This page is useful as a quick reference to some of the terminology you may encounter on your journey with NETs.
Cancer is a broad group of various diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumours, and invade nearby parts of the body. The cancer may also spread to more distant parts of the body through the lymphatic system or bloodstream. Not all tumours are cancerous. Benign tumours do not grow uncontrollably, do not invade neighbouring tissues, and do not spread throughout the body. There are over 200 different known cancers that afflict humans.
Metastasis describes the spread of a cancer from one organ to another non-adjacent organ. The original site of the cancer cells is known as the primary tumour. The new secondary occurrences of disease are called metastases or local metastases (or mets). ‘Metastasis’ comes from the a Greek word meaning “displacement”
Debulking (Tumour Debulking)
If the tumour has spread (metastasised), surgery may still be possible to remove the part of the tumour that is producing too many hormones. This is often referred to as tumour debulking.
Tumour / Neoplasm
A tumour is a mass of tissue formed by a new growth of cells, normally independent of the surrounding structures. Originally, a tumour meant any form of swelling whether abnormal or not. Neoplasm is a mass of tissue as a result of abnormal proliferation of cell growth (neoplasia). Neoplasms may be benign, pre-malignant (carcinoma in situ) or malignant (cancer).
Some neoplasms do not form a tumour. These include leukaemia and most forms of carcinoma in situ.
In modern medicine, the term tumour means a neoplasm that has formed a lump.
A benign tumour lacks the ability to spread to another non-adjacent organ. The term “benign” implies a mild and non-progressive disease. Benign tumours may still produce negative health effects, though many kinds of benign tumours are harmless to human health.
A premalignant condition (or precancerous condition) implies a significantly increased risk of cancer. If left untreated, these conditions may lead to cancer.
Malignancy / Malignant
Malignancy (from Latin male “badly” + -gnus “born”) is the tendency of a medical condition, especially tumours, to become progressively worse and to potentially result in death. Malignancy is most familiar as a characterization of cancer. A malignant tumour is capable of invading into adjacent tissues, and may be capable of spreading to distant tissues.
Neuroendocrine tumours (NETs)
Neuroendocrine tumours or NETs, is the umbrella term for a group of relatively uncommon cancers, often called the ‘quiet cancers’. This is because NETs are often slow growing and so the symptoms can take time to develop, may be vague, or attributed to more common and less serious problems such as irritable bowel syndrome (IBS), Crohn’s disease, peptic ulcer disease or gastritis.
Neuroendocrine cancer is formed in the neuroendocrine system, which is made up of neuroendocrine cells found in the respiratory and digestive tracts. The respiratory tract includes the bronchial tubes and lungs. The digestive tract starts at the mouth and ends at the rectum. Many are benign, while some are malignant.
Neuroendocrine cells are also found in the endocrine glands, such as the adrenal glands, pancreas, thyroid and pituitary. These cells are also found in the ovaries and the testes.
How NETs are formed is still not fully understood. As with all forms of cancer, NETs arise when cells multiply rapidly in the body. Normal cells in our body divide in a controlled manner, but in cancer the control signals go wrong. This causes abnormal cells to form, which divide quickly resulting in tumour growth.
Small intestinal neuroendocrine tumours were first distinguished from other tumours in 1907. They were named carcinoid tumours because their slow growth was considered to be “cancer-like” rather than truly cancerous. It was only later discovered that they could also be malignant.
Gastroenteropancreatic (GEP) NET
The name for NETs has changed in recent times. Carcinoid is sometimes still used, but the more accurate description is NET or Gastroenteropancreatic (GEP) NET. The term GEP came about because the tumours often arise in the cells of the stomach (gastro), intestines (entero) and the pancreas:
- “G” – gastro (stomach)
- “E” – entero (intestines)
- “P” – pancreatic (pancreas)
Foregut / Midgut / Hindgut
Foregut tumours are found in the lungs, stomach, pancreas, gall bladder and duodenum.
Midgut tumours are found in the jejunum, ileum, appendix and right colon.
Hindgut tumours are found in the left colon and rectum.
Functioning and non-functioning pancreatic tumours
The group of tumours that arise in the pancreas can be classified into two different groups; functioning and non-functioning. The functioning group will produce a number of clinical syndromes that are related to where they originate, for example, an insulinoma will over-secrete insulin and gastrinomas are gastrin-secreting tumours. The non-functioning group may secrete certain hormones and peptides like other NETs, but the release of these chemicals does not cause an identifiable ‘syndrome’ or collection of symptoms. This can make diagnosis difficult and explains why so many cases are picked up incidentally.
