title: Systematic comparison of sporadic and syndromic pancreatic islet cell tumors.
abstract: Pancreatic islet cell tumors (ICTs) occur as sporadic neoplasias or as a manifestation of multiple endocrine neoplasia type 1 (MEN1) and von Hippel-Lindau disease (VHL). Molecular classification of ICTs is mandatory for timely diagnosis and surveillance. Systematic comparison of VHL-ICTs and sporadic ICTs has been lacking. Our registry-based approaches used the German NET-Registry with 259 patients with neuroendocrine tumors (NETs), who were primarily diagnosed with NETs, and the German VHL-Registry with 485 molecular genetically confirmed patients who had undergone magnetic resonance imaging or computed tomography of the abdomen. All patients provided blood DNA for testing of the MEN1 and VHL genes for intragenic mutations and large deletions. In the NET-Registry, 9/101 patients (8.9%) with ICTs had germline mutations, 8 in MEN1 and 1 in VHL. In the VHL-Registry, prevalence of NETs was 52/487 (10.6%), and all were ICTs. Interestingly, of those with VHL p.R167W, 47% developed ICTs, compared to 2% of those with p.Y98H. In total, there were 92 truly sporadic, i.e. mutation-negative ICT patients. Comparing these with the 53 VHL-ICT patients, the statistically significant differences were predominance of female gender (P=0.01), multifocal ICTs (P=0.0029), and lower malignancy rate (P<0.001) in VHL-ICTs compared to sporadic cases. VHL was prevalent in <0.5% of NETs, while NETs occur in ∼10% of VHL, virtually exclusively as ICTs, which are rarely the first presentation. Patients with NETs should not be subjected to genetic testing of the VHL gene, unless they have multifocal ICTs, other VHL-associated tumors, and/or a family history for VHL.
authors.affiliation: Department of Nephrology, Albert-Ludwigs-University, Freiburg, Germany.
authors.forename: Zoran
authors.initials: Z
authors.lastname: Erlic
authors.forename: Ursula
authors.initials: U
authors.lastname: Ploeckinger
authors.forename: Alberto
authors.initials: A
authors.lastname: Cascon
authors.forename: Michael M
authors.initials: MM
authors.lastname: Hoffmann
authors.forename: Laura
authors.initials: L
authors.lastname: von Duecker
authors.forename: Aurelia
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authors.lastname: Winter
authors.forename: Gerit
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authors.lastname: Kammel
authors.forename: Janina
authors.initials: J
authors.lastname: Bacher
authors.forename: Maren
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authors.lastname: Sullivan
authors.forename: Berend
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authors.lastname: Isermann
authors.forename: Lars
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authors.lastname: Fischer
authors.forename: Andreas
authors.initials: A
authors.lastname: Raffel
authors.forename: Wolfram Trudo
authors.initials: WT
authors.lastname: Knoefel
authors.forename: Matthias
authors.initials: M
authors.lastname: Schott
authors.forename: Tobias
authors.initials: T
authors.lastname: Baumann
authors.forename: Oliver
authors.initials: O
authors.lastname: Schaefer
authors.forename: Tobias
authors.initials: T
authors.lastname: Keck
authors.forename: Richard P
authors.initials: RP
authors.lastname: Baum
authors.forename: Ioana
authors.initials: I
authors.lastname: Milos
authors.forename: Mihaela
authors.initials: M
authors.lastname: Muresan
authors.forename: Mariola
authors.initials: M
authors.lastname: Peczkowska
authors.forename: Andrzej
authors.initials: A
authors.lastname: Januszewicz
authors.forename: Kenko
authors.initials: K
authors.lastname: Cupisti
authors.forename: Anke
authors.initials: A
authors.lastname: Tönjes
authors.forename: Mathias
authors.initials: M
authors.lastname: Fasshauer
authors.forename: Jan
authors.initials: J
authors.lastname: Langrehr
authors.forename: Peter
authors.initials: P
authors.lastname: von Wussow
authors.forename: Abbas
authors.initials: A
authors.lastname: Agaimy
authors.forename: Günter
authors.initials: G
authors.lastname: Schlimok
authors.forename: Regina
authors.initials: R
authors.lastname: Lamberts
authors.forename: Thorsten
authors.initials: T
authors.lastname: Wiech
authors.forename: Kurt Werner
authors.initials: KW
authors.lastname: Schmid
authors.forename: Alexander
authors.initials: A
authors.lastname: Weber
authors.forename: Mercedes
authors.initials: M
authors.lastname: Nunez
authors.forename: Mercedes
authors.initials: M
authors.lastname: Robledo
authors.forename: Charis
authors.initials: C
authors.lastname: Eng
authors.forename: Hartmut P H
authors.initials: HP
authors.lastname: Neumann
mesh_terms: D007516:Adenoma, Islet Cell; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D004273:DNA, Neoplasm / Q000737:chemistry / Q000235:genetics; D005260:Female; D014644:Genetic Variation; D018095:Germ-Line Mutation; D005858:Germany / Q000453:epidemiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D018761:Multiple Endocrine Neoplasia Type 1 / Q000453:epidemiology / Q000235:genetics*; D018358:Neuroendocrine Tumors / Q000453:epidemiology / Q000235:genetics; D016133:Polymerase Chain Reaction; D015995:Prevalence; D017422:Sequence Analysis, DNA; D055815:Young Adult; D006623:von Hippel-Lindau Disease / Q000453:epidemiology / Q000235:genetics*
chemical_list: D004273:DNA, Neoplasm