What Are Neuroendocrine Tumors (NETs)?

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Neuroendocrine tumors (NETs) are a rare tumor type that originate in neuroendocrine cells, which are a type of specialized cells. Neuroendocrine cells produce hormones, and they are usually stimulated by nerve impulses.

A hormone is a chemical that is produced by endocrine tissue and released into the bloodstream to send messages to other parts of the body.

Because NETs are comprised of cells that produce hormones, the tumors are capable of producing hormones. NETs produce symptoms by causing hormonal imbalances in the body, and they can also metastasize (spread to other areas of the body).

Other names for neuroendocrine tumors are “neuroendocrine neoplasia,” and “neuroendocrine neoplasm.”

Anatomical Features

NETs are referred to as epithelial neoplasms (abnormal growth of cells arising from and composed of epithelial cells in the body). Epithelial cells line the surfaces of the body, such as blood vessels and organs.

Neuroendocrine cells are comprised of epithelial cells. Scattered neuroendocrine neoplasms can be found alone or in small nests.

Neuroendocrine cells function differently depending on where they are located in the body. These cells produce hormones with a range of effects, such as promoting growth or influencing how the body responds to stress.

When mutations occur in neuroendocrine cells, the cells begin to grow out of control, forming NETs.

neuroendocrine tumor ribbon
Chinnapong / Getty Images

Types of Neuroendocrine Tumors

There are many different types of NETs originating in different regions of the body.  

NETs can be broken down into two basic categories:

  • Functional NETs result in a specific set of symptoms due to the production of excess hormones
  • Nonfunctional NETss do not usually cause symptoms

Further classification of NETs breaks the tumors down into a few types, including:

  • Carcinoid tumors: This type arises in the lungs, appendix, thymus, or digestive tract. They can also grow in the brain, bone, skin, lymph nodes, testes, and ovaries. Carcinoid tumors can arise from the pancreas (but this is rare).
  • Pancreatic NETs are sometimes referred to as islet cell tumors. These can develop within or outside the pancreas.
  • Pheochromocytoma: This is a rarer type of NET that usually arises in the adrenal gland, but can grow in other parts of the body as well.

Other subtypes of NETs include:

  • Gastroenteropancreatic NET
  • Hereditary paraganglioma-pheochromocytoma
  • Merkel cell carcinoma
  • Paragangliomas

Where Neuroendocrine Tumors Are Found

NETs can develop anywhere in the body. However, most are found in the gastrointestinal tract (digestive tract), pancreas, lungs, rectum, or appendix. They can be benign (noncancerous) or malignant (cancerous). They usually grow very slowly over time, but some types are rapid-growing.

According to the Cancer Research Center, approximately 5 out of every 10 NETs arise from the digestive system, and approximately 2 out of every 10 begin in the lung.

The tumors are named for the area they arise in. For example, a NET that arises in the lungs is called a primary lung NET. If the NET metastasizes to another part of the body, it would be described as a secondary tumor anywhere besides its original location.

Areas that primary NETs are commonly found include:

  • Stomach
  • Small and large intestine
  • Pancreas
  • Rectum
  • Lung
  • Esophagus (the food pipe)
  • Appendix
  • Skin
  • Prostate
  • Uterus (womb)
  • Pituitary gland
  • Adrenal gland
  • Parathyroid gland

Sometimes, it isn't possible to determine where a NET originated; this is referred to as cancer of unknown primary (CUP).

Neuroendocrine Tumor Symptoms

Most NETs are slow to develop and it may take years before symptoms emerge. The symptoms of a NET can vary depending on several factors, such as the size and location of the tumor, the type of tumor, and whether or not the tumor has metastasized.

When there aren't early symptoms, NETs can be very difficult to diagnose. Many NETs don't produce symptoms until they produce hormones, enlarge, or metastasize.  

Causes

The actual cause of NETs is not definitively known. According to the National Center for Advancing Translation Sciences, most NETs are sporadic and are not linked with hereditary factors.

Associated Conditions

Although neuroendocrine tumors are not considered hereditary, certain conditions that increase the risk are hereditary. Some types of NETs are associated with tumor syndromes, such as:

  • Multiple endocrine neoplasia type 1: This is an inherited condition characterized by tumors of the endocrine system.
  • Von Hippel-Lindau disease: This is an inherited condition characterized by growths in many parts of the body.
  • Tuberous sclerosis: This is a genetic condition characterized by benign tumors throughout the body, including the brain, kidneys, and heart.
  • Neurofibromatosis type 1: This is a genetic condition that affects the skin, bones, and nervous system, involving benign growths along the nerves.

Genetic testing may be necessary for people who have been diagnosed with NETs. The primary goal of testing would be to look for inherited conditions or syndromes that can increase a person’s risk for NETs.

If you have a family history of one of these syndromes, your healthcare provider may order genetic testing.

