PDF herunterladen
Horm Metab Res 2011; 43(12): 825-831
DOI: 10.1055/s-0031-1291307
Review
© Georg Thieme Verlag KG Stuttgart · New York

Neuroendocrine Neoplasms of the Gastroenteropancreatic System: Pathology and Classification

M. Anlauf
1   Institute of Pathology and Endocrine Tumor Center, University Clinic of Düsseldorf, Düsseldorf, Germany
› Institutsangaben
Weitere Informationen

Publikationsverlauf

received 11. September 2011

accepted 04. Oktober 2011

Publikationsdatum:
21. November 2011 (online)

Auch verfügbar auf
    Lizenzen und Reprints

Abstract

Neuroendocrine neoplasms (NEN) appear homogeneous in terms of morphology, but constitute a very heterogeneous group of tumors in terms of biological and clinical features. NEN may occur in any organ, but are most commonly observed in the lung and the gastroenteropancreatic system (GEP). The European Neuroendocrine Tumor Society (ENETS) developed guidelines in the last 5 years to standardize and improve the diagnosis and therapy of GEP-NEN. Taking these guidelines into account, the TNM classification of the Union for International Cancer Control (UICC) was introduced in 2009. The new GEP-NEN classification of the World Health Organization (WHO) was presented 1 year later. According to the guidelines of the ENETS, the UICC, and the WHO, the pathology classification of NEN of GEP consists of several basic components: (1) evidence of the neuroendocrine nature of the tumor, (2) histological distinction between well and poorly differentiated tumors, (3) proliferation-based grading. (4) TNM staging (including data about vascular invasion and resection margins), (5) with reference to the clinical question: evidence of hormones and biogenic amines, and (6) optional, especially in cases of initial diagnosis of NEN: expression of the somatostatin receptor type 2A. Based on these criteria, a standardized prognostic stratification of GEP-NEN can be performed in combination with other clinical parameters. The novel classifications constitute the basis for selecting the procedures of molecular and metabolic imaging as well as for tumor-specific treatments and permit comparisons of larger tumor populations. Close interdisciplinary cooperation is a prerequisite.

Key words

grading - hormones - molecular imaging - neuroendocrine tumor - TNM classification
 

