Precursor lesions in patients with multiple endocrine neoplasia type 1-associated duodenal gastrinomas.
OBJECTIVE
The identification of precursor lesions has a great impact on the understanding of tumorigenesis. Precursor lesions of endocrine tumors are known to occur in the setting of the MEN1 syndrome. The aim of this study was to test the hypothesis that MEN1-associated duodenal gastrinomas originate from diffuse preneoplastic gastrin cell changes. Precursor lesions may precede the development of duodenal gastrinomas because, in contrast to sporadic gastrinomas, these tumors are usually multiple.


METHODS
The distribution of endocrine cells in the nontumorous duodenal tissue was analyzed qualitatively and quantitatively for 25 patients operated on for a duodenal gastrinoma. MEN1 status was assessed clinically and by polymerase chain reaction-based mutational analysis.


RESULTS
Fourteen of 25 patients with gastrinoma had proliferative, hyperplastic lesions consisting of gastrin cells in the nontumorous duodenal mucosa, similar to the gastric enterochromaffin-like cell lesions observed in chronic atrophic gastritis. All patients with Zollinger-Ellison syndrome with proven MEN1 had such proliferative gastrin cell lesions, and all patients with Zollinger-Ellison syndrome without precursor lesions were MEN1 negative.


CONCLUSIONS
Duodenal gastrinomas in MEN1, but not sporadic duodenal gastrinomas, are associated with proliferative gastrin cell changes within the nontumorous mucosa. It is likely that these lesions precede the development of MEN1-associated duodenal gastrinomas.
Anlauf
Martin
M
Department of Pathology, Univeristy of Kiel, Germany. manlauf@path.uni-kiel.de
Perren
Aurel
A
Meyer
Cora Lu
CL
Schmid
Sonja
S
Saremaslani
Parvin
P
Kruse
Marie L
ML
Weihe
Eberhard
E
Komminoth
Paul
P
Heitz
Philipp U
PU
Klöppel
Günter
G
D000328:Adult; D000368:Aged; D053379:Chromogranin A; D002864:Chromogranins / Q000235:genetics; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000032:analysis; D004379:Duodenal Neoplasms / Q000235:genetics / Q000473:pathology*; D004386:Duodenum / Q000473:pathology*; D005260:Female; D005753:Gastric Mucosa / Q000473:pathology; D019863:Gastrin-Secreting Cells / Q000473:pathology; D015408:Gastrinoma / Q000235:genetics / Q000473:pathology*; D006801:Humans; D006965:Hyperplasia; D019394:Ki-67 Antigen / Q000235:genetics; D008297:Male; D008875:Middle Aged; D018761:Multiple Endocrine Neoplasia Type 1 / Q000235:genetics / Q000473:pathology*; D016133:Polymerase Chain Reaction; D011230:Precancerous Conditions / Q000235:genetics / Q000473:pathology*
D053379:Chromogranin A; D002864:Chromogranins; D004273:DNA, Neoplasm; D019394:Ki-67 Antigen