Non-functioning pancreatic NETs

Non-functioning pancreatic neuroendocrine tumours (NETs) are tumours that originate in specialised cells of the pancreas.

What are non-functioning pancreatic NETs?

Non-functioning pancreatic neuroendocrine tumours (NETs) originate from specialised neuroendocrine cells of the pancreas. These tumours are characterised by lack of any symptoms or signs relating to too much hormone production in contrast to functioning pancreatic NETs such as insulinoma, gastrinoma or somatostatinoma, which are associated with distinct clinical features due to hormone over-production.

Non-functioning pancreatic NETs do however produce small (or biologically inactive) quantities of hormones such as pancreatic polypeptide, calcitonin or neurotensin, which do not cause any symptoms. Patients with these tumours show signs and symptoms due to the size of the tumour or its spread to adjacent organs such as lymph nodes or liver. In some patients the tumours are diagnosed by chance during radiological investigations for other conditions.

What causes non-functioning pancreatic NETs?

Non-functioning pancreatic NETs are caused by uncontrolled division and reproduction of specialised neuroendocrine cells of the pancreas. The exact trigger for their uncontrolled division is not known. Most of these tumours arise sporadically although, in about 1 out of 10 patients, a non-functioning pancreatic NET may be associated with a genetic condition such as multiple endocrine neoplasia type 1 syndrome or von Hippel-Lindau disease.

What are the signs and symptomsof non-functioning pancreatic NETs?

The signs and symptoms associated with non-functioning pancreatic NETs depend on their size or spread to the adjacent organs. Symptoms may include abdominal pain, an abdominal lump, nausea, weight loss and jaundice.

As these tumours are not associated with hormone over-production, they are not usually detected until a late stage. These tumours are usually large in size (average size of 3–4 cm) with evidence of spread to adjacent organs such as the liver or bone in a majority of patients (80–85%) at the time of diagnosis.

How common are non-functioning pancreatic NETs?

Non-functioning pancreatic NETs are extremely rare with prevalence of about 3–4 cases per million per year. Sixty to 80% of all pancreatic endocrine tumours are non-functioning.

Most patients are diagnosed in their 40s to 60s. The inherited forms of non-functioning pancreatic NET (as in multiple neuroendocrine neoplasia type 1 syndrome) are diagnosed at a much earlier age (20s to 30s). These tumours affect men and women in equal numbers.

Are non-functioning pancreatic NETs inherited?

Most of these tumours occur sporadically and are not inherited. In 1 out of 10 patients these may be inherited as part of a genetic condition called multiple neuroendocrine neoplasia type 1 syndrome, von Hippel-Lindau disease or tuberous sclerosis. Multiple endocrine neoplasia type 1 syndrome is characterised by endocrine tumours in multiple glands such as the pituitary gland, parathyroid glands and gastrointestinal-pancreatic endocrine system. Non-functioning pancreatic NETs are usually present in 50–60% of individuals with multiple endocrine neoplasia type 1 syndrome.  

Von Hippel-Lindau disease is characterised by tumours in multiple organs such as the kidneys, eyes, adrenal glands (phaeochromocytoma) or cerebellum. Non-functioning pancreatic NETs are present in about 10–15% of these patients.

How are non-functioning pancreatic NETs diagnosed?

In a patient suspected of having non-functioning pancreatic NETs, radiological investigations such as computerised tomography (CT) or magnetic resonance imaging (MRI) scans are carried out initially to evaluate the size of the tumour and to look for any possible spread to other organs such as lymph nodes or the liver.

Blood tests are carried out to check for over-production of hormones such as insulin, glucagon, somatostatin or vasoactive intestinal peptide to rule out a functional pancreatic NET. Measurement of chromogranin A or pancreatic polypeptide levels is useful for diagnosis of the condition and assessing the size and impact of the tumour. Most of these investigations can be carried out as an outpatient.

The diagnosis of non-functioning pancreatic NETs can only be confirmed if a tissue sample from a patient suspected of having this condition is obtained (from a biopsy or post-surgery), marked with special stains, and assessed under the microscope.

A special scan (somatostatin receptor scintigraphy/Octreoscan) may be carried out to assess the extent and spread of the disease and responsiveness of the tumour to medical therapy. With this type of scan, the doctor will inject a substance known as octreotide (which has been made mildly radioactive) into your body. The octreotide sticks to the tumour cells so the doctor can then use a scanner to identify where the octreotide is and therefore where the tumour cells are. This will help identify whether the tumour has spread or whether it is confined to one place.

How are non-functioning pancreatic NETs treated?

Wherever possible, the definitive treatment of non-functioning pancreatic NETs is surgery. However, as most of the tumours are large in size or have spread to other organs at the time of diagnosis, surgical treatment is not possible in the majority of patients.

Medical therapy includes use of somatostatin analogues such as octreotide/lanreotide to stabilise the disease; they can be given as monthly injections. Chemotherapy (with streptozotocin/doxorubicin/etoposide) is useful to treat aggressive tumours that have spread to other organs or show poor response to medical therapy. Newer drugs such as everolimus and sunitinib have been shown to improve outcome in patients with advanced non-functioning pancreatic NETs.

There are many factors that affect which type of treatment is right for each individual patient and the exact treatment that each patient receives will be tailored to their condition.

Are there any side-effects to the treatment?

Surgery is associated with potential side-effects including risk of an infection, feeling pain after surgery and possibly losing a lot of blood during surgery. Somatostatin analogue therapy is associated with side-effects such as nausea, diarrhoea, worsening of diabetic control and gallstone formation. Chemotherapy is associated with side-effects such as reduced immunity to infection, loss of hair (alopecia) and gastrointestinal disturbance. Patients should discuss any concerns about these potential side-effects with their doctor or specialist.

What are the longer-term implications of non-functioning pancreatic NETs?

In cases of non-functioning pancreatic NETs where there is no evidence of spread to the liver or bone, and surgery can be carried out to remove the tumour, patients have a good survival rate and should go on to lead full and active lives. Patients treated with surgery will need to attend regular hospital checks to assess for recurrence of the tumour using blood tests or radiological investigations.

Last reviewed: Dec 2016