NEUROENDOCRINE TUMOURS

Lung NETs (also known as bronchial or pulmonary NETs) can be subdivided into five types:

• Typical lung NETs (also known as TCs, typical carcinoids) – These tend to exhibit a slow growth rate and are the most common lung NETs
• Atypical lung NETs (or AC, atypical carcinoids) – These can grow rapidly and tend to metastasise
• Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECHs) NETs – These are very rare and can cause the pulmonary neuroendocrine cells in the lungs to become too large. These tumours can be very small. The affected tumours don’t usually change significantly or rapidly, but DIPNECHs may be considered a precancerous condition and progress to typical or atypical pulmonary NETs.
• Small cell neuroendocrine carcinoma – This is a rare form of pulmonary NET, similar to small cell lung cancer
• Large cell neuroendocrine carcinoma – This is believed to be the most aggressive form of lung NET

Typical lung NETs account for almost 90% of cases. These grow slowly and rarely spread outside the lungs (less than 15% of cases).

Together, typical and atypical lung NETs represent 40% of all NETs.

Small cell neuroendocrine carcinoma and large cell neuroendocrine carcinoma are the rarest but most active lung NETs. They develop at the same rate as lung cancers.

This is an extremely rare type of NET.

It is generally diagnosed when tissue is analysed for more common types of breast cancer.

The adrenal glands are located on top of the kidneys and produce hormones involved in blood pressure control or stress management.

There are three types of neuroendocrine tumours that can appear inside or near to these glands: adrenocortical carcinomas, pheochromocytomas and paragangliomas.

• Adrenocortical carcinoma (ACC) – A cancer affecting the outer layer of the adrenal gland. It can cause the release of excessive amounts of hormones, including adrenaline, norepinephrine and steroids, which help the body maintain blood pressure as well as salt and sugar levels.
• Pheochromocytomas (pheos) and paragangliomas – These are rare tumours of the adrenal gland that originate in the inner part of the gland (medulla). Similar tumours can appear on the outside of the adrenal glands; these are paragangliomas (extra-adrenal).

Gastric neuroendocrine tumors are found in the stomach. There are three types:

• Type 1 – These NETs are usually small, and often multiple; they represent the least aggressive type.
• Type 2 – These NETs are associated with elevated stomach acid levels and also tend to be associated with Zollinger-Ellison syndrome (or cluster of symptoms). These NETs are usually large and can metastasize.
• Type 3 – These are the largest gastric NETs and have a high risk of metastasis, making this type very aggressive. These NETs may not be associated with high levels of gastrin or stomach acid.

The liver is very rarely the primary site of a NET-type cancer. NETs present in the liver are often due to the spread (metastasis or secondary tumours) of cancer cells from another organ.

The liver is the most common site for secondary NETs. Its dominant role in body functioning and blood circulation promotes the formation of metastases.

The pancreas is an organ that produces insulin and other hormones.
There are two types of pancreatic NETs:

• Functional – These are pancreatic NETs that cause a specific set of symptoms (syndromes) such as insulinoma, gastrinoma, somatostatinoma, glucagonoma and VIPoma.
• Non-functional – Do not cause syndromes, but common symptoms include back pain, jaundice, stomach pain and weight loss.

Small intestine NETs (also known as jejunal, ileal or ileocaecal NETs) are the most common intestinal NETs.

They tend to grow slowly and may cause symptoms similar to irritable bowel syndrome or carcinoid syndrome, or may cause no symptoms at all.

Therefore, it can be difficult to benefit from an early diagnosis.

Tumours in the appendix that are less than 1 cm in size are often removed and cured with surgery.

Larger goblet cell NETs are a more aggressive form of appendiceal NETs and tend to spread.

Ovarian NETs are often secondary NETs originating from a primary site in the bowel or appendix.

Primary ovarian NETs are extremely rare. To date, two types of tumours have been identified:

• Ovarian neuroendocrine tumours (NETs), which are slow growing (low to moderate grade).
• Ovarian neuroendocrine carcinomas (NEC), which behave more like ovarian cancers (high grade) and can cause carcinoid syndrome.

Gynaecological NETs (uterus, cervix, vagina and vulva) are very rare. They are usually only diagnosed when tissue is examined for signs of other cancers that are more commonly found in these areas.

Two types of tumours are found in the uterus and the cervix:

• Neuroendocrine tumours (NETs) – These are tumour cells that grow more slowly.
• Neuroendocrine carcinomas (NEC) – These are more aggressive tumours which tend to grow faster and spread beyond their primary site, potentially leading to the development of secondary tumours in other organs.

Vagina and vulva NETs are the rarest type of NETs. They are classified in the same way as NETs of the ovary, i.e. as neuroendocrine carcinomas and neuroendocrine tumours. NETs of the testicles and prostate

As with NETs of the female reproductive system, NETs of the testicles and prostate can be classified as carcinomas or tumours, depending on how the cells look under a microscope.

Colonic NETs are rare and can cause symptoms such as a change in bowel habits, abdominal or stomach pain, weight loss and bleeding, which are similar to symptoms of its more common counterpart, bowel cancer. Colonic NETs are usually aggressive and have a tendency to spread.

Merkel cell carcinoma (MCC) is a rare and aggressive type of skin cancer that forms on the surface or in the top layers of the epidermis. It starts to develop in neuroendocrine cells known as Merkel cells. These cells secrete hormones into the blood when they are stimulated by the nervous system.

The thyroid is a gland located in the neck, which produces hormones that affect blood pressure, body temperature, heart rate and metabolism.

Medullary thyroid cancer (MTC) is a rare form of cancer of the thyroid gland. This gland is part of the endocrine system.

There are two types of MTC:

• Sporadic MTC (or isolated MTC), when a patient has no family history
• Multiple endocrine neoplasia type 2 (or MEN2), in the case of an inherited (genetic) disorder

There are three distinct variants of multiple endocrine neoplasia (MENs): MEN1, MEN2, MEN3 (types 2 and 3 are also known as MEN2a and MEN2b).

MEN syndromes are inherited disorders. MEN disorders lead to the development of growths (tumours) in several glands of the endocrine system. The affected glands then secrete abnormally high levels of hormones – the body’s chemical messengers – which, in turn, leads to the appearance of various symptoms. Each growth can develop alone or independently of the MEN (referred to as an “associated endocrine growth”).