nach oben

Wiener klinisches Magazin

Erschienen in:

14.01.2020 | Pathologie

Neuroendokrine Neoplasien

Zwei Familien mit sehr unterschiedlichen Charakteristika vereint in einer Klassifikation

verfasst von: Prof. Dr. Günter Klöppel

Erschienen in: Wiener klinisches Magazin | Ausgabe 2/2020

Einloggen, um Zugang zu erhalten

Zusammenfassung

Alle neuroendokrinen Neoplasien (NEN) sind durch die Expression von Synaptophysin und Chromogranin A (oder B) charakterisiert, dennoch sind sie keine homogene Tumorgruppe. Paradigmatisch für diese Tumoren sind die NEN des gastroenteropankreatischen (GEP) Systems. Hier stehen sich 2 NEN-Familien gegenüber: Überwiegend gut differenzierte und gering proliferative NEN, auch neuroendokrine Tumoren (NET) genannt, sowie schlecht differenzierte und hoch proliferative NEN, die als neuroendokrine Karzinome (NEC) bezeichnet werden. GEP-NET werden weiterhin anhand ihrer proliferativen Aktivität in G1, G2 und G3 unterteilt. NEC sind definitionsgemäß G3-Karzinome. Die morphologische Dichotomie der NEN wird begleitet von Unterschieden in der Epidemiologie, Genetik, Klinik und Prognose und hat möglicherweise ihre Ursache in einer Abstammung aus unterschiedlichen Progenitorzellen. Genetisch zeichnen sich die NEC durch TP53- und RB1-Alterationen aus, die den NET fehlen und bei der Unterscheidung von NET G3 zu NEC hilfreich sind. Der Vergleich der GEP-NEN-WHO-Klassifikation mit NEN-Klassifikationen anderer Organsysteme offenbart Unterschiede in der Terminologie und den Kriterien der Kategorisierung. Außerdem fehlt ein Gradingsystem. Gemeinsam ist allen NEN-Klassifizierungen jedoch, dass sie zwischen 2 Tumorfamilien mit unterschiedlicher Differenzierung und Prognose unterscheiden. Dies erlaubt, den NEN einen einheitlichen Klassifikationsrahmen zu geben.

Vorheriger Artikel Flächendeckend in Österreich

Nächster Artikel Herausfordernd, aber nicht unbezwingbar

Anlauf M, Perren A, Henopp T, Rudolph T, Garbrecht N, Schmitt A, Raffel A, Gimm O, Weihe E, Knoefel WT, Dralle H, Heitz PU, Komminoth P, Klöppel G (2007) Allelic deletion of the MEN1 gene in duodenal gastrin and somatostatin cell neoplasms and their precursor lesions. Gut 56:637–644CrossRef

Anlauf M, Schlenger R, Perren A, Bauersfeld J, Koch CA, Dralle H, Raffel A, Knoefel WT, Weihe E, Ruszniewski P, Couvelard A, Komminoth P, Heitz PU, Klöppel G (2006) Microadenomatosis of the endocrine pancreas in patients with and without the multiple endocrine neoplasia type 1 syndrome. Am J Surg Pathol 30:560–574CrossRef

Becker JC, Stang A, Hausen AZ, Fischer N, DeCaprio JA, Tothill RW, Lyngaa R, Hansen UK, Ritter C, Nghiem P, Bichakjian CK, Ugurel S, Schrama D (2018) Epidemiology, biology and therapy of Merkel cell carcinoma: conclusions from the EU project IMMOMEC. Cancer Immunol Immunother 67:341–351. https://doi.org/10.1007/s00262-017-2099-3 CrossRefPubMed

Bosman FT, Carneiro F, Hruban RH, Theise ND (Hrsg) (2010) WHO classification of tumours of the digestive system. IARC, Pages

Capella C, Heitz PU, Höfler H, Solcia E, Klöppel G (1995) Revised classification of neuroendocrine tumours of the lung, pancreas and gut. Virchows Arch 425:547–560CrossRef

