Neuroendocrine tumors (NETs): Full guide

What are neuroendocrine tumors?

Neuroendocrine cells are special cells spread all through the body. They act a bit like nerve cells and a bit like hormone-making cells. They release hormones and other chemicals that help control things like digestion and blood sugar.

A neuroendocrine tumor, or NET, starts when these cells grow out of control. NETs can start almost anywhere. The most common places are the small intestine, the pancreas, the lungs, the rectum, the appendix, and the stomach. You may also hear the older name carcinoid tumor.

Many NETs grow slowly, sometimes over many years. Some cause no signs at all and are found by chance on a scan or during surgery for something else. Others make extra hormones that cause symptoms, such as flushing, diarrhea, or low blood sugar.

NETs are different from small cell lung cancer and other fast-growing neuroendocrine carcinomas. Those are separate diseases with different treatment. This guide is mostly about well-differentiated NETs, the slower kind.

Even when a NET has spread, it can often be controlled for a long time. Many people live for years, and sometimes decades, with good quality of life. A team that sees many NET patients can make a big difference.

Types

Small intestine NET

One of the most common types. It often spreads to nearby lymph nodes and the liver before it is found. When it has spread to the liver, it is the type most likely to cause carcinoid syndrome.

Pancreatic NET (pNET)

Starts in the hormone-making cells of the pancreas. It is very different from the common type of pancreatic cancer and is treated differently. Some make hormones and some do not.

Lung NET (typical and atypical carcinoid)

Typical carcinoids grow very slowly. Atypical carcinoids grow a bit faster. Both are different from small cell lung cancer. Surgery is the main treatment when the tumor has not spread.

Rectal, appendix, and stomach NETs

These are often small and found early, sometimes during a colonoscopy, an upper endoscopy, or surgery for appendicitis. Many small ones are cured by removing them.

Functional NET

A NET that makes extra hormones that cause symptoms. Examples are insulinoma (low blood sugar), gastrinoma (stomach ulcers and diarrhea), glucagonoma (a skin rash and high blood sugar), and VIPoma (severe watery diarrhea).

Nonfunctional NET

A NET that does not make enough hormones to cause symptoms. Most pancreatic NETs are this kind. They may be found because of pain, a lump, or by chance on a scan.

Neuroendocrine carcinoma (NEC)

A fast-growing, poorly differentiated cancer, such as small cell or large cell types. It is treated more like small cell lung cancer, usually with chemotherapy. It is a different disease from the slower NETs on this page.

Tests you may have

Biopsy with Ki-67

A small piece of tumor is looked at under a microscope. The lab checks how the cells look and measures Ki-67, a marker of how fast the cells are dividing. This sets the grade.

CT or MRI scans

Detailed pictures that show where the tumor is and whether it has spread. MRI is very good at finding spots in the liver.

Somatostatin receptor PET scan

Most NETs have many receptors (docking spots) for a hormone called somatostatin. For this scan, a small amount of a radioactive tracer that sticks to these receptors is given in a vein. Names include Ga-68 DOTATATE and Cu-64 DOTATATE. It finds NET spots well and shows if treatments that target these receptors may work.

FDG PET scan

A different PET scan that lights up fast-growing cells. It may be used for higher-grade tumors. Spots that light up on this scan may act more aggressively.

5-HIAA urine or blood test

5-HIAA is a breakdown product of serotonin, a chemical many small intestine NETs make. It helps confirm carcinoid syndrome. Some foods, like bananas, avocados, pineapple, tomatoes, plums, kiwi, and