Glucagon cell adenomatosis: A newly recognized disease of the endocrine pancreas

Tobias Henopp, Martin Anlauf, Anja Schmitt, Regina Schlenger, A. Zalatnai, Anne Couvelard, Philippe Ruszniewski, Klaus Peter Schaps, Yvonne M H Jonkers, Ernst Jan M Speel, Natalia S. Pellegata, Philipp U. Heitz, Paul Komminoth, Aurel Perren, Günter Klöppel

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Background: Glucagon-producing tumors are either solitary neoplasms of the pancreas, occasionally associated with a glucagonoma syndrome, or multiple neoplasms associated with multiple endocrine neoplasia type 1 (MEN1). We observed a previously undescribed multicentric glucagon-producing tumor disease that is not related to MEN1. Methods: Pancreatic tissue from four patients showing multiple neuroendocrine microadenomas and in two cases also macrotumors were screened for hormones using immunohistochemical and morphometric methods. MEN1, von Hippel-Lindau, and p27 germ line and somatic mutation analysis was performed. Deletion of MEN1 (11q13), von Hippel-Lindau (3p25), and the centromere 11 and 3 gene locus was determined by fluorescence in situ hybridization. DNA copy number changes were studied using array comparative genomic hybridization. Results: The pancreatic tissue from the four patients contained more than 870 microadenomas and 10 macrotumors, all of which expressed exclusively glucagon and none of which showed evidence of malignancy. In addition, many islets were unusually large and showed glucagon cell hyperplasia. There was no clinical or molecular evidence of any hereditary tumor disease, and changes in the MEN1 gene wereonly seen in individual tumors. Array comparative genomic hybridization of one macrotumor and 20 pooled microadenomas revealed a homogeneous diploid chromosome set. Conclusions: The findings are sufficiently distinctive to suggest a new neoplastic disease of the endocrine pancreas that we recommend calling glucagon cell adenomatosis. Clinically, this disease may be an incidental finding, or it may lead to a glucagonoma syndrome.

Original languageEnglish
Pages (from-to)213-217
Number of pages5
JournalJournal of Clinical Endocrinology and Metabolism
Volume94
Issue number1
DOIs
Publication statusPublished - Jan 2009

Fingerprint

Multiple Endocrine Neoplasia Type 1
Glucagon
Islets of Langerhans
Tumors
Glucagonoma
Neoplasms
Comparative Genomic Hybridization
Genes
Tissue
DNA Copy Number Variations
Chromosomes
Inborn Genetic Diseases
Incidental Findings
Germ-Line Mutation
Centromere
Diploidy
Fluorescence In Situ Hybridization
Pancreatic Neoplasms
Fluorescence
Hyperplasia

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Endocrinology
  • Biochemistry, medical
  • Endocrinology, Diabetes and Metabolism

Cite this

Glucagon cell adenomatosis : A newly recognized disease of the endocrine pancreas. / Henopp, Tobias; Anlauf, Martin; Schmitt, Anja; Schlenger, Regina; Zalatnai, A.; Couvelard, Anne; Ruszniewski, Philippe; Schaps, Klaus Peter; Jonkers, Yvonne M H; Speel, Ernst Jan M; Pellegata, Natalia S.; Heitz, Philipp U.; Komminoth, Paul; Perren, Aurel; Klöppel, Günter.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 94, No. 1, 01.2009, p. 213-217.

Research output: Contribution to journalArticle

Henopp, T, Anlauf, M, Schmitt, A, Schlenger, R, Zalatnai, A, Couvelard, A, Ruszniewski, P, Schaps, KP, Jonkers, YMH, Speel, EJM, Pellegata, NS, Heitz, PU, Komminoth, P, Perren, A & Klöppel, G 2009, 'Glucagon cell adenomatosis: A newly recognized disease of the endocrine pancreas', Journal of Clinical Endocrinology and Metabolism, vol. 94, no. 1, pp. 213-217. https://doi.org/10.1210/jc.2008-1300
Henopp, Tobias ; Anlauf, Martin ; Schmitt, Anja ; Schlenger, Regina ; Zalatnai, A. ; Couvelard, Anne ; Ruszniewski, Philippe ; Schaps, Klaus Peter ; Jonkers, Yvonne M H ; Speel, Ernst Jan M ; Pellegata, Natalia S. ; Heitz, Philipp U. ; Komminoth, Paul ; Perren, Aurel ; Klöppel, Günter. / Glucagon cell adenomatosis : A newly recognized disease of the endocrine pancreas. In: Journal of Clinical Endocrinology and Metabolism. 2009 ; Vol. 94, No. 1. pp. 213-217.
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AU - Couvelard, Anne

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