Pancreatic Neuroendocrine Tumors

Pancreatic neuroendocrine tumors are complex tumors with unique characteristics that require specialized treatment. At Penn Medicine, our team focuses on these uncommon neuroendocrine tumors (NETs), giving you the best chance for effective care.

We have the experience to offer surgery when possible and further options when you need them. We prioritize the most pressing needs, protecting your health and quality of life while keeping an eye on your future.

What Are Pancreatic Neuroendocrine Tumors (Islet Cell Tumors)?

Among the various types of neuroendocrine tumors, some develop in the pancreas, the organ providing digestive help and blood sugar control. These pancreatic neuroendocrine tumors — pancreatic NETs, or PNETs — are less common than NETs in the gastrointestinal tract.

Pancreatic NETs are not the same as pancreatic adenocarcinoma, which accounts for more than 90 percent of pancreatic cancers. Key differences include:

  • Cell types: Pancreatic NETs form in endocrine cells, which release hormones. These cells sit in clusters called islets, which is why pancreatic neuroendocrine tumors are also called islet cell tumors. Pancreatic adenocarcinoma develops in exocrine cells, which release digestive enzymes.
  • Symptoms: Pancreatic NETs and adenocarcinomas share some symptoms. But pancreatic NETs also cause their own signs of disease if their cells continue releasing hormones. About half of pancreatic neuroendocrine tumors behave this way.
  • Outlook: Pancreatic adenocarcinoma is usually a fast-moving disease. Pancreatic NETs grow slowly in most cases. So even though the disease has often metastasized (spread) by diagnosis, the prognosis for pancreatic NETs is typically more promising. The exception is a more unusual type called pancreatic neuroendocrine carcinoma (pancreatic NEC). These tumors grow and spread quickly.

Risk Factors for Pancreatic Neuroendocrine Tumors and Genetics

Doctors are often not sure why pancreatic neuroendocrine tumors form. Occasionally, a genetic mutation (also known as a variant) inherited from a parent leads to a pancreatic NET. Less than 10 percent of cases fall in this category. These variants are usually found in one of two genes:

Learn more about our genetic testing for neuroendocrine tumors, and our genetic counseling.

Pancreatic Neuroendocrine Tumor Types and Symptoms

Sometimes symptoms of a pancreatic NET occur because the tumor has grown large or turned malignant (cancerous) and spread. These symptoms can overlap with other conditions, including more common forms of pancreatic cancer.

Signs and symptoms include:

  • Back or belly pain
  • Bone pain
  • Diarrhea
  • Indigestion
  • Jaundice (yellowing of skin or eyes)
  • Loss of appetite
  • Lump in the belly
  • Shortness of breath or coughing
  • Unintended weight loss

About half of pancreatic NETs release hormones that upset the body’s normal balance. This hormonal disruption may cause noticeable symptoms to show up while a tumor is still small.

The particular symptoms experienced depend on the form of tumor, named after the principal hormone released:

Gastrinomas in the Pancreas

Gastrinomas are one of the more common hormone-releasing NETs in the pancreas and may also occur in the duodenum (small intestine’s first section). Sometimes there are multiple tumors. Gastrinomas release gastrin, which boosts stomach acid. Symptoms cause Zollinger-Ellison syndrome (ZES) and include:

  • Diarrhea
  • Peptic ulcers (painful sores on the lining of the stomach or small intestine)
  • Steatorrhea (oily stools)

Insulinomas

Insulinomas are another common, hormone-releasing pancreatic NET. Diagnosis requires staying in the hospital for several days for testing. The tumors release extra insulin, which leads to:

  • Hypoglycemia (low blood sugar, which can cause neuroglycopenia, or brain function interference)
  • Obesity

Glucagonomas

These tumors release glucagon, a hormone that increases blood sugar. Symptoms include:

  • Anemia (low red blood cell count)
  • Blood clots
  • Diabetes
  • Glossitis (swollen and inflamed tongue)
  • Necrolytic migratory erythema (particular rash around the genitals, anus, buttocks, groin and lower legs)
  • Unintended weight loss

VIPomas

These tumors release the hormone vasoactive intestinal peptide (VIP), causing:

  • Achlorhydria (lack of hydrochloric acid in stomach juices)
  • Flushing (warmth and redness in the face)
  • Hypercalcemia (too much calcium in the blood)
  • Hyperglycemia (high blood sugar)
  • Hypokalemia (low potassium)
  • Metabolic acidosis (too much acid in the body)
  • Watery diarrhea

Somatostatinomas

These rare tumors release somatostatin, leading to:

  • Diabetes
  • Diarrhea
  • Gallstones
  • Hyperglycemia (high blood sugar)
  • Hypochlorhydria (low stomach acid)
  • Steatorrhea (oily stools)
  • Unintended weight loss

Pancreatic Polypeptidomas

These rare tumors release pancreatic polypeptide, sometimes causing:

  • Belly pain
  • Hepatomegaly (enlarged liver)
  • Watery diarrhea

Why Choose the Abramson Cancer Center for a Pancreatic NET?

With their distinct behaviors and characteristics, pancreatic NETs require an experienced team. Each member of our team is used to seeing these uncommon tumors. We care for a broad range of cases, for accurate diagnosis and effective treatment.

