Advertisement

Gastrointestinal Neuroendocrine Tumors

  • Shih-Fan Kuan
Chapter
Part of the Molecular Pathology Library book series (MPLB, volume 3)

Abstract

Gastrointestinal neuroendocrine tumors (GI-NETs) arise from diffuse neuroendocrine system cells, which express neuroendocrine markers, produce certain peptide or amine hormones, and contain dense core secretory granules. NETs still retain these features after the transformation of normal neuroendocrine cells.

Keywords

Neuroendocrine Tumor Carcinoid Syndrome Typical Carcinoid Large Cell Neuroendocrine Carcinoma Goblet Cell Carcinoid 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. 1.
    Dayal Y. The neuroendocrine cell system of the gut and pancreas: introduction and historical perspectives. In: Dayal Y, ed. CRC Press; 1991:1–32.Google Scholar
  2. 2.
    DeLellis RA: The neuroendocrine system and its tumors: an overview, Am J Clin Pathol. 2001; 115 suppl:S5-S16.Google Scholar
  3. 3.
    Soga J, Tazawa K. Pathologic analysis of carcinoids. Histologic reevaluation of 62 cases. Cancer. 1971;28:990–998.CrossRefPubMedGoogle Scholar
  4. 4.
    Smith DM Jr, Haggitt RC. A comparative study of generic stains for carcinoid secretory granules. Am J Surg Pathol. 1983;7:61–68.CrossRefPubMedGoogle Scholar
  5. 5.
    Fahrenkamp AG, Wibbeke C, Winde G, et al. Immunohistochemical distribution of chromogranins A and B and secretogranin II in neuroendocrine tumours of the gastrointestinal tract. Virchows Arch. 1995;426:361–367.CrossRefPubMedGoogle Scholar
  6. 6.
    Taupenot L, Harper KL, O’Connor DT. The chromogranin-secretogranin family [see comment]. N Engl J Med. 2003;348:1134–1149.CrossRefPubMedGoogle Scholar
  7. 7.
    Wiedenmann B, Franke WW, Kuhn C, Moll R, Gould VE. Synaptophysin: a marker protein for neuroendocrine cells and neoplasms. Proc Natl Acad Sci USA. 1986;83:3500–3504.CrossRefPubMedGoogle Scholar
  8. 8.
    Rode J, Dhillon AP, Doran JF, Jackson P, Thompson RJ. PGP 9.5, a new marker for human neuroendocrine tumours. Histo­pathology. 1985;9:147–158.CrossRefPubMedGoogle Scholar
  9. 9.
    Schmechel D, Marangos PJ, Brightman M. Neurone-specific enolase is a molecular marker for peripheral and central neuroendocrine cells. Nature. 1978;276:834–836.CrossRefPubMedGoogle Scholar
  10. 10.
    Williams ED, Sandler M. The classification of carcinoid tumours. Lancet. 1963;1:238–239.CrossRefPubMedGoogle Scholar
  11. 11.
    van Bogaert LJ. The diffuse endocrine system and derived tumours. Histological and histochemical characteristics. Acta Histochem. 1982;70:122–129.PubMedGoogle Scholar
  12. 12.
    Jaffee IM, Rahmani M, Singhal MG, Younes M. Expression of the intestinal transcription factor CDX2 in carcinoid tumors is a marker of midgut origin. Arch Pathol Lab Med. 2006;130:1522–1526.PubMedGoogle Scholar
  13. 13.
    Rindi G, Leiter AB, Kopin AS, Bordi C, Solcia E. The “normal” endocrine cell of the gut: changing concepts and new evidences. Ann N Y Acad Sci. 2004;1014:1–12.CrossRefPubMedGoogle Scholar
  14. 14.
    DeLellis RA, Dayal Y, Wolfe HJ. Carcinoid tumors. Changing concepts and new perspectives. Am J Surg Pathol. 1984;8:295–300.CrossRefPubMedGoogle Scholar
  15. 15.
    Solcia E, Kloppel G, Sobin LH. Endocrine tumors of the gastrointestinal tract. In: Solcia E, Kloppel G, Sobin LH, eds. New York: Springer-Verlag; 2000:61–68.Google Scholar
  16. 16.
    Kloppel G, Perren A, Heitz PU. The gastroenteropancreatic neuroendocrine cell system and its tumors: the WHO classification. Ann N Y Acad Sci. 2004;1014:13–27.CrossRefPubMedGoogle Scholar
  17. 17.
    Rindi G, Kloppel G, Alhman H, et al. TNM staging of foregut (neuro)endocrine tumors: a consensus proposal including a grading system. Virchows Arch. 2006;449:395–401.CrossRefPubMedGoogle Scholar
