Pancreatic neuroendocrine tumours (PNETs) are rare, slow-growing tumours. They are also called pancreatic endocrine tumours (PETs) or pancreatic islet cell tumours. Pancreatic neuroendocrine tumours can be either benign or malignant.
Pancreatic endocrine tumours start in the hormone-producing cells of the pancreas. They make up about 5% of all pancreatic cancers and are considered more treatable than exocrine pancreatic cancers.
Anatomy and physiology of the pancreas
Pancreatic neuroendocrine tumours are made up of endocrine cells that are usually found in islet cells throughout the pancreas. They make up a small percentage of the pancreas, and are part of the body’s endocrine system. The islet cells produce and release the following hormones into the blood:
- insulin
- reduces the amount of sugar (glucose) in the blood
- stimulates the liver, muscles and fatty tissues to absorb and store the extra sugar
- glucagon
- increases the amount of sugar in the blood
- stimulates the liver and other body tissues to release stored sugar
- somatostatin
- slows the release of other hormones produced by the pancreas
- pancreatic polypeptide
- regulates the hormones released by the pancreas
Find out more about anatomy of the pancreas.
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Risk factors
Most people with PNETs do not have any identifiable risk factors. Rarely, PNETs may be caused by inherited or genetic conditions, such as multiple endocrine neoplasia (MEN) syndromes. Recognizing symptoms and getting regular checkups are the best ways to detect PNETs early. The sooner symptoms are reported, the sooner a doctor can diagnose and treat the cancer.
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Signs and symptoms
Pancreatic neuroendocrine tumours cause a variety of signs and symptoms. The majority of tumours are slow-growing and symptoms result from the growth of the tumour and the effects of specific hormones it produces. Many PNETs may be small and non-functional (do not produce hormones), causing no symptoms at all.
Pancreatic neuroendocrine tumours are named for the type of pancreatic hormone that they produce. The types of pancreatic neuroendocrine tumours are:
Insulinoma
Insulin-producing tumours are the most common pancreatic neuroendocrine tumour, but only 10% of insulinomas are malignant. They produce too much of the hormone insulin, which reduces the blood sugar (glucose) level. Some insulinoma tumours also secrete other pancreatic hormones.
- Malignant insulinomas are usually larger than benign tumours, often larger than 6 cm.
- Multiple tumours are found in about 10% of people diagnosed with insulinoma.
The signs and symptoms of insulinoma are related to low blood sugar (hypoglycemia) and may include:
- light-headedness and fainting
- sweating
- rapid heartbeat and awareness of heart beating (palpitations)
- changes in behaviour (jittery, nervous, irritable or confused)
With extremely low blood sugar, the person may experience:
- loss of consciousness
- seizure
- coma
Insulinoma tumours are associated with a group of signs and symptoms called Whipple’s triad:
- low blood sugar (glucose) level
- symptoms of hypoglycemia
- giving the person sugar quickly relieves the symptoms and brings the blood sugar back up to normal
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Gastrinoma
Gastrin-producing tumours are the most common malignant pancreatic neuroendocrine tumour. They can also develop in the stomach and first part of the small bowel (duodenum). Gastrinoma tumours produce too much of the hormone gastrin. Gastrin increases stomach acid production, which can cause peptic ulcers that can bleed and perforate. The signs and symptoms of too much gastrin are known as Zollinger-Ellison syndrome.
- At the time of diagnosis, most gastrinoma tumours have already spread to other organs (metastasized).
- Most tumours are larger than 3 cm, and there may be several tumours at the same time.
- Most gastrinomas are found in the duodenum. The head of the pancreas is the second most common site.
The signs and symptoms of gastrinoma are related to high levels of stomach acid and are similar to those of stomach ulcers:
- persistent stomach pain
- severe heartburn, which can lead to
- severe diarrhea and fatty stools (steatorrhea)
- bleeding in the stomach
- vomiting
- low red blood cell count (anemia)
- weight loss
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VIPoma
VIP-producing tumours are the third most commonly diagnosed type of pancreatic neuroendocrine tumour, but they are very rare. VIPomas produce too much of the hormone vasoactive intestinal peptide (VIP), which increases bowel activity. VIP is normally produced by the cells of the gastrointestinal tract.
- Almost all VIPomas are malignant. Most people will have metastatic disease at the time of diagnosis.
- VIPomas are more commonly diagnosed in women.
VIPoma is associated with a group of signs and symptoms called WDHA syndrome (also called Verner-Morrison syndrome or pancreatic cholera):
- massive amounts of watery diarrhea
- abnormally low potassium level in the blood (hypokalemia) caused by diarrhea
- little or no stomach acid (achlorhydria)
Most of the signs and symptoms of VIPoma are caused by the low level of potassium and may include:
- muscle problems
- lethargy
- flushing
- changes in heart rhythm
- dehydration (caused by the diarrhea)
- abdominal pain and cramping
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Glucagonoma
Glucagon-producing tumours make up less than 1% of all pancreatic neuroendocrine tumours. Up to 80% of glucagonomas are malignant. Glucagonomas produce too much of the hormone glucagon, which increases blood sugar. They may also overproduce other hormones.
Glucagonoma is associated with a group of signs and symptoms called glucagonoma syndrome:
- skin rash called necrolytic migratory erythema (NME)
- red, swollen skin
- blisters
- can be itchy and painful
- most common on legs, groin and buttocks
- blood clots in the leg (deep vein thrombosis)
- diarrhea
- depression
Other signs and symptoms of glucagonoma include:
- painful or swollen tongue (glossitis)
- mouth sores (stomatitis)
- diabetic symptoms
- unusual thirst
- frequent urination
- unusual weight loss
- extreme fatigue or lack of energy
- abdominal pain
- blood clots in the lung (pulmonary embolism)
- muscle wasting
- slow speech
- changes to vision
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Somatostatinoma
Somatostatinomas produce too much of the hormone somatostatin, which blocks many of the other hormones produced by the pancreas (insulin, gastrin and glucagon). This very rare pancreatic neuroendocrine tumour is slow growing and is not usually diagnosed early. Almost all somatostatinomas are malignant.
The signs and symptoms of somatostatinoma include:
- diabetic symptoms
- gallstones
- diarrhea and fatty stools (steatorrhea)
- abdominal pain
- nausea and vomiting
- loss of appetite
- low levels of stomach acid (achlorhydria)
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Non-functioning pancreatic neuroendocrine tumours
Non-functioning neuroendocrine tumours may produce hormones, but only in very small amounts. These hormones do not cause symptoms or abnormal blood tests. Some of these tumours have no evidence of hormone production. Approximately 30% of pancreatic neuroendocrine tumours are non-functioning.
- Almost all non-functioning pancreatic neuroendocrine tumours are malignant.
- Most people with this type of tumour have metastases at the time of diagnosis.
- These tumours are commonly diagnosed between the ages of 30 and 40 years.
The signs and symptoms are caused by the growth and spread of the tumour:
- abdominal pain
- lump in the abdomen
- jaundice
- blockage of the small intestine (bowel obstruction)
- blockage of the bile ducts and gallbladder
- bleeding of the tumour into the stomach or small intestine
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Other rare pancreatic neuroendocrine tumours
There is very little information about these extremely rare types of pancreatic neuroendocrine tumours.
GRHoma
- These tumours cause an increase in growth-hormone releasing hormone (GRH), which stimulates the pituitary gland to release growth hormone. Too much growth hormone causes abnormal growth of bones and cartilage. This disorder is called acromegaly.
- GRHomas are more commonly diagnosed in women.
PPoma
- These tumours cause an increase in pancreatic polypeptide (PP), which can cause diarrhea.
ACTHoma
- These tumours cause increased levels adrenocorticotropic hormone (ACTH). This hormone regulates the release of cortisol, a steroid produced by the adrenal glands. ACTHoma causes Cushing’s syndrome.
- ACTHomas can be very fast-growing and aggressive cancers.
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Diagnosis
In recent years, the reported incidence of neuroendocrine tumours has increased. This increase may be due to more awareness of the disease and better diagnostic tests.
Find out more about tests used to diagnose and stage neuroendocrine cancer.
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Pathology and staging
Different types of neuroendocrine tumours can affect the pancreas. Pancreatic neuroendocrine tumours can be either benign or malignant. They may produce hormones (functioning) or may not produce hormones (non-functioning). Pancreatic neuroendocrine tumours are named according to the type of pancreatic hormone that they overproduce. They may be further classified into the following groups based on the WHO classification:
- benign or potentially malignant tumours
- well-differentiated neuroendocrine cancer
- poorly differentiated neuroendocrine cancer
- mixed neuroendocrine tumours
- rare neuroendocrine-like tumours
Staging is a way of describing or classifying a cancer based on the extent of cancer in the body. There is no detailed or generally accepted staging system for pancreatic neuroendocrine tumours. Tumours may be staged in the following general categories:
Localized
Localized pancreatic neuroendocrine tumours occur only in one place in the pancreas.
Regionalized
Regionalized pancreatic neuroendocrine tumours occur in several places in the pancreas.
Metastatic
Metastatic pancreatic neuroendocrine tumours have spread to the lymph nodes near the pancreas or to distant sites.
Recurrent
Recurrent pancreatic neuroendocrine tumours have come back after treatment. They may recur in the same location as the original cancer or in another part of the body (metastatic pancreatic neuroendocrine tumours).
Find out more about grading, disease progression and prognosis and survival.
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Treatment
Each person with pancreatic neuroendocrine tumours will have a treatment plan designed for them by their healthcare team. The team will recommend treatment options based on the specific characteristics of the cancer and the unique needs of the person.
Find out more about treatment options for neuroendocrine cancer and their side effects and follow-up after treatment.
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