title: Sporadic versus hereditary gastrinomas of the duodenum and pancreas: distinct clinico-pathological and epidemiological features.
abstract: Gastrinomas are defined as gastrin secreting tumors that are associated with Zollinger-Ellison syndrome (ZES). ZES is characterized by elevated fasting gastrin serum levels, positive secretin stimulation test and clinical symptoms such as recurrent peptic ulcer disease, gastroesophageal reflux disease and occasional diarrhea. Genetically, nonhereditary (sporadic) gastrinomas are distinguished from hereditary gastrinomas, which are associated with multiple endocrine neoplasia type 1 (MEN1) syndrome. In general, duodenal gastrinomas are small and solitary if they are sporadic and multiple as well as hereditary. The sporadic gastrinomas occur in the duodenum or in the pancreas while the hereditary gastrinomas almost all occur in the duodenum. Our series of 77 sporadic duodenal neuroendocrine tumors (NETs) includes 18 patients (23.4%) with gastrinomas and ZES. Of 535 sporadic NETs in the pancreas collected from the NET archives of the departments of pathology in Zurich, Switzerland, and Kiel, Germany, 24 patients (4.5%) suffered from sporadic pancreatic gastrinomas and ZES. These NETs have to be distinguished from tumors with immunohistochemical positivity for gastrin but without evidence of ZES. An additional 19 patients suffered from MEN1 and ZES. These patients showed exclusively duodenal gastrinomas, but not pancreatic gastrinomas. The prognosis of sporadic and MEN1-associated duodenal gastrinomas is better than that of pancreatic gastrinomas, since they progress slowly to liver metastasis. In summary, sporadic and MEN1-associated gastrinomas in the duodenum and pancreas show different clinico-pathological and genetic features. The incidence of sporadic duodenal gastrin-producing tumors is increasing, possibly due to optimized diagnostic procedures. In contrast, pancreatic MEN1-associated gastrinomas seem to be extremely rare. A considerable subset of tumors with immunohistochemical expression of gastrin but without evidence of ZES should be designated as functionally inactive NETs expressing gastrin, but not as gastrinomas.
authors.affiliation: Department 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: Nele
authors.initials: N
authors.lastname: Garbrecht
authors.forename: Tobias
authors.initials: T
authors.lastname: Henopp
authors.forename: Anja
authors.initials: A
authors.lastname: Schmitt
authors.forename: Regina
authors.initials: R
authors.lastname: Schlenger
authors.forename: Andreas
authors.initials: A
authors.lastname: Raffel
authors.forename: Markus
authors.initials: M
authors.lastname: Krausch
authors.forename: Oliver
authors.initials: O
authors.lastname: Gimm
authors.forename: Claus F
authors.initials: CF
authors.lastname: Eisenberger
authors.forename: Wolfram T
authors.initials: WT
authors.lastname: Knoefel
authors.forename: Henning
authors.initials: H
authors.lastname: Dralle
authors.forename: Paul
authors.initials: P
authors.lastname: Komminoth
authors.forename: Philipp U
authors.initials: PU
authors.lastname: Heitz
authors.forename: Aurel
authors.initials: A
authors.lastname: Perren
authors.forename: Gunter
authors.initials: G
authors.lastname: Klöppel
mesh_terms: D004379:Duodenal Neoplasms / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics / Q000473:pathology*; D015408:Gastrinoma / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics / Q000473:pathology*; D005755:Gastrins / Q000235:genetics / Q000378:metabolism; D005858:Germany / Q000453:epidemiology; D006801:Humans; D018761:Multiple Endocrine Neoplasia Type 1 / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics / Q000473:pathology*; D011379:Prognosis; D013557:Switzerland / Q000453:epidemiology; D015043:Zollinger-Ellison Syndrome / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics / Q000473:pathology
chemical_list: D005755:Gastrins