Pancreatic neuroendocrine tumors (NETs) form when the cells of the pancreas that make hormones multiply too rapidly. These tumors, previously called islet cell tumors, make up less than 5% of new pancreatic cancers. Their symptoms are different than symptoms of pancreatic adenocarcinomas. They’re also diagnosed and treated differently. This webpage focuses only on pancreatic NETs.
Pancreatic NETs are subdivided into two main types, functional and non-functional.
Functional NETs produce very high amounts of hormones. Because of this, they cause noticeable symptoms. These tumors are named based on the type of hormone they overproduce.
- Insulinomas make excess insulin. This causes low blood sugar. They are the most common type of pancreatic NET. These tumors are frequently diagnosed at a small size, so they can often be cured with surgery.
- Gastrinomas make excess gastrin and stomach acid. This often results in severe acid reflux and ulcers.
- Glucagonomas make excess glucagon, which causes high blood sugar and unusual rashes.
- Somatostatinomas make excess somatostatin, which controls the level of several other hormones. These tumors are extremely rare.
- VIPomas make excess vasoactive intestinal peptide (VIP). This hormone helps control several important digestive functions.
Non-functional NETs don’t produce hormones at a high enough level to cause noticeable symptoms. Because of this, these tumors often grow quite large before being diagnosed. Non-functional pancreatic NETs are more common than functional pancreatic NETs.
The exact cause of pancreatic NETs is not known. These tumors are occasionally associated with genetic syndromes, such as:
- Multiple endocrine neoplasia, type 1 (MEN1)
- Von Hippel-Lindau (VHL)
- Neurofibromatosis (NF)
Signs and symptoms differ between functional and non-functional pancreatic NETs.
Symptoms of functional pancreatic NETs
- Insulinomas: Symptoms of low blood sugar including, blurred vision, headache, lightheadedness, fatigue, weakness, irritability, confusion, hunger and increased sweating.
- Gastrinomas: Chronic stomach ulcers, abdominal pain, gastric reflux and diarrhea.
- Glucagonomas: Symptoms of high blood sugar (including headaches, frequent urination, dry skin and mouth, and feeling hungry, thirsty or tired), rashes on the face, stomach or legs, blood clots, diarrhea, unexplained weight loss or sores on tongue or corners of the mouth.
- Somatostatinomas: Symptoms of high blood sugar (including, headaches, frequent urination, dry skin and mouth, and feeling hungry, tired or thirsty), diarrhea, foul-smelling stool that floats, gallstones, jaundice or unexplained weight loss.
- VIPomas: Excess diarrhea, dehydration, muscle ache, weakness or cramps due to low potassium in the blood, abdominal pain or cramps and unexplained weight loss.
Symptoms of non-functional pancreatic NETs
Non-functional pancreatic NETs do not produce large amounts of hormones. This means that these tumors can grow or spread without causing noticeable symptoms. When symptoms do occur, they can include:
- Weight loss
- Pain in the abdomen or back, and possibly a lump in the abdomen
- Jaundice, or yellowing of the skin and whites of the eyes
These symptoms do not always mean you have a pancreatic NET. However, it is important to discuss any of these symptoms with your doctor.
A biopsy, in which a piece of the suspected tumor is removed and then studied, is almost always required to definitively diagnose pancreatic NETs. Several other diagnostic tests may also be used to identify, locate and stage (determine extent of) the disease.
Unusual levels of certain substances may indicate the presence of a pancreatic NET. Blood tests are used to check the levels of these substances, which include:
- Hormones made by functional pancreatic NETs. These include insulin, gastrin, glucagon, somatostatin, pancreatic polypeptide (PP) or vasoactive intestinal peptide (VIP).
- A protein called Chromogranin A (CgA). Levels of this protein can be raised by many medications and conditions, including non-functional pancreatic NETs. It’s sometimes evaluated when a pancreatic NET is suspected, but isn’t definitively diagnostic of the disease.
Many of the imaging tests and methods that are used to detect and biopsy pancreatic adenocarcinomas are used to diagnose pancreatic NETs. The most common diagnostic imaging method for pancreatic NETs is a CT scan.
In some cases, somatostatin receptor imaging can be used to visualize pancreatic NETs. This method uses a substance called octreotate, which attaches to most pancreatic NETs and can then be seen on imaging tests. These tests are more commonly used in pancreatic NET staging, rather than diagnosis.
Several other specific tests can be used to help diagnose functional pancreatic NETs. The particular tests your doctor orders will be based on your symptoms.
Pancreatic neuroendocrine tumor staging
If you’re diagnosed with a pancreatic NET, your doctor will determine the stage of the disease. Staging is a way of classifying cancer by how much disease is in the body and if it has spread. This helps the doctor plan the best way to treat your pancreatic NET. Once the staging classification is determined, it stays the same even if treatment is successful or the cancer spreads.
(Source: American Joint Committee on Cancer (AJCC) 2018 Staging Manual)
Stage I: The tumor is less than 2 cm and is contained within the pancreas.
Stage II: The tumor is 2 cm or larger and may have grown into nearby organs. This stage is divided into IIA and IIB.