Champaneria MC, Modlin IM, Kidd M, Eick GN (2006) Friedrich Feyrter: a precise intellect in a diffuse system. Neuroendocrinology 83:394–404. https://doi.org/10.1159/000096050 CrossRefPubMed

DeLellis RA, Lloyd RV, Heitz PU, Eng C (2004) Pathology and genetics of tumours of endocrine organs. IARC Press, Lyon

Derks JL, Leblay N, Lantuejoul S, Dingemans AC, Speel EM, Fernandez-Cuesta L (2018) New insights into the molecular characteristics of pulmonary carcinoids and large cell neuroendocrine carcinomas, and the impact on their clinical management. J Thorac Oncol 13:752–766. https://doi.org/10.1016/j.jtho.2018.02.002 CrossRefPubMed

van Eeden S, Offerhaus GJ (2006) Historical, current and future perspectives on gastrointestinal and pancreatic endocrine tumors. Virchows Arch 448:1–6. https://doi.org/10.1007/s00428-005-0082-4 CrossRefPubMed

10.

Feyrter F (1938) Über diffuse endokrine epitheliale Organe. J.A. Barth, Leipzig

11.

Francis JM, Kiezun A, Ramos AH, Serra S, Pedamallu CS, Qian ZR, Banck MS, Kanwar R, Kulkarni AA, Karpathakis A, Manzo V, Contractor T, Philips J, Nickerson E, Pho N, Hooshmand SM, Brais LK, Lawrence MS, Pugh T, McKenna A, Sivachenko A, Cibulskis K, Carter SL, Ojesina AI, Freeman S, Jones RT, Voet D, Saksena G, Auclair D, Onofrio R, Shefler E, Sougnez C, Grimsby J, Green L, Lennon N, Meyer T, Caplin M, Chung DC, Beutler AS, Ogino S, Thirlwell C, Shivdasani R, Asa SL, Harris CR, Getz G, Kulke M, Meyerson M (2013) Somatic mutation of CDKN1B in small intestine neuroendocrine tumors. Nat Genet 45:1483–1486. https://doi.org/10.1038/ng.2821 CrossRefPubMedPubMedCentral

12.

Furlan A, Dyachuk V, Kastriti ME, Calvo-Enrique L, Abdo H, Hadjab S, Chontorotzea T, Akkuratova N, Usoskin D, Kamenev D, Petersen J, Sunadome K, Memic F, Marklund U, Fried K, Topilko P, Lallemend F, Kharchenko PV, Ernfors P, Adameyko I (2017) Multipotent peripheral glial cells generate neuroendocrine cells of the adrenal medulla. Science. https://doi.org/10.1126/science.aal3753 CrossRefPubMedPubMedCentral

13.

George J, Lim JS, Jang SJ, Cun Y, Ozretic L, Kong G, Leenders F, Lu X, Fernandez-Cuesta L, Bosco G, Muller C, Dahmen I, Jahchan NS, Park KS, Yang D, Karnezis AN, Vaka D, Torres A, Wang MS, Korbel JO, Menon R, Chun SM, Kim D, Wilkerson M, Hayes N, Engelmann D, Putzer B, Bos M, Michels S, Vlasic I, Seidel D, Pinther B, Schaub P, Becker C, Altmuller J, Yokota J, Kohno T, Iwakawa R, Tsuta K, Noguchi M, Muley T, Hoffmann H, Schnabel PA, Petersen I, Chen Y, Soltermann A, Tischler V, Choi CM, Kim YH, Massion PP, Zou Y, Jovanovic D, Kontic M, Wright GM, Russell PA, Solomon B, Koch I, Lindner M, Muscarella LA, la Torre A, Field JK, Jakopovic M, Knezevic J, Castanos-Velez E, Roz L, Pastorino U, Brustugun OT, Lund-Iversen M, Thunnissen E, Kohler J, Schuler M, Botling J, Sandelin M, Sanchez-Cespedes M, Salvesen HB, Achter V, Lang U, Bogus M, Schneider PM, Zander T, Ansen S, Hallek M, Wolf J, Vingron M, Yatabe Y, Travis WD, Nurnberg P, Reinhardt C, Perner S, Heukamp L, Buttner R, Haas SA, Brambilla E, Peifer M, Sage J, Thomas RK (2015) Comprehensive genomic profiles of small cell lung cancer. Nature 524:47–53. https://doi.org/10.1038/nature14664 CrossRefPubMedPubMedCentral

14.

