A neuroendocrine tumor (NET) is a type of cancer that starts from neuroendocrine cells. These are specialized cells with features of both nerve cells and hormone-producing cells that help regulate important body functions by releasing hormones in response to signals from the nervous system. Neuroendocrine cells are found throughout the body, which means neuroendocrine tumors can start in many different places.
Neuroendocrine tumors are most commonly found in the gastrointestinal tract, including the stomach, small intestine, appendix, and colon, as well as in the pancreas and lungs. They can also develop in the thyroid gland, adrenal glands, skin, and other areas. Depending on where the tumor starts and how it behaves, it may grow slowly over many years or spread quickly to other parts of the body.
Neuroendocrine tumors can be either well-differentiated, meaning the cells look similar to normal neuroendocrine cells and tend to grow slowly, or poorly differentiated, meaning the cells look very abnormal and tend to grow more aggressively. The grade of the tumor helps doctors predict how the tumor is likely to behave and how it should be treated.
Are all neuroendocrine tumors cancerous?
Yes. All neuroendocrine tumors are considered malignant, or cancerous, because they have the potential to spread to other parts of the body. However, their growth rate and behavior can vary widely. Some neuroendocrine tumors grow very slowly and may not spread for many years. Others grow quickly and behave more aggressively.
The grade of the tumor, which is based on how fast the cells are growing and dividing, helps predict how the tumor is likely to behave.
What are the different types of neuroendocrine tumors?
Neuroendocrine tumors are classified based on their microscopic features, growth rate, and location in the body.
Well-differentiated neuroendocrine tumors
These tumors look similar to normal neuroendocrine cells when examined under the microscope. They are divided into three grades:
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Grade 1 (G1) – slow-growing
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Grade 2 (G2) – moderately growing
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Grade 3 (G3) – fast-growing but still well-differentiated
The term carcinoid tumor is sometimes used to describe a well-differentiated neuroendocrine tumor in the lungs.
Poorly differentiated neuroendocrine carcinoma
This is a high-grade cancer made up of very abnormal, fast-growing cells. There are two main types:
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Small cell neuroendocrine carcinoma – Most common in the lungs, but it can also occur in other parts of the body.
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Large cell neuroendocrine carcinoma – Also most often seen in the lungs, but can arise elsewhere.
These tumors are aggressive and often require chemotherapy or other systemic treatments.
Other specific types of neuroendocrine tumors
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Medullary thyroid carcinoma – A type of thyroid cancer that starts in neuroendocrine cells in the thyroid and often produces calcitonin. Some cases are linked to a genetic condition called multiple endocrine neoplasia type 2 (MEN2).
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Merkel cell carcinoma – A rare but aggressive neuroendocrine skin cancer. It is often associated with the Merkel cell polyomavirus.
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Paraganglioma – A neuroendocrine tumor that starts in nerve tissue (paraganglia), often in the head, neck, or spine.
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Pheochromocytoma – A tumor that starts in the adrenal glands. It may produce hormones that cause symptoms such as high blood pressure, headaches, or sweating.
What are the symptoms of a neuroendocrine tumor?
Symptoms depend on the location of the tumor and whether it is producing hormones. Some tumors do not cause any symptoms and are found by chance during testing for another reason.
When symptoms do occur, they may include:
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Pain or pressure in the affected area.
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Weight loss.
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Diarrhea or constipation.
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Flushing (redness and warmth in the face or neck).
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Wheezing or trouble breathing (for tumors in the lungs).
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Low or high blood sugar levels (for tumors in the pancreas).
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High blood pressure, headaches, or sweating (for adrenal tumors).
What causes neuroendocrine tumors?
In most cases, the cause is unknown. However, some neuroendocrine tumors are linked to inherited genetic conditions, including:
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Multiple endocrine neoplasia type 1 (MEN1)
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Multiple endocrine neoplasia type 2 (MEN2)
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Von Hippel-Lindau (VHL) disease
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Neurofibromatosis type 1 (NF1)
Chronic inflammation or long-term damage to organs containing neuroendocrine cells may also increase the risk of developing these tumors.
How are neuroendocrine tumors graded?
Grading describes how quickly the tumor cells are growing and dividing. For well-differentiated neuroendocrine tumors, the grade is based on:
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Mitotic count – The number of dividing cells seen under the microscope.
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Ki-67 index – A test that measures how many cells are actively growing.
Tumors are classified as:
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Grade 1 (G1) – Low grade, slow-growing.
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Grade 2 (G2) – Intermediate grade, moderate growth.
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Grade 3 (G3) – High grade, faster-growing.
Poorly differentiated neuroendocrine carcinomas are automatically considered high-grade.
What do neuroendocrine tumors look like under the microscope?
Under the microscope, neuroendocrine tumors are made of small to medium-sized cells arranged in groups or patterns such as nests, ribbons, or rosettes. The cells typically have:
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Round or oval nuclei with a speckled appearance called salt and pepper chromatin
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Pale or pink cytoplasm, which is the body of the cell
These features help pathologists recognize the tumor as neuroendocrine in origin.
What tests are used to confirm the diagnosis?
Pathologists use immunohistochemistry to confirm that a tumor is made of neuroendocrine cells. This test looks for specific proteins that are normally made by neuroendocrine cells.
The most commonly tested proteins include:
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Synaptophysin
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Chromogranin A
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CD56
For tumors in the pancreas or other hormone-producing organs, additional tests may look for specific hormones such as insulin, glucagon, or somatostatin.
What is the prognosis for someone with a neuroendocrine tumor?
The prognosis depends on many factors, including:
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The location of the tumor.
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The grade and differentiation of the tumor.
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The size of the tumor.
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Whether it has spread to other parts of the body.
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The person’s overall health.
Many well-differentiated, low-grade neuroendocrine tumors grow slowly and can be managed successfully for many years. High-grade or poorly differentiated tumors tend to grow faster and may require more intensive treatment.
With early diagnosis and proper treatment, many people with neuroendocrine tumors can live long and active lives.
Questions to ask your doctor
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What type of neuroendocrine tumor do I have?
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Where is the tumor located and has it spread?
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What is the grade and stage of the tumor?
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What treatments are available and what do you recommend?
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Are genetic tests or additional imaging needed?
Other helpful resources
North American Neuroendocrine Tumour Society
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