ABSTRACT
Neuroendocrine neoplasia (NEN) is a group of neoplasia containing tumours which are different from each other in morphological, genetic, biologic and clinical aspects. The classifications providing correct prognostic information are important for the ideal clinical approach to NENs and as they display biologic varieties depending on the organ of origin the classifications also vary. The general features and classifications of gastroenteropancreatic and lung NENs are discussed in this review.
References
1Rindi G, Klimstra DS, Abedi-Ardekani, B, et al. A common classification framework for neuroendocrine neoplasms: an International Agency for Research on Cancer (IARC) and World Health Organization (WHO) expert consensus proposal. Modern Pathology 2018;31:1770-1786.
2WHO Classification of Tumours Editorial Board. WHO Classification of Tumours of the Digestive System, 5th ed. Lyon: IARC Press, 2019.
3WHO Classification of Tumours Editorial Board. WHO Classification of Thoracic Tumours. 5th ed. Lyon: IARC Press, 2021.
4Schimmack S, Svejda B, Lawrence B, Kidd M, Modlin IM. The diversity and commonalities of gastroenteropancreatic neuroendocrine tumors. Langenbecks Arch Surg 2011;396:273-298.
5Rosai J. The origin of neuroendocrine tumors and the neural crest saga. Mod Pathol 2011;24(Suppl 2):S53-57.
6Oberndorfer S. Karzinoide tumoren des Dünndarms. Frankf Z Pathol 1907;1:425-432.
7Masson P. Appendicite neurogéne and carcinoides. Ann Anat Pathol 1924;1:3-59.
8Capella C, Heitz PU, Höfler H, Solcia E, Klöppel G. Revised classification of neuroendocrine tumours of the lung, pancreas and gut. Virchows Arch 1995;425:547-560.
9Chetty R. Requiem for the term ‘carcinoid tumour’ in the gastrointestinal tract? Can J Gastroenterol 2008;22:357-358.
10Dasari A, Mehta K, Byers LA, Sorbye H, Yao JC. Comparative study of lung and extrapulmonary poorly differentiated neuroendocrine carcinomas: A SEER database analysis of 162,983 cases. Cancer 2018;124:807-815.
11Walter T, Tougeron D, Baudin E, et al. Poorly differentiated gastro-entero-pancreatic neuroendocrine carcinomas: Are they really heterogeneous? Insights from the FFCD-GTE national cohort. Eur J Cancer 2017;79:158-165.
12Klöppel G. Neuroendocrine Neoplasms: Dichotomy, Origin and Classifications. Visc Med 2017;33:324-330.
13Lloyd RV, Osamura RY, Klöppel G, Rosai J: WHO Classification of Tumours of Endocrine Organs. Lyon, IARC Press, 2017.
14Yao JC, Hassan M, Phan A, et al. One hundred years after “carcinoid”: epidemiology of and prognostic factors for neuroendocrine tumors in 35,825 cases in the United States. J Clin Oncol 2008;26:3063-3072.
15Uccella S, La Rosa S, Volante M, Papotti M. Immunohistochemical Biomarkers of Gastrointestinal, Pancreatic, Pulmonary, and Thymic Neuroendocrine Neoplasms. Endocr Pathol 2018;29:150-168.
16Volante M, Brizzi MP, Faggiano A, et al. Somatostatin receptor type 2A immunohistochemistry in neuroendocrine tumors: a proposal of scoring system correlated with somatostatin receptor scintigraphy. Mod Pathol 2007;20:1172-1182.
17Anlauf M, Schlenger R, Perren A, et al. G. Microadenomatosis of the endocrine pancreas in patients with and without the multiple endocrine neoplasia type 1 syndrome. Am J Surg Pathol 2006;30:560-574.
18van Velthuysen ML, Groen EJ, van der Noort V, van de Pol A, Tesselaar ME, Korse CM. Grading of neuroendocrine neoplasms: mitoses and Ki-67 are both essential. Neuroendocrinology 2014;100:221-227.
19Nieser M, Henopp T, Brix J, et al. Loss of Chromosome 18 in Neuroendocrine Tumors of the Small Intestine: The Enigma Remains. Neuroendocrinology 2017;104:302-312.
20Yang Z, Klimstra DS, Hruban RH, Tang LH. Immunohistochemical Characterization of the Origins of Metastatic Well-differentiated Neuroendocrine Tumors to the Liver. Am J Surg Pathol 2017;41:915-922.
21Murphy CE, McCormick KA, Shankaran V, et al. Grade Assignment by Ki-67 Proliferative Index, Mitotic Count, and Phosphohistone H3 Count in Surgically Resected Gastrointestinal and Pancreatic Neuroendocrine Tumors. Pancreas 2017;46:1359-1365.
22Gerdes J, Schwab U, Lemke H, Stein H. Production of a mouse monoclonal antibody reactive with a human nuclear antigen associated with cell proliferation. Int J Cancer 1983;31:13-20.
23Reid MD, Bagci P, Ohike N, et al. Calculation of the Ki67 index in pancreatic neuroendocrine tumors: a comparative analysis of four counting methodologies. Mod Pathol 2015;28:686-694.
24Klimstra DS. Pathology reporting of neuroendocrine tumors: essential elements for accurate diagnosis, classification, and staging. Semin Oncol 2013;40:23-36.
25Tang LH, Gonen M, Hedvat C, Modlin IM, Klimstra DS. Objective quantification of the Ki67 proliferative index in neuroendocrine tumors of the gastroenteropancreatic system: a comparison of digital image analysis with manual methods. Am J Surg Pathol 2012;36:1761-1770.
26 Öztürk Sari Ş, Taşkin OÇ, Yegen G, Özlük Y, Güllüoğlu M. Ki67 Scoring in Pancreatic Neuroendocrine Tumors By a New Method. Appl Immunohistochem Mol Morphol 2018;26:283-287.
27 La Rosa S, Inzani F, Vanoli A, et al. Histologic characterization and improved prognostic evaluation of 209 gastric neuroendocrine neoplasms. Hum Pathol 2011;42:1373-1384.
28Klöppel 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.
29Vanoli A, La Rosa S, Klersy C, et al. Four Neuroendocrine Tumor Types and Neuroendocrine Carcinoma of the Duodenum: Analysis of 203 Cases. Neuroendocrinology 2017;104:112-125.
30Kim JY, Hong SM. Recent Updates on Neuroendocrine Tumors From the Gastrointestinal and Pancreatobiliary Tracts. Arch Pathol Lab Med 2016;140:437-448.
31Modlin IM, Champaneria MC, Chan AK, Kidd M. A three-decade analysis of 3,911 small intestinal neuroendocrine tumors: the rapid pace of no progress. Am J Gastroenterol 2007;102:1464-1473.
32Maggard MA, O’Connell JB, Ko CY. Updated population-based review of carcinoid tumors. Ann Surg 2004;240:117-122.
33Burke AP, Thomas RM, Elsayed AM, Sobin LH. Carcinoids of the jejunum and ileum: an immunohistochemical and clinicopathologic study of 167 cases. Cancer 1997;79:1086-1093.
34Volante M, Daniele L, Asioli S, et al. Tumor staging but not grading is associated with adverse clinical outcome in neuroendocrine tumors of the appendix: a retrospective clinical pathologic analysis of 138 cases. Am J Surg Pathol 2013;37:606-612.
35Gastrointestinal Pathology Study Group of Korean Society of Pathologists, Sohn JH, Cho MY, et al. Prognostic Significance of Defining L-Cell Type on the Biologic Behavior of Rectal Neuroendocrine Tumors in Relation with Pathological Parameters. Cancer Res Treat 2015;47:813-822.
36Sugimoto S, Hotta K, Shimoda T, et al. The Ki-67 labeling index and lymphatic/venous permeation predict the metastatic potential of rectal neuroendocrine tumors. Surg Endosc 2016;30:4239-4248.
37Fischer L, Kleeff J, Esposito I, et al. Clinical outcome and long-term survival in 118 consecutive patients with neuroendocrine tumours of the pancreas. Br J Surg 2008;95:627-635.
38Tsutsumi K, Ohtsuka T, Mori Y, et al. Analysis of lymph node metastasis in pancreatic neuroendocrine tumors (PNETs) based on the tumor size and hormonal production. J Gastroenterol 2012;47:678-685.
39Falconi 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;103:153-171.
40Jensen RT, Berna MJ, Bingham DB, Norton JA. Inherited pancreatic endocrine tumor syndromes: advances in molecular pathogenesis, diagnosis, management, and controversies. Cancer 2008;113(7 Suppl):1807-1843.
41Sorbye H, Welin S, Langer SW, et al. Predictive and prognostic factors for treatment and survival in 305 patients with advanced gastrointestinal neuroendocrine carcinoma (WHO G3): the NORDIC NEC study. Ann Oncol 2013;24:152-160.
42Sorbye H, Strosberg J, Bamdin E, Klimstra DS, Yao JC. Gastroenteropancreatic high-grade neuroendocrine carcinoma. Cancer 2014;120:2814-2823.
43Faggiano A, Sabourin JC, Ducreux M, et al. Pulmonary and extrapulmonary poorly differentiated large cell neuroendocrine carcinomas: diagnostic and prognostic features. Cancer 2007;110:265-274.
44Welin S, Sorbye H, Sebjornsen S, Knappskog S, Busch C, Oberg K. Clinical effect of temozolomide-based chemotherapy in poorly differentiated endocrine carcinoma after progression on first-line chemotherapy. Cancer 2011;117:4617-4622.
45Pellat A, Cottereau AS, Terris B, Coriat R. Neuroendocrine Carcinomas of the Digestive Tract: What Is New? Cancers (Basel) 2021;13:3766.
46Korse CM, Taal BG, van Velthuysen ML, Visser O. Incidence and survival of neuroendocrine tumours in the Netherlands according to histological grade: experience of two decades of cancer registry. Eur J Cancer 2013;49:1975-1983.
47Alese OB, Jiang R, Shaib W, et al. High-Grade Gastrointestinal Neuroendocrine Carcinoma Management and Outcomes: A National Cancer Database Study. Oncologist 2019;24:911-920.
48Iwasa S, Morizane C, Okusaka T, et al. Cisplatin and etoposide as first-line chemotherapy for poorly differentiated neuroendocrine carcinoma of the hepatobiliary tract and pancreas. Jpn J Clin Oncol 2010;40:313-318.
49Kim JY, Hong SM, Ro JY. Recent updates on grading and classification of neuroendocrine tumors. Ann Diagn Pathol 2017;29:11-16.
50Nicholson SA, Beasley MB, Brambilla E, et al. Small cell lung carcinoma (SCLC): a clinicopathologic study of 100 cases with surgical specimens. Am J Surg Pathol 2002;26:1184-1197.
51Guinee DG Jr, Fishback NF, Koss MN, Abbondanzo SL, Travis WD. The spectrum of immunohistochemical staining of small-cell lung carcinoma in specimens from transbronchial and open-lung biopsies. Am J Clin Pathol 1994;102:406-414.
52Rossi G, Mengoli MC, Cavazza A, et al. Large cell carcinoma of the lung: clinically oriented classification integrating immunohistochemistry and molecular biology. Virchows Arch 2014;464:61-68.
53Pelosi G, Rodriguez J, Viale G, Rosai J. Typical and atypical pulmonary carcinoid tumor overdiagnosed as small-cell carcinoma on biopsy specimens: a major pitfall in the management of lung cancer patients. Am J Surg Pathol 2005;29:179-187.
54Swarts DR, van Suylen RJ, den Bakker MA, et al. Interobserver variability for the WHO classification of pulmonary carcinoids. Am J Surg Pathol 2014;38:1429-1436.