  18. 18.
    Rindi G, Kloppel G, Couvelard A, et al. TNM staging of midgut and hindgut (neuro) endocrine tumors: a consensus proposal including a grading system. Virchows Arch. 2007;451:757–762.CrossRefPubMedGoogle Scholar
  19. 19.
    Modlin IM, Lye KD, Kidd M. A 5-decade analysis of 13,715 carcinoid tumors. Cancer. 2003;97:934–959.CrossRefPubMedGoogle Scholar
  20. 20.
    Rindi G, Villanacci V, Ubiali A. Biological and molecular aspects of gastroenteropancreatic neuroendocrine tumors. Digestion. 2000;62(suppl 1):19–26.CrossRefPubMedGoogle Scholar
  21. 21.
    Chandrasekharappa SC, Guru SC, Manickam P, et al. Positional cloning of the gene for multiple endocrine neoplasia-type 1. Science. 1997;276:404–407.CrossRefPubMedGoogle Scholar
  22. 22.
    Bordi C, Corleto VD, Azzoni C, et al. The antral mucosa as a new site for endocrine tumors in multiple endocrine neoplasia type 1 and Zollinger-Ellison syndromes. J Clin Endocrinol Metab. 2001;86:2236–2242.CrossRefPubMedGoogle Scholar
  23. 23.
    Pipeleers-Marichal M, Somers G, Willems G, et al. Gastrinomas in the duodenums of patients with multiple endocrine neoplasia type 1 and the Zollinger-Ellison syndrome [see comment]. N Engl J Med. 1990;322:723–727.CrossRefPubMedGoogle Scholar
  24. 24.
    Klein A, Clemens J, Cameron J. Periampullary neoplasms in von Recklinghausen’s disease. Surgery. 1989;106:815–819.PubMedGoogle Scholar
  25. 25.
    Kheir SM, Halpern NB. Paraganglioma of the duodenum in association with congenital neurofibromatosis. Possible relationship. Cancer. 1984;53:2491–2496.CrossRefPubMedGoogle Scholar
  26. 26.
    Lollgen RM, Hessman O, Szabo E, Westin G, Akerstrom G. Chromosome 18 deletions are common events in classical midgut carcinoid tumors. Int J Cancer. 2001;92:812–815.CrossRefPubMedGoogle Scholar
  27. 27.
    D’Adda T, Candidus S, Denk H, Bordi C, Hofler H. Gastric neuroendocrine neoplasms: tumour clonality and malignancy-associated large X-chromosomal deletions. J Pathol. 1999;189:394–401.CrossRefPubMedGoogle Scholar
  28. 28.
    Higham AD, Bishop LA, Dimaline R, et al. Mutations of RegIalpha are associated with enterochromaffin-like cell tumor development in patients with hypergastrinemia [see comment]. Gastroenterology. 1999;116:1310–1318.CrossRefPubMedGoogle Scholar
  29. 29.
    Modlin IM, Sandor A. An analysis of 8305 cases of carcinoid tumors. Cancer. 1997;79:813–829.CrossRefPubMedGoogle Scholar
  30. 30.
    Hoang MP, Hobbs CM, Sobin LH, Albores-Saavedra J. Carcinoid tumor of the esophagus: a clinicopathologic study of four cases. Am J Surg Pathol. 2002;26:517–522.CrossRefPubMedGoogle Scholar
  31. 31.
    Ready AR, Soul JO, Newman J, Matthews HR. Malignant carcinoid tumour of the oesophagus [see comment]. Thorax. 1989;44:594–596.CrossRefPubMedGoogle Scholar
  32. 32.
    Voillemot N, Potet F, Mary JY, Lewin MJ. Gastrin cell distribution in normal human stomachs and in patients with Zollinger-Ellison syndrome. Gastroenterology. 1978;75:61–65.PubMedGoogle Scholar
  33. 33.
    Modlin IM, Nangia AK. The pathobiology of the human enterochromaffin-like cell. Yale J Biol Med. 1992;65:775-792. discussion 827–779.PubMedGoogle Scholar
  34. 34.
    Freston JW, Borch K, Brand SJ, et al. Effects of hypochlorhydria and hypergastrinemia on structure and function of gastrointestinal cells. A review and analysis. Dig Dis Sci. 1995;40:50S-62S.CrossRefPubMedGoogle Scholar
  35. 35.
    McCloy RF, Arnold R, Bardhan KD, et al. Pathophysiological effects of long-term acid suppression in man. Dig Dis Sci. 1995;40:96S-120S.CrossRefPubMedGoogle Scholar
  36. 36.