Gosset A, Masson P (1914) Tumeurs endocrines de l’appendice. Presse Med 25:237–240

15.

Heetfeld M, Chougnet CN, Olsen IH, Rinke A, Borbath I, Crespo G, Barriuso J, Pavel M, O’Toole D, Walter T (2015) Characteristics and treatment of patients with G3 gastroenteropancreatic neuroendocrine neoplasms. Endocr Relat Cancer 22:657–664. https://doi.org/10.1530/erc-15-0119 CrossRefPubMed

16.

Hermann G, Konukiewitz B, Schmitt A, Perren A, Klöppel G (2011) Hormonally defined pancreatic and duodenal neuroendocrine tumors differ in their transcription factor signatures: expression of ISL1, PDX1, NGN3, and CDX2. Virchows Arch 459:147–154. https://doi.org/10.1007/s00428-011-1118-6 CrossRefPubMed

17.

Hijioka S, Hosoda W, Matsuo K, Ueno M, Furukawa M, Yoshitomi H, Kobayashi N, Ikeda M, Ito T, Nakamori S, Ishii H, Kodama Y, Morizane C, Okusaka T, Yanagimoto H, Notohara K, Taguchi H, Kitano M, Yane K, Maguchi H, Tsuchiya Y, Komoto I, Tanaka H, Tsuji A, Hashigo S, Kawaguchi Y, Mine T, Kanno A, Murohisa G, Miyabe K, Takagi T, Matayoshi N, Yoshida T, Hara K, Imamura M, Furuse J, Yatabe Y, Mizuno N (2017) Rb loss and KRAS mutation are predictors of the response to platinum-based chemotherapy in pancreatic neuroendocrine neoplasm with grade 3: A Japanese multicenter pancreatic NEN-G3 study. Clin Cancer Res. https://doi.org/10.1158/1078-0432.ccr-16-3135 CrossRefPubMed

18.

Jesinghaus M, Konukiewitz B, Keller G, Kloor M, Steiger K, Reiche M, Penzel R, Endris V, Arsenic R, Hermann G, Stenzinger A, Weichert W, Pfarr N, Klöppel G (2017) Colorectal mixed adenoneuroendocrine carcinomas and neuroendocrine carcinomas are genetically closely related to colorectal adenocarcinomas. Mod Pathol 30:610–619. https://doi.org/10.1038/modpathol.2016.220 CrossRefPubMed

19.

Jiao Y, Shi C, Edil BH, de Wilde RF, Klimstra DS, Maitra A, Schulick RD, Tang LH, Wolfgang CL, Choti MA, Velculescu VE, Diaz LA Jr., Vogelstein B, Kinzler KW, Hruban RH, Papadopoulos N (2011) DAXX/ATRX, MEN1, and mTOR pathway genes are frequently altered in pancreatic neuroendocrine tumors. Science 331:1199–1203. https://doi.org/10.1126/science.1200609 CrossRefPubMedPubMedCentral

20.

Karpathakis A, Dibra H, Pipinikas C, Feber A, Morris T, Francis J, Oukrif D, Mandair D, Pericleous M, Mohmaduvesh M, Serra S, Ogunbiyi O, Novelli M, Luong T, Asa SL, Kulke M, Toumpanakis C, Meyer T, Caplin M, Meyerson M, Beck S, Thirlwell C (2016) Prognostic impact of novel molecular subtypes of small intestinal neuroendocrine tumor. Clin Cancer Res 22:250–258. https://doi.org/10.1158/1078-0432.ccr-15-0373 CrossRefPubMed

21.

