Pancreatic neuroendocrine tumours (NETs) develop when the hormone-producing cells of the pancreas, previously known as islet cells, begin to multiply too quickly. These tumours are a rare type of pancreatic cancer, making up less than 5% of all new pancreatic cancer diagnoses. Importantly, they present with different symptoms and are diagnosed and treated differently from pancreatic adenocarcinomas.
Pancreatic NETs are broadly categorised into two main types: functional and non-functional.
These tumours produce high levels of hormones, leading to noticeable symptoms. They are named according to the specific hormone they overproduce:
Produce excess insulin, causing low blood sugar (hypoglycaemia). They are the most common type and are often small when diagnosed, which frequently allows for a surgical cure.
Produce excess gastrin and stomach acid, commonly resulting in severe acid reflux and ulcers.
Produce excess glucagon, which can lead to high blood sugar and distinctive rashes.
Produce excess somatostatin, a hormone that regulates other hormones. These are extremely rare.
Produce excess Vasoactive Intestinal Peptide (VIP), a hormone that helps control several important digestive functions.
These tumours do not produce hormone levels high enough to cause noticeable symptoms. As a result, they often grow quite large before a diagnosis is made. Non-functional pancreatic NETs are, in fact, more common than the functional types.
The precise cause of pancreatic NETs remains unknown. However, they are occasionally linked to certain genetic syndromes, including:
Multiple endocrine neoplasia, type 1 (MEN1)
Von Hippel-Lindau (VHL)
Neurofibromatosis (NF)
The signs and symptoms of pancreatic NETs differ significantly between the functional and non-functional types.
The symptoms are typically related to the overproduction of specific hormones:
Symptoms of low blood sugar, such as blurred vision, headache, lightheadedness, fatigue, weakness, irritability, confusion, hunger, and increased sweating.
Persistent stomach ulcers, abdominal pain, gastric reflux, and diarrhoea.
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, diarrhoea, unexplained weight loss, or sores on the tongue or corners of the mouth.
Symptoms of high blood sugar (including headaches, frequent urination, dry skin and mouth, and feeling hungry, tired or thirsty), diarrhoea, foul-smelling stool that floats (steatorrhoea), gallstones, jaundice (yellowing of the skin and eyes), or unexplained weight loss.
Excessive diarrhoea, dehydration, muscle ache, weakness, or cramps due to low blood potassium, abdominal pain or cramps, and unexplained weight loss.
Since non-functional tumours do not produce large amounts of hormones, they can grow or spread without causing obvious symptoms. When symptoms do eventually appear, they may include:
It is important to remember that these symptoms do not automatically mean a pancreatic NET is present. You must discuss any of these symptoms with your doctor.
A definitive diagnosis of a pancreatic NET almost always requires a biopsy, where a small sample of the suspected tumour is removed and examined by a pathologist. Several other diagnostic and imaging tests are also used to identify, locate, and stage the disease (determine its extent).
Blood tests are used to check for unusual levels of certain substances, which may indicate a pancreatic NET:
Levels of hormones produced by functional NETs, such as insulin, gastrin, glucagon, somatostatin, pancreatic polypeptide (PP), or vasoactive intestinal peptide (VIP).
A protein whose levels can be raised by many conditions and medications, including non-functional pancreatic NETs. It is sometimes used in the workup for a suspected NET but is not a definitive diagnostic tool.
Many of the same imaging methods used to detect and biopsy pancreatic adenocarcinomas are employed for pancreatic NETs. The most common diagnostic imaging method is a CT scan.
In certain situations, somatostatin receptor imaging may be used to visualise the NETs. This method involves administering a substance called octreotate intravenously; this substance attaches to most pancreatic NETs and can then be seen on the imaging test. These tests are more commonly used for staging the disease rather than initial diagnosis.
Specific tests tailored to the patient's symptoms may also be ordered by the doctor to help diagnose functional pancreatic NETs.
Staging is the process of classifying the cancer based on how much disease is in the body and whether it has spread. This classification is vital for the doctor to plan the best course of treatment. The determined stage remains the same throughout the patient's journey, even if the cancer is successfully treated or later spreads.
The tumour is less than 2 cm and is confined entirely within the pancreas.
The tumour is 2 cm or larger and may have grown into nearby organs. This stage is split into IIA and IIB:
The tumour has grown into nearby organs or blood vessels, or has spread to the lymph nodes. This stage is split into IIIA and IIIB:
The tumour has spread to distant areas of the body. It may or may not have grown to nearby areas outside of the pancreas or spread to nearby lymph nodes.
A range of treatments are available for pancreatic NETs, including:
Surgery offers the best chance of a cure for pancreatic NETs that are contained entirely within the pancreas. The specific procedure depends on the tumour's type, size, and location.
Used for larger tumours to remove the affected parts of the pancreas. These are complex operations. Studies conducted at major cancer centres like SSCHRC, with extensive surgical experience, have shown greater success rates and lower risk.
Used for small tumours confined to the pancreas, this procedure removes only the small affected portion.
A technique where the tumour is removed without removing any part of the pancreas.
For NETs that have spread outside the pancreas, surgery may be used to help manage negative side effects. In select cases, liver surgery may be performed to remove metastases (tumour spread) in the liver.
Hormone therapy is an option when surgery is not possible. It uses somatostatin analogues (such as octreotide or lanreotide) to slow tumour growth and help prevent the cancer from spreading.
It can also be used to lower the level of hormones produced by functional pancreatic NETs, which can reduce the negative side effects caused by the excess hormones.
Chemotherapy can be used to stop tumour growth and shrink larger tumours. Common chemotherapy drugs used to treat pancreatic NETs include:
Typically, two or more of these drugs are given in combination, depending on a patient's ability to tolerate the treatment. The most common combinations are Temozolomide with capecitabine, and Fluorouracil (5-FU) with doxorubicin and streptozocin.
Targeted therapies are a form of precision medicine designed to slow or stop cancer growth by specifically targeting unique features on the cancer cells. Three targeted therapies are used for pancreatic NETs:
A targeted therapy specifically for pancreatic NETs caused by von Hippel-Lindau disease (VHL). It works by blocking a protein that encourages tumour growth in VHL-related tumours.
Works by blocking one of the pathways cancer cells use to grow and divide.
Prevents the tumour from developing new blood vessels, which are necessary for its growth and survival.
PRRT has recently been approved for treating somatostatin-receptor positive pancreatic NETs. This radiation therapy involves the intravenous delivery of a radioactive drug called lutetium Lu 177 dotatate, which attaches directly to the tumour to deliver radiation.
If pancreatic NETs have spread to the liver, liver-directed therapy may be employed. These procedures are performed by specialised interventional radiologists who inject the therapy (such as radioactive beads) into the blood vessels feeding the liver tumours. This treatment can slow the growth of liver tumours and may also shrink them.
Some pancreatic NETs are so slow-growing that the risks associated with treatment may outweigh the risks of not treating for a period of time. In such cases, careful observation (or "watchful waiting") may be adopted as a treatment strategy. This approach can be used for some tumours confined to the pancreas, as well as for some cases of metastatic disease.