Risk Factors

Factors that may increase a person’s risk of developing NETs include:

  • Inherited syndromes
  • Race: NETs are more common among white people than among Black people.
  • Ethnicity
  • Gender: NETs are slightly more common in women than in men.
  • Age
  • Environment
  • Diet

Treatment

The specific type of treatment recommended for a NET can depend on many different factors, including:

  • The size of the tumor(s)
  • The location of the tumor(s)
  • Whether the tumor(s) have metastasized
  • The type of tumor
  • The aggressiveness of the tumor(s)
  • The tumor's hormone-producing properties
  • Other factors, such as your general health condition

Surgery for NETs

Surgery to remove the tumor is the most common type of treatment for NETs. Most NETs are treated very successfully with surgery alone.

However, if surgery is not successful, there are several other types of management options available, including non-surgical therapies that aim to shrink the tumor, stop it from growing, and manage symptoms.

Carcinoid Crisis

Those who have carcinoid syndrome have a high risk of developing carcinoid crisis during surgery. This is a rare disorder that involves rapid heartbeat, trouble breathing, and more. Your anesthesiologist may need to administer emergency treatment if you have a carcinoid crisis during surgery. Octreotide is a medication that's is often administered via intravenous therapy before surgery to prevent carcinoid crisis.

Treatment Team

If you have been diagnosed with neuroendocrine cancer, you may need to see several physicians, including:

  • An oncologist: A physician specialized in treating cancer
  • A surgical oncologist: A surgeon who specializes in the treatment of cancer
  • An endocrinologist: A medical doctor who treats conditions of the endocrine system
  • A radiation oncologist: A medical doctor who administers radiation for cancer treatment
  • A gastroenterologist: A medical doctor who specializes in the treatment of conditions of the gastrointestinal (digestive) tract
  • A nuclear medicine physician: A physician who uses radiopharmaceuticals to diagnose and treat disease

Your multi-disciplinary care team may be comprised of other healthcare providers, such as:

  • A dietitian
  • An oncology nurse (specially trained to care for cancer patients)
  • A nurse specialist
  • A mental health counselor

Health Insurance and Advocacy

Because there are many types of specialty care for the treatment of NETs, you may have to pay attention to getting approval for different aspects of your care.

Coverage

If you plan to be treated at a specialty clinic, such as a neuroendocrine tumor center, you may need to get approval from your insurance payer for out-of-network care.

According to the Carcinoid Cancer Foundation, most insurers state that if they cannot provide a qualified medical professional for your specific condition, they will authorize a consultation with an out-of-network provider.

Some insurance plans might cover services that are out of state. Be sure to read your coverage contract.

Getting Your Treatment Covered by Insurance

According to founding board member, Julie Portelli, at the Carcinoid Cancer Center, when you’ve been denied for medical treatment or for seeing an out-of-network specialist for your neuroendocrine cancer, “Don't give up—now you have to prove to your insurance company where in their contract it calls for the service or treatment you are requesting.”

One treatment that commonly gets denied for payment by many insurance providers is peptide receptor radionuclide therapy (PRRT). You can learn more about filing a claim with your insurance company for this treatment at PRRTinfo.org.

According to PRRT.org, some insurance companies cover PRRT.

These include:

  • Aetna (partial coverage)
  • Nationwide Better Health
  • Cigna (self-funded and Medicare Advantage)
  • United Healthcare (self-funded)
  • Blue Shield of CA
  • Blue Cross / Blue Shield of the following states: Michigan, Minnesota, Nebraska, Iowa, Illinois, Pennsylvania, Texas

Don't automatically assume that because you have one of the plans on the list that your PRRT will be covered. Insurance plans can differ from region to region, even in the same state. Also, coverage policies often change, so be sure to refer to your coverage contract.

Portelli says to be sure to pursue a legal appeal process. The Northern California CarciNET Community has further advice on the steps to file for authorization to see a medical provider or visit a center that is out of network.

Another resource you can use to learn more about the legal process of filing an appeal for denied insurance claims is the Cancer Legal Resource Center.

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Article Sources
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  1. Canadian Cancer Society. The neuroendocrine system.

  2. National Center for Advancing Translation Sciences. Neuroendocrine tumor. Updated April 25, 2019.

  3. Centers for Disease Control and Prevention (CDC). Malignant neuroendocrine neoplasms. Updated October 4, 2013.

  4. Canadian Cancer Society. What are neuroendocrine tumours?

  5. Neuroendocrine Tumor Research Foundation. Causes of neuroendocrine tumors.

  6. Neuroendocrine Tumor Research Foundation. Genetic testing for neuroendocrine tumors.

  7. American Society of Clinical Oncology. Neuroendocrine tumor of the gastrointestinal tract: Risk factors. Updated October, 2019.

  8. American Society of Clinical Oncology. Neuroendocrine tumors: Types of treatment.Updated April 2019

  9. The Carcinoid Cancer Foundation. Resources for carcinoid and NET cancer insurance appeals.

  10. PRRTinfo.org. Working with your insurance.