Kasajima A, Konukiewitz B, Oka N, Suzuki H, Sakurada A, Okada Y, Kameya T, Ishikawa Y, Sasano H, Weichert W, Kloppel G (2018) Clinicopathologic profiling of lung carcinoids with a Ki67 index greater than 20. Neuroendocrinology. https://doi.org/10.1159/000495806 CrossRefPubMed

22.

Klimstra DS (2016) Pathologic classification of neuroendocrine neoplasms. Hematol Oncol Clin North Am 30:1–19. https://doi.org/10.1016/j.hoc.2015.08.005 CrossRefPubMed

23.

Klöppel G, Anlauf M, Perren A (2007) Endocrine precursor lesions of gastroenteropancreatic neuroendocrine tumors. Endocr Pathol 18:150–155CrossRef

24.

Klöppel G, La Rosa S (2018) Ki67 labeling index: assessment and prognostic role in gastroenteropancreatic neuroendocrine neoplasms. Virchows Arch 472:341–349. https://doi.org/10.1007/s00428-017-2258-0 CrossRefPubMed

25.

Konukiewitz B, Agaimy A, Weichert W, Klöppel G (2018) Neuroendocrine neoplasms of the head and neck. Pathologe. https://doi.org/10.1007/s00292-017-0404-8 CrossRefPubMed

26.

Konukiewitz B, Jesinghaus M, Steiger K, Schlitter AM, Kasajima A, Sipos B, Zamboni G, Weichert W, Pfarr N, Klöppel G (2018) Pancreatic neuroendocrine carcinomas reveal a closer relationship to ductal adenocarcinomas than to neuroendocrine tumors G3. Hum Pathol. https://doi.org/10.1016/j.humpath.2018.03.018 CrossRefPubMed

27.

Konukiewitz B, Schlitter AM, Jesinghaus M, Pfister D, Steiger K, Segler A, Agaimy A, Sipos B, Zamboni G, Weichert W, Esposito I, Pfarr N, Klöppel G (2017) Somatostatin receptor expression related to TP53 and RB1 alterations in pancreatic and extrapancreatic neuroendocrine neoplasms with a Ki67-index above 20. Mod Pathol 30:587–598. https://doi.org/10.1038/modpathol.2016.217 CrossRefPubMed

28.

Lloyd RV, Osamura RY, Klöppel G, Rosai J (2017) WHO classification of tumours of endocrine organs. IARC Press, Lyon

29.

Mafficini A, Scarpa A (2019) Genetics and epigenetics of gastroenteropancreatic neuroendocrine neoplasms. Endocr Rev. https://doi.org/10.1210/er.2018-00160 CrossRefPubMedPubMedCentral

30.

Marinoni I, Kurrer AS, Vassella E, Dettmer M, Rudolph T, Banz V, Hunger F, Pasquinelli S, Speel EJ, Perren A (2014) Loss of DAXX and ATRX are associated with chromosome instability and reduced survival of patients with pancreatic neuroendocrine tumors. Baillieres Clin Gastroenterol 146:453–460.e455. https://doi.org/10.1053/j.gastro.2013.10.020 CrossRef

31.

de Mestier L, Cros J, Neuzillet C, Hentic O, Egal A, Muller N, Bouche O, Cadiot G, Ruszniewski P, Couvelard A, Hammel P (2017) Digestive system mixed neuroendocrine-non-neuroendocrine neoplasms. Neuroendocrinology 105:412–425. https://doi.org/10.1159/000475527 CrossRefPubMed

32.

Nieser M, Henopp T, Brix J, Stoss L, Sitek B, Naboulsi W, Anlauf M, Schlitter AM, Klöppel G, Gress T, Moll R, Bartsch DK, Heverhagen AE, Knoefel WT, Kaemmerer D, Haybaeck J, Fend F, Sperveslage J, Sipos B (2017) Loss of chromosome 18 in neuroendocrine tumors of the small intestine: the enigma remains. Neuroendocrinology 104:302–312. https://doi.org/10.1159/000446917 CrossRefPubMed

33.

