Clinical, genetic and radiographic analysis of 108 patients with von Hippel-Lindau disease (VHL) manifested by pancreatic neuroendocrine neoplasms (PNETs).
BACKGROUND
von Hippel-Lindau (vHL) disease is an autosomal dominant syndrome associated with neoplasms in multiple organs, which includes the pancreas. Here, we report the greatest single center experience in patients with vHL pancreatic endocrine neoplasm (PNETs).


METHODS
Between December 1998 and November 2006, 633 patients with vHL were evaluated and those with PNETs were enrolled on a prospective protocol.


RESULTS
Overall, 108 vHL patients had PNETs (17%). Nine patients had metastatic disease (8.3%) from their PNET. Patients with lesions greater than 3 cm (n = 25) were more likely to develop metastases than patients with lesions less than 3 cm (n = 83) (P < .005). Thirty-nine patients underwent resection. Germline sequencing showed that 78% of patients with metastases (7/9) had exon 3 mutations compared with 46% of patients without metastases (32/98; P < .01). Tumor doubling time was calculated for the largest PNET. The group with metastases had an average tumor doubling time of 337 days (range, 180-463 days) compared with 2630 days (range, 103-9614 days) for those without metastases (P < .0001).


CONCLUSIONS
By implementing a system of selective operative resection based on defined criteria, vHL patients with PNETs can be managed safely. For patients with small primary lesions (<3 cm), without a mutation of exon 3 and slow tumor doubling time (>500 days), a nonoperative approach may be appropriate for these nonfunctional neoplasms.
Blansfield
Joseph A
JA
Tumor Angiogenesis Section, Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, Md. 20892, USA.
Choyke
Lynda
L
Morita
Shane Y
SY
Choyke
Peter L
PL
Pingpank
James F
JF
Alexander
H Richard
HR
Seidel
Geoffrey
G
Shutack
Yvonne
Y
Yuldasheva
Nargiza
N
Eugeni
Michelle
M
Bartlett
David L
DL
Glenn
Gladys M
GM
Middelton
Lindsay
L
Linehan
W Marston
WM
Libutti
Steven K
SK
D000293:Adolescent; D000328:Adult; D000368:Aged; D018278:Carcinoma, Neuroendocrine / Q000000981:diagnostic imaging / Q000235:genetics* / Q000401:mortality / Q000601:surgery*; D018389:Codon, Nonsense; D005260:Female; D005500:Follow-Up Studies; D016368:Frameshift Mutation; D017353:Gene Deletion; D006801:Humans; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D010190:Pancreatic Neoplasms / Q000000981:diagnostic imaging / Q000235:genetics* / Q000401:mortality / Q000601:surgery*; D018579:Patient Selection; D011446:Prospective Studies; D011859:Radiography; D012307:Risk Factors; D006623:von Hippel-Lindau Disease / Q000000981:diagnostic imaging / Q000235:genetics* / Q000401:mortality
D018389:Codon, Nonsense