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Clinical Trial
. 2007 Dec;142(6):814-8; discussion 818.e1-2.
doi: 10.1016/j.surg.2007.09.012.

Clinical, genetic and radiographic analysis of 108 patients with von Hippel-Lindau disease (VHL) manifested by pancreatic neuroendocrine neoplasms (PNETs)

Joseph A Blansfield  1 , Lynda Choyke, Shane Y Morita, Peter L Choyke, James F Pingpank, H Richard Alexander, Geoffrey Seidel, Yvonne Shutack, Nargiza Yuldasheva, Michelle Eugeni, David L Bartlett, Gladys M Glenn, Lindsay Middelton, W Marston Linehan, Steven K Libutti
Affiliations
Clinical Trial

Clinical, genetic and radiographic analysis of 108 patients with von Hippel-Lindau disease (VHL) manifested by pancreatic neuroendocrine neoplasms (PNETs)

Joseph A Blansfield et al. Surgery. 2007 Dec.

Erratum in

  • Surgery. 2008 Feb;143(2):302

Abstract

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.

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Figures

Figure 1:
Figure 1:
Scatterplot of the tumor diameters of primary PNETs comparing patients with and without metastatic disease. Sixty-seven percent of patients with metastatic disease (6 patients out of 9) compared with nineteen percent of patient without metastatic disease (19 patients out of 99) had primary lesions which were greater than three centimeters in diameter (p<0.0046).
Figure 2:
Figure 2:
The rate of growth of the diameter of the primary PNET in patients with vHL. The dashed lines are growth rates for individuals who had metastatic disease. The solid lines are growth rates for individuals without metastases.
Figure 3:
Figure 3:
Treatment and follow-up recommendations for patients with PNETs.
See this image and copyright information in PMC

References

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