What are NETS?

Neuroendocrine tumours (NETs) is the umbrella term for a group of unusual, often slow-growing cancers. These tumours develop from secretory cells found throughout the body and which are particularly concentrated in the gastrointestinal system, lung, pancreas, ovary and testes. These cells are referred to as the diffuse endocrine system to separate them from the discrete endocrine organs such as pituitary, thyroid, parathyroid and adrenal glands.

The term neuroendocrine implies that these cells have received some nervous connections (neuro-) and the cells have the ability to secrete hormones (endocrine).

The diffuse endocrine system is made up of neuroendocrine cells found in the respiratory and digestive tracts. These neuroendocrine cells have been also known as Kulchitsky cells, enterochromaffin cells or amine precursor uptake decarboxylase (APUD) cells.

Neuroendocrine cells are also located in the discrete endocrine glands of adrenals, pancreas, thyroid  and pituitary. These cells are also found in the ovaries and the testes.

NET cancers develop when these specialized cells undergo changes causing them to divide uncontrollably and grow into an abnormal tissue mass (tumour).

The development of NETs is still not fully understood. As with all forms of cancer, NETs arise when cells multiply rapidly and in an abnormal way in the body.

Normally, all cells in the body replicate and grow in a tightly controlled manner. When this cell behaviour is disrupted, the cells divide and grow in an erratic and uncontrolled way. These cells are now behaving like a cancer cells. The cause for this change is not known, but increasing age, exposures to toxins (teratogens), a hereditary susceptibility can all play a part.  Most NETs occur without any hereditary link, but there are cases where NETs are present as part of a familial endocrine cancer syndrome such as MEN1, MEN 2, neurofibromatosis type 1 or Von Hippel Lindau.

Neuroendocrine cells and were first described over a century ago and the term carcinoid was given to them in 1907 by Obendorfer. He described a tumour of the small intestine that grew much more slowly than normal cancers and erroneously classed it as ‘benign’. Unfortunately this misunderstanding still permeates throughout the medical community, worldwide. However, in the middle of the 20^th century it became evident that these slow-growing tumours could be malignant and spread from the primary site to other parts of the body.

Today, the description carcinoid tumour is being slowly replaced in medical literature by the term NETs or gastroenteropancreatic tumours (GEPs). However, some doctors do still use the term carcinoid tumour or just carcinoid when they refer to NETs that develop in the stomach, duodenum, small intestine, appendix, colon or rectum.

There are a number of different types of NETs and they all have a slightly different way of presenting themselves, both in terms of symptoms and how they look under a microscope (histology).

The naming of NET tumours is derived from the anatomical area from which they are found in the body and some are named based on the predominant hormone that they secrete.

Carcinoids – lung, thymic, gastric, duodenal, pancreatic, small intestine, appendiceal, colon, rectal, ovarian and carcinoid tumors of unknown origin (unknown primary)

Pancreatic NET or pNET can be functioning (actively secreting hormones) or Non-functioning (no appreciable hormone production). These are futher subdivided into types that indicate the hormones they produce. Unfortunately the non functioning pancreatic NETs 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

Phaeochromocytomas, these are tumours of the adrenal glands (located on top of the kidneys) and can actively secrete noradrenaline and adrenaline causing symptoms such as high blood pressure, palpitations, sweating, nervousness, headaches, loss of weight

Paragangliomas, closely related to phaeochromocytomas but arise along the sympathetic chain. Present as painless masses but some secrete adrenaline and noradrenaline. 1-3% can metastasise. Up to 30% of paragangliomas are inherited.

Multiple endocrine Neoplasias (MEN), 

Merkel cell carcinoma, or primary neuroendocrine carcinoma of skin. These tumours occur as firm, painless reddish coloured nodules particularly on sun exposed areas of skin. They can grow rapidly and can metastasise to other organs.

Why do NET cancers behave differently in different people?

Different NETs affect people in different ways in terms of how the tumour grows, the symptoms produced, whether or not they spread and how they spread. However, all NETs share some similar characteristics.

The histology (what the tumours look like under a microscope) is very important in order to classify the cancer into a type, and therefore allow the medical team to be able to plan appropriate treatment. Although NETs share similar characteristics, the diagnosis and the way the cancer may behave could be different.

The most important aspect of NET patient care is that it is tailored to suit the individual, and that this care is provided by a specialist in the field of NETs. Quality of life is paramount for the patient, and so teamwork is essential to provide a solid plan of treatment and follow-up.

There has been much research work done by specialist healthcare professionals and progress has been made in terms of understanding these tumours. It is important to ensure that people with NETs are seen by specialists in order to access all the knowledge available.

A NET cancer patient should ideally be referred to a centre where there is a multidisciplinary team that works together to ensure the best outcomes for each patient. This team would normally include gastroenterologists, surgeons, oncologists, endocrinologists, radiologists, nuclear medicine specialists, histopathologists and clinical nurse specialists.

When caught at an early stage, NET cancers can often be cured with surgery. As with all cancers, if a surgical cure is possible, this should be the first line of treatment. Patients must still be followed for at least ten years to ensure there is no recurrence of the cancer. Unfortunately, many patients are diagnosed later on, when the cancer has spread to other parts of the body. Even when the tumours have spread, the disease and its symptoms can often be controlled for many years.