    Rindi G, Luinetti O, Cornaggia M, Capella C, Solcia E. Three subtypes of gastric argyrophil carcinoid and the gastric neuroendocrine carcinoma: a clinicopathologic study [see comment]. Gastroenterology. 1993;104:994–1006.PubMedGoogle Scholar
  37. 37.
    Solcia E, Rindi G, Fiocca R, et al. Distinct patterns of chronic gastritis associated with carcinoid and cancer and their role in tumorigenesis. Yale J Biol Med. 1992;65:793-804. discussion 827–799.PubMedGoogle Scholar
  38. 38.
    Richards AT, Hinder RA, Harrison AC. Gastric carcinoid tumours associated with hypergastrinaemia and pernicious anaemia - regression of tumors by antrectomy. A case report. S Afr Med J. 1987;72:51–53.PubMedGoogle Scholar
  39. 39.
    Maury CP, Tornroth T, Teppo AM. Atrophic gastritis in Sjogren’s syndrome. Morphologic, biochemical, and immunologic findings. Arthritis Rheum. 1985;28:388–394.CrossRefPubMedGoogle Scholar
  40. 40.
    D’Adda T, Keller G, Bordi C, Hofler H. Loss of heterozygosity in 11q13-14 regions in gastric neuroendocrine tumors not associated with multiple endocrine neoplasia type 1 syndrome. Lab Invest. 1999;79:671–677.PubMedGoogle Scholar
  41. 41.
    Azzoni C, Doglioni C, Viale G, et al. Involvement of BCL-2 oncoprotein in the development of enterochromaffin-like cell gastric carcinoids. Am J Surg Pathol. 1996;20:433–441.CrossRefPubMedGoogle Scholar
  42. 42.
    Solcia E, Capella C, Fiocca R, Rindi G, Rosai J. Gastric argyrophil carcinoidosis in patients with Zollinger-Ellison syndrome due to type 1 multiple endocrine neoplasia. A newly recognized association. Am J Surg Pathol. 1990;14:503–513.CrossRefPubMedGoogle Scholar
  43. 43.
    Bordi C, D’Adda T, Azzoni C, Ferraro G. Pathogenesis of ECL cell tumors in humans. Yale J Biol Med. 1998;71:273–284.PubMedGoogle Scholar
  44. 44.
    Cadiot G, Lehy T, Mignon M. Gastric endocrine cell proliferation and fundic argyrophil carcinoid tumors in patients with the Zollinger-Ellison syndrome. Acta Oncol. 1993;32:135–140.CrossRefPubMedGoogle Scholar
  45. 45.
    Richards ML, Gauger P, Thompson NW, Giordano TJ. Regression of type II gastric carcinoids in multiple endocrine neoplasia type 1 patients with Zollinger-Ellison syndrome after surgical excision of all gastrinomas. World J Surg. 2004;28:652–658.CrossRefPubMedGoogle Scholar
  46. 46.
    Borch K, Ahren B, Ahlman H, Falkmer S, Granerus G, Grimelius L. Gastric carcinoids: biologic behavior and prognosis after differentiated treatment in relation to type. Ann Surg. 2005;242:64–73.CrossRefPubMedGoogle Scholar
  47. 47.
    Rindi G, Solcia E. Endocrine hyperplasia and dysplasia in the pathogenesis of gastrointestinal and pancreatic endocrine tumors. Gastroenterol Clin North Am. 2007;36:851–865.CrossRefPubMedGoogle Scholar
  48. 48.
    Solcia E, Bordi C, Creutzfeldt W, et al. Histopathological classification of nonantral gastric endocrine growths in man. Digestion. 1988;41:185–200.CrossRefPubMedGoogle Scholar
  49. 49.
    Solcia E, Fiocca R, Rindi G, Villani L, Cornaggia M, Capella C. The pathology of the gastrointestinal endocrine system. Endocrinol Metab Clin North Am. 1993;22:795–821.PubMedGoogle Scholar
  50. 50.
    Solcia E, Fiocca R, Villani L, Luinetti O, Capella C. Hyperplastic, dysplastic, and neoplastic enterochromaffin-like-cell proliferations of the gastric mucosa. Classification and histogenesis. Am J Surg Pathol. 1995;19(suppl 1):S1-S7.PubMedGoogle Scholar
  51. 51.
    Capella C SE, Sobin LH, Arnold R, Endocrine tumors of the small intestine. In: Hamilton SR AL, ed. Lyon: IARC Press; 2000:77–82.Google Scholar
  52. 52.
    Donow C, Pipeleers-Marichal M, Schroder S, Stamm B, Heitz PU, Kloppel G. Surgical pathology of gastrinoma. Site, size, multicentricity, association with multiple endocrine neoplasia type 1, and malignancy. Cancer. 1991;68:1329–1334.CrossRefPubMedGoogle Scholar
  53. 53.
    Thom AK, Norton JA, Axiotis CA, Jensen RT. Location, incidence, and malignant potential of duodenal gastrinomas. Surgery. 1991;110:1086-1091. discussion 1091–1083.PubMedGoogle Scholar
  54. 54.
    Merchant SH, VanderJagt T, Lathrop S, Amin MB. Sporadic duodenal bulb gastrin-cell tumors: association with Helicobacter pylori gastritis and long-term use of proton pump inhibitors. Am J Surg Pathol. 2006;30:1581–1587.CrossRefPubMedGoogle Scholar
  55. 55.
    Dayal Y, Doos WG, O’Brien MJ, Nunnemacher G, DeLellis RA, Wolfe HJ. Psammomatous somatostatinomas of the duodenum. Am J Surg Pathol. 1983;7:653–665.CrossRefPubMedGoogle Scholar
  56. 56.
    Dayal Y, Tallberg KA, Nunnemacher G, DeLellis RA, Wolfe HJ. Duodenal carcinoids in patients with and without neurofibromatosis. A comparative study. Am J Surg Pathol. 1986;10:348–357.CrossRefPubMedGoogle Scholar
  57. 57.
    Fendrich V, Ramaswamy A, Slater EP, Bartsch DK. Duodenal somatostatinoma associated with Von Recklinghausen’s disease. J Hepatobiliary Pancreat Surg. 2004;11:417–421.CrossRefPubMedGoogle Scholar
  58. 58.
    Karasawa Y, Sakaguchi M, Minami S, et al. Duodenal somatostatinoma and erythrocytosis in a patient with von Hippel-Lindau disease type 2A. Intern Med. 2001;40:38–43.CrossRefPubMedGoogle Scholar
  59. 59.
    de Herder WW. Tumours of the midgut (jejunum, ileum and ascending colon, including carcinoid syndrome). Best Pract Res Clin Gastroenterol. 2005;19:705–715.CrossRefPubMedGoogle Scholar
  60. 60.
    Bishop AE, Pietroletti R, Taat CW, Brummelkamp WH, Polak JM. Increased populations of endocrine cells in Crohn’s ileitis. Virchows Archiv A Pathol Anat Histopathol. 1987;410:391–396.CrossRefGoogle Scholar
  61. 61.
    Burke AP, Sobin LH, Federspiel BH, Shekitka KM, Helwig EB. Goblet cell carcinoids and related tumors of the vermiform appendix. Am J Clin Pathol. 1990;94:27–35.PubMedGoogle Scholar
  62. 62.
    Anderson NH, Somerville JE, Johnston CF, Hayes DM, Buchanan KD, Sloan JM. Appendiceal goblet cell carcinoids: a clinicopathological and immunohistochemical study. Histopathology. 1991;18:61–65.CrossRefPubMedGoogle Scholar
  63. 63.
    Stancu M, Wu T-T, Wallace C, Houlihan PS, Hamilton SR, Rashid A. Genetic alterations in goblet cell carcinoids of the vermiform appendix and comparison with gastrointestinal carcinoid tumors. Mod Pathol. 2003;16:1189–1198.CrossRefPubMedGoogle Scholar
  64. 64.
    Kuroda N, Mizushima S, Guo L, et al. Goblet cell carcinoid of the appendix: investigation of the expression of beta-catenin and E-cadherin. Pathol Int. 2001;51:283–287.CrossRefPubMedGoogle Scholar
  65. 65.
    Lin BT, Gown AM. Mixed carcinoid and adenocarcinoma of the appendix: report of 4 cases with immunohistochemical studies and a review of the literature. Appl Immunohistochem Mol Morphol. 2004;12:271–276.PubMedGoogle Scholar
  66. 66.
    Kortbeek J, Kelly JK, Preshaw RM. Carcinoid tumors and inflammatory bowel disease. J Surg Oncol. 1992;49:122–126.CrossRefPubMedGoogle Scholar
  67. 67.
    Higaki S, Nishiaki M, Mitani N, Yanai H, Tada M, Okita K. Effectiveness of local endoscopic resection of rectal carcinoid tumors. Endoscopy. 1997;29:171–175.CrossRefPubMedGoogle Scholar
  68. 68.
    Oberg K. Interferons in the management of neuroendocrine tumors and their possible mechanism of action. Yale J Biol Med. 1992;65:519-529. discussion 531–516.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Shih-Fan Kuan
    • 1
  1. 1.Department of PathologyUniversity of Pittsburgh Medical CentersPittsburghUSA

Personalised recommendations