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Evaluation and management of pancreatic lesions in patients with von Hippel–Lindau disease

Nature Reviews Clinical Oncology volume 13, pages 537–549 (2016)Cite this article

Subjects

Key Points

  • Pancreatic lesions occur in two-thirds of patients with von Hippel–Lindau (VHL) disease

  • Cystic pancreatic lesions or serous cystadenomas, which occur in almost 50% of all patients with VHL disease, are not malignant and rarely require intervention

  • Pancreatic neuroendocrine tumours (pNETs) associated with VHL disease have a variable natural history, which necessitates lifelong follow-up monitoring using imaging, but are less aggressive than sporadic pNETs

  • Surgical removal of VHL-associated pNETs with diameters ≥3 cm and ≥2 cm in the pancreatic body and head, respectively, or that are growing rapidly (doubling time <500 days) should be considered

  • Additional criteria for consideration of surgical removal of VHL-associated pNETs include obvious signs of malignancy, such as locoregional invasion and/or regional or distant metastases

  • A multidisciplinary-team approach is of paramount importance in the management of patients with VHL-disease-associated pancreatic lesions.

Abstract

von Hippel–Lindau (VHL) disease is a heritable cancer-predisposition syndrome with multiorgan involvement. Pancreatic lesions are detected in approximately two-thirds of patients with VHL disease at some point during their lifetime. In these patients, cystic pancreatic lesions are almost exclusively benign and, unless symptomatic, do not require surgical or endoscopic intervention; however, solid pancreatic lesions can often be recognized through imaging screens, and are commonly found to be nonfunctioning pancreatic neuroendocrine tumours (pNETs) with malignant potential. The natural history of these VHL-associated pNETs is variable, and lacks clinical or imaging features that predict disease progression or metastatic potential, and generally needs to be managed more conservatively than their sporadic counterparts. Treatment options for such lesions, which range from active surveillance to surgical intervention, can nevertheless be associated with considerable morbidity and even mortality. Of note, although several guidelines have been established for the management of tumours associated with VHL syndrome, none of these have specifically focused on pancreatic lesions. Thus, we aim to characterize the types of pancreatic lesions associated with VHL disease and their natural history, to identify particular lesions that necessitate treatment, and to define what forms of treatment should be undertaken.

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Figure 1: Imaging of pancreatic lesions in a patients with von Hippel–Lindau (VHL) disease.
Figure 2: Diagnostic imaging workup of a pancreatic neuroendocrine tumour (pNET) arising in a patient with von Hippel–Lindau disease.
Figure 3: Management algorithm for patients with von Hippel–Lindau disease and pancreatic lesions based on our analysis of the retrospective data and expert recommendations.

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Acknowledgements

We would like to thank the patients with von Hippel–Lindau disease who participated in our clinical protocols and their families. The work of the authors is supported in part by the Intramural Research Program of the Center for Cancer Research, National Cancer Institute, National Institutes of Health, USA.

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Authors and Affiliations

  1. Endocrine Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Building 10, Room 4–5940, Bethesda, 20891–1201, Maryland, USA

    Xavier M. Keutgen & Electron Kebebew

  2. Department of Digestive Oncology, Beaujon University Hospital (AP-HP - PRES Paris 7 Diderot), 100 boulevard du Général Leclerc, 92110, Clichy, France

    Pascal Hammel

  3. Molecular Imaging Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Building 10, Room B3B69F, Bethesda, 20892–1088, Maryland, USA

    Peter L. Choyke

  4. Department of Surgery, Montefiore Medical Center, 111 East 210th Street, Bronx, 10467, New York, USA

    Steven K. Libutti

  5. Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, 10461, New York, USA

    Steven K. Libutti

  6. Department of Genitourinary Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, 1155 Pressler Street, Unit 1374, Houston, 77030–3721, Texas, USA

    Eric Jonasch

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X.M.K. and E.K. researched the data for the article. X.M.K., P.H., and E.K. contributed substantially to discussions of the content. X.M.K. wrote the article, and all authors reviewed and/or edited the manuscript before submission.

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Keutgen, X., Hammel, P., Choyke, P. et al. Evaluation and management of pancreatic lesions in patients with von Hippel–Lindau disease. Nat Rev Clin Oncol 13, 537–549 (2016). https://doi.org/10.1038/nrclinonc.2016.37

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