What are pancreatic neuroendocrine tumors (islet cell tumors)?
Pancreatic neuroendocrine tumors—pancreatic NETs , or PNETs—are complex tumors with unique characteristics that require specialized treatment. These rare growths form in the islet cells (hormone-releasing cells) of the pancreas. PNETs tend to be slow growing, and may be benign or malignant (cancerous).
At Penn Medicine, our team focuses on these uncommon neuroendocrine tumors, 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.
PNETS vs. pancreatic adenocarcinoma
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.
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 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 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
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
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
These rare tumors release somatostatin, leading to:
- Diabetes
- Diarrhea
- Gallstones
- Hyperglycemia (high blood sugar)
- Hypochlorhydria (low stomach acid)
- Steatorrhea (oily stools)
- Unintended weight loss
These rare tumors release pancreatic polypeptide, sometimes causing:
- Belly pain
- Hepatomegaly (enlarged liver)
- Watery diarrhea
Pancreatic NET risk factors 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:
- MEN1: These variants lead to multiple endocrine neoplasia type 1, or MEN1. People with the condition are much more likely to develop a range of tumors. One possibility is gastrinoma or insulinoma, types of pancreatic NETs. People with MEN1 also have a higher risk for other NETs, including gastrointestinal neuroendocrine tumors and lung neuroendocrine tumors.
- VHL: These variants cause Von Hippel-Lindau syndrome, associated with a variety of tumors. Fewer than one in five people with the condition develop a pancreatic NET, usually one that doesn’t release hormones. People with VHL may also develop another type of NET called pheochromocytoma.
Learn more about our genetic testing for neuroendocrine tumors, and our genetic counseling.
Pancreatic neuroendocrine tumor diagnosis
PNETs are typically discovered after symptoms from hormone release, symptoms caused by tumor growth or spread, or during imaging performed for another medical reason. Because some tumors do not produce hormones and symptoms can overlap with many other conditions, diagnosis may be delayed. Evaluation may include blood tests to measure hormone levels, CT or MRI imaging, endoscopy and biopsy procedures, and specialized PET/CT imaging to identify tumors and better understand how the disease is behaving.
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.
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.
Overall, we can remove pancreatic NETs more often than pancreatic adenocarcinomas. We may even recommend neuroendocrine tumor surgery for diseases that have 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.
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.
For diseases that have spread more widely, Penn Medicine offers many effective options, including chemotherapy, radiation therapy, and targeted therapy, as well as treatments not widely available elsewhere. 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, including:
- Medications: Somatostatin analogs (SSAs) mimic the hormone somatostatin, which most pancreatic NETs will take into their cells. Monthly injections can control cancer growth and relieve symptoms tied to hormone release. We may recommend other supportive drugs such as medicines that block gastric acid (for gastrinomas).
- Liver therapy: When we can’t remove liver tumors with surgery, other treatments can shrink them fairly quickly.
- 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.
- Clinical trials: We develop new medications and other treatments through clinical trials and may have one that fits your needs.
Experienced, innovative care for rare pancreatic tumors
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.
- 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.
- 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.
- 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.
Rated “exceptional” by The National Cancer Institute
Penn Medicine’s Abramson Cancer Center is a world leader in cancer research, patient care, and education. Our status as a national leader in cancer care is reflected in our continuous designation as a Comprehensive Cancer Center by the National Cancer Institute (NCI) since 1973, one of 7 such centers in the United States. The ACC is also a member of the National Comprehensive Cancer Network, one of a select few cancer centers in the U.S., that are working to promote equitable access to high-quality, advanced cancer care.
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