Neuroendocrine tumours (NETs): symptoms, types and treatment

There is no single set of symptoms. Cancer Research UK says that you usually start by seeing your GP if you have symptoms, and that you might not have symptoms at all and be diagnosed during tests for another condition. What you notice depends on the organ involved and whether the tumour is releasing hormones.

The best-described group of symptoms is carcinoid syndrome. It is caused by NETs that make large amounts of hormones and other proteins, most commonly serotonin, which are released into the bloodstream. Cancer Research UK says it is most common in people with a small bowel NET that has spread to the liver, and can also happen with lung and pancreatic NETs, though less often.

• Flushing of the face, neck and chest, which may feel warm and itchy. Cancer Research UK says about 85 in 100 people with carcinoid syndrome have this. It can be unpredictable, and some people notice triggers such as certain foods, coffee, alcohol, stress or exercise.

• Diarrhoea, which about 80 in 100 people with carcinoid syndrome have. It can be severe.

• Tummy (abdominal) pain.

• Red spidery marks on the skin from small broken blood vessels.

• Wheezing, a fast heartbeat or palpitations, and fluid build-up in the legs and ankles.

Neuroendocrine cells are found throughout the body, in almost all organs and endocrine glands, including the food pipe, stomach, lungs, small and large bowel, pancreas and appendix. They respond to signals from the nervous system by making and releasing hormones. For example, Cancer Research UK says neuroendocrine cells in the small bowel make serotonin, which helps control the muscles that move food through the bowel.

When a cancer starts in these cells, they can grow out of control and may produce higher than normal levels of hormones. Doctors may use the term neuroendocrine neoplasm (NEN), which means the same as neuroendocrine cancer. "Carcinoid" is an older term for NETs that doctors do not use often now.

A pathologist looks at the cells under a microscope and reports how abnormal they look (differentiation) and how quickly they are dividing (grade). Cancer Research UK uses these to separate the two key groups.

Doctors usually name the cancer after the part of the body where it starts (the primary site). Cancer Research UK lists these types:

• Lung neuroendocrine cancer: NETs here include typical and atypical carcinoids; NECs include small cell and large cell types.

• Stomach neuroendocrine cancer.

• Small bowel neuroendocrine cancer, in the duodenum, jejunum or ileum.

• Large bowel and rectal neuroendocrine cancer, which are less common than other types of bowel cancer.

• Pancreatic neuroendocrine tumours, including insulinoma, gastrinoma, glucagonoma, VIPoma and somatostatinoma. Non-functioning pancreatic NETs, which do not overproduce hormones, are the most common pancreatic type.

• Merkel cell carcinoma, a skin cancer that is also classed as a neuroendocrine carcinoma.

Cancer Research UK says the cause of most neuroendocrine cancers is not known. Most are not inherited. There are some rare inherited conditions that raise the risk of some NETs: multiple endocrine neoplasia type 1 (MEN1), neurofibromatosis type 1, von Hippel-Lindau disease and tuberous sclerosis.

On MEN1, it says research shows that by the age of 80, up to 80 in 100 people with the condition develop a NET of the pancreas or duodenum. Other factors it lists are age (neuroendocrine cancer can occur at any age but is most common from 55), smoking (which raises the risk of lung neuroendocrine carcinoma), a close relative with cancer, diabetes (some evidence for pancreatic NETs, though most people with diabetes will not develop one) and long-term stomach inflammation called atrophic gastritis for some stomach NETs.

Your GP will refer you to a specialist if you have symptoms that could be due to cancer. Cancer Research UK says your doctor organises blood tests, scans and tests to look inside the body, and may take a biopsy. Which tests you have depends on the suspected site.

For suspected carcinoid syndrome, Cancer Research UK lists blood tests (including chromogranin A and NT-proBNP, a protein that helps assess how well the heart is working), a urine test for 5-HIAA (the substance serotonin breaks down into, usually collected over 24 hours), a CT scan to see whether the tumour has spread to the liver, radioactive scans such as gallium dotatate PET, and an echocardiogram if carcinoid heart disease is suspected.

Treatment depends on whether it is a NET or a NEC, where it starts, how fast it grows, its size and whether it has spread. Cancer Research UK says the most common treatment is surgery, and that surgery is the main treatment for NETs. For some NETs you might not need treatment straight away, and your doctor monitors the cancer with regular tests.

• Somatostatin analogues: medicines that reduce and control high hormone levels in NETs that cause symptoms.

• Chemotherapy: a common treatment for NECs, or for NETs that have spread.

• Targeted drugs and immunotherapy for some tumours.

• Peptide receptor radionuclide therapy (PRRT): a radioactive medicine that attaches to somatostatin receptors on some NETs and delivers radiation to the cells.

• External radiotherapy.

• Liver-directed treatments for NETs in the liver: trans-arterial embolisation, which blocks the blood supply, and radiofrequency or microwave ablation, which use heat.

• Regular follow-up appointments with your doctor or nurse after treatment.

Cancer Research UK describes two rare complications of carcinoid syndrome, which doctors check for regularly. Carcinoid heart disease involves a build-up of plaque or scar tissue in the heart valves and muscle. It happens in up to 50 in 100 people with carcinoid syndrome. Symptoms are usually vague and may not appear until it is severe: breathlessness, tiredness, swelling from fluid build-up and weight loss.

Carcinoid crisis is a more serious form of carcinoid syndrome. It can happen for no reason, and in some people anaesthetic or treatments such as surgery or chemotherapy can set it off. Symptoms are severe and may include sudden large changes in blood pressure, palpitations, wheezing, sudden severe flushing and very severe diarrhoea.

Cancer Research UK says carcinoid crisis is a medical emergency. If you have been diagnosed with a NET and think you have sudden severe symptoms of this kind, it says to contact your doctor and go to your local A&E; in an emergency, call 999.

If you have not been diagnosed but notice a change that is not normal for you, such as ongoing flushing, persistent diarrhoea or unexplained tummy pain, see your GP. Use NHS 111 if you are unsure where to turn.

On the NHS, care usually begins with a GP referral, then specialist tests, and treatment planned by a team that may include a gastroenterologist, a medical oncologist, a surgeon and a neuroendocrine tumour clinical nurse specialist. Because NETs are uncommon and varied, treatment may be coordinated at a specialist centre. Some people have initial tests or consultations privately. Whichever route you take, make sure the results reach your NHS team so decisions about treatment and follow-up are based on the full picture.