Pavel ME, Singh S, Strosberg JR, Bubuteishvili-Pacaud L, Degtyarev E, Neary MP, Carnaghi C, Tomasek J, Wolin E, Raderer M, Lahner H, Valle JW, Pommier R, Van Cutsem E, Tesselaar MET, Fave GD, Buzzoni R, Hunger M, Eriksson J, Cella D, Ricci JF, Fazio N, Kulke MH, Yao JC (2017) Health-related quality of life for everolimus versus placebo in patients with advanced, non-functional, well-differentiated gastrointestinal or lung neuroendocrine tumours (RADIANT-4): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial The Lancet. Oncology. https://doi.org/10.1016/s1470-2045(17)30471-0 CrossRefPubMed

34.

Pearse AG, Polak JM (1974) Endocrine tumours of neural crest origin: neurolophomas, apudomas and the APUD concept. Med Biol 52:3–18PubMed

35.

Perigny M, Hammel P, Corcos O, Larochelle O, Giraud S, Richard S, Sauvanet A, Belghiti J, Ruszniewski P, Bedossa P, Couvelard A (2009) Pancreatic endocrine microadenomatosis in patients with von Hippel-Lindau disease: characterization by VHL/HIF pathway proteins expression. Am J Surg Pathol 33:739–748. https://doi.org/10.1097/PAS.0b013e3181967992 CrossRefPubMed

36.

Perren A, Anlauf M, Henopp T, Rudolph T, Schmitt A, Raffel A, Gimm O, Weihe E, Knoefel WT, Dralle H, Heitz PU, Komminoth P, Klöppel G (2007) Multiple endocrine neoplasia type 1: loss of one MEN1 allele in tumors and monohormonal endocrine cell clusters, but not in islet hyperplasia of the pancreas. A combined FISH and immunofluorescence study J. Clin Endocrinol Metab 92:1118–1128CrossRef

37.

Pipeleers-Marichal M, Somers G, Willems G, Foulis A, Imrie C, Bishop AE, Polak JM, Hacki WH, Stamm B, Heitz PU et al (1990) Gastrinomas in the duodenums of patients with multiple endocrine neoplasia type 1 and the Zollinger-Ellison syndrome. N Engl J Med 322:723–727. https://doi.org/10.1056/NEJM199003153221103 CrossRefPubMed

38.

Raj N, Shah R, Stadler Z, Mukherjee S, Chou J, Untch B, Li J, Kelly V, Saltz LB, Mandelker D, Ladanyi M, Berger MF, Klimstra DS, Reidy-Lagunes D, Osoba M (2018) Real-time genomic characterization of metastatic pancreatic neuroendocrine tumors has prognostic implications and identifies potential germline actionability. JCO Precis Oncol. https://doi.org/10.1200/po.17.00267 CrossRefPubMedPubMedCentral

39.

Rindi G, Klimstra DS, Abedi-Ardekani B, Asa SL, Bosman FT, Brambilla E, Busam KJ, de Krijger RR, Dietel M, El-Naggar AK, Fernandez-Cuesta L, Kloppel G, McCluggage WG, Moch H, Ohgaki H, Rakha EA, Reed NS, Rous BA, Sasano H, Scarpa A, Scoazec JY, Travis WD, Tallini G, Trouillas J, van Krieken JH, Cree IA (2018) A common classification framework for neuroendocrine neoplasms: an International Agency for Research on Cancer (IARC) and World Health Organization (WHO) expert consensus proposal. Mod Pathol 31:1770–1786. https://doi.org/10.1038/s41379-018-0110-y CrossRefPubMedPubMedCentral

40.

Rindi G, Klöppel G, Ahlman H, Caplin M, Couvelard A, de Herder WW, Eriksson B, Falchetti A, Falconi M, Komminoth P, Körner M, Lopes JM, McNicol AM, Nilsson O, Perren A, Scarpa A, Scoazec JY, Wiedenmann B, Frascati Consensus Conference participants, European Neuroendocrine Tumor Society (ENETS) (2006) TNM staging of foregut (neuro)endocrine tumors: a consensus proposal including a grading system. Virchows Arch 449:395–401CrossRef

41.