- IIA: The tumor is less than 4 cm and is contained within the pancreas.
- IIB: The tumor is larger than 4 cm and is either still contained within the pancreas or has grown into the small intestine or bile duct.
Stage III: The tumor has grown into nearby organs or blood vessels, or spread to the lymph nodes. This stage is divided into IIIA and IIIB.
- IIIA: The tumor has grown into nearby organs, such as the stomach, spleen, colon or adrenal gland, or into large blood vessels. It has not spread to nearby lymph nodes or distant areas of the body.
- IIIB: The tumor has spread to nearby lymph nodes, but has not spread to distant areas of the body. It may or may not have grown into nearby areas outside of the pancreas.
Stage IV: The tumor has spread to distant areas of the body, and may or may not have grown to nearby areas outside of the pancreas or spread to nearby lymph nodes.
Several types of treatments are used for pancreatic NETs, including:
- Hormone therapy
- Targeted therapy
- Peptide receptor radionuclide therapy (PRRT)
- Liver-directed therapy
The best way to treat pancreatic NETs that are contained within the pancreas is through surgery. Many cases can be cured this way. The type of surgical procedure used varies depending on the type, size and location of the tumor.
If the tumor is large, either a pancreatoduodenectomy (or, more commonly, the Whipple procedure) or distal pancreatectomy may be used to remove the parts of the pancreas affected by the tumor. These operations are extremely complex. Studies have shown that they are more successful and have less risk when performed by doctors at major cancer centers with extensive experience.
A central pancreatectomy may be used if the tumor is small and confined to the pancreas. This procedure removes only the small part of the pancreas affected by the tumor.
Sometimes the surgeon can remove the tumor without removing any part of the pancreas. This is called enucleation.
For pancreatic NETs that have spread outside of the pancreas, surgery can be used to reduce some of the negative side effects. In select cases, liver surgery can be used to remove liver metastases.
Hormone therapy can be used when surgery is not possible. This therapy uses somatostatin analogues, such as octreotide or lanreotide, to slow a tumor’s growth. It can also be used to prevent the cancer from spreading.
Hormone therapy can also be used to reduce the level of hormones produced by functional pancreatic NETs. This may reduce negative side effects of these tumors.
Chemotherapy can be used to stop a tumor from growing, and to shrink larger tumors. Chemotherapy drugs commonly used to treat pancreatic NETs include:
- Fluorouracil (5-FU)
Based on a patient’s ability to tolerate therapy, two or more of the chemotherapy drugs above are typically given in combination. The most common combinations are:
- Temozolomide with capecitabine
- Fluorouracil (5-FU) with doxorubicin and streptozocin
Targeted therapies are a type of precision medicine. They slow or stop the growth of cancer by targeting specific features on cancer cells. There are three targeted therapies that are used to treat pancreatic NETs.
- Belzutifan, a targeted therapy for pancreatic NETs caused by von Hippel-Lindau disease (VHL). This therapy blocks a protein that induces tumor growth in VHL-related tumors.
- Everolimus, which blocks one of the ways that cancer cells use to grow and divide.
- Sunitinib, which prevents the tumor from creating new blood vessels, which are needed to grow and survive.
Peptide receptor radionuclide therapy
Peptide receptor radionuclide therapy (PRRT) was recently approved to treat somatostatin-receptor positive pancreatic NETs. This type of radiation therapy uses an intravenous delivery of a radioactive drug called lutetium Lu 177 dotatate. This drug delivers radiation by attaching to the tumor directly.
When pancreatic NETs spread to the liver, liver-directed therapy can be used. These are procedures performed by specialized interventional radiologists. The doctors inject the therapy, such as radioactive beads, into the blood vessels feeding the liver tumors. This treatment slows the growth of liver tumors and can also shrink them.
Some pancreatic NETs grow so slowly that the risks of treating may outweigh the risks of not treating for a period of time. In these cases, careful observation can be used as a treatment strategy. This can apply to some tumors contained within the pancreas as well some cases of metastatic disease.
Pancreatic NETs are rare and not frequently seen in most cancer centers. MD Anderson’s large patient volume gives our doctors the opportunity to treat more pancreatic NETs than most centers. We have a dedicated team of doctors who are highly experienced treating this rare cancer.
Highly experienced pancreatic cancer surgeons
When pancreatic NETs are contained within the pancreas, the best course of treatment is surgery. These surgical procedures are extremely complex, and studies have shown that the best outcomes occur when they are performed at a major cancer center by an experienced surgeon. Our surgeons are among the most experienced and skilled in the nation. MD Anderson has:
- The highest 5-year survival rate reported in the surgical literature for patients who have undergone surgery for pancreatic cancer.
- Less than a 1% mortality rate after surgery for pancreatic cancer. That is over 6% lower than the national average.
- Among the shortest average length of hospital stay after surgery for pancreatic cancer.
History and success leading pancreatic NET clinical trials
MD Anderson doctors have played major roles in the approval of several pancreatic NET treatment options, including everolimus, octreotide, lanreotide, and Lu 177 dotatate.
We’re currently leading clinical trials to find new pancreatic NET treatment options as well.
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