When you come to our program, you’ll find:

  • Expertise: Our doctors are recognized experts in their fields, with a deep understanding of pancreatic NET nuances. They help craft national treatment guidelines and participate in national working groups dedicated to research and improved care. Learn more about our neuroendocrine tumor team.
  • Collaboration: Doctors from a range of specialties meet at a weekly neuroendocrine tumor board to discuss cases. They identify individualized treatment recommendations, as well as the most effective timing and order of therapies — crucial for pancreatic NETs. Learn more about our Neuroendocrine Tumor Program, including our tumor board.
  • Options: Pancreatic NETs often need a variety of treatments spread over years. We offer a full range of options, from surgery and liver therapy to targeted therapy and nuclear medicine. We also develop new options. In fact, we ran the trial that led to the first nuclear medicine approval for pancreatic NETs. Learn more about neuroendocrine tumor research and clinical trials.
  • Support: At our program, a nurse navigator helps with appointment scheduling and many other needs. We also provide GI symptom management for neuroendocrine tumors — diarrhea control is a frequent concern — and other ways to support neuroendocrine tumors.

Diagnosing Pancreatic Neuroendocrine Tumors

There are three main ways pancreatic NETS are discovered. Some people have symptoms from hormone release and see a doctor. Others experience symptoms of tumor growth or spread. Still, others undergo a scan for another medical reason and learn they might have a pancreatic growth.

Still, symptoms may not appear right away, especially if tumors don’t release hormones. When symptoms do occur, they can overlap with a range of conditions. Definitive answers can get delayed as a result. Most people age diagnosed between 30 and 60, and many have diseases that’s spread to the liver or elsewhere, like lymph nodes, bones and lungs.

Our thorough evaluation may include:

  • CT and MRI of the belly and pelvis
  • Endoscopy (examination with thin tubes with lights and cameras) of the GI tract, along with biopsy when needed
  • Needle biopsy if still needed, to analyze tumor cells to see if they are well-differentiated and how fast they’re dividing and multiplying
  • Blood tests to determine hormone levels
  • PET/CT imaging, either specially tailored for NETs or more general for aggressive cancers (learn more about nuclear medicine for neuroendocrine tumors)

How We Treat Pancreatic Neuroendocrine Tumors

We create personalized treatment recommendations for you, based on a thorough review by our neuroendocrine tumor board. We consider:

  • Tumor size and rate of growth
  • Whether the tumor is releasing hormones and, if so, what kind
  • Whether cancer has spread and how extensively
  • If the liver is involved and how much disease it contains
  • Your symptoms
  • Your preferences and overall health

Treatment may involve watchful waiting, surgery to remove tumors or therapy for more extensive cancer:

Watchful Waiting for Pancreatic NETs

Occasionally, pancreatic NETs get discovered when they’re still quite small and slow-growing and haven’t spread. In those cases, we may recommend just monitoring the tumor, since pancreatic surgery comes with some risks. We’re more likely to suggest this approach when tumors aren’t releasing hormones or otherwise causing complications.

If the tumor grows too large, we can then consider surgery.

Surgery to Remove Pancreatic NETs

Overall, we can remove pancreatic NETs more often than pancreatic adenocarcinomas. We may even recommend neuroendocrine tumor surgery for diseases that has spread, as long as it’s not too extensive. For example, we can combine procedures for both the pancreas and the liver.

Our surgeons consider a minimally invasive approach whenever possible, for a shorter hospital stay and faster recovery. We may remove just the tumor or a larger section of the pancreas. One such treatment, the Whipple procedure, removes:

  • Head of the pancreas
  • Duodenum
  • Gallbladder
  • Nearby lymph nodes

Even if we can’t remove all the cancer, we may still recommend surgery to reduce the size of a tumor. This approach, called debulking, can keep the disease under control for a while.

Pancreatic NET Treatment for More Extensive Disease

For diseases that have spread more widely, our team has many effective options, including some not widely available. Our tumor board helps determine which ones are most likely to work, with the fewest side effects.

Since even metastatic disease tends to grow slowly, many people eventually need a range of therapies over a number of years. We take special care with pacing and sequencing of treatment so you have options when you need them.

Options include:

  • Somatostatin analogs (SSAs): These medications are one type of drug therapy for neuroendocrine tumors. They mimic the hormone somatostatin, which most pancreatic NETs will take into their cells. SSAs are typically the first therapy tried when surgery isn’t possible or the disease requires more treatment. Monthly injections can control cancer growth and relieve symptoms tied to hormone release.
  • Liver therapy: When we can’t remove liver tumors with surgery, other treatments can shrink them fairly quickly. Learn more about liver-directed therapy for neuroendocrine tumors.
  • Peptide receptor radionuclide therapy (PRRT): We deliver targeted radiation with a molecule taken up by pancreatic NET cells. The radiation can stop cancer from progressing for a number of years. Unlike surgery or more focused liver treatment, PRRT hits cancerous cells across the body. Since we can only use it so many times, we may recommend saving it until needed. Learn more about nuclear medicine for neuroendocrine tumors and PRRT.
  • Clinical trials: We develop new medications and other treatments through clinical trials and may have one that fits your needs. Learn more about neuroendocrine tumor research and clinical trials.
  • Targeted therapy: Another type of drug therapy, these emerging medications interfere with the ways tumors grow. We often turn to targeted therapy when tumors aren’t good matches for PRRT.
  • Chemotherapy: This drug therapy destroys rapidly dividing cells, with the potential to shrink tumors and reduce the amount of disease. Different types of medicines may be needed to treat well-differentiated, slower-growing tumors than for poorly differentiated, more aggressive tumors. Learn more about chemotherapy.
  • Radiation therapy: Radiation given by a machine outside the body can treat metastatic sites in the bones and lungs. Learn more about radiation therapy.
  • Other medications: We may recommend other supportive drugs such as medicines that block gastric acid (for gastrinomas).

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To make an appointment, please call 800-789-7366 or request a callback.