Rindi G, Klöppel G, Couvelard A, Komminoth P, Körner M, Lopes JM, McNicol AM, Nilsson O, Perren A, Scarpa A, Scoazec JY, Wiedenmann B (2007) TNM staging of midgut and hindgut (neuro)endocrine tumors: a consensus proposal including a grading system. Virchows Arch 451:757–762CrossRef

42.

Rindi G, Wiedenmann B (2011) Neuroendocrine neoplasms of the gut and pancreas: new insights. Nat Rev Endocrinol 8:54–64. https://doi.org/10.1038/nrendo.2011.120 CrossRefPubMed

43.

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

44.

Scarpa A, Chang DK, Nones K, Corbo V, Patch AM, Bailey P, Lawlor RT, Johns AL, Miller DK, Mafficini A, Rusev B, Scardoni M, Antonello D, Barbi S, Sikora KO, Cingarlini S, Vicentini C, McKay S, Quinn MC, Bruxner TJ, Christ AN, Harliwong I, Idrisoglu S, McLean S, Nourse C, Nourbakhsh E, Wilson PJ, Anderson MJ, Fink JL, Newell F, Waddell N, Holmes O, Kazakoff SH, Leonard C, Wood S, Xu Q, Nagaraj SH, Amato E, Dalai I, Bersani S, Cataldo I, Dei Tos AP, Capelli P, Davi MV, Landoni L, Malpaga A, Miotto M, Whitehall VL, Leggett BA, Harris JL, Harris J, Jones MD, Humphris J, Chantrill LA, Chin V, Nagrial AM, Pajic M, Scarlett CJ, Pinho A, Rooman I, Toon C, Wu J, Pinese M, Cowley M, Barbour A, Mawson A, Humphrey ES, Colvin EK, Chou A, Lovell JA, Jamieson NB, Duthie F, Gingras MC, Fisher WE, Dagg RA, Lau LM, Lee M, Pickett HA, Reddel RR, Samra JS, Kench JG, Merrett ND, Epari K, Nguyen NQ, Zeps N, Falconi M, Simbolo M, Butturini G, Van Buren G, Partelli S, Fassan M, Khanna KK, Gill AJ, Wheeler DA, Gibbs RA, Musgrove EA, Bassi C, Tortora G, Pederzoli P, Pearson JV, Waddell N, Biankin AV, Grimmond SM (2017) Whole-genome landscape of pancreatic neuroendocrine tumours. Nature 543:65–71. https://doi.org/10.1038/nature21063 CrossRef

45.

Schimmack S, Svejda B, Lawrence B, Kidd M, Modlin IM (2011) The diversity and commonalities of gastroenteropancreatic neuroendocrine tumors. Langenbecks Arch Surg 396:273–298. https://doi.org/10.1007/s00423-011-0739-1 CrossRefPubMed

46.

Schmid KW, Kroll M, Hittmair A, Maier H, Totsch M, Gasser R, Finkenstett G, Hogue-Angeletti R, Fischer-Colbrie R (1991) Chromogranin A and B in adenomas of the pituitary. An immunohistochemical study of 42 cases. Am J Surg Pathol 15:1072–1077CrossRef

47.

Schmitt AM, Marinoni I, Blank A, Perren A (2016) New genetics and genomic data on pancreatic neuroendocrine tumors: implications for diagnosis, treatment, and targeted therapies. Endocr Pathol 27:200–204. https://doi.org/10.1007/s12022-016-9447-2 CrossRefPubMed

48.

Schonhoff SE, Giel-Moloney M, Leiter AB (2004) Minireview: development and differentiation of gut endocrine cells. Endocrinology 145:2639–2644. https://doi.org/10.1210/en.2004-0051 CrossRefPubMed

49.

Solcia E, Klöppel G, Sobin L (2000) Histological typing of endocrine tumours. Springer, BerlinCrossRef

50.

Swarts DR, Ramaekers FC, Speel EJ (2012) Molecular and cellular biology of neuroendocrine lung tumors: evidence for separate biological entities. Biochim Biophys Acta 1826:255–271. https://doi.org/10.1016/j.bbcan.2012.05.001 CrossRefPubMed

51.

Szczyrba J, Niesen A, Wagner M, Wandernoth PM, Aumüller G, Wennemuth G (2017) Neuroendocrine cells of the prostate derive from the neural crest. J Biol Chem 292:2021–2031. https://doi.org/10.1074/jbc.M116.755082 CrossRefPubMed

52.

Tang LH, Untch BR, Reidy DL, O’Reilly E, Dhall D, Jih L, Basturk O, Allen PJ, Klimstra DS (2016) Well-differentiated Neuroendocrine tumors with a morphologically apparent high-grade component: a pathway distinct from poorly differentiated neuroendocrine carcinomas. Clin Cancer Res 22:1011–1017. https://doi.org/10.1158/1078-0432.ccr-15-0548 CrossRefPubMed

53.

Volante M, Brizzi MP, Faggiano A, La Rosa S, Rapa I, Ferrero A, Mansueto G, Righi L, Garancini S, Capella C, De Rosa G, Dogliotti L, Colao A, Papotti M (2007) Somatostatin receptor type 2A immunohistochemistry in neuroendocrine tumors: a proposal of scoring system correlated with somatostatin receptor scintigraphy. Mod Pathol 20:1172–1182. https://doi.org/10.1038/modpathol.3800954 CrossRefPubMed

54.

Wiedenmann B, Franke WW, Kuhn C, Moll R, Gould VE (1986) Synaptophysin: a marker protein for neuroendocrine cells and neoplasms. Proc Natl Acad Sci U S A 83:3500–3504CrossRef

55.

Woischke C, Schaaf CW, Yang HM, Vieth M, Veits L, Geddert H, Markl B, Stommer P, Schaeffer DF, Frolich M, Blum H, Vosberg S, Greif PA, Jung A, Kirchner T, Horst D (2016) In-depth mutational analyses of colorectal neuroendocrine carcinomas with adenoma or adenocarcinoma components. Mod Pathol. https://doi.org/10.1038/modpathol.2016.150 CrossRefPubMed

56.

Yachida S, Vakiani E, White CM, Zhong Y, Saunders T, Morgan R, de Wilde RF, Maitra A, Hicks J, Demarzo AM, Shi C, Sharma R, Laheru D, Edil BH, Wolfgang CL, Schulick RD, Hruban RH, Tang LH, Klimstra DS, Iacobuzio-Donahue CA (2012) Small cell and large cell neuroendocrine carcinomas of the pancreas are genetically similar and distinct from well-differentiated pancreatic neuroendocrine tumors. Am J Surg Pathol 36:173–184. https://doi.org/10.1097/PAS.0b013e3182417d36 CrossRefPubMedPubMedCentral

Titel: Neuroendokrine Neoplasien
Zwei Familien mit sehr unterschiedlichen Charakteristika vereint in einer Klassifikation
verfasst von: Prof. Dr. Günter Klöppel
Publikationsdatum: 14.01.2020
Verlag: Springer Vienna
Erschienen in: Wiener klinisches Magazin / Ausgabe 2/2020
Print ISSN: 1869-1757
Elektronische ISSN: 1613-7817
DOI: https://doi.org/10.1007/s00740-019-00325-0

Springer Medizin Österreich

Zusammenfassung

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 2/2020

Herausfordernd, aber nicht unbezwingbar

Verzerrte Informationen

Mikrobiom und Immuntherapien bei Tumorerkrankungen

Moderne Konzepte zur dynamischen Konservierung von Leber und Nieren im Rahmen einer Transplantation

Flächendeckend in Österreich

Molekularpathologische Diagnostik an zytologischen Präparaten