Systematic comparison of sporadic and syndromic pancreatic islet cell tumors.
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.
Erlic
Zoran
Z
Department of Nephrology, Albert-Ludwigs-University, Freiburg, Germany.
Ploeckinger
Ursula
U
Cascon
Alberto
A
Hoffmann
Michael M
MM
von Duecker
Laura
L
Winter
Aurelia
A
Kammel
Gerit
G
Bacher
Janina
J
Sullivan
Maren
M
Isermann
Berend
B
Fischer
Lars
L
Raffel
Andreas
A
Knoefel
Wolfram Trudo
WT
Schott
Matthias
M
Baumann
Tobias
T
Schaefer
Oliver
O
Keck
Tobias
T
Baum
Richard P
RP
Milos
Ioana
I
Muresan
Mihaela
M
Peczkowska
Mariola
M
Januszewicz
Andrzej
A
Cupisti
Kenko
K
Tönjes
Anke
A
Fasshauer
Mathias
M
Langrehr
Jan
J
von Wussow
Peter
P
Agaimy
Abbas
A
Schlimok
Günter
G
Lamberts
Regina
R
Wiech
Thorsten
T
Schmid
Kurt Werner
KW
Weber
Alexander
A
Nunez
Mercedes
M
Robledo
Mercedes
M
Eng
Charis
C
Neumann
Hartmut P H
HP
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*
D004273:DNA, Neoplasm