NETs
What are NETs?
NETs (neuroendocrine tumors) occur when neuroendocrine cells stop functioning normally and start to develop and/or function abnormally.
NETs are named for the part of your body in which they first form. So if you have a NET that started in your lung, you will be diagnosed with a lung NET; your lung is then determined as the primary site of your cancer.
Below is a list of the different types of NETs. Click on the part of the body where you think the NET is to display the corresponding information.
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Testicular/Prostate NET
Testicle
Neuroendocrine may not be suspected at the time of investigation and a confirmed diagnosis may not be possible until the tumour ( or a collection of cells from the tumour) is examined under a microscope – at this point they will be divided into :
- Primary testicular NET
- Teratoma with neuroendocrine tumour presence
- Secondary disease from a primary elsewhere in the body e.g. small bowel
Primary Testicular NET is rare, less than 1% of all testicular cancers. However unlike most testicular cancers there is no concentrated age range – primary testicular NET can be found in boys as young as 10 to older gentleman of 80 and above. Carcinoid syndrome is a rare , and probably late, symptom of primary testicular NET : is seen in less than 10% of those with this diagnosis – occurs when neuroendocrine cancer cells spread beyond the testicle to other parts of the body such as the lungs or liver. Treatment is dependent on whether the cancer is primary or secondary, the cell type and whether, for primary disease, the cancer has spread elsewhere.
Prostate
Neuroendocrine may not be suspected at the time of investigation (95% of all prostate cancers are adenocarcinomas) and a confirmed diagnosis may not be possible until the tumour ( or a collection of cells from the tumour) is examined under a microscope – at this point they will be divided into :
- Prostate cancer (adenocarcinoma) with/without neuroendocrine tumour cells present – neuroendocrine cells are present in 10-100% of all prostate cancers and are androgen insensitive. This may affect how well prostate cancer responds to treatments – the more neuroendocrine cells present the more resistant the tumour may be to conventional treatments.or
- Prostate Neuroendocrine tumour :
- Neuroendocrine tumour : where the tumour cells tend to be less distorted (well differentiated) and are thought to grow less rapidly
- Neuroendocrine Small cell carcinoma : where the tumour cells tend to be more distorted (poorly differentiated) and grow more rapidly – and have the ability to spread beyond their primary site. It is not uncommon for there to be secondary site disease already present at the time of diagnosis with this cell type.
- Large cell neuroendocrine carcinoma : where cell distortion may vary, but growth rate is the same as with small cell.
Treatment is dependent on the cell type and whether the cancer has spread elsewhere.
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Rectal NET
These tumours are often found incidentally as patients may have minor symptoms. If symptoms are present they may be bleeding from the rectum or change in bowel habit. They account for around 16% of all neuroendocrine tumours.
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Phaeochromocytoma
Phaeochromoytomas, often known as ‘phaeos’ (‘fee-ohs’), are rare tumours of the adrenal gland arising from the inner section of the gland called the medulla. Similar tumours can arise from sites other than the adrenal gland and these are called extra-adrenal paragangliomas.
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Pancreatic NET
These NETs can be split into 2 types; functioning and non-functioning. The functioning ones will have a related syndrome and include:
- Insulinoma
- Gastrinoma
- VIPoma
- Somatostatinoma
- Glucagonoma
The non functioning pancreatic NETs will not have an associated syndrome and the patient may present with symptoms such as jaundice, weight loss, back pain or abdominal pain. Around 20-40% of these patients will be diagnosed with a genetically inherited condition called MEN1.
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Ovarian NET
This type of NET is quite rare ( about 30 cases per year) and are found in the ovary. They tend to be faster growing NETs with only about 30% being less aggressive.