  • References

  • 1 Ahlman H, Nilsson O, McNicol AM, Ruszniewski P, Niederle B, Ricke J, Jensen R, Kos-Kudła B, Oberg K, O’Connor JM, Pavel ME, Vullierme MP. Frascati Consensus Conference participants. Poorly-Differentiated Endocrine Carcinomas of Midgut and Hindgut Origin. Neuroendocrinology 2008; 87: 40-46
    CrossrefPubMedSuche in Google Scholar
  • 2 Anlauf M, Garbrecht N, Henopp T, Schmitt A, Schlenger R, Raffel A, Krausch M, Gimm O, Eisenberger CF, Knoefel WT, Dralle H, Komminoth P, Heitz PU, Perren A, Klöppel G. Sporadic versus hereditary gastrinomas of the duodenum and pancreas: distinct clinico-pathological and epidemiological features. World J Gastroenterol 2006; 12: 5440-5446
    PubMedSuche in Google Scholar
  • 3 Anlauf M, Perren A, Klöppel G. Endocrine precursor lesions and microadenomas of the duodenum and pancreas with and without MEN1: criteria, molecular concepts and clinical significance. Pathobiology 2007; 74: 279-284
    CrossrefPubMedSuche in Google Scholar
  • 4 Heitz PU, Komminoth P, Perren A, Klimstra DS, Dayal Y, Bordi C, LeChago J, Centeno BA, Klöppel G. Pancreatic endocrine tumours: introduction. In: DeLellis RA, Lloyd RV, Heitz PU, Eng C. (eds.) Pathology and genetics: tumours of endocrine organs. WHO classification of tumors. Lyon: IARC Press; 2004: 177-182
    Suche in Google Scholar
  • 5 Klöppel G, Anlauf M. Epidemiology, tumour biology and histopathological classification of neuroendocrine tumours of the gastrointestinal tract. Best Pract Res Clin Gastroenterol 2005; 19: 507-517
    CrossrefPubMedSuche in Google Scholar
  • 6 Klöppel G, Anlauf M. Gastrinoma – morphological aspects. Wien Klin Wochenschr 2007; 119: 579-584
    CrossrefPubMedSuche in Google Scholar
  • 7 Klöppel G, Couvelard A, Perren A, Komminoth P, McNicol AM, Nilsson O, Scarpa A, Scoazec JY, Wiedenmann B, Papotti M, Rindi G, Plöckinger U. Mallorca Consensus Conference participants; European Neuroendocrine Tumor Society . ENETS Consensus Guidelines for the Standards of Care in Neuroendocrine Tumors: towards a standardized approach to the diagnosis of gastroenteropancreatic neuroendocrine tumors and their prognostic stratification. Neuroendocrinology. 2009; 90: 162-166
    PubMedSuche in Google Scholar
  • 8 O’Toole D, Salazar R, Falconi M, Kaltsas G, Couvelard A, de Herder WW, Hyrdel R, Nikou G, Krenning E, Vullierme MP, Caplin M, Jensen R, Eriksson B. Frascati Consensus Conference; European Neuroendocrine Tumor Society . Rare Functioning Pancreatic Endocrine Tumors. Neuroendocrinology 2006; 84: 189-195
    CrossrefPubMedSuche in Google Scholar
  • 9 Rindi G, Arnold R, Bosman FT, Capella C, Klimstra DS, Klöppel G, Komminoth P, Solcia P. Nomenclature and classification of Neuroendocrine neoplasms of the digestive system. In: Bosman FT, Carneiro F, Hruban RH, Theise ND. (eds.) WHO classification of tumors of the digestive system. Lyon: IARC; 2010: 13-14
    Suche in Google Scholar
  • 10 Solcia E, Klöppel G, Sobin LH (In collaboration with 9 pathologists from 4 countries). Histological typing of endocrine tumours. Second Edition. WHO international histological classification of tumours. Berlin: Springer; 2000
    Suche in Google Scholar
  • 11 Klöppel G, Rindi G, Perren A, Komminoth P, Klimstra DS. The ENETS and AJCC/UICC TNM classifications of the neuroendocrine tumors of the gastrointestinal tract and the pancreas: a statement. Virchows Arch 2010; 456: 595-597
    CrossrefPubMedSuche in Google Scholar
  • 12 Sobin LH, Gospodarowicz MK, Wittekind C. (eds.) TNM classification of malignant tumours. 7th edition, New York: Wiley; 2009
  • 13 Klöppel G, Rindi G, Anlauf M, Perren A, Komminoth P. Site-specific biology and pathology of gastroenteropancreatic neuroendocrine tumors. Virchows Arch 2007; 451 (Suppl. 01) 9-27
    CrossrefPubMedSuche in Google Scholar
  • 14 Eissele R, Anlauf M, Schäfer MKH, Eiden LE, Arnold R, Weihe E. Expression of vesicular monoamine transporters in endocrine hyperplasia and endocrine tumors of the oxyntic stomach. Digestion 1999; 60: 428-439
    CrossrefPubMedSuche in Google Scholar
  • 15 Garbrecht N, Anlauf M, Schmitt A, Henopp T, Sipos B, Raffel A, Eisenberger CF, Knoefel WT, Pavel M, Fottner C, Musholt TJ, Rinke A, Arnold R, Berndt U, Plöckinger U, Wiedenmann B, Moch H, Heitz PU, Komminoth P, Perren A, Klöppel G. Somatostatin-producing neuroendocrine tumors of the duodenum and pancreas: incidence, types, biological behavior, association with inherited syndromes, and functional activity. Endocr Relat Cancer 2008; 15: 229-241
    CrossrefPubMedSuche in Google Scholar
  • 16 Garcia-Carbonero R, Capdevila J, Crespo-Herrero G, Díaz-Pérez JA, Martínez Del Prado MP, Alonso Orduña V, Sevilla-García I, Villabona-Artero C, Beguiristain-Gómez A, Llanos-Muñoz M, Marazuela M, Alvarez-Escola C, Castellano D, Vilar E, Jiménez-Fonseca P, Teulé A, Sastre-Valera J, Benavent-Viñuelas M, Monleon A, Salazar R. Incidence, patterns of care and prognostic factors for outcome of gastroenteropancreatic neuroendocrine tumors (GEP-NETs): results from the National Cancer Registry of Spain (RGETNE). Ann Oncol 2010; 21: 1794-17803
    CrossrefPubMedSuche in Google Scholar
  • 17 Ploeckinger U, Kloeppel G, Wiedenmann B, Lohmann R. Representatives of 21 German NET Centers. The German NET-registry: an audit on the diagnosis and therapy of neuroendocrine tumors. Neuroendocrinology 2009; 90: 349-363
    CrossrefPubMedSuche in Google Scholar
  • 18 Schmitt AM, Riniker F, Anlauf M, Schmid S, Soltermann A, Moch H, Heitz PU, Klöppel G, Komminoth P, Perren A. Islet 1 (Isl1) expression is a reliable marker for pancreatic endocrine tumors and their metastases. Am J Surg Pathol 2008; 32: 420-425
    CrossrefPubMedSuche in Google Scholar
  • 19 Vinik AI, Woltering EA, Warner RR, Caplin M, O’Dorisio TM, Wiseman GA, Coppola D, Go VL. North American Neuroendocrine Tumor Society (NANETS). NANETS consensus guidelines for the diagnosis of neuroendocrine tumors. Pancreas 2010; 39: 713-734
    CrossrefPubMedSuche in Google Scholar
  • 20 Miederer M, Seidl S, Buck A, Scheidhauer K, Wester HJ, Schwaiger M, Perren A. Correlation of immunohistopathological expression of somatostatin receptor 2 with standardised uptake values in 68Ga-DOTATOC PET/CT. Eur J Nucl Med Mol Imaging 2009; 36: 48-52
    CrossrefPubMedSuche in Google Scholar
  • 21 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. 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
    CrossrefPubMedSuche in Google Scholar
  • 22 Henopp T, Anlauf M, Schmitt A, Schlenger R, Zalatnai A, Couvelard A, Ruszniewski P, Schaps KP, Jonkers YM, Speel EJ, Pellegata NS, Heitz PU, Komminoth P, Perren A, Klöppel G. Glucagon cell adenomatosis: a newly recognised disease of the endocrine pancreas. J Clin Endocrinol Metab 2009; 94: 213-217
    PubMedSuche in Google Scholar
  • 23 Scarpa A, Mantovani W, Capelli P, Beghelli S, Boninsegna L, Bettini R, Panzuto F, Pederzoli P, delle Fave G, Falconi M. Pancreatic endocrine tumors: improved TNM staging and histopathological grading permit a clinically efficient prognostic stratification of patients. Mod Pathol 2010; 23: 824-833
    CrossrefPubMedSuche in Google Scholar
  • 24 Falconi M, Plockinger U, Kwekkeboom DJ, Manfredi R, Korner M, Kvols L, Pape UF, Ricke J, Goretzki PE, Wildi S, Steinmuller T, Oberg K, Scoazec JY. Frascati Consensus Conference; European Neuroendocrine Tumor Society. Well-Differentiated Pancreatic Nonfunctioning Tumors/Carcinoma. Neuroendocrinology 2006; 84: 196-211
    CrossrefPubMedSuche in Google Scholar
  • 25 Nilsson O, Van Cutsem E, Delle Fave G, Yao JC, Pavel ME, McNicol AM, Sevilla Garcia MI, Knapp WH, Keleştimur F, Sauvanet A, Pauwels S, Kwekkeboom DJ, Caplin M. Frascati Consensus Conference; European Neuroendocrine Tumor Society . Poorly Differentiated Carcinomas of the Foregut (Gastric, Duodenal and Pancreatic). Neuroendocrinology 2006; 84: 212-215
    CrossrefPubMedSuche in Google Scholar
  • 26 Adams S, Baum RP, Hertel A, Schumm-Dräger PM, Usadel KH, Hörsch G. Metabolic (PET) and receptor (SPET) imaging of well- and less well-differentiated tumours: comparison with the expression of the Ki-67 antigen. Nucl Med Commun 1998; 19: 641-647
    CrossrefPubMedSuche in Google Scholar
  • 27 Baum RP, Prasad V. PET and PET/CT. Imaging of Neuroendocrine Tumors. In: Wahl RL. (ed.) Principles and Practice of PET and PET/CT. 2nd Edition, Wolters Kluwer/Lippincott Williams & Wilkins; 2008: 411-437
    Suche in Google Scholar
  • 28 Baum RP, Prasad V, Hommann M, Hörsch D. Receptor PET/CT imaging of neuroendocrine tumors. Recent Results Cancer Res 2008; 170: 225-242
    PubMedSuche in Google Scholar
  • 29 Pape UF, Jann H, Müller-Nordhorn J, Bockelbrink A, Berndt U, Willich SN, Koch M, Röcken C, Rindi G, Wiedenmann B. Prognostic relevance of a novel TNM classification system for upper gastroenteropancreatic neuroendocrine tumors. Cancer 2008; 113: 256-265
    CrossrefPubMedSuche in Google Scholar
  • 30 Rindi G, Klöppel G, Alhman H, Caplin M, Couvelard A, de Herder WW, Erikssson B, Falchetti A, Falconi M, Komminoth P, Körner M, Lopes JM, McNicol AM, Nilsson O, Perren A, Scarpa A, Scoazec JY, Wiedenmann B. and all other Frascati Consensus Conference participants; European Neuroendocrine Tumor Society . TNM staging of foregut (neuro)endocrine tumors: a consensus proposal including a grading system. Virchows Arch 2006; 449: 395-401
    CrossrefPubMedSuche in Google Scholar
  • 31 Rindi G, Klöppel G, Couvelard A, Komminoth P, Körner M, Lopes JM, McNicol AM, Nilsson O, Perren A, Scarpa A, Scoazec JY, Wiedenmann B. TNM staging of midgut and hindgut (neuro) endocrine tumors: a consensus proposal including a grading system. Virchows Arch 2007; 451: 757-762
    CrossrefPubMedSuche in Google Scholar