title: Microadenomatosis of the endocrine pancreas in patients with and without the multiple endocrine neoplasia type 1 syndrome.
abstract: It has been suggested that microadenomatosis of the endocrine pancreas is a hallmark of the multiple endocrine neoplasia type 1 syndrome (MEN1). This study attempts to elucidate the relationship between pancreatic microadenomatosis and the MEN1 and von Hippel-Lindau (VHL) syndromes. Pancreatic tissue specimens from 37 patients (with either microadenomatosis or the MEN1 syndrome) were analyzed using immunohistochemistry, confocal laser scanning microscopy, and morphometric methods. The MEN1 and the VHL status were assessed on the basis of clinical criteria (all patients) and PCR-based mutational analysis (15 and 5 patients, respectively). Pancreatic microadenomatosis was found in 35 of 37 patients, 28 of whom fulfilled the clinicopathologic criteria and 13 the genetic criteria for MEN1, whereas none of the patients had evidence of a VHL syndrome. Microadenomas were present in 26 of the 28 MEN1 patients, and all these tumors were consistently multihormonal. Five of the 9 patients with microadenomatosis and no clinical evidence for MEN1 or VHL also lacked mutations for the respective genes. Five of these 9 patients suffered from hyperinsulinism and revealed multiple insulin-positive tumors. The other patients were nonsymptomatic and showed multiple glucagon-expressing neoplasms. In microadenomatosis patients with and without the MEN1 syndrome, a subset of morphologically normal-appearing islets showed increased endocrine cell proliferation. In conclusion, endocrine multihormonal microadenomatosis of the pancreas is a feature of MEN1. In addition, a monohormonal type of pancreatic microadenomatosis was identified that consisted of either insulinomas or glucagon-producing tumors and was not associated with MEN1 or VHL.
authors.affiliation: Departments of Pathology, University of Kiel, Michaelisstrasse 11, 24105 Kiel, Germany. manlauf@path.uni-kiel.de
authors.forename: Martin
authors.initials: M
authors.lastname: Anlauf
authors.forename: Regina
authors.initials: R
authors.lastname: Schlenger
authors.forename: Aurel
authors.initials: A
authors.lastname: Perren
authors.forename: Juliane
authors.initials: J
authors.lastname: Bauersfeld
authors.forename: Christian A
authors.initials: CA
authors.lastname: Koch
authors.forename: Henning
authors.initials: H
authors.lastname: Dralle
authors.forename: Andreas
authors.initials: A
authors.lastname: Raffel
authors.forename: Wolfram T
authors.initials: WT
authors.lastname: Knoefel
authors.forename: Eberhard
authors.initials: E
authors.lastname: Weihe
authors.forename: Philippe
authors.initials: P
authors.lastname: Ruszniewski
authors.forename: Anne
authors.initials: A
authors.lastname: Couvelard
authors.forename: Paul
authors.initials: P
authors.lastname: Komminoth
authors.forename: Philipp U
authors.initials: PU
authors.lastname: Heitz
authors.forename: Günter
authors.initials: G
authors.lastname: Klöppel
mesh_terms: D007516:Adenoma, Islet Cell / Q000150:complications* / Q000473:pathology*; D000328:Adult; D000368:Aged; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D018613:Microscopy, Confocal; D008875:Middle Aged; D018761:Multiple Endocrine Neoplasia Type 1 / Q000150:complications* / Q000235:genetics / Q000473:pathology*; D009154:Mutation; D010190:Pancreatic Neoplasms / Q000150:complications* / Q000473:pathology*; D016133:Polymerase Chain Reaction; D006623:von Hippel-Lindau Disease / Q000150:complications / Q000235:genetics / Q000473:pathology