- The Neuroendocrine System is made up of specific cells that help regulate normal bodily functions
- Neuroendocrine Neoplasm or NEN is a new umbrella term that includes neuroendocrine cancer
- NET or Neuroendocrine Tumour is now used for neuroendocrine cancer that has a slow to moderate growth – with cells, that under a microscope, are described as well-differentiated
- NEC or Neuroendocrine Carcinoma is the term for neuroendocrine cancer that grows more rapidly and has cells, that under a microscope, are described as poorly-differentiated
What is Neuroendocrine Cancer?
Neuroendocrine Cancer was first described as a specific disease in the mid-1800’s and yet few have heard of it. However, NET (Neuroendocrine Tumour) has been used for some time now, as an umbrella term to describe cancer of the Neuroendocrine System.
In 1907, the term ‘Carcinoid’ was applied – from the German word for “cancer-like”. This term became very popular amongst the medical community of the time, as it was believed that neuroendocrine cancer behaved very differently to common cancers. It was thought that all neuroendocrine cancers were very indolent, that is, very slow growing and unlikely to spread or behave in the same way as other malignancies.
By the 1950’s however, it was clear that these ‘Carcinoids’ could behave like common cancers, and that whilst many may grow slowly, they shared other cancers’ ability to spread to other parts of the body, and some could indeed grow as rapidly.
More recently, a new term has been proposed and is now being used, though mostly in medical publications – Neuroendocrine Neoplasm (neoplasm means new growth) – though in practice, you may still hear ‘carcinoid’ and NET mentioned.
Neuroendocrine Neoplasm, or NEN, has been introduced as the new umbrella term to help clarify the differences between all abnormal growths of the neuroendocrine system – benign or malignant. For example adenomas are benign but are can occur in neuroendocrine cells.
More importantly, this new term was to help distinguish between the two specific types of neuroendocrine cancer : NET and NEC.
- NET or Neuroendocrine Tumour has a particular appearance under the microscope – the abnormal changes seen are called ‘well-differentiated’.
- NEC or Neuroendocrine Carcinoma – these changes are called poorly differentiated.
Both have variable rates of growth, with NET more likely to show slow to moderate growth and NEC more likely to grow rapidly.
The terminology can be confusing and old wording may still be used, even by experts!
What is the Neuroendocrine System?
Our bodies are made up of billions of cells – each with their own appearance and function, for example, blood cells, bone cells, neuroendocrine cells.
Neuroendocrine cells are present throughout our bodies and create a network to keep us well by monitoring what is happening within our bodies and communicating with each other to release specific substances such as gut hormones to help our bodies function normally. This network is the Neuroendocrine System.
What type of hormones neuroendocrine cells release depends on what part of the body they are in, for example:
- In the digestive system they produce hormones that help to break down food in our gut and move food through the small and large bowel – helping both nutritional uptake and eliminating waste.
- In the respiratory system they produce hormones that help with the development of our lungs and to regulate breathing.
- In the brain they produce hormones such as oxytocin (which not only plays a role in breastfeeding, but also social bonding) and melatonin (produced in the pineal gland – and helps regulate our sleep-wake pattern).
- In the adrenal glands they produce the hormones that control our ‘fight or flight response’ – which can affect blood pressure, heart rate and may make us feel anxious.
Cancer of the Neuroendocrine System can therefore produce a number of different symptoms or, in fact, none at all – it all depends on which neuroendocrine cells are affected.
As yet there is no clearly identifiable cause.
How are Neuroendocrine Cancers formed?
How NETs/NECs are formed is still not fully understood. But we can apply some of knowledge we have about normal cells and common cancer cell development.
Normal cells have rules : they develop and grow in a controlled manner, do what they are programmed to do, then die off to be replaced by new cells – they have a life-span, if damaged they try to repair themselves or die off, they tend not travel to other parts of the body and, if they do grow beyond normal size – they tend to push against neighbouring cells, rather than through them.
In cancer the control signals go wrong and the rules are forgotten! There is uncontrolled growth, lack of cell repair and replacement or death, they will travel to other parts of the body and settle (metastasise), and when they do grow beyond their normal size they will invade neighbouring cells and structures (infiltration).
Most neuroendocrine cancers occur without any hereditary link – they are ‘sporadic’, but there are cases where they occur as part of a ‘familial’ or genetic endocrine syndrome such as MEN1, MEN 2, neurofibromatosis type 1 or Von Hippel Lindau.Click here to read our Guide to Neuroendocrine Tumours
What are the different types of Neuroendocrine cancer?
The difference in type of neuroendocrine cancer can be made by using several classifications:
- Site: where in the body it occurs – eg Lung, Small bowel, Pancreas, Skin, etc
- Grade: the rate at which it grows – this is an assessment of how many cancer cells within the growth are actively replicating and growing – the ‘mitotic rate’ aka MiB1 or Ki67
- Differentiation: the degree of abnormality of the cancer cell :
Well-differentiated refers to abnormal cancer cells that retain some resemblance to their original cell. Poorly differentiated cells have lost most, if not all resemblance.
