Skip to main content

Advertisement

SpringerLink
Log in

Hyperplasia to Neoplasia Sequence of Duodenal and Pancreatic Neuroendocrine Diseases and Pseudohyperplasia of the PP-cells in the Pancreas

  • Published:
Endocrine Pathology Aims and scope Submit manuscript

Abstract

Hyperplastic changes of the neuroendocrine cell system may have the potential to evolve into neoplastic diseases. This is particularly the case in the setting of genetically determined and hereditary neuroendocrine tumor syndromes such as MEN1. The review discusses the MEN1-associated hyperplasia–neoplasia sequence in the development of gastrinomas in the duodenum and glucagon-producing tumors in the pancreas. It also presents other newly described diseases (e.g., glucagon cell adenomatosis and insulinomatosis) in which the tumors are (or most likely) also preceded by islet cell hyperplasia. Finally, the pseudohyperplasia of PP-rich islets in the pancreatic head is defined as a physiologic condition clearly differing from other hyperplastic–neoplastic neuroendocrine diseases.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Anlauf M, Garbrecht N, Henopp T et al. Sporadic versus hereditary gastrinomas of the duodenum and pancreas: distinct clinico-pathological and epidemiological features. World J. Gastroenterol. 12: 5440-5446, 2006.

    PubMed  Google Scholar 

  2. Kloppel G Classification and pathology of gastroenteropancreatic neuroendocrine neoplasms. Endocrine-related cancer 18 Suppl 1: S1-16, 2011.

    Article  PubMed  Google Scholar 

  3. Capella C, Riva C, Rindi G et al. Histopathology, hormone products, and clinicopathological profile of endocrine tumors of the upper small intestine: a study of 44 cases. Endocr. Pathol. 2: 92-110, 1991.

    Article  Google Scholar 

  4. Anlauf M, Enosawa T, Henopp T et al. 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. American Journal of Surgical Pathology 32: 1101-1105, 2008.

    Article  PubMed  Google Scholar 

  5. Anlauf M, Perren A, Henopp T et al. Allelic deletion of the MEN1 gene in duodenal gastrin and somatostatin cell neoplasms and their precursor lesions. Gut 56: 637-644, 2007.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  6. Merchant SH, VanderJagt T, Lathrop S, Amin MB Sporadic duodenal bulb gastrin-cell tumors: association with Helicobacter pylori gastritis and long-term use of proton pump inhibitors. American Journal of Surgical Pathology 30: 1581-1587, 2006.

    Article  PubMed  Google Scholar 

  7. Anlauf M, Schlenger R, Perren A et al. Microadenomatosis of the endocrine pancreas in patients with and without the multiple endocrine neoplasia type 1 syndrome. American Journal of Surgical Pathology 30: 560-574, 2006.

    Article  PubMed  Google Scholar 

  8. Perren A, Anlauf M, Henopp T et al. 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: 1118-1128, 2007.

    Article  CAS  PubMed  Google Scholar 

  9. Henopp T, Anlauf M, Schmitt A et al. Glucagon cell adenomatosis: a newly recognized disease of the endocrine pancreas. The Journal of clinical endocrinology and metabolism 94: 213-217, 2009.

    Article  CAS  PubMed  Google Scholar 

  10. Zhou C, Dhall D, Nissen NN, Chen CR, Yu R Homozygous P86S mutation of the human glucagon receptor is associated with hyperglucagonemia, alpha cell hyperplasia, and islet cell tumor. Pancreas 38: 941-946, 2009.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  11. Yu R, Dhall D, Nissen NN, Zhou C, Ren SG Pancreatic neuroendocrine tumors in glucagon receptor-deficient mice. PloS one 6: e23397, 2011.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  12. Yu R Pancreatic alpha-Cell Hyperplasia: Facts and Myths. The Journal of clinical endocrinology and metabolism: jc20132952, 2013.

  13. Anlauf M, Bauersfeld J, Raffel A et al. Insulinomatosis. A multicentric insulinoma disease that frequently causes early recurrent hyperinsulinemic hypoglycemia. American Journal of Surgical Pathology 33: 339-346, 2009.

    Article  PubMed  Google Scholar 

  14. Perigny M, Hammel P, Corcos O et al. Pancreatic endocrine microadenomatosis in patients with von Hippel-Lindau disease: characterization by VHL/HIF pathway proteins expression. The American journal of surgical pathology 33: 739-748, 2009.

    Article  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  16. Bommer G, Friedel U, Heitz PU, Klöppel G Pancreatic PP cell distribution and hyperplasia: Immunocytochemical morphology in normal pancreas, chronic pancreatitis and pancreatic carcinoma. Virchows Archiv [A] Pathologische Anatomie 387: 319-331, 1980.

    CAS  Google Scholar 

  17. Ouyang D, Dhall D, Yu R Pathologic pancreatic endocrine cell hyperplasia. World journal of gastroenterology : WJG 17: 137-143, 2011.

    Article  PubMed Central  PubMed  Google Scholar 

  18. Lohr M, Kloppel G Residual insulin positivity and pancreatic atrophy in relation to duration of chronic type 1 (insulin-dependent) diabetes mellitus and microangiopathy. Diabetologia 30: 757-762, 1987.

    Article  CAS  PubMed  Google Scholar 

  19. Albers MB et al., Pancreatic polypeptide rich islets in the posterior portion of the pancreatic head—a tumor mimic in somatostatin receptor scintigraphy. The Pancreas 2013 (in press).

Download references

Author information

Authors and Affiliations

  1. Department of Pathology, Technical University, Ismaningerstr. 22, 81675, München, Germany

    Günter Klöppel

  2. Überregionale Gemeinschaftspraxis, Institut für Pathologie und Zytologie, St. Vincenz Krankenhaus, Limburg, Germany

    Martin Anlauf

  3. Institute of Pathology, University Hospital Bern, Berne, Switzerland

    Aurel Perren

  4. Department of Pathology and Neuropathology, University Hospital Tübingen, Tübingen, Germany

    Bence Sipos

Authors
  1. Günter Klöppel
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Martin Anlauf
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Aurel Perren
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Bence Sipos
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Günter Klöppel.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Klöppel, G., Anlauf, M., Perren, A. et al. Hyperplasia to Neoplasia Sequence of Duodenal and Pancreatic Neuroendocrine Diseases and Pseudohyperplasia of the PP-cells in the Pancreas. Endocr Pathol 25, 181–185 (2014). https://doi.org/10.1007/s12022-014-9317-8

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12022-014-9317-8

Keywords

Search

Navigation