PMID- 18957496
OWN - NLM
STAT- MEDLINE
DCOM- 20090212
LR  - 20181201
IS  - 0021-972X (Print)
IS  - 0021-972X (Linking)
VI  - 94
IP  - 1
DP  - 2009 Jan
TI  - Glucagon cell adenomatosis: a newly recognized disease of the endocrine pancreas.
PG  - 213-7
LID - 10.1210/jc.2008-1300 [doi]
AB  - 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 were only 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.
FAU - Henopp, Tobias
AU  - Henopp T
AD  - Department of Pathology, University of Tubingen, Liebermeisterstr. 8, 72076 
      Tubingen, Germany. Tobias.Henopp@med.uni-tuebingen.de
FAU - Anlauf, Martin
AU  - Anlauf M
FAU - Schmitt, Anja
AU  - Schmitt A
FAU - Schlenger, Regina
AU  - Schlenger R
FAU - Zalatnai, Attila
AU  - Zalatnai A
FAU - Couvelard, Anne
AU  - Couvelard A
FAU - Ruszniewski, Philippe
AU  - Ruszniewski P
FAU - Schaps, Klaus-Peter
AU  - Schaps KP
FAU - Jonkers, Yvonne M H
AU  - Jonkers YM
FAU - Speel, Ernst-Jan M
AU  - Speel EJ
FAU - Pellegata, Natalia S
AU  - Pellegata NS
FAU - Heitz, Philipp U
AU  - Heitz PU
FAU - Komminoth, Paul
AU  - Komminoth P
FAU - Perren, Aurel
AU  - Perren A
FAU - Kloppel, Gunter
AU  - Kloppel G
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20081028
PL  - United States
TA  - J Clin Endocrinol Metab
JT  - The Journal of clinical endocrinology and metabolism
JID - 0375362
RN  - 0 (MEN1 protein, human)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 147604-94-2 (Cyclin-Dependent Kinase Inhibitor p27)
RN  - 9007-92-5 (Glucagon)
RN  - EC 2.3.2.27 (Von Hippel-Lindau Tumor Suppressor Protein)
RN  - EC 6.3.2.- (VHL protein, human)
SB  - IM
MH  - Adenoma/genetics/metabolism/*pathology
MH  - Adult
MH  - Cyclin-Dependent Kinase Inhibitor p27/genetics
MH  - Female
MH  - Glucagon/*metabolism
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Male
MH  - Pancreatic Neoplasms/genetics/metabolism/*pathology
MH  - Proto-Oncogene Proteins/genetics
MH  - Von Hippel-Lindau Tumor Suppressor Protein/genetics
EDAT- 2008/10/30 09:00
MHDA- 2009/02/13 09:00
CRDT- 2008/10/30 09:00
PHST- 2008/10/30 09:00 [pubmed]
PHST- 2009/02/13 09:00 [medline]
PHST- 2008/10/30 09:00 [entrez]
AID - jc.2008-1300 [pii]
AID - 10.1210/jc.2008-1300 [doi]
PST - ppublish
SO  - J Clin Endocrinol Metab. 2009 Jan;94(1):213-7. doi: 10.1210/jc.2008-1300. Epub 
      2008 Oct 28.