- Function: this refers to the hormone and chemical production and release by these cells. Non-functioning neuroendocrine cancer cells usually retain their ability to release normal amounts of hormone or chemicals. Functioning neuroendocrine cancer cells produce and release abnormal amounts of the hormone or chemical they are usually responsible for. This results in specific symptoms eg an insulinoma releases too much insulin resulting in hypoglycaemic (low blood sugar) symptoms. Left untreated this ‘hyper-secretion’ can be life-threatening.
- Stage: tells us whether the cancer is localised (limited to the area in which it arises) or disseminated (has spread to other places in the body). Commonly, there are 4 stages:
1 = confined to the area in which it starts
2 = has spread to surrounding cells or tissue
3 = has spread beyond surrounding tissues and to nearby lymph nodes
4 = has spread to another place within the body, including lymph nodes.
- Familial or Sporadic: that is, whether the cancer has developed as part of a genetic condition or has occurred without there being a genetic link.
Why do Neuroendocrine Cancers behave differently in different people?
Different neuroendocrine cancers affect people in different ways depending on where they are, how slowly or rapidly they are growing, their differentiation, whether they are functioning or non-functioning, whether they are associated with symptoms or not, what stage they are at and whether they have a genetic link or not.
They can also appear to behave differently when other factors are in play, for example, co-morbidties (other health conditions), age, access to expert healthcare, treatments, responses to treatment and life-choices (decisions made regarding care and treatment).
Although neuroendocrine cancers may share similar characteristics, the diagnosis and the way the cancer may behave can be different.
Therefore, the most important aspect of neuroendocrine cancer patient care is that it is tailored to suit the individual, and that this care is provided by a specialist neuroendocrine cancer team. In the UK there are specialist neuroendocrine cancer Centres and Clinics – (nb centres have gone through European accreditation – a process of formal assessment of services and expertise, clinics may have similar expertise and services but have not -yet- applied to undergo this process).
UKINETs (The UK and Ireland Neuroendocrine Tumour Society) has put together a list of all specialist centres and clinics which can be found by on their website.
Quality of life is paramount, therefore, neuroendocrine cancer expertise, specialist multi-disciplinary teamwork and patient involvement is essential to provide an agreed and appropriate plan of treatment and follow-up. Evidence shows that access to appropriate specialist service improves care, experience and outcomes.
A multidisciplinary team usually includes healthcare professionals from several clinical areas: gastroenterology, surgery, oncology, endocrinology, radiology, nuclear medicine, histopathology, clinical science, dietetics and clinical specialist nursing. Extended team membership may also include respiratory medicine, cardiothoracics, cardiology, immunology, dermatology and psychology.
Psychosocial support is also an essential part of patient-centred care, as a diagnosis of cancer is one of the biggest challenges a person can face. This challenge can feel even harder to deal with when diagnosed with a rare or uncommon cancer – particularly one that doesn’t always conform to people’s perceptions or expectations of cancer ‘you look well’, ‘oh you’re not on chemo?’.
Those living with neuroendocrine cancer have reported the difficulties in being confronted by a lack of both public and medical awareness, difficulties in gaining their diagnosis, being given a different diagnosis, having limited access to reliable, accurate information and expertise – feeling alone, adrift, isolated, scared and uncertain about their future.
Support is available and it is important that people are referred to or signposted appropriately. Details of the support services available from us at NET Patient Foundation can be found here.
It is vital that provision is made to ensure there is adequate emotional, mental and spiritual support for, not only the individual diagnosed, but their immediate loved ones too. Access to a clinical nurse specialist has been shown to improve patient’s experience, as has access to pastoral care, whether through formal counselling or peer group support. There are a number of neuroendocrine cancer charities and advocacy groups across the world, dedicated to the provision of reliable, accurate information and support services for those affected by this cancer. Details of these global groups can be found here.
Can Neuroendocrine Cancer be cured?
As with more common cancers, the earlier in the development of a cancer it is diagnosed, the higher the possibility of cure is.
There are certain types of neuroendocrine cancer, where if diagnosed early, often incidentally, cure through surgery, is possible. For example, post appendectomy diagnosis of a small, localised Grade 1 appendiceal NET at the tip of the appendix, with no evidence of local or distant disease.
The current reality is, however, that due to a number of reasons, not least the differences and variations in signs and symptoms, if present at all, between 60-80% of those diagnosed with neuroendocrine cancer will have stage 4 disease at the time of diagnosis.
But, no cure or ‘incurable’ is NOT the same as ‘terminal’, and many people living with neuroendocrine cancer are doing just that – living. . .and many are living long and well, with the support of their families, support network and specialist neuroendocrine cancer team.
There has been an enormous amount of dedicated research into neuroendocrine cancers and their treatments – with ongoing trials and further investigation into possible origins being undertaken. For further information click here.
There are National, European and International guidelines on diagnosing, treating and promoting standards of care of Neuroendocrine cancers.
Many of the experts in your specialist neuroendocrine cancer multidisciplinary team, will have contributed to these publications – many are involved, if not leading the way, to improving not only our understanding, but also the earlier diagnosis and treatment of these cancers, all ultimately working towards a cure.
From diagnosis, throughout treatment and beyond, our team and our services at NET patient Foundation are here to offer guidance, support, education and information to anyone affected by a Neuroendocrine Cancer.