Types of neuroendocrine cancer

Neuroendocrine cancer can develop in many organs, and the different types are grouped by where the tumour started (called the primary site). Common primary sites include:

• gastrointestinal (GI) tract
• lung
• pancreas

Neuroendocrine cancers can be neuroendocrine tumours (NETs) or neuroendocrine carcinomas (NECs) based on how closely the cancer cells look like normal cells (differentiation).

NETs are made up of cancer cells that look and act much like normal cells (well differentiated). Most NETs are slow growing and are less likely to spread. Between 80% and 90% of neuroendocrine cancers are NETs.

NECs are made up of cancer cells that look very abnormal compared to normal cells (poorly differentiated). All NECs are fast growing and are more likely to spread than NETs. Based on the size and shape of the cells, NECs can be small cell NECs (SCNECs) or large cell NECs (LCNECs).

Neuroendocrine cancer can also be described as functional or non-functional.

Functional tumours make too much of a certain hormone and cause symptoms.

Non-functional tumours make normal amounts of hormones that usually don’t cause any symptoms. About 60% of NETs are non-functional. Almost all NECs are non-functional.

Gastrointestinal (GI) neuroendocrine cancer develops in the lining of the GI tract and is mostly found in the small intestine and the rectum. This cancer can also appear in the stomach, colon, esophagus and appendix.

Neuroendocrine cells in the GI tract make hormones that help break down food in the gut and control the muscles that move the food through the stomach and intestines. Functional neuroendocrine cancer cells release more of these hormones than we normally need and cause symptoms.

GI neuroendocrine tumours (GI NETs) are well differentiated. Most GI NETs grow slowly.

GI neuroendocrine carcinomas (GI NECs) are poorly differentiated. They are fast growing and more aggressive than GI NETs.

GI neuroendocrine cancer can be divided into subtypes based on where the cancer started, such as:

• stomach NETs and NECs
• small intestine NETs and NECs
• colon NETs and NECs
• rectum NETs and NECs
• appendix NETs and NECs

Lung neuroendocrine cancer develops in the lungs or airways, often in the airways that branch off from the windpipe into the lungs (bronchi).

Neuroendocrine cells in the lungs act like sensors and make hormones that control the airflow. Functional neuroendocrine cancer cells release more of these hormones than we normally need and cause symptoms.

Lung neuroendocrine tumours (lung NETs) are well differentiated. There are 2 subtypes of lung NETs:

• Typical carcinoid tumours tend to grow slowly and are usually in the central part of the lung.
• Atypical carcinoid tumours tend to grow slowly and are usually in the outer part of the lung.

Lung neuroendocrine carcinomas (lung NECs) are poorly differentiated. There are 2 subtypes of lung NECs:

• Small cell lung carcinoma (SCLC), more often known as small cell lung cancer, is usually in the central part of the lung. SCLC is very aggressive and often spreads quickly.
• Lung large cell neuroendocrine carcinoma (lung LCNEC) is a kind of non–small cell lung cancer. Lung LCNEC also often grows fast and spreads quickly.

Pancreatic neuroendocrine cancer starts in the islet cells of the pancreas. Islet cells form clusters that include different types of cells that make hormones, including alpha cells (A cells) that make glucagon, beta cells (B cells) that make insulin and delta cells (D cells) that make somatostatin.

Functional neuroendocrine cancer cells release more hormones than we normally need and cause symptoms.

Pancreatic neuroendocrine tumours (pNETs) are well differentiated. For functional pNETs, there are different subtypes. Their naming is based on the hormone they overproduce:

• gastrinoma– produces too much gastrin that affects the amount of stomach acid made
• insulinoma– produces too much insulin that increases blood sugar level
• glucagonoma– produces too much glucagon that lowers blood sugar level
• somatostatinoma– produces too much somatostatin that affects digestion
• VIPoma– produces too much VIP that affects muscles in the gastrointestinal tract
• ACTHoma– produces too much ACTH that increases steroid level

Pancreatic neuroendocrine carcinomas (pNECs) are poorly differentiated. They are fast growing and more aggressive than pNETs.

Since neuroendocrine cells are spread throughout the body, neuroendocrine cancer can develop in many different places. The following are also types of neuroendocrine cancer:

• medullary carcinoma – a type of thyroid cancer that starts in the C cells of the thyroid
• Merkel cell carcinoma– a type of non-melanoma skin cancer
• neuroendocrine cancer of the ovary or testicle
• paraganglioma – a type of adrenal gland cancer that starts in the chromaffin cells outside the adrenal glands
• pheochromocytoma – a type of adrenal gland cancer that starts in the chromaffin cells of the adrenal glands
• parathyroid cancer or parathyroid adenoma
• pituitary neuroendocrine cancer
• thymic neuroendocrine cancer

Mixed neuroendocrine non-neuroendocrine neoplasms (MiNENs) are rare tumours that contain a neuroendocrine component and a non-neuroendocrine component. The neuroendocrine component is often a NEC. An example of the non-neuroendocrine component is adenocarcinoma.

Because MiNENs have 2 types of cancer cells, they are not considered to be neuroendocrine cancers. MiNENs are a separate group of cancers that have their own treatment plans.