What are Neuroendocrine Tumours? (NETs)

Neuroendocrine tumour (NET) is a label that has been used as an umbrella term for a group of tumours that start in neuroendocrine cells.  However, the terminology, or naming, is constantly being updated as we learn more about them, for example, you may hear them describe as ‘carcinoid’ – a term originating over a hundred years ago, meaning ‘cancer-like’. 

The updated terminology is Neuroendocrine Neoplasms (neoplasm = a new and abnormal growth of tissue in a part of the body) or NEN. 

NEN includes all new and abnormal growths found to originate in neuroendocrine cells – whether benign (not cancerous) or malignant (cancerous) – that is, until accurate understanding of the cell behaviour is known. Then:

  • Neuroendocrine Tumour (NET) is used to describe slow to moderate malignant growth. 
  • Neuroendocrine Cancer (NEC) is used to describe high grade or rapid malignant growth.

Malignant neuroendocrine growths (NETs/NECs) occur when neuroendocrine cells stop working normally and start to grow abnormally.

They are found most commonly in the lung, gastrointestinal system or pancreas, but they can also originate in many other places throughout the body.

We use the term ‘neuroendocrine cancer’ throughout this website as we only provide information on malignant NETs & NECs.


What are Neuroendocrine Cells?

Neuroendocrine cells exist throughout the body and are there to produce hormones and other chemicals to ensure our bodies function normally. These cells make up a coordinated system – the neuroendocrine system – a network of communication to control and regulate that hormone and chemical release.


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

Why are there different terms used for Neuroendocrine Cancer?

The terminology can be confusing. For example, a neuroendocrine cancer may be called a carcinoid, a NET, a NEN, a GEP-NET, a pNET, or by the hormone it overproduces, for example, an insulinoma. 

The key reason for the changes in terminology is down to the changes and advances in knowledge of this group of cancers.

Neuroendocrine cancer was first identified as a specific disease in the mid 1800s. The term ‘carcinoid’ was applied, in 1907, to describe a tumour that grew much more slowly than normal cancer- it was ‘cancer-like’. 

However, by the 1950s, it became quite clear that these ‘carcinoids’ could spread from one part of the body to another, like any other form of cancer and far from all being ‘slow-growing’, their growth rate and behaviour could also be variable and aggressive.

Although being phased out of common usage as a term to describe all neuroendocrine neoplasms, ‘Carcinoid’ still has a current place in the terminology to describe specific types of neuroendocrine cancer, (for example in neuroendocrine malignancy of the lung – Typical and Atypical Carcinoid are still used) or to describe one of the syndromes associated with neuroendocrine cancer – ‘Carcinoid Syndrome’.

But please don’t worry too much about the terminology, we explain all of this in our patient information.

What are the different types of Neuroendocrine cancer?

The difference in type of neuroendocrine cancer can be made by using several classifications:

  1. Site: where in the body it occurs – eg Lung, Small bowel, Pancreas, Skin, etc
  2. 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 
  3. 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.
  4. 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.
  5. 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.
  6. 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?’, etc . . .

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. 

We are here every step of the way – whether it’s over the phone, on our website or face to face at one of our NET Natter groups  or Patient Education Events.

Different types of NETs

Read and download information on all types of NETs based on the European Neuroendocrine Tumour Society guidelines. 

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Patient Information

Our patient information provides information to help guide you through your diagnosis, treatments and beyond. 

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Videos About NETs

Browse our NET TV video library. Including videos on FAQ’s, a complete guide to your NET pathway and lots more. 

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