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NET of Unknown Primary (CUP)
Sometimes a NET is diagnosed by the secondaries that are found, and the primary site is not visible. This is not common but it can happen. Cancers are named and treated according to where they started developing even if they have spread to other parts of the body. For example if you have a bowel NET that has spread to the liver, it is a bowel NET with liver metastases or secondaries. It is not called liver cancer. This is because the cells in the liver are actually cancerous bowel cells. They are not liver cells that have become cancerous. Normally it is easy to find the primary cancer. Either it will cause symptoms or it will be seen on a scan. Sometimes secondary cancers are found in one or more parts of the body, but the doctor can’t find the primary site. This is called a NET of unknown primary (CUP NET). This can happen for a number of NETs e.g ileal,pancreatic, rectum, colon or lung. You may need to have further specialist scans like a (68)Ga-DOTA-NOC PET/CT, although there are very few of these scanners in the UK. Not finding the primary tumour will not affect most treatment options and there is research ongoing into the best way to try and find these tumours and manage them.
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Multiple Endocrine Neoplasia
MEN stands for Multiple Endocrine Neoplasia, of which there are three distinct types – MEN1, MEN2 and MEN3. MEN2 was formerly called MEN2a and MEN3 was formerly called MEN2b, and indeed there are similarities between the two. Multiple Endocrine Neoplasia syndromes are inherited disorders – This means that they can be passed down in families, with each child of an affected parent having a 1 in 2 or 50% risk of inheritance. MEN disorders cause more than one gland of the body’s endocrine (gland) system to develop growths (tumours). The affected glands then produce abnormally increased amounts of hormones, the body’s chemical messengers, which in turn cause a variety of different symptoms. Each growth may occur alone or independently of MEN and are here referred to as associated endocrine growths.
Useful links
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Merkel Cell Carcinoma
Merkel Cell Carcinoma (MCC) is a rare, more aggressive type of skin cancer that forms on or just under the skin. MCC is believed to start in neuroendocrine cells called Merkel cells. These cells release hormones into the blood when stimulated by the nervous system . Merkel cells are believed to play a role in making the skin sensitive to touch.
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Medullary Thyroid Cancer
Medullary Thyroid Cancer, or MTC, is a rare form of cancer of the thyroid gland. This gland is part of the endocrine system as shown. When there is no family history of the disease and MTC occurs as an isolated case, it is called sporadic MTC. 1 in 4 or 25% of cases of MTC occur as part of a rare inherited (genetic) disorder called Multiple Endocrine Neoplasia Type 2 (MEN2).
Useful links
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Lung NET
These are neuroendocrine tumours of the lung and can be split into 5 different types. A small proportion of patients may have an associated ‘carcinoid syndrome’:
- DIPNECH – Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia tends to be low grade process and patients can present with a persistent cough and shortness of breath.
- Typical Lung NET – these tend to have a slower rate of growth and are the most common lung NET
- Atypical Lung NET – these can be faster growing NETs and tend to metastasise.
- Small cell Neuroendocrine Carcinoma – this is a rare presentation for a lung NET and is similar to small cell lung cancer
- Large Cell neuroendocrine carcinoma – this would be the most aggressive form of lung NET.
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Liver NET
The liver is very rarely the primary site for a NET cancer, but NET cancers may spread to the liver. Cancers are named and treated according to where they started developing even if they have spread to other parts of the body. For example, if you have a bowel NET that has spread to the liver, it is a bowel NET with liver metastases or secondaries. It is not called liver cancer. This is because the cells in the liver are actually cancerous bowel cells. They are not liver cells that have become cancerous.
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Ileum NET
These are the most common bowel NETs. Around 30% have an associated ‘carcinoid syndrome’. Symptoms are rarely noticeable in the early stages of the disease and therefore the tumour may have already spread at the time of diagnosis.
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Goblet Cell NET
This is a more aggressive form of appendiceal NET type called goblet cell carcinoma. These arise from the appendix but have a different shape under the microscope and can metastasise.
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Gastric NET
These are neuroendocrine tumours found in the stomach and there are 3 types:
- Type 1 – these are associated with high gastrin levels, pernicious anaemia and vitamin B deficiency and are small, often multiple tumours and are the least aggressive type of gastric NET
- Type 2 – these are associated with high levels of gastric acid and also tend to have an associated syndrome (group of symptoms) called Zollinger-Ellison syndrome. They tend to be larger tumours and can metastasise
- Type 3 – These are the largest of gastric NETs and are of high risk to metastasise. They may not be related to high gastrin levels or high levels of gastric acid and are the most aggressive type of gastric NET
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Duodenal NET
These are rare NETs of another part of the small bowel. This is the first part of the bowel after the stomach. 75% of NETs found in the duodenum are associated with high gastrin levels and a collection of symptoms known as ‘Zollinger Ellison Syndrome’. Symptoms may include pain, ulcers that do not heal, diarrhoea, vomiting and anaemia.
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Colon NET
This is a rare NET of the large bowel. Not normally associated with ‘carcinoid syndrome’. Symptoms are associated with tumour size: abdominal pain, weight loss and bleeding from the rectum. These are often aggressive types of NET and have a high risk of metastasising.
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Cervical NET
Gynaecological NETs are extremely rare and of those that are diagnosed, the ovary is the most common primary site
Cervix
Neuroendocrine may not be suspected at the time of investigation and a confirmed diagnosis may not be possible until the tumour ( or a collection of cells from the tumour) is examined under a microscope – at this point they will be divided into :
- primary NETs ( that is they start within the ovary, uterus or cervix)
- secondary NETs ( that is they have grown from tumour cells from elsewhere in the body – for example, a small bowel primary NET spread to the ovary)
Primary NETs can be further divided into :
- Neuroendocrine Carcinomas (NECs) : the tumour cells tend to be more distorted (poorly differentiated) and grow more rapidly – and have the ability to spread beyond their primary site, this can lead to secondary tumours elsewhere in the body.
- Neuroendocrine Tumours (NETs) : the tumour cells tend to be less distorted (well differentiated) and are thought to grow less rapidly
The most common neuroendocrine tumour of the cervix (about 2% of all cervical cancers) is a form of NEC called small cell carcinoma. There is also a form called large cell neuroendocrine carcinoma. These tend to grow rapidly and have the ability to spread beyond their primary site. There are also 2 forms of cervical NETs – typical and atypical carcinoid – these are believed to grow less rapidly. Treatment will depend on whether the cancer is primary or secondary, the cell type and whether, for primary disease, the cancer has spread elsewhere.
Uterus
Endometrial neuroendocrine tumours account for less than 1% of all endometrial cancers. They, like tumours of the cervix are more likely to be NECs rather than NETs, are usually small cell carcinomas and therefore have a more rapid growth rate, with the ability to spread elsewhere. Treatment will depend on whether the cancer is primary or secondary, the cell type and whether, for primary disease, the cancer has spread elsewhere.
Vaginal / Vulval
Incredibly rare, with only a few incidences reported worldwide. Cell types as for cervix and uterus.
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Breast NET
This is an extremely rare type of NET. They were first named in 1977. Diagnosis tends to happen once the patient has had tests for the more common types of breast cancer and the tissue has been studied.
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Appendiceal NET
Appendiceal NETs are usually discovered incidentally and if small curative surgery is often performed.
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Adrenocortical Carcinoma
There are several different types of tumours that can occur in the adrenal gland.They can develop in either the outer part of the gland (the cortex) or the inner part of the gland (the medulla).Tumours can be benign (not cancer) or malignant (cancer). Benign tumours of the cortex are called adrenocortical adenomas, and malignant tumours are called adrenocortical carcinomas (ACC). Adrenocortical carcinoma (ACC) is often know simply as adrenal cancer and affects 1-2 people per million per year, making it a rare form of cancer. ACC in adults tends to occur in the 4th to the 5th decade of life. Most ACC’s occur sporadically (meaning that they do not run in families), but they may sometimes be part of a congenital (present at birth) and/or familial (have a genetic family connection) condition. There is now a website for people affected by ACC: http://www.accsupport.org.uk