Managing Pancreatic Tumors

The most common pancreatic lesions in VHL are cysts and serous cystadenomas that can be single or multiple and can be found in 35% to 75% of patients with VHL, varying by kindred.² Cysts are by far the most common, representing 70% of lesions. While these cysts and cystadenomas can interfere with the proper delivery of enzymes and hormones necessary to digestion, and while they may compress the intestine or bile ducts, they are not cancer and will not metastasize. Most cystic lesions are benign and do not cause symptoms.

The pancreas may be so filled with cysts that there is little normal pancreas tissue left. In some cases this can lead to pancreatic insufficiency, or diabetes. Solid lesions of the pancreas associated with VHL are less common and are usually neuroendocrine tumors or microcystic adenomas, which can appear solid on contrast-enhanced CT imaging. Neuroendrocrine tumors are usually "nonfunctional", meaning they do not generate chemicals that can be seen in the urine or bloodstream. They are therefore difficult to find and may not be seen unless the physician is specifically looking for them.

Cysts and cystadenomas are benign; neuroendocrine tumors, however, are cancer and can metastasize, usually to the liver.

Pancreatic lesions often occur in the same families where pheochromocytomas occur. In the Jennings study,³ 13 of the 30 patients with pancreatic lesions also had pheochromocytomas. We are still reviewing the patterns of mutation in our patient population. I am hopeful that once we have completed genetic analysis, we may be able to tell from the genetic mutation who is likely to need early surgery and who does not.

While neuroendocrine tumors themselves rarely cause death, they do metastasize, and there is a growing appreciation for the consequences of leaving them untreated. The purpose of this study was to establish diagnostic and management criteria that would minimize the risk of metastatic cancer from neuroendocrine tumors of the pancreas and maximize the preservation of pancreatic tissue in people with VHL.

From December 1988 through November 1997, 256 patients with VHL were screened at the U.S. National Institutes of Health. This study included follow-up of these patients through March 1998. During the study period a total of 30 (12%) out of 256 patients were identified with solid lesions of the pancreas. Four of these had evidence of metastatic disease at the time of diagnosis. Of the 18 whose tumor tissue was studied under a microscope, 17 were confirmed to have neuroendocrine tumors.

Tumor sizes were measured for all patients, and a comparison was made between the size of the largest primary tumor in patients with evidence of metastatic disease. In patients with liver metastases, the largest primary tumor was 3 to 8 cm. in diameter. In patients with no metastases, the primary tumor was 1 to 5 cm. No patient with a tumor less than 3 cm was found to have any evidence of metastatic disease. There was no correlation between the number of pancreatic lesions and the presence of metastatic disease.

Given the potential for malignancy with neuroendocrine tumors and the fact that in this series of patients more than 94% of the enhancing lesions were confirmed to be neuroendocrine tumors, we have adopted a strategy of presuming that all solid enhancing lesions of the pancreas are neuroendocrine tumors until proven otherwise by careful pathologic examination. Cystic disease of the pancreas and microcystic adenomas are benign conditions. But neuroendocrine tumors of the pancreas in VHL can behave in a malignant fashion.

Solid lesions of the pancreas tend to be multiple in VHL and can occur in the head, body, or tail of the pancreas (see Figure 1). Even after resection, the remaining pancreas is at risk for development of new lesions, as is the case in other organs affected by VHL. This led us to adopt an organ-sparing strategy for the pancreas similar to the approach for managing renal tumors and adrenal tumors associated with VHL. If possible we perform an enucleation of these solid lesions, a kind of scooping out of the tumor, taking care to preserve as much normal pancreatic tissue as possible. This can be difficult in these patients, who often have many cysts at the same time. We use ultrasound imaging during the surgery, directly on the pancreas. This intraoperative ultrasound has been an important tool in these surgeries, helping to identify lesions not seen on previous imaging studies and for clearly mapping the pancreatic duct, allowing even large tumors to be safely removed.

Figure 1: VHL in the pancreas. Shows several cysts, and a tumor in the head of the pancreas. Figure courtesy of Dr. Choyke.

Neuroendocrine tumors associated with VHL tend to be slow growing. In our experience, the presence of metastases appears to correlate with the size of the primary tumor. Therefore we have outlined an approach summarized in Table 1. Patients with VHL who have solid lesions of the pancreas detected on contrast-enhanced CT scans have their tumors carefully measured. Lesions less than 1 cm in size are monitored with serial scanning performed at 12-month intervals. Tumors that are 1 to 3 cm are managed depending on location. If lesions are found to be in the head of the pancreas, they are removed when they reach approximately 2 cm in size. Because of anatomic constraints in this region and the desire to perform an enucleation rather than a resection of the head of the pancreas, we favor removal of these tumors before they reach a prohibitive size. Lesions in the body or tail of the pancreas that can be resected by removing part of the pancreas are monitored until they reach approximately 2 to 3 cm. Patients who are undergoing an abdominal exploration for the management of a different VHL-associated tumor, such as a renal lesion or a pheochromocytoma, are also evaluated for management of their pancreatic lesions.

We have attempted to establish a rational approach for the diagnosis and management of solid lesions of the pancreas. On the basis of this review of our experience with these tumors, we believe that the guidelines illustrated in Table 1 will minimize the risk of metastatic disease yet maximally preserve pancreatic function. It is our hope that by using this systematic approach we will not only gain a better understanding of the natural history of these lesions but also establish procedures that reduce the risks associated with pancreatic neuroendocrine tumors in VHL.

1. Abridged from Libutti et al, "Pancreatic neuroendocrine tumors associated with von Hippel-Lindau disease: diagnostic and management recommendations." Surgery (1998) 124:1153-9.
2. Neumann, HPH et al, Pancreatic lesions in the von Hippel-Lindau syndrome, Gastroenterology (1991) 101:465-71. Also Hough DM et al., Pancreatic lesions in von Hippel-Lindau disease: prevalence, clinical significance, and CT findings, AJR (1994) 162:1091-4.

3. Jennings MC et al, Abdominal manifestation of von Hippel-Lindau disease and the radiological screening protocol for an affected family. Clin. Radiol. (1988) 39:363-7.

Well, surgery is all over and I am back in the swing of things at work and taking summer classes at school. I ended up being at NIH for about a month... my body was not very receptive to the whole idea of food. The surgery took 12 hours and they had to take out my gallbladder as well as remove the tumors. They turned out to be neuroendocrine tumors. The physicians there did a wonderful job and I felt well not long after the surgery. I was just waiting to eat real food. All is said and done and I am glad it is over. Thank you for your support during this time. It was nice to have someone who'd been there with VHL. -- Sarah S., Minnesota

As printed in the VHL Family Forum 7:3, September 1999.  For permission to reprint, please contact VHL Family Alliance, editor@vhl.org. Further information is available from the VHL Family Alliance, info@vhl.org.