Chromogranin A and B
A blood test may show the presence of certain NET ‘markers’, such as chromogranin A and B. If the results of this test suggest the presence of a NET, further imaging tests will be carried out to confirm the diagnosis. This blood test is usually used to monitor the activity and progression of NETs within the body.
5-HIAA (hydroxyindoleacetic acid) is a substance that is naturally produced and eliminated by the body. Normally, only small amounts are present in the urine. Elevated levels in a urine sample may indicate a NET, although further tests are required to confirm the diagnosis. 5-HIAA is tested by collecting urine over a 24 hour period. It is very important that certain foods are avoided both before and during the urine collection period as these can interfere with the 5-HIAA levels. This test is usually used to monitor the activity and progression of NETs within the body.
An endoscopy is an examination where a flexible camera, called an endoscope, is used to examine the digestive tract. The tube can be inserted down the back of the throat (gastroscopy) or via the rectum (colonoscopy). In both cases you will be offered sedation. If abnormal-looking tissues are found during this procedure, a sample can be collected and examined under a microscope. A tissue biopsy like this can be the only definitive test for a NET cancer.
Ultrasound scans use sound waves to build up a visual picture of the inside of the body. They are completely painless. These scans are usually done in the hospital X-ray department. The ultrasound scanner has a microphone which gives off sound waves. The microphone is passed over your body and the sound waves bounce off the organs inside your body, and are picked up again by the microphone. The microphone is linked to a computer which turns the reflected sound waves into a picture.
This involves taking a piece of tissue from the suspect tumour and analysing it in the laboratory by a specialist called a histopathologist. The specialist may review the biopsy sample and give your tumour a ‘proliferative index’ i.e. a measure of the number of cells in the tumour that are dividing (proliferating). A proliferation index of less than 2% means that the tumour is very slow growing, while a value above 10% suggests faster growth. Being able to look at the tumour under the microscope can be the only way to determine exactly what type of NET cancer it is.
CT Scan (Computerised Tomography)
A CT scanner is a special type of X-ray machine which uses ionising radiation to provide a three dimensional picture of the inside of the body. It can be used to determine the position and size of tumours, and regular scans are useful to find out more about the rate of tumour growth and how the tumour is responding to treatment. Before the scan, you may be asked to have an injection or drink a fluid containing a dye that shows up on the scan.
MRI Scan (Magnetic Resonance Imaging)
An MRI scan can be used to locate a tumour. Magnetism is used instead of X-rays to produce soft tissue images that can distinguish between normal and diseased tissue. If a tumour is identified in this way, further tests may be needed to confirm the type of tumour.
These scans use a body imaging technique. Cells that receive hormonal messages do so through receptors on the surface of the cells. For reasons that are not fully understood, many NET cells possess especially strong receptors; for example, GEP-NETs often have strong receptors for somatostatin, a very common hormone. The OctreoScan uses a synthetic form of somatostatin, which is chemically bound to a radioactive substance. This is injected via a vein in the arm and then observed 24 hours later using a radio-sensitive scan. These scans can diagnose and locate around 80-90% of GEP-NETs, although further scans, such as PET scans may still be required.
PET scan (Positron emission tomography)
PET Scan is a medical imaging technique using computer analysis to produce a three-dimensional image or picture of functional processes in the body. In modern scanners, three dimensional imaging is often accomplished with the aid of a CT X-ray scan performed on the patient during the same session, in the same machine.
Multidisciplinary team (MDT)
NET cancer care can be complex involving a range of investigations, treatments and healthcare professionals. Often there is more than one treatment option available, and so there has to be collaboration amongst all key healthcare professional groups who are making clinical decisions for you. This collaboration is called a multidisciplinary team or MDT. The MDT management approach is now being used across the world in the care of people with NETs.
Multiple Endocrine Neoplasias (MEN)
Multiple Endocrine Neoplasias (MEN) syndromes are three related disorders affecting the thyroid and other hormonal (endocrine) glands of the body. MEN has previously been known as familial endocrine adenomatosis.
The three forms of MEN are MEN1 (Wermer’s syndrome), MEN2A (Sipple syndrome), and MEN2B (previously known as MEN3). Each is an autosomal dominant genetic condition which predisposes to hyperplasia (excessive growth of cells) and tumour formation in a number of endocrine glands.
Gastrinomas are tumours associated with a rare gastroenterological disorder known as Zollinger-Ellison syndrome (ZES). They occur primarily in the pancreas and duodenum (beginning of the small intestine) and secrete large quantities of the hormone gastrin, triggering gastric acid production that produces ulcers. Gastrinomas are an integral part of the Zollinger-Ellison syndrome (ZES). This syndrome consists of ulcer disease in the upper gastrointestinal tract, marked increases in the secretion of gastric acid in the stomach, and tumours of the islet cells in the pancreas. The tumours produce large amounts of gastrin that are responsible for the characteristics of Zollinger-Ellison syndrome. Gastrinomas may occur randomly and sporadically, or they may be inherited as part of a genetic condition called multiple endocrine neoplasia type 1 (MEN-1) syndrome.
Tumour that arises from the insulin-producing cells in the pancreas (insulin-secreting cells of the islets of Langerhans).
A glucagon-secreting tumour, usually derived from pancreatic islet cells (alpha cells of the islets of Langerhans).
A type of pancreatic tumour that causes changes in secretion of vasoactive intestinal polypeptide (VIP). VIP causes dilation of blood vessels throughout the body and secretion of fluid and salt in the intestinal tract, resulting in diarrhoea.
Goblet Cell Carcinoids
Goblet cell carcinoids, abbreviated GCC and also known as crypt cell carcinoma and neuroendocrine tumour with goblet cell differentiation, are a rare biphasic gastrointestinal tract tumour that consists of a neuroendocrine component and a conventional carcinoma.
A gastroenterologist specialises in diseases affecting the gastrointestinal tract, which includes the organs from mouth to anus, along the alimentary canal.
An endocrinologist specialises in the endocrine system, its diseases, and its specific secretions called hormones, and is concerned with study of the biosynthesis, storage, chemistry, biochemical and physiological function of hormones and with the cells of the endocrine glands and tissues that secrete them.
An oncologist is a physician who specialises in the diagnosis and treatment of cancer. Oncology is concerned with the diagnosis of cancer in a person, therapy (e.g. surgery, chemotherapy, radiotherapy), follow-up of cancer patients after successful treatment, and palliative care of patients with terminal malignancies.
Somatostatin is a substance produced naturally in many parts of the body. It can stop the over-production of hormones that cause symptoms such as diarrhoea, flushing and wheezing. Lanreotide and octreotide are somatostatin analogues i.e. drugs that copy or mimic the action of somatostatin.
Interferon is a naturally occurring substance that is produced by the body’s immune system during an illness such as a viral infection e.g. flu. It is sometimes referred to as biological therapy or immunotherapy and is used to treat some patients with NETs. Sometimes interferon is given on its own, but quite often it is given as a combination therapy with somatostatin analogues. It may not be a suitable therapy for all NET patients.
Some people may be given chemotherapy e.g. to treat pancreatic and bronchial NETs, and also for some NET tumours which are growing a little quicker than they might normally do. The histology of your tumour will help determine whether chemotherapy will be appropriate for you or not. If you have chemotherapy the oncology team, who are specialists in this field, will look after you.
If the tumour has spread to the liver, you may be offered hepatic artery embolisation (HAE). In this procedure, a catheter is placed in the groin, and then threaded up to the hepatic artery that supplies blood to the tumours in the liver. Tiny particles called embospheres (or microspheres) are injected through the catheter into the artery. These particles swell and block the blood supply to the tumour, which can cause the tumour to shrink or even die. This treatment can also be combined with systemic treatments for people with liver metastases and metastases outside of the liver. It is a procedure that would be done by a specialist called an interventional radiologist. You will be sedated for the treatment.
Sometimes this embolisation process is combined with chemotherapy and called Hepatic Artery Chemoembolisation (HACE), or Transcatheter Arterial Chemoembolisation (TACE), or radiotherapy (Radioactive Microsphere Therapy [RMT] or Selective Internal Radiation Therapy [SIRT]).
Radiofrequency Ablation (RFA) is used if there are relatively few secondary tumours. A needle is inserted into the centre of the tumour and a current is applied to generate heat, which kills the tumour cells.
Radionuclide Therapy \ PRRT
Radionuclide therapy is also called peptide receptor radionuclide therapy (PRRT) or hormone-delivered radiotherapy. This treatment involves a similar strategy as that applied in an octreotide scan, but the dose of radiation is high enough to prevent further tumour growth or even kill the tumour.
This treatment is not available in Ireland but is offered by some very specialist centres around Europe. One such centre is the university hospital in Uppsala, Sweden which has close links with several Irish hospitals. This treatment is accessible to Irish NET patients through the EU’s E112 system as part of their overall healthcare strategy.
Radioactive substances are chemically combined with hormones that are known to accumulate in a NET. This combination is injected, the hormones enter the tumour and the attached radiation will kill the tumour cells.