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Endokrines Pankreas

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Pathologie

Zusammenfassung

Das Kapitel konzentriert sich auf die morphologisch-pathogenetische Diskussion und bildliche Dokumentation des Diabetes mellitus und der neuroendokrinen Neoplasien. Bei den Tumoren wird speziell auf die Prognose in Abhängigkeit von Differenzierungsgrad und Hormonproduktion eingegangen. Weiterhin enthält das Kapitel alle seltenen Erkrankungen des endokrinen Pankreas, wie die Nesidioblastose bei Kindern und Erwachsenen. Das Kapitel ist für Pathologen und Kliniker gleichermaßen informativ.

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Literatur

  1. Agaimy A, Erlenbach-Wünsch K, Konukiewitz B, Schmitt AM, Rieker RJ, Vieth M, Kiesewetter F, Hartmann A, Zamboni G, Perren A, Klöppel G (2013) ISL1 expression is not restricted to pancreatic well-differentiated neuroendocrine neoplasms, but is also commonly found in well and poorly differentiated neuroendocrine neoplasms of extrapancreatic origin. Modern Pathology 26:995–1003

    CAS  PubMed  Google Scholar 

  2. Albazaz R, Da Costa PE, Verbeke CS (2006) Pancreatic polypeptide cell hyperplasia of the pancreas. J Clin Pathol 59:1087–1090

    PubMed Central  CAS  PubMed  Google Scholar 

  3. Albers N, Löhr M, Bogner U, Loy V, Klöppel G (1989) Nesidioblastosis of the pancreas in an adult with persistent hyperinsulinemic hypoglycemia. Am J Clin Pathol 91:94–98

    Google Scholar 

  4. Anlauf M, Wieben D, Perren A, Sipos B, Komminoth P, Raffel A, Kruse ML, Fottner C, Knoefel WT, Mönig H, Heitz PU, Klöppel G (2005) Persistent hyperinsulinemic hypoglycemia in 15 adults with diffuse nesidioblastosis. Am J Clin Pathol 92:524–533

    Google Scholar 

  5. Anlauf M, Schlenger R, Perren A et al (2006) Microadenomatosis of the endocrine pancreas in patients with and without the multiple endocrine neoplasia type 1 syndrome. Am J Surg Pathol 30:560–574

    PubMed  Google Scholar 

  6. Anlauf M, Enosawa T, Henopp T et al (2008) Primary lymph node gastrinoma or occult duodenal microgastrinoma with lymph node metastases in a MEN1 patient: the need for a systematic search for the primary tumor. Am J Surg Pathol 32:1101–1105

    PubMed  Google Scholar 

  7. Anlauf M, Bauersfeld J, Raffel A et al (2009) Insulinomatosis. A multicentric insulinoma disease that frequently causes early recurrent hyperinsulinemic hypoglycemia. Am J Surg Pathol 33:339–346

    PubMed  Google Scholar 

  8. Arva NC, Pappas JG, Bhatla T, Raetz EA, Macari M, Ginsburg HB, Hajdu CH (2012) Well-differentiated pancreatic neuroendocrine carcinoma in tuberous sclerosis – case report and review of the literature. Am J Surg Pathol 36:149–153

    PubMed  Google Scholar 

  9. Ashton MA (1995) Strumal carcinoid of the ovary associated with hyperinsulinaemic hypoglycaemia and cutaneous melanosis. Histopathology 27:463–467

    CAS  PubMed  Google Scholar 

  10. Atkinson MA, Maclaren NK (1994) The pathogenesis of insulin dependent diabetes mellitus. N Engl J Med 331:1428–1436

    CAS  PubMed  Google Scholar 

  11. Basturk O, Hruban R, Krasinskas A, Jang K-T, Liu X, Vakiani E, Zhang L, Frankel W, Giordano T, Bellizi A, Chen J-H, Deshpande, Yang Z, Klimstra DS (2013) High-grade neuroendocrine carcinomas of the pancreas: a clinicopathologic analysis of 60 cases (abstract). Mod Pathol 26:2–423A

    Google Scholar 

  12. Bertrams J, Sodomann P, Gries FA, Sachsse B, Jahnke K (1981) Die HLA-Assoziation des insulinpftlichtigen Diabetes mellitus, Typ  I. Dtsch Med Wochenschr 106:927–932

    CAS  PubMed  Google Scholar 

  13. Binnick AN, Spencer SK, Dennison WL, Horton ES (1977) Glucagonoma syndrome. Arch Dermatol 113:749–754

    CAS  PubMed  Google Scholar 

  14. Binnick AN, Spencer SK, Dennison WL, Horton ES (1977) Glucagonoma syndrome. Report of two cases and literature review. Arch Dermatol 113:749–754

    CAS  PubMed  Google Scholar 

  15. Bloom SR, Polak JM, Pearse AGE (1973) Vasoactive intestinal peptide and watery-diarrhea syndrome. Lancet ii:1416

    Google Scholar 

  16. Blum D, Dorchy H, Mouraux T et al (1993) Congenital absence of insulin cells in a neonate with diabetes mellitus and mutase-deficient methylmalonic acidaemia. Diabetologia 36:352–357

    CAS  PubMed  Google Scholar 

  17. Bojestig M, Amqvist HJ, Hermansson G, Karlberg BE, Ludvigsson J (1994) Declining incidence of nephropathy in insulin-dependent diabetes mellitus. N Engl J Med 330:15–18

    CAS  PubMed  Google Scholar 

  18. Bommer G, Friedel U, Heitz PU, Klöppel G (1980) PP cell distribution and hyperplasia: Immunocytochemical morphology in the normal pancreas, chronic pancreatitis and pancreatic carcinoma. Virchows Arch A Pathol Anat Histol 387:319–331

    CAS  PubMed  Google Scholar 

  19. Bordi C, DeVita O, Pollice L (1985) Full pancreatic endocrine differentiation in a mediastinal teratoma. Hum Pathol 16:961–964

    CAS  PubMed  Google Scholar 

  20. Borromeo CM, Pottier X, In’t Veld PA, Pipeleers-Marichal MA, Kaufmann L, Pipeleers DG, Van Schravendijk CF (2005) Heterogeneity in distribution of amyloid-positive islets in type-2 diabetic patients. Virchows Arch 446:232–238

    CAS  PubMed  Google Scholar 

  21. Bosman FT, Carneiro F, Hruban RH, Theise N (2010) WHO classification of tumours of the digestive tract, liver, biliary tree and pancreas. IARC Press, Lyon

    Google Scholar 

  22. Bottazzo GF, Florin-Christensen A, Doniach D (1974) Islet-cell antibodies in diabetes mellitus with autoimmune polyendocrine deficiencies. Lancet ii:1279–1283

    Google Scholar 

  23. Bouwens L, Pipeleers DG (1998) Extra-insular beta cells associated with ductules are frequent in adult human pancreas. Diabetologia 41:629–633

    CAS  PubMed  Google Scholar 

  24. Bouwens L, Klöppel G (1996) Islet cell neogenesis in the pancreas. Virchows Arch 427:553–560

    CAS  PubMed  Google Scholar 

  25. Butler AE, Janson J, Bonner-Weir S, Ritzel R, Rizza RA, Butler PC (2003) β-cell deficit and increased β-cell apoptosis in humans with type 2 diabetes. Diabetes 52:102–110

    CAS  PubMed  Google Scholar 

  26. Capella C, Solcia E, Frigerio B et al (1977) The endocrine cells of the pancreas and related tumours. Ultrastructural study and classification. Virchows Arch A Pathol Anat Histol 373:327–352

    CAS  PubMed  Google Scholar 

  27. Capella C, Polak JM, Buffa R et al (1983) Morphologic patterns and diagnostic criteria of VIP-producing endocrine tumors. A histologic, histochemical, ultrastructural and biochemical study of 32 cases. Cancer 52:1860–1874

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  29. Corbo V, Dalai I, Scardoni M, Barbi S, Beghelli S, Bersani S, Albarello L, Doglioni C, Schott C, Capelli P, Chilosi M, Boninsegna L, Becker KF, Falconi M, Scarpa A (2010) MEN1 in pancreatic endocrine tumors: analysis of gene and protein status in 169 sporadic neoplasms reveals alterations in the vast majority of cases. Endocr Relat Cancer 17:771–783

    CAS  PubMed  Google Scholar 

  30. Craighead JE (1977) Viral diabetes. In: Volk BW, Wellmann KF (Hrsg) The diabetic pancreas. BailIiere Tindall, London, S 467–488

    Google Scholar 

  31. DeFronzo RA (1992) Pathogenesis of type 2 (non-insulin dependent): a balanced overview. Diabetologia 35:389–397

    CAS  PubMed  Google Scholar 

  32. Deshpande V, Fernandez-del Castillo C, Muzikansky A et al (2004) Cytokeratin 19 is a powerful predictor of survival in pancreatic endocrine tumors. Am J Surg Pathol 28:1145–1153

    PubMed  Google Scholar 

  33. de Herder WW, Niederle B, Scoazec JY et al (2006) Well-differentiated pancreatic tumor/carcinoma: insulinoma. Neuroendocrinology 84:183–188

    PubMed  Google Scholar 

  34. de Wilde RF, Heaphy CM, Maitra A, Meecker AK, Edil BH, Wolfgang CL, Ellison TA, Schulick RD, Molenaar IQ, Valk GD, Vriens MR, Borel Rinkes IH, Offerhaus GJ, Hruban RH, Matsukuma KE (2012) Loss of ATRX or DAXX expression and concomitant acquisitionof the alternative lengthening of telomeres phenotype are late events in a small subset of MEN-1 syndrome pancreatic neuroendocrine tumors. Mod Pathol 25:1033–1039

    PubMed Central  PubMed  Google Scholar 

  35. Dhawan S, Georgia S, Bhushan A (2007) Formation and regeneration oft the endocrine pancreas. Current Opinion in Cell Biology 19:634–645

    PubMed Central  CAS  PubMed  Google Scholar 

  36. Dietel M, Klöppel G (2013) Mamma, Weibliches Genitale, Schwangerschaft und Kindererkrankungen. Springer, Berlin

    Google Scholar 

  37. Donow C, Pipeleers-Marichal M, Stamm B, Heitz PU, Klöppel G (1990) Pathologie des Insulinoms und des Gastrinoms. Dtsch Med Wochenschr 115:1386–1391

    CAS  PubMed  Google Scholar 

  38. Donow C, Pipeleers-Marichal M, Schröder S et al (1991) Surgical pathology of gastrinoma. Site, size, multicentricity, association with multiple endocrine neoplasia type I, and malignancy. Cancer 68:1329–1334

    CAS  PubMed  Google Scholar 

  39. Fleury A, Flejou JF, Sauvanet A et al (1998) Calcitonin-secreting tumors of the pancreas: about six cases. Pancreas 16:545–550

    CAS  PubMed  Google Scholar 

  40. Florez JC (2008) Newly identified loci highlight beta cell dysfunction as a key cause of type 2 diabetes: where are the insulin resistance genes? Diabetologia 51:1100–1110

    CAS  PubMed  Google Scholar 

  41. Foulis AK, Farquharson MA (1986) Aberrant expression of HLA-DR antigens by insulin-containing B-cells in recent onset type I diabetes mellitus. Diabetes 35:1215–1224

    CAS  PubMed  Google Scholar 

  42. Foulis AK, Farquharson MA, Cameron SO et al (1990) A search for the presence of the enteroviral capsid protein VPI in pancreases of patients with type I (insulin-dependent) diabetes and pancreases and hearts of infants who died of coxsackieviral myocarditis. Diabetologia 33:290–298

    CAS  PubMed  Google Scholar 

  43. Foulis AK, Liddie CN, Farquharson MA, Richmond JA, Weir RS (1986) The histopathology of the pancreas in type I (insulin-dependent) diabetes mellitus: A 25-year review of deaths in patients under 20 years of age in the United Kingdom. Diabetologia 29:267–274

    CAS  PubMed  Google Scholar 

  44. Foulis AK, Farquharson MA, Meager A (1987) Immunoreactive alpha-interferon in insulin secreting B-cells in type 1 (insulin-dependent) diabetes mellitus. Lancet ii:1423–1428

    Google Scholar 

  45. Foulis AK, Francis ND, Farquharson MA, Boylston A (1988) Massive synchronous B-cell necrosis causing type 1 (insulin dependent) diabetes; a unique histopathological case report. Diabetologia 31:46–50

    CAS  PubMed  Google Scholar 

  46. Franko J, Feng W, Yip L, Genovese E, Moser AJ (2010) Non-functional neuroendocrine carcinoma of the pancreas: incidence, tumor biology, and outcomes in 2,158 patients. J Gastrointest Surg 14:541–548

    PubMed  Google Scholar 

  47. Froguel P, Zouali H, Vionnet N et al (1993) Familial hyperglycemia due to mutations in glucokinase. Definition of a subtype of diabetes mellitus. N Engl J Med 328:697–792

    CAS  PubMed  Google Scholar 

  48. Ganda OP (1980) Pathogenesis of macrovascular disease in the human diabetic. Diabetes 29:931–942

    CAS  PubMed  Google Scholar 

  49. Garbrecht N, Anlauf M, Schmitt A, Henoppipos B, Raffel A, Eisenberger CF, Knoefel WT, Pavel M, Fottner C, Musholt T, Rinke A, Arnold R, Berndt U, Plöckinger U, Wiedenmann B, Moch H, Heitz PhU, Komminoth P, Perren A, Klöppel G (2008) Somatostatin-producing neuroendocrine tumors of the duodenum and pancreas: incidence, types, biological behavior, association with inherited syndromes, and functional activity. Endocrine-Related Cancer 15:229–241

    PubMed  Google Scholar 

  50. Gepts W (1965) Pathologic anatomy of the pancreas in juvenile diabetes mellitus. Diabetes 14:619–633

    CAS  PubMed  Google Scholar 

  51. Gepts W, de Mey J (1978) Islet cell survival determined by morphology. An immunocytochemical study of the islets of Langerhans in juvenile diabetes mellitus. Diabetes 27(1):251–261

    PubMed  Google Scholar 

  52. Gepts W (1980) Pancreatic pathology of juvenile diabetes mellitus. In: Podolsky S, Viswanathan M (Hrsg) Secondary diabetes: The spectrum of the diabetic syndromes. Raven Press, New York, S 15–32

    Google Scholar 

  53. Goossens A, Gepts W, Saudubray JM et al (1989) Diffuse and focal nesidioblastosis: A clinicopathological study of 24 patients with persistent neonatal hyperinsulinemic hypoglycemia. Am J Surg Pathol 13:766–775

    CAS  PubMed  Google Scholar 

  54. Gorsuch AN, Lister J, Dean BM et al (1981) Evidence for a long prediabetic period in type I (insulin-dependent) diabetes mellitus. Lancet ii:1363–1365

    Google Scholar 

  55. Gössner W, Korting GW (1960) Metastasierendes InselzeIlkarzinom vom A-Zelltyp bei einem Fall von Pemphigus foliaceus mit Diabetes renalis. Dtsch Med Wochenschr 11:434–437

    Google Scholar 

  56. Guarda LA, Silva EG, Ordonez NG et al (1983) Clear cell islet cell tumor. Am J Clin Pathol 79:512–517

    CAS  PubMed  Google Scholar 

  57. Halfdanarson TR, Rabe KG, Rubin J, Petersen GM (2008) Pancreatic neuroendocrine tumors (PNETs): incidence, prognosis and recent trend toward improved survival. Ann Oncol 19:1727–1733

    PubMed Central  CAS  PubMed  Google Scholar 

  58. He J, Zhao F, Li H, Zhou K, Zhu B (2011) Pancreatic paraganglioma: A case report of CT manifestations and literature review. Quant Imaging Med Surg 1:41–43

    PubMed Central  PubMed  Google Scholar 

  59. Heitz PU, Klöppel G, Häcki WH, Polak JM, Pearse AGE (1977) Nesidioblastosis: the pathologic basis of persistent hyperinsulinemic hypoglycemia in infants. Morphologic and quantitative analysis of seven cases based on specific immunostaining and electron microscopy. Diabetes 26:632–642

    CAS  PubMed  Google Scholar 

  60. Heitz PU, Klöppel G, Polak JM, Staub J-J (1981) Ectopic hormone production by endocrine tumors: localization of hormones at the cellular level by immunocytochemistry. Cancer 48:2029–2037

    CAS  PubMed  Google Scholar 

  61. Heitz PU, Kasper M, Polak JM, Klöppel G (1982) Pancreatic endocrine tumours. Immunohistochemical analysis of 125 tumours. Hum Pathol 13:263–271

    CAS  PubMed  Google Scholar 

  62. Heitz, Komminoth P, Perren A et al (2004) Pancreatic endocrine tumours: introduction. In: DeLellis RA, Lloyd RV, Heitz PU, Eng C (Hrsg) Pathology and genetics: tumours of endocrine organs. WHO classification of tumors. IARC Press, Lyon, S 177–182

    Google Scholar 

  63. 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 (2009) Glucagon cell adenomatosis: a newly recognized disease of the endocrine pancreas. J Clin Endocrinol Metab 94:213–217

    CAS  PubMed  Google Scholar 

  64. Henopp T, Anlauf M, Biskup S, Klöppel G, Sipos B (2012) Genetic alterations in glucagon cell adenomatosis. In: Proceedings from 9th Annual European Neuroendocrine Tumor Society Conference for the Diagnosis and Treatment of Neuroendocrine Tumor Disease March 7–9, 2012, Copenhagen, Denmark. (Abstract C57)

    Google Scholar 

  65. 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

    CAS  PubMed  Google Scholar 

  66. Hoang MP, Hruban RH, Albores-Saavedra J (2001) Clear cell endocrine pancreatic tumor mimicking renal cell carcinoma: a distinctive neoplasm of von Hippel-Lindau disease. Am J Surg Pathol 25:602–609

    CAS  PubMed  Google Scholar 

  67. Höfler H, Denk H, Lackinger E, Helleis G, Polak JM, Heitz PU (1986) Immunocytochemical demonstration of intermediate filament cytoskeleton proteins in human endocrine tissues and (neuro-) endocrine tumours. Virchows Arch [A] Pathol Anat 409:609–626

    Google Scholar 

  68. Honicky RE, DePapp EW (1973) Mediastinal teratoma with endocrine function. Am J Dis Child 126:650

    CAS  PubMed  Google Scholar 

  69. Hultquist GT, Olding LB (1981) Endocrine pathology of infants of diabetic mothers. Acta Endocrinol (Suppl) 241:97

    Google Scholar 

  70. In’t Veld P, Lievens D, DeGrijse J, Ling Z, Van der Auwers B, Pipeleers-Marichal M, Gorus F, Pipeleers D (2007) Screening for insulitis in adult autoantibody-positive organ donors. Diabetes 56:2400–2404

    PubMed  Google Scholar 

  71. In’t Veld P, De Munck N, VanBelle K, Buelens N, Ling Z, Weets I, Haentjes P, Pipeleers-Marichal M, Gorus F, Pipeleers D (2010) Beta-cell replication is increased in donor organs from young patients after prolonged life support. Diabetes 59:1702–1708

    PubMed  Google Scholar 

  72. In’t Veld P (2011) Insulitis in human type 1 diabetes: The quest for an elusive lesion. Islets 3:131–138

    PubMed Central  PubMed  Google Scholar 

  73. Isenberg JI, Walsh JH, Grossman MI (1973) Zollinger-Ellison syndrome. Gastroenterology 65:140–165

    CAS  PubMed  Google Scholar 

  74. Jaffe R, Hashida Y, Yunis EJ (1980) Pancreatic pathology in hyperinsulinemic hypoglycemia of infancy. Lab Invest 42:356–365

    CAS  PubMed  Google Scholar 

  75. Jeanrenaud B (1979) Insulin and obesity. Diabetologia 17:133–138

    CAS  PubMed  Google Scholar 

  76. Jenson AB, Rosenberg HS, Notkills AL (1980) Pancreas islet-cell damage in children with fatal viral infections. Lancet ii:354–358

    Google Scholar 

  77. Jiao Y, Shi C, Edil BH et al (2011) DAXX/ATRX, MEN1, and mTOR pathway genes are frequently altered in pancreatic neuroendocrine tumors. Science 331:1199–1203

    PubMed Central  CAS  PubMed  Google Scholar 

  78. Kaemmerer D, Prasad V, Daffner W, Hörsch D, Klöppel G, Hommann M, Baum RP (2009) Neoadjuvant peptide receptor radionuclide therapy for an inoperable neuroendocrine pancreatic tumor. World J Gastroenterol 15:5867–5870

    PubMed Central  PubMed  Google Scholar 

  79. Kanakis G, Kaltsas G, Granberg D, Grimelius L, Papaioannou D, Tsolakis AV, Öberg K (2012) Unusual complication of a pancreatic neuroendocrine tumor presenting with malignant hypercalcemia. J Clin Endocrinol Metab 97:E627–631

    CAS  PubMed  Google Scholar 

  80. Kapran Y, Bauersfeld J, Anlauf M, Sipos B, Klöppel G (2006) Multihormonality and entrapment of islets in pancreatic endocrine tumors. Virchows Arch 448:394–398

    CAS  PubMed  Google Scholar 

  81. Kimura W, Kuroda A, Morioka Y (1991) Clinical pathology of endocrine tumors of the pancreas. Analysis of autopsy cases. Dig Dis Sci 36:933–942

    CAS  PubMed  Google Scholar 

  82. Klimstra DS, Arnold R, Capella C, Hruban RH, Klöppel G, Komminoth P, Solcia E, Rindi G (2010) Neuroendocrine tumors of the pancreas. In: Bosman FT, Carneiro F, Hruban RH, Theise ND (Hrsg) World Health Organization Classification of Tumours of the Digestive System. IARC, Lyon, France, S 322–326

    Google Scholar 

  83. Klöppel G, Bommer G, Commandeur G, Heitz PU (1978) The endocrine pancreas in chronic pancreatitis. Immunocytochemical and ultrastructural studies. Virchows Arch [A] Pathol Anat 377:157–174

    Google Scholar 

  84. Klöppel G (1981) Endokrines Pankreas und Diabetes melllitus. In: Doerr W, Seifert G (Hrsg) Spezielle pathologische Anatomie, Bd. 14. Springer, Berlin, S 523–728

    Google Scholar 

  85. Klöppel G, Drenck CR, Oberholzer M, Heitz PU (1984) Morphometric evidence for a striking B-cell reduction at the clinical onset of type I diabetes. Virchows Arch [A] Pathol Anat 403:441–452

    Google Scholar 

  86. Klöppel G (1985) Experimental insulitis. In: Volk BW, Arquilla ER (Hrsg) The diabetic pancreas, 2. Aufl. Plenum, New York, S 467–492

    Google Scholar 

  87. Klöppel G, Löhr M, Habich K, Oberholzer M, Heitz PU (1985) Islet pathology and the pathogenesis of type l and type 2 diabetes mellitus revisited. Surv Synth Pathol Res 4:110–125

    PubMed  Google Scholar 

  88. Klöppel G, Willemer S, Stamm B, Häcki WH, Heitz PU (1986) Pancreatic lesions and hormonal profile of pancreatic tumors in multiple endocrine neoplasia type I. An immunocytochemical study of nine patients. Cancer 57:1824–1832

    PubMed  Google Scholar 

  89. Klöppel G (1997) Exokrines Pankreas. In: Remmele W (Hrsg) Pathologie, Bd. 3. Springer, Berlin, S 336–386

    Google Scholar 

  90. Klöppel G, In (1997) Morphology of the pancreas in normal and diabetic states. In: Alberti KGMM, DeFronzo RA, Keen H, Zimmet P (Hrsg) International textbook of diabetes mellitus, 2. Aufl. John Wiley & Sons, Chichester, S 287–314 (chapter 13)

    Google Scholar 

  91. Klöppel G, Anlauf M (2007) Gastrinoma - morphological aspects. Wien Klin Wochenschr 119:579–584

    PubMed  Google Scholar 

  92. Klöppel G, Anlauf M, Raffel A, Perren A, Knoefel WT (2008) Adult diffuse nesidioblastosis: genetically or environmentally induced? Hum Pathol 39:3–8

    PubMed  Google Scholar 

  93. Klöppel G, Couvelard A, Perren A, Komminoth P, McNicole AM, Nilsson O, Scarpa A, Scoazec JY, Wiedenmann B, Papotti M et al (2009) 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 90:162–166

    PubMed  Google Scholar 

  94. Klöppel G (2011) Classification and pathology of gastroenteropancreatic neuroendocrine neoplasms. Endocrine-Related Cancer 18:S1–S7

    PubMed  Google Scholar 

  95. Konukiewitz B, Enosawa T, Kloppel G (2011) Glucagon expression in cystic pancreatic neuroendocrine neoplasms: an immunohistochemical analysis. Virchows Arch 458:47–53

    CAS  PubMed  Google Scholar 

  96. Krejs GJ, Orci L, Conlon JM et al (1979) Somatostatinoma syndrome. Biochemical, morphologic and clinical features. N Engl J Med 301:285–292

    CAS  PubMed  Google Scholar 

  97. Kumar D, Gemayel NS, Deapen D et al (1993) North American twins with IODM. Genetic, etiological, and clinical significance of disease concordance according to age, zygosity, and the interval after diagnosis in first twin. Diabetes 42:1351–1363

    CAS  PubMed  Google Scholar 

  98. Laidlaw GF (1938) Nesidioblastoma, the islet tumor of the pancreas. Am J Pathol 14:125–134

    PubMed Central  CAS  PubMed  Google Scholar 

  99. La Rosa S, Marando A, Ghezzi F, Colombo P, Finzi G, Capella C (2011) Cushing’s syndrome due to a pancreatic neuroendocrine tumor metastatic to the ovaries: a clinicopathological description of a case. Endocr Pathol 22:118–124

    PubMed  Google Scholar 

  100. La Rosa S, Franzi F, Albarello L, Schmitt A, Bernasconi B, Tibiletti MG, Finzi G, Placidi C, Perren A, Capella C (2011) Serotonin-producing enterochromaffin cell tumors of the pancreas: clinicopathologic study of 15 cases and comparison with intestinal enterochromaffin cell tumors. Pancreas 40:883–895

    PubMed  Google Scholar 

  101. La Rosa S, Marando A, Sessa F, Capella C (2012) Mixed Adenoneuroendocrine Carcinomas (MANECs) of the Gastrointestinal Tract: An Update. Cancers 4:11–30

    PubMed Central  PubMed  Google Scholar 

  102. La Rosa S, Adsay V, Albarello L, Asioli S, Casnedi S, Franzi F, Marando A, Notohara K, Sessa F, Vanoli A, Zhang L, Capella C (2012) Clinicopathologic study of 62 acinar cell carcinomas of the pancreas: insights into the morphology and immunophenotype and search for prognostic markers. Am J Surg Pathol 36:1782–1795

    PubMed  Google Scholar 

  103. Larson AM, Hedgire SS, Deshpande V, Stemmer-Rachamimov AO, Harisinghani MG, Ferrone CR, Shah U, Thiele EA (2012) Pancreatic neuroendocrine tumors in patients with tuberous sclerosis complex. Clin Genet 82:558–563

    CAS  PubMed  Google Scholar 

  104. Lernmark A (1987) Islet cell antibodies. Diabet Med 4:285–292

    CAS  PubMed  Google Scholar 

  105. Lernmark A, Klöppel G, Stenger D et al (1995) Heterogeneity of islet pathology in two infants with recent onset diabetes mellitus. Virchows Arch 425:631–640

    CAS  PubMed  Google Scholar 

  106. Lo CY, Lam KY, Kung AW et al (1997) Pancreatic insulinomas. A 15-year experience. Arch Surg 132:926–930

    CAS  PubMed  Google Scholar 

  107. Löhr M, Klöppel G (1987) Residual insulin positivity and pancreatic atrophy in relation to duration of chronic type I (insulin-dependent) diabetes mellitus and microangiopathy. Diabetologia 30:757–762

    PubMed  Google Scholar 

  108. Löhr M, Schmitt P, Klöppel G (1988) Inselveränderungen beim Insulin-abhängigen Diabetes im Alter. Immunzytochemische Pankreasuntersuchungen bei einer diabetischen Patientin mit Hypothyreose. Pathologe 9:103–108

    PubMed  Google Scholar 

  109. Löhr M, Goertchen P, Nizze H et al (1989) Islet changes associated with advanced cystic fibrosis. An immunocytochemical and morphometrical study. Virchows Arch [A] Pathol Anat 414:179–185

    Google Scholar 

  110. Majumder S, Grabska J, Trikudanathan G, Kowalczyk P, Stoica-Mustafa E, Dasanu CA (2012) Functional ’composite’ pheochromocytoma-ganglioneuroma presenting as a pancreatic mass. Pancreatology 12:211–214

    PubMed  Google Scholar 

  111. Malaisse-Lagae F, Stefan Y, Cox J, Perrelet A, Orci L (1979) Identification of a lobe in the adult human pancreas rich in pancreatic polypeptide. Diabetologia 17:361–365

    CAS  PubMed  Google Scholar 

  112. Marquard J, Palladino AA, Stanley CA, Mayatepek E, Meissner T (2011) Rare forms of congenital hyperinsulinism. Seminars in Pediatric Surgery 20:38–41

    PubMed  Google Scholar 

  113. Martella EM, Ferraro G, Azzoni C et al (1997) Pancreatic-polypeptide cell hyperplasia associated with pancreatic or duodenal gastrinomas. Hum Pathol 28:149–153

    CAS  PubMed  Google Scholar 

  114. Maton PN, Gardner JD, Jensen RT (1986) Cushing’s syndrome in patients with the Zollinger-Ellison syndrome. N Engl J Med 315:1–5

    CAS  PubMed  Google Scholar 

  115. McCall CM, Shi C, Klein AP, Konukiewitz B, Edil BH, Ellison TA, Wolfgang CL, Schulick RD, Klöppel G, Hruban RH (2012) Serotonin expression in pancreatic neuroendocrine tumors correlates with a trabecular histologic pattern and large duct involvement. Hum Pathol 43:1169–1176

    PubMed Central  CAS  PubMed  Google Scholar 

  116. Missiaglia E, Dalai I, Barbi S, Beghelli S, Falconi M, della Peruta M, Piemonti L, Capurso G, Di Florio A, delle Fave G, Pederzoli P, Croce CM, Scarpa A (2009) Pancreatic endocrine tumors: expression profiling evidences a role for AKT-mTOR pathway. J Clin Oncol 28:245–255

    PubMed Central  PubMed  Google Scholar 

  117. Miyazaki K, Funakoshi A, Nishihara S et al (1986) Aberrant insulinoma in the duodenum. Gastroenterology 90:1280–1285

    CAS  PubMed  Google Scholar 

  118. Nawroth PP (1999) Kompendium Diabetologie. Springer, Berlin

    Google Scholar 

  119. O‘Brien TD, Butler PC, Westermark P, Johnson KH (1993) Islet amyloid polypeptide: A review of its biology and potential roles in the pathogenesis of diabetes mellitus. Vet Pathol 30:317–332

    PubMed  Google Scholar 

  120. Ogilvie RF (1964) The endocrine pancreas in human diabetes. In: Brolin SE, Hellmann B, Knutsen H (Hrsg) The structure and metabolism of the pancreatic islet. Series 3. Pergamon Press, Oxford, S 499–511

    Google Scholar 

  121. Osterby R (1992) Glomerular structural changes in type I (insulin-dependent) diabetes mellitus: causes, consequences, and prevention. A review Diabetologia 35:803–812

    CAS  PubMed  Google Scholar 

  122. Padberg B, Schröder S, Capella C et al (1995) Multiple endocrine neoplasia type I (MEN I) revisited. Virchows Arch 426:541–548

    CAS  PubMed  Google Scholar 

  123. Papotti M, Bongiovanni M, Volante M et al (2002) Expression of somatostatin receptor types 1–5 in 81 cases of gastrointestinal and pancreatic endocrine tumors. A correlative immunohistochemical and reverse-transcriptase polymerase chain reaction analysis. Virchows Arch 440:461–475

    CAS  PubMed  Google Scholar 

  124. Pavel M et al. Barcelona Consensus Conference participants (2012) ENETS Consensus Guidelines for the management of patients with liver and other distant metastases from neuroendocrine neoplasms of foregut, midgut, hindgut, and unknown primary. Neuroendocrinology 95:157–176

    CAS  PubMed  Google Scholar 

  125. Pearse AGE, Polak JM (1974) Endocrine tumours of neural crest origin: Neurolophomas, apudomas and the APUD concept. Med Biol 5:3–18

    Google Scholar 

  126. Perez-Montiel MD, Frankel WL, Suster S (2003) Neuroendocrine carcinomas of the pancreas with ’Rhabdoid’ features. Am J Surg Pathol 27:642–649

    PubMed  Google Scholar 

  127. Perigny M, Hammel P, Corcos O et al (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

    PubMed  Google Scholar 

  128. Perren A, Wiesli P, Schmid S et al (2006) Pancreatic endocrine tumors are a rare manifestation of the neurofibromatosis type 1 phenotype: molecular analysis of a malignant insulinoma in a NF-1 patient. Am J Surg Pathol 30:1047–1051

    PubMed  Google Scholar 

  129. Perren A, Anlauf M, Komminoth P (2007) Molecular profiles of gastroenteropancreatic endocrine tumors. Virchows Arch 451(1):39–46

    Google Scholar 

  130. Perren A, Anlauf M, Henopp T et al (2007) Multiple endocrine neoplasia type 1 (MEN1): loss of one MEN1 allele in tumors and monohormonal endocrine cell clusters but not in islet hyperplasia of the pancreas. J Clin Endocrinol Metab 92:1118–1128

    CAS  PubMed  Google Scholar 

  131. Pipeleers-Marichal MA, Somers G, Willems et al (1990) Gastrinomas in the duodenums of patients with multiple endocrine neoplasia type l and the Zollinger-Ellison syndrome. N Engl J Med 322:723–727

    CAS  PubMed  Google Scholar 

  132. Polak M, Cave H (2007) Neonatal diabetes mellitus: a disease linked to multiple mechanisms. Orphanet J Rare Dis 2:12

    PubMed Central  PubMed  Google Scholar 

  133. Rahier J, Wallon J, Henquin JC (1981) Cell populations in the endocrine pancreas of human neonates and infants. Diabetologia 20:540–546

    CAS  PubMed  Google Scholar 

  134. Rahier J, Loozen S, Goebbels RM, Abrahem M (1987) The haemochromatotic human pancreas: A quantitative immunohistochemical and ultrastructural study. Diabetologia 30:5–12

    CAS  PubMed  Google Scholar 

  135. Rahier J, Guiot Y, Goebbels RM, Sempoux C, Henquin JC (2008) Pancreatic β-cell mass in European subjects with type 2 diabetes. Diabetes, Obesity and Metabolism 10(4):32–42

    PubMed  Google Scholar 

  136. Rahier J, Guiot Y, Sempoux C (2011) Morphologic analysis of focal and diffuse forms of congenital hyperinsulinism. Sem Ped Surg 20:3–12

    Google Scholar 

  137. Rayfield EJ, Yoon IW (1981) Role of viruses in diabetes. In: Cooperstein SJ, WatkinsD (Hrsg) The islets of Langerhans. Biochemistry, physiology and pathology. Academic Press, New York, S 427–451

    Google Scholar 

  138. Reinecke-Lüthge A, Koschoreck F, Klöppel G (2000) The molecular basis of persistent hyperinsulinemic hypoglycemia of infancy and its pathologic substrates. Virchows Arch 436:1–5

    PubMed  Google Scholar 

  139. 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 (2006) TNM staging of foregut (neuro)endocrine tumors: a consensus proposal including a grading system. Virchows Arch 449:395–401

    PubMed Central  CAS  PubMed  Google Scholar 

  140. Rindi G, Falconi M, Klersy C, Albarello L, Boninsegna L, Buchler MW, Capella C, Caplin M, Couvelard A, Doglioni C, Delle Fave G, Fischer L, Fusai G, de Herder WW, Jann H, Komminoth P, de Krijger RR, La Rosa S, Luong TV, Pape U, Perren A, Ruszniewski P, Scarpa A, Schmitt A, Solcia E, Wiedenmann B (2012) TNM Staging of Neoplasms of the Endocrine Pancreas: Results from a Large International Cohort Study. J Natl Cancer Inst 104:764–777

    CAS  PubMed  Google Scholar 

  141. Roth J, Klöppel G, Madsen OD, Storch MJ, Heitz PU (1992) Distribution patterns of proinsulin and insulin in human insulinomas: an immunohistochemical analysis in 76 tumors. Virchows Arch [B] Cell Pathol 63:51–61

    CAS  Google Scholar 

  142. Ruttmann E, Klöppel G, Bommer G, Kiehn M, Heitz PU (1980) Pancreatic glucagonoma with and without syndrome. Immunocytochemical study of 5 tumour cases and review of the literature. Virchows Arch A Pathol Anat Histol 388:51–67

    Google Scholar 

  143. Saeger W, Schulte HM, Kloppel G (1986) Morphology of a GHRH producing pancreatic islet cell tumour causing acromegaly. Virchows Arch A Pathol Anat Histopathol 409:547–554

    CAS  PubMed  Google Scholar 

  144. Scarpa A, Mantovani W, Capelli P, Beghelli S, Boninsegna L, Bettini R, Panzuto F, Pederzoli P, delle Fave G, Falconi M (2010) Pancreatic endocrine tumors: improved TNM staging and histopathological grading permit a clinically efficient prognostic stratification of patients. Modern Pathology 23:824–833

    CAS  PubMed  Google Scholar 

  145. Schmitt AM, Anlauf M, Rousson V, Schmid S, Kofler A, Riniker F, Bauersfeld J, Barghorn A, Probst-Hensch N-M, Moch H, Heitz PU, Klöppel G, Komminoth P, Perren A (2007) WHO 2004 criteria and CK19 are reliable prognostic markers in pancreatic endocrine tumors. Am J Surg Pathol 31:21:1677–1682

    PubMed  Google Scholar 

  146. Schmitt AM, Riniker F, Anlauf M et al (2008) Islet 1 (Isl1) expression is a reliable marker for pancreatic endocrine tumors and their metastases. Am J Surg Pathol 32:420–425

    PubMed  Google Scholar 

  147. Schmitt AM, Schmid S, Rudolph T et al (2009) VHL inactivation is an important pathway for the development of malignant sporadic pancreatic endocrine tumors. Endocrine-Related Cancer 16:1219–1227

    CAS  PubMed  Google Scholar 

  148. Sempoux C, Guiot Y, Dubois D, Moulin P, Rahier J (2001) Morphological evidence for abnormal ß-cell function. Diabetes 50(1):172–S177

    Google Scholar 

  149. Sempoux C, Guiot Y, Jaubert F, Rahier J (2004) Focal and diffuse forms of congenital hyperinsulinism: the keys for differential diagnosis. Endocrine Pathology 15:241–246

    PubMed  Google Scholar 

  150. Sessa F, Arcidiaco M, Valenti L et al (1997) Metastatic psammomatous somatostatinoma of the pancreas causing severe ketoacidotic diabetes cured by surgery. Endocr Pathol 8:327–333

    PubMed  Google Scholar 

  151. Singh R, Basturk O, Klimstra DS et al (2006) Lipid-rich variant of pancreatic endocrine neoplasms. Am J Surg Pathol 30:194–200

    PubMed  Google Scholar 

  152. Sipos S, Sperveslage J, Anlauf M et al (2015) J Clin Endocrinol Metab 100:E783–788

    Google Scholar 

  153. Smith AE, Levi AW, Nadasdy T et al (2001) The pigmented ″black″ neuroendocrine tumor of the pancreas: a question of origin. Cancer 92:1984–1991

    CAS  PubMed  Google Scholar 

  154. Speel EJ, Richter J, Moch H et al (1999) Genetic differences in endocrine pancreatic tumor subtypes detected by comparative genomic hybridization. Am J Pathol 155:1787–1794

    PubMed Central  CAS  PubMed  Google Scholar 

  155. Speel EJ, Scheidweiler AF, Zhao J et al (2001) Genetic evidence for early divergence of small functioning and nonfunctioning endocrine pancreatic tumors: gain of 9Q34 is an early event in insulinomas. Cancer Res 61:5186–5192

    CAS  PubMed  Google Scholar 

  156. Stefanini P, Carboni M, Patrassi N, Basoli A (1974) Beta-islet cell tumors of the pancreas: results of a study on 1067 cases. Surg 75:597–609

    CAS  Google Scholar 

  157. Stolte M, Rüschoff J, Klöppel G (2013) Pathologie. Verdauungstrakt und Peritoneum. Springer, Berlin

    Google Scholar 

  158. Thakker RV (1993) The molecular genetics of the multiple endocrine neoplasia syndromes. Clin Endocrinol 38:1–14

    CAS  Google Scholar 

  159. Triponez F, Goudet P, Dosseh D et al (2006) Is surgery beneficial for MEN1 patients with small (or=2cm), nonfunctioning pancreaticoduodenal endocrine tumor? An analysis of 65 patients from the GTE. World J Surg 30:654–662

    PubMed  Google Scholar 

  160. van Eeden S, de Leng WW, Offerhaus GJ et al (2004) Ductuloinsular tumors of the pancreas: endocrine tumors with entrapped nonneoplastic ductules. Am J Surg Pathol 28:813–820

    PubMed  Google Scholar 

  161. Volante M, La Rosa S, Castellano I et al (2006) Clinico-pathological features of a series of 11 oncocytic endocrine tumours of the pancreas. Virchows Arch 448:545–551

    PubMed  Google Scholar 

  162. Volk BW, Wellmann KF (1977) The diabetic pancreas. BailIiere Tindall, London

    Google Scholar 

  163. Walter T, Hervieu V, Adham M et al (2011) Primary neuroendocrine tumors of the main pancreatic duct: a rare entity. Virchows Arch 458:537–546

    PubMed  Google Scholar 

  164. Weiss DE, Vogel H, Lopes MB, Chang SD, Katznelson L (2011) Ectopic acromegaly due to a pancreatic neuroendocrine tumor producing growth hormone-releasing hormone. Endocr Pract 17:79–84

    PubMed  Google Scholar 

  165. Westermark P, Wilander E (1978) The influence of amyloid deposits on the islet volume in maturity onset diabetes mellitus. Diabetologia 15:417–442

    CAS  PubMed  Google Scholar 

  166. Westermark P, Wilander E, Westermark GT, Johnson KH (1987) Islet amyloid polypeptide-like immunoreactivity in the islet B cells of type 2 (non-insulin-dependent) diabetic and non-diabetic individuals. Diabetologia 30:887–892

    CAS  PubMed  Google Scholar 

  167. Willcox A, Richardson SJ, Bone AJ, Foulis AK, Morgan NG (2008) Analysis of islet inflammation in human type 1 diabetes. Clin Exp Immunol 155:173–181

    Google Scholar 

  168. Willcox A, Richardson SJ, Bone AJ, Foulis AK, Morgan NG (2010) Evidence of increased islet cell proliferation in patients with recent-onset type 1 diabetes. Diabetologia 53:2020–2028

    CAS  PubMed  Google Scholar 

  169. Willcox A, Richardson SJ, Bone AJ, Foulis AK, Morgan NG (2011) Immunohistochemical analysis of the relationship between islet cell proliferation and the production of the enteroviral capseid protein, VP1, in the islets of patients with recent-onset type 1 diabetes. Diabetologia 54:2417–2420

    CAS  PubMed  Google Scholar 

  170. Wöckel W, Scheibner K (1977) Aplasie des Pankreas mit Diabetes mellitus, intrahepatischer Gallengangsaplasie und weiteren Missbildungen bei einem hypotrophen Neugeborenen. Zentralbl Allg Pathol Pathol Anat 121:186–194

    Google Scholar 

  171. Yachida S, Vakiani E, White CM et al (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

    PubMed Central  PubMed  Google Scholar 

  172. Yang Z, Tang LH, Klimstra DS (2011) 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 35:853–860

    PubMed  Google Scholar 

  173. Yoon JW, Austin M, Onodera T, Notkins AL (1979) Virus-induced diabetes mellitus. Isolation of a virus from the pancreas of a child with diabetic ketoacidosis. N Engl J Med 300:1173–1179

    CAS  PubMed  Google Scholar 

  174. Yoon KH, Ko SH, Cho JH, Ahn YB, Song KH, Yoo SJ, Kang MI, Cha By, Lee KW, Son HY, Kang SK, Kim HS, Lee IK, Bonner-Weir S (2003) Selective beta-cell loss and alpha cell expansion in patients with type 2 diabetes mellitus in Korea. J Clin Endocrinol Metab 88:2300–2308

    CAS  PubMed  Google Scholar 

  175. Zee SY, Hochwald SN, Conlon KC, Brennan MF, Klimstra DS (2005) Pleomorphic pancreatic endocrine neoplasms: a variant commonly confused with adenocarcinoma. Am J Surg Pathol 29:1194–1200

    PubMed  Google Scholar 

  176. Zhao J, Moch H, Scheidweiler AF et al (2001) Genomic imbalances in the progression of endocrine pancreatic tumors. Genes Chromosomes Cancer 32:364–372

    CAS  PubMed  Google Scholar 

  177. Zhou C, Dhall D, Nissen NN, Chen C, Yu R (2009) Homozygous P86S mutation oft he human glucagon receptor is associated with hyperglucagonemia, alpha cell hyperplasia, and islet cell tumor. Pancreas 38:941–946

    PubMed Central  CAS  PubMed  Google Scholar 

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Klöppel, G., Komminoth, P., Heitz, P.U. (2016). Endokrines Pankreas. In: Amann, K., Kain, R., Klöppel, G. (eds) Pathologie. Pathologie. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-04566-0_24

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