PMID- 19011561
OWN - NLM
STAT- MEDLINE
DCOM- 20090325
LR  - 20090226
IS  - 1532-0979 (Electronic)
IS  - 0147-5185 (Linking)
VI  - 33
IP  - 3
DP  - 2009 Mar
TI  - Insulinomatosis: a multicentric insulinoma disease that frequently causes early 
      recurrent hyperinsulinemic hypoglycemia.
PG  - 339-46
LID - 10.1097/PAS.0b013e3181874eca [doi]
AB  - BACKGROUND: Multicentric insulinoma disease was characterized with regard to its 
      histopathology, multiple endocrine neoplasia type 1 (MEN1) status, precursor 
      lesions, and the risk of hyperinsulinemic hypoglycemia recurrence. METHODS: 
      Fourteen patients with multicentric insulinoma disease were compared with 267 
      patients with sporadic and familial insulinomas. The tumors were classified 
      according to the World Health Organization (WHO) criteria. The MEN1 status was 
      defined clinically and by germline mutation analysis. Detection of the MEN1 gene 
      locus was performed using fluorescence in situ hybridization. The surgical 
      interventions and the duration of disease-free survival were recorded. RESULTS: 
      Fourteen patients (5%) without evidence of MEN1 showed 53 macrotumors and 285 
      microtumors expressing exclusively insulin. In addition, they had small 
      proliferative insulin-expressing monohormonal endocrine cell clusters (IMECCs). 
      No allelic loss of the MEN1 locus was detected in 64 tumors. All but one patient 
      had benign disease. Recurrent hypoglycemia occurred in 6/14 patients (11 
      recurrences; mean time to relapse 8.4 y). Thirteen patients with MEN1 (4.6%) 
      showed 41 insulinomas and 133 tumors expressing islet hormones other than 
      insulin. IMECCs were not detected. Allelic loss of the MEN1 locus was found in 
      17/19 insulinomas. Recurrent hypoglycemia occurred in 4/13 patients (4 
      recurrences; mean time to relapse 14.5 y). Solitary insulinomas were found in 
      254/281 patients (90.4%). IMECCs were absent. There was no recurrent hypoglycemia 
      in 84 patients with benign insulinomas. CONCLUSIONS: Insulinomatosis is 
      characterized by the synchronous and metachronous occurrence of insulinomas, 
      multiple insulinoma precursor lesions, and rare development of metastases, but 
      common recurrent hypoglycemia. This disease differs from solitary sporadic and 
      MEN1-associated insulinomas.
FAU - Anlauf, Martin
AU  - Anlauf M
AD  - Department of Pathology, University of Kiel, Kiel, Germany.
FAU - Bauersfeld, Juliane
AU  - Bauersfeld J
FAU - Raffel, Andreas
AU  - Raffel A
FAU - Koch, Christian A
AU  - Koch CA
FAU - Henopp, Tobias
AU  - Henopp T
FAU - Alkatout, Ibrahim
AU  - Alkatout I
FAU - Schmitt, Anja
AU  - Schmitt A
FAU - Weber, Achim
AU  - Weber A
FAU - Kruse, Marie L
AU  - Kruse ML
FAU - Braunstein, Stefan
AU  - Braunstein S
FAU - Kaserer, Klaus
AU  - Kaserer K
FAU - Brauckhoff, Michael
AU  - Brauckhoff M
FAU - Dralle, Henning
AU  - Dralle H
FAU - Moch, Holger
AU  - Moch H
FAU - Heitz, Philipp U
AU  - Heitz PU
FAU - Komminoth, Paul
AU  - Komminoth P
FAU - Knoefel, Wolfram T
AU  - Knoefel WT
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
PL  - United States
TA  - Am J Surg Pathol
JT  - The American journal of surgical pathology
JID - 7707904
SB  - IM
MH  - Adult
MH  - Female
MH  - Humans
MH  - Hyperinsulinism/*etiology/genetics
MH  - Hypoglycemia/*etiology/genetics
MH  - In Situ Hybridization, Fluorescence
MH  - Insulinoma/*complications/genetics
MH  - Male
MH  - Middle Aged
MH  - Multiple Endocrine Neoplasia Type 1/complications/genetics
MH  - Mutation
MH  - Pancreatic Neoplasms/*complications/genetics
MH  - Retrospective Studies
EDAT- 2008/11/18 09:00
MHDA- 2009/03/26 09:00
CRDT- 2008/11/18 09:00
PHST- 2008/11/18 09:00 [pubmed]
PHST- 2009/03/26 09:00 [medline]
PHST- 2008/11/18 09:00 [entrez]
AID - 10.1097/PAS.0b013e3181874eca [doi]
PST - ppublish
SO  - Am J Surg Pathol. 2009 Mar;33(3):339-46. doi: 10.1097/PAS.0b013e3181874eca.