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Histopathology of Neuroendocrine Neoplasms of the Gastrointestinal System


Authors: Mikuš Kuracinová Kristína;  Janega Pavol;  Janegová Andrea;  Čierna Zuzana
Authors‘ workplace: Ústav patologickej anatómie, LF UK a UN, Bratislava
Published in: Klin Onkol 2018; 31(3): 167-177
Category: Reviews
doi: https://doi.org/10.14735/amko2018167

Overview

Background:
Tumors arising from neuroendocrine cells are defined as epithelial neoplasms with predominantly neuroendocrine differentiation. They comprise a distinct group of tumors with a characteristic histological structure and functional properties that develop at various sites, particularly the gastrointestinal system (67%) and lungs (25%). Although such tumors are usually slow-growing and indolent, almost all have malignant potential and most can produce active hormones. Clinical signs vary, and many are dependent on the site at which the tumor develops. Although these tumors were identified more than 130 years, their classification remains unclear.

Purpose:
This review provides a comprehensive overview of the human neuroendocrine system and its neoplasms, from their discovery to current terminology and classifications. In addition, the clinical symptomatology and macroscopic/microscopic features of tumors arising from endocrine cells of the gastrointestinal tract are described, with an emphasis on their classification, diagnostic criteria for their grading and TNM (tumor, node, metastasis) staging, and how these tumors differ according to their localization in the gastrointestinal tract.

Conclusion:
Tumors arising from neuroendocrine cells are rare and can cause typical symptoms of carcinoid syndrome. However, most of these tumors are asymptomatic, which, together with their typical small size and localization in the gut, makes them difficult to access endoscopically and often leads to diagnosis at an advanced stage. To successfully diagnose and treat tumors arising from neuroendocrine cells, they should be assessed using a differential diagnostic procedure and be histopathologically classified, graded, and staged according to specified criteria and the latest classifications and guidelines. Although the terms “carcinoid”, “neuroendocrine tumor”, and “neuroendocrine carcinoma” are often used synonymously in the literature and by professionals, more precise terminology is required for nomenclature and classification.

Key words:
gastrointestinal neuroendocrine neoplasms – neuroendocrine tumors – neuroendocrine carcinomas – classification – NET – NEC

The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study.

The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.

Submitted: 21. 3. 2018

Accepted: 16. 4. 2018


 


Sources

1. Ramage JK, Ahmed A, Ardill J et al. Guidelines for the management of gastroenteropancreatic neuroendocrine (including carcinoid) tumours (NETs). Gut 2012; 61 (1): 6–32. doi: 10.1136/gutjnl-2011-300831.

2. Rosai J. The origin of neuroendocrine tumors and the neural crest saga. Mod Pathol 2011; 24 (Suppl 2): S53–S57. doi: 10.1038/modpathol.2010.166.

3. Matějka VM, Fiala O, Tupý R et al. Chylózní ascites jako závažná komplikace neuroendokrinního tumoru ilea – kazuistika. Klin Onkol 2013; 26 (5): 358–361. doi: 10.14735/amko2013358.

4. Esmati E, Babaei M, Matini A et al. Neuroendocrine carcinoma of the tongue. J Cancer Res Ther 2015; 11 (3): 659. doi: 10.4103/0973-1482.139395.

5. Dvorackova J, Macak J, Brzula P et al. Primary neuroendocrine carcinoma of the kidney. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2013; 157 (3): 257–260. doi: 10.5507/bp.2012.053.

6. Li Z, Chen CJ, Wang JK et al. Neuroendocrine differentiation of prostate cancer. Asian J Androl 2013; 15 (3): 328–332. doi: 10.1038/aja.2013.7.

7. Moratalla Charcos LM, Pastor Navarro T, Cortes Vizcaino V et al. Large-cell neuroendocrine carcinoma of prostate. Arch Esp Urol 2013; 66 (4): 368–371.

8. Lindboe CF. Large cell neuroendocrine carcinoma of the ovary. APMIS. 2007; 115 (2): 169–176. doi: 10.1111/j.1600-0463.2007.apm_570.x.

9. Aslam MF, Choi C, Khulpateea N. Neuroendocrine tumour of the ovary. J Obstet Gynaecol 2009; 29 (5): 449–451. doi: 10.1080/01443610902946903.

10. Hanna MY, Leung E, Rogers C et al. Primary large-cell neuroendocrine tumor of the breast. Breast J 2013; 19 (2): 204–206. doi: 10.1111/tbj.12081.

11. Rehman A. Primary neuroendocrine carcinoma of the breast. J Coll Physicians Surg Pak 2013; 23 (4): 282–284. doi: 04.2013/JCPSP.282284.

12. Ueda G, Yamasaki M. Neuroendocrine carcinoma of the uterus. Curr Top Pathol 1992; 85: 309–335.

13. Schmidt D. Neuroendocrine tumors of the uterus. Verh Dtsch Ges Pathol 1997; 81: 260–265.

14. Tan EH, Tan CH. Imaging of gastroenteropancreatic neuroendocrine tumors. World J Clin Oncol 2011; 2 (4): 28–43. doi: 10.5306/wjco.v2.i1.28.

15. Vítek P, Strenkova J, Sedláčkova E et al. Registr neuroendokrinních nádorů (NET) v ČR po třech letech sběru dat. Klin Onkol 2013; 26 (4): 271–280.  doi: 10.14735/amko2013271.

16. Leoncini E, Boffetta P, Shafir M et al. Increased incidence trend of low-grade and high-grade neuroendocrine neoplasms. Endocrine 2017; 58 (2): 368–379.  doi: 10.1007/s12020-017-1273-x.

17. de Herder WW, Rehfeld JF, Kidd M et al. A short history of neuroendocrine tumours and their peptide hormones. Best Pract Res Clin Endocrinol Metab 2016; 30 (1): 3–17. doi: 10.1016/j.beem.2015.10.004.

18. Modlin IM, Shapiro MD, Kidd M et al. Siegfried oberndorfer and the evolution of carcinoid disease. Arch Surg 2007; 142 (2): 187–197. doi: 10.1001/archsurg.142.2.187.

19. Rehfeld JF, Federspiel B, Bardram L. A neuroendocrine tumor syndrome from cholecystokinin secretion. N Engl J Med 2013; 368 (12): 1165–1166.  doi: 10.1056/NEJMc1215137.

20. Williams ED, Sandler M. The classification of carcinoid tumours. Lancet 1963; 1 (7275): 238–239.

21. Capella C, Heitz PU, Hofler H et al. Revised classification of neuroendocrine tumours of the lung, pancreas and gut. Virchows Arch 1995; 425 (6): 547–560.

22. Bosman FT CF, Hruban RH, Theise ND. WHO Classification of tumours of the digestive system. Fourth edition. WHO 2010: 417.

23. Travis WD, Brambilla E, Nicholson AG et al. The 2015 World Health Organization classification of lung tumors: Impact of genetic, clinical and radiologic advances since the 2004 classification. J Thorac Oncol 2015; 10 (9): 1243–1260. doi: 10.1097/JTO.0000000000000630.

24. Lloyd RV, Osamura RY, Klöppel G et al. WHO classification of tumours of endocrine organs. Fourth edition. WHO 2017: 355.

25. Klimstra DS, Modlin IR, Coppola D et al. The pathologic classification of neuroendocrine tumors: a review of nomenclature, grading, and staging systems. Pancreas 2010; 39 (6): 707–712. doi: 10.1097/MPA.0b013e3181ec 124e.

26. Rindi G, Arnold R, Bosman FT et al. Nomenclature and classification of neuroendocrine neoplasms of the digestive system. 4th edition. In: Classification of tumour of the digestive system. Lyon: IARC Press 2010.

27. Travis WD. The concept of pulmonary neuroendocrine tumours. In: Travis WD, Brambilla E, Muller-Hermelink (eds). Pathology and genetics of tumours of the lung, pleura, thymus and heart. Lyon: IARC Press; 2004.

28. Enets.org. [online]. Available from: https: //www.enets.org/current_guidelines.html.

29. Hirabayashi K, Zamboni G, Nishi T et al. Histopathology of gastrointestinal neuroendocrine neoplasms. Frontiers in oncology 2013; 3: 2. doi: 10.3389/fonc.2013.00002.

30. 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 (4): 395–401. doi: 10.1007/s00428-006-0250-1.

31. 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 (4): 757–762. doi: 10.1007/s00428-007-0452-1.

32. Yang Z, Tang LH, Klimstra DS. Effect of tumor heterogeneity on the assessment of Ki67 labeling index in well-differentiated neuroendocrine tumors metastatic to the liver: implications for prognostic stratification. Am J Surg Pathol 2011; 35 (6): 853–860. doi: 10.1097/ PAS.0b013e31821a0696.

33. Kim JY, Hong SM, Ro JY. Recent updates on grading and classification of neuroendocrine tumors. Annals of diagnostic pathology 2017; 29: 11–16. doi: 10.1016/j.anndiagpath.2017.04.005.

34. Brierley JD, Gospodarowicz MK, Wittekind C (eds). TNM Classification of malignant tumours. Hoboken: Wiley Blackwell 2017: 253.

35. Amin MB, Edge S, Greene F (eds). AJCC Cancer Staging Manual. New York: Springer 2017: 1032.

36. Pape UF, Niederle B, Costa F et al. ENETS consensus guidelines for neuroendocrine neoplasms of the appendix (excluding goblet cell carcinomas). Neuroendocrinology 2016; 103 (2): 144–152. doi: 10.1159/000443165.

37. Riihimaki M, Hemminki A, Sundquist K et al. The epidemiology of metastases in neuroendocrine tumors. Int J Cancer 2016; 139 (12): 2679–2686. doi: 10.1002/ijc.30400.

38. Elizabeth A. Montgomery MD LVM. Biopsy interpretation of the gastrointestinal tract mucosa: volume 2: neoplastic. Philadephia: Lippincott Williams & Wilkins 2012: 352.

39. Kumar V, Abbas A, Fausto N (eds). Robins and cotran pathologic basis of disease. Eighth edition. Philadephia: Elsevier 2010: 1464.

40. Ramage JK, Davies AH, Ardill J et al. Guidelines for the management of gastroenteropancreatic neuroendocrine (including carcinoid) tumours. Gut 2005 54   (Suppl 4): 1–16. doi: 10.1136/gut.2004.053314.

41. Rorstad O. Prognostic indicators for carcinoid neuroendocrine tumors of the gastrointestinal tract. J Surg Oncol 2005; 89 (3): 151–160. doi: 10.1002/jso.20179.

42. Jes A. Circulating markers for endocrine tumours of the gastrointestinal tract. Ann Clin Biochem 2008; 45 (5): 451. doi: 10.1258/acb.2008.200825.

43. Modlin IM, Oberg K, Chung DC et al. Gastroenteropancreatic neuroendocrine tumours. Lancet Oncol 2008; 9 (1): 61–72. doi: 10.1016/S1470-2045 (07) 70410-2.

44. Uskul BT, Turker H, Dincer IS et al. A primary tracheal carcinoid tumor masquerading as chronic obstructive pulmonary disease. South Med J 2008; 101 (5): 546–549. doi: 10.1097/SMJ.0b013e31816bf624.

45. Modlin IM, Kidd M, Latich I et al. Current status of gastrointestinal carcinoids. Gastroenterology 2005; 128 (6): 1717–1751.

46. Oberg KE. Gastrointestinal neuroendocrine tumors. Ann Oncol 2010; 21 (Suppl 7): 72–80. doi: 10.1093/annonc/mdq290.

47. Salyers WJ, Vega KJ, Munoz JC et al. Neuroendocrine tumors of the gastrointestinal tract: Case reports and literature review. World J Gastrointest Oncol 2014; 6 (8): 301–310. doi: 10.4251/wjgo.v6.i8.301.

48. Egashira A, Morita M, Kumagai R et al. Neuroendocrine carcinoma of the esophagus: Clinicopathological and immunohistochemical features of 14 cases. PloS One 2017; 12 (3): e0173501. doi: 10.1371/journal.pone.0173501.

49. Deng HY, Ni PZ, Wang YC et al. Neuroendocrine carcinoma of the esophagus: clinical characteristics and prognostic evaluation of 49 cases with surgical resection. Journal of thoracic disease 2016; 8 (6): 1250–1256.  doi: 10.21037/jtd.2016.04.21.

50. Jung M, Kim JW, Jang JY et al. Recurrent gastric neuroendocrine tumors treated with total gastrectomy. World J Gastroenterol 2015; 21 (46): 13195–13200.  doi: 10.3748/wjg.v21.i46.13195.

51. Kulke MH, Shah MH, Benson AB et al. Neuroendocrine tumors, version 1.2015. J Natl Compr Canc Netw 2015; 13 (1): 78–108.

52. Delle Fave G, O‘Toole D, Sundin A et al. ENETS Consensus guidelines update for gastroduodenal nNeuroendocrine neoplasms. Neuroendocrinology 2016; 103 (2): 119–124. doi: 10.1159/000443168.

53. Scherubl H, Cadiot G, Jensen RT et al. Neuroendocrine tumors of the stomach (gastric carcinoids) are on the rise: small tumors, small problems? Endoscopy 2010; 42 (8): 664–671. doi: 10.1055/s-0030-1255564.

54. von Rosenvinge EC, Wank SA, Lim RM. Gastric masses in multiple endocrine neoplasia type I-associated Zollinger-Ellison syndrome. Gastroenterology 2009; 137 (4): 1222–1537. doi: 10.1053/j.gastro.2009.03.050.

55. Dias AR, Azevedo BC, Alban LBV et al. Gastric Neuroendocrine Tumor: Review and Update. Arq Bras Cir Dig 2017; 30 (2): 150–154. doi: 10.1590/0102-6720201700020016.

56. 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.

57. Delle Fave G, Capurso G, Milione M et al. Endocrine tumours of the stomach. Best Pract Res Clin Gastroenterol 2005; 19 (5): 659–673. doi: 10.1016/j.bpg.2005.05.002.

58. Modlin IM, Oberg K, Chung DC et al. Gastroenteropancreatic neuroendocrine tumours. Lancet Oncol 2008; 9 (1): 61–72. doi: 10.1016/S1470-2045 (07) 70410-2.

59. Makhlouf HR, Burke AP, Sobin LH. Carcinoid tumors of the ampulla of Vater: a comparison with duodenal carcinoid tumors. Cancer 1999; 85 (6): 1241–1249.

60. Pasieka JL. Carcinoid tumors. Surg Clin North Am 2009; 89 (5): 1123–1137. doi: 10.1016/j.suc.2009.06. 008.

61. Louthan O. Neuroendokrinní nádory rekta. Klin Onkol 2009; 22 (5): 195–201.

62. Batcher E, Madaj P, Gianoukakis AG. Pancreatic neuroendocrine tumors. Endocr Res 2011; 36 (1): 35–43. doi: 10.3109/07435800.2010.525085.

63. Krampitz GW, Norton JA. Pancreatic neuroendocrine tumors. Curr Probl Surg 2013; 50 (11): 509–545. doi: 10.1067/j.cpsurg.2013.08.001.

64. Klimstra DS, Beltran H, Lilenbaum R et al. The spectrum of neuroendocrine tumors: histologic classification, unique features and areas of overlap. Am Soc Clin Oncol Educ Book 2015: 92–103. doi: 10.14694/EdBook_AM.2015.35.92.

65. Falconi M, Eriksson B, Kaltsas G et al. ENETS consensus guidelines update for the management of patients with functional pancreatic neuroendocrine tumors and non-functional pancreatic neuroendocrine tumors. Neuroendocrinology 2016; 103 (2): 153–171. doi: 10.1159/000443171.

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