956–8. Scholar
  19. 19.
    Hoda KM, Rodriguez SA, Faigel DO. EUS-guided sampling of suspected GI stromal tumors. Gastrointest Endosc. 2009;69:1218–23. Scholar
  20. 20.
    Hou YY, Tan YS, Xu JF, et al. Schwannoma of the gastrointestinal tract: a clinicopathological, immunohistochemical and ultrastructural study of 33 cases. Histopathology. 2006;48:536–45. Scholar
  21. 21.
    Hwang JH, Rulyak SD, Kimmey MB, American Gastroenterological Association Institute. American Gastroenterological Association Institute technical review on the management of gastric subepithelial masses. Gastroenterology. 2006;130:2217–28. Scholar
  22. 22.
    Hwang JH, Saunders MD, Rulyak SJ, et al. A prospective study comparing endoscopy and EUS in the evaluation of GI subepithelial masses. Gastrointest Endosc. 2005;62:202–8.CrossRefGoogle Scholar
  23. 23.
    Ishikawa N, Fuchigami T, Kikuchi Y, et al. EUS for gastric lymphangioma. Gastrointest Endosc. 2000;52:798–800. Scholar
  24. 24.
    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. Scholar
  25. 25.
    Kim HS, Lee SY, Lee YD, et al. Gastric lymphangioma. J Korean Med Sci. 2001;16:229. Scholar
  26. 26.
    Kim JY, Lee JM, Kim KW, et al. Ectopic pancreas: CT findings with emphasis on differentiation from small gastrointestinal stromal tumor and leiomyoma. Radiology. 2009;252:92–100. Scholar
  27. 27.
    Kovacević I, Ljubicić N, Cupić H, et al. Helicobacter pylori infection in patients with Brunner’s gland adenoma. Acta Medica Croat Cas Hravatske Akad Med Znan. 2001;55:157–60.Google Scholar
  28. 28.
    Lee CK, Chung I-K, Lee S-H, et al. Endoscopic partial resection with the unroofing technique for reliable tissue diagnosis of upper GI subepithelial tumors originating from the muscularis propria on EUS (with video). Gastrointest Endosc. 2010;71:188–94. Scholar
  29. 29.
    Liu R, Adler DG. Duplication cysts: diagnosis, management, and the role of endoscopic ultrasound. Endosc Ultrasound. 2014;3:152–60. Scholar
  30. 30.
    Martín J, Poveda A, Llombart-Bosch A, et al. Deletions affecting codons 557-558 of the c-KIT gene indicate a poor prognosis in patients with completely resected gastrointestinal stromal tumors: a study by the Spanish Group for Sarcoma Research (GEIS). J Clin Oncol Off J Am Soc Clin Oncol. 2005;23:6190–8. Scholar
  31. 31.
    Matsui M, Goto H, Niwa Y, et al. Preliminary results of fine needle aspiration biopsy histology in upper gastrointestinal submucosal tumors. Endoscopy. 1998;30:750–5. Scholar
  32. 32.
    Matsushita M, Hajiro K, Okazaki K, Takakuwa H. Gastric inflammatory fibroid polyps: endoscopic ultrasonographic analysis in comparison with the histology. Gastrointest Endosc. 1997;46:53–7.CrossRefGoogle Scholar
  33. 33.
    Mayoral W, Salcedo JA, Montgomery E, Al-Kawas FH. Biliary obstruction and pancreatitis caused by Brunner’s gland hyperplasia of the ampulla of Vater: a case report and review of the literature. Endoscopy. 2000;32:998–1001. Scholar
  34. 34.
    McDermott FD, Heeney A, Courtney D, et al. Rectal carcinoids: a systematic review. Surg Endosc. 2014;28:2020–6. Scholar
  35. 35.
    Menon L, Buscaglia JM. Endoscopic approach to subepithelial lesions. Ther Adv Gastroenterol. 2014;7:123–30. Scholar
  36. 36.
    Messer J, Waye JD. The diagnosis of colonic lipomas–the naked fat sign. Gastrointest Endosc. 1982;28:186–8.CrossRefGoogle Scholar
  37. 37.
    Miettinen M, Lasota J. Gastrointestinal stromal tumors. Gastroenterol Clin N Am. 2013;42:399–415. Scholar
  38. 38.
    Miettinen M, Lasota J. Gastrointestinal stromal tumors: pathology and prognosis at different sites. Semin Diagn Pathol. 2006;23:70–83.CrossRefGoogle Scholar
  39. 39.
    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.CrossRefGoogle Scholar
  40. 40.
    Miettinen M, Wang Z-F, Lasota J. DOG1 antibody in the differential diagnosis of gastrointestinal stromal tumors: a study of 1840 cases. Am J Surg Pathol. 2009;33:1401–8. Scholar
  41. 41.
    Min KW. Small intestinal stromal tumors with skeinoid fibers. Clinicopathological, immunohistochemical, and ultrastructural investigations. Am J Surg Pathol. 1992;16:145–55.CrossRefGoogle Scholar
  42. 42.
    Minoda Y, Akahoshi K, Oya M, et al. Gastric glomus tumor diagnosed by endoscopic ultrasound-guided fine-needle aspiration biopsy: report of a case. Fukuoka Igaku Zasshi Hukuoka Acta Medica. 2014;105:105–9.PubMedGoogle Scholar
  43. 43.
    Mocellin S, Nitti D. Gastrointestinal carcinoid: epidemiological and survival evidence from a large population-based study (n = 25 531). Ann Oncol mdt. 2013; 377.
  44. 44.
    Modlin IM, Kidd M, Latich I, et al. Current status of gastrointestinal carcinoids. Gastroenterology. 2005;128:1717–51.CrossRefGoogle Scholar
  45. 45.
    Modlin IM, Lye KD, Kidd M. A 5-decade analysis of 13,715 carcinoid tumors. Cancer. 2003;97:934–59. Scholar
  46. 46.
    Murray MA, Kwan V, Williams SJ, Bourke MJ. Detachable nylon loop assisted removal of large clinically significant colonic lipomas. Gastrointest Endosc. 2005;61:756–9.CrossRefGoogle Scholar
  47. 47.
    Nilsson B, Bümming P, Meis-Kindblom JM, 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. Scholar
  48. 48.
    Pantanowitz L, Antonioli DA, Pinkus GS, et al. Inflammatory fibroid polyps of the gastrointestinal tract: evidence for a dendritic cell origin. Am J Surg Pathol. 2004;28:107–14.CrossRefGoogle Scholar
  49. 49.
    Pappo AS, Janeway KA. Pediatric gastrointestinal stromal tumors. Hematol Oncol Clin North Am. 2009;23:15–34, vii. Scholar
  50. 50.
    Park SH, Han JK, Kim TK, et al. Unusual gastric tumors: radiologic-pathologic correlation. Radiographics. 1999;19:1435–46. Scholar
  51. 51.
    Raju GS, Gomez G. Endoloop ligation of a large colonic lipoma: a novel technique. Gastrointest Endosc. 2005;62:988–90. Scholar
  52. 52.
    Rubin BP, Fletcher JA, Fletcher CDM. Molecular insights into the histogenesis and pathogenesis of gastrointestinal stromal tumors. Int J Surg Pathol. 2000;8:5–10.CrossRefGoogle Scholar
  53. 53.
    Scarpa M, Bertin M, Ruffolo C, et al. A systematic review on the clinical diagnosis of gastrointestinal stromal tumors. J Surg Oncol. 2008;98:384–92. Scholar
  54. 54.
    Scherübl H. Rectal carcinoids are on the rise: early detection by screening endoscopy. Endoscopy. 2009;41:162–5. Scholar
  55. 55.
    Schildhaus H-U, Cavlar T, Binot E, et al. Inflammatory fibroid polyps harbour mutations in the platelet-derived growth factor receptor alpha (PDGFRA) gene. J Pathol. 2008;216:176–82. Scholar
  56. 56.
    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. Scholar
  57. 57.
    Troller R, Soll C, Breitenstein S. Glomus tumour of the stomach. BMJ Case Rep. 2016, 2016:bcr2015214135.
  58. 58.
    Vassiliou I, Tympa A, Theodosopoulos T, et al. Gastric glomus tumor: a case report. World J Surg Oncol. 2010;8:19. Scholar
  59. 59.
    Walden DT, Marcon NE. Endoscopic injection and polypectomy for bleeding Brunner’s gland hamartoma: case report and expanded literature review. Gastrointest Endosc. 1998;47:403–7.CrossRefGoogle Scholar
  60. 60.
    Wardlaw R, Smith JW. Gastric carcinoid tumors. Ochsner J. 2008;8:191–6.PubMedPubMedCentralGoogle Scholar
  61. 61.
    Wiech T, Walch A, Werner M. Histopathological classification of nonneoplastic and neoplastic gastrointestinal submucosal lesions. Endoscopy. 2005;37:630–4. Scholar
  62. 62.
    Wildi SM, Hoda RS, Fickling W, et al. Diagnosis of benign cysts of the mediastinum: the role and risks of EUS and FNA. Gastrointest Endosc. 2003;58:362–8.PubMedGoogle Scholar
  63. 63.
    Zangara J, Kushner H, Drachenberg C, et al. Iron deficiency anemia due to a Brunner’s gland hamartoma. J Clin Gastroenterol. 1998;27:353–6.CrossRefGoogle Scholar
  64. 64.
    Zhong D-D, Wang C-H, Xu J-H, et al. Endoscopic ultrasound features of gastric schwannomas with radiological correlation: a case series report. World J Gastroenterol (WJG). 2012;18:7397–401. Scholar

Copyright information

© SAGES 2019

Authors and Affiliations

  1. 1.Division of Gastroenterology, Hepatology, and EndoscopyBrigham and Women’s HospitalBostonUSA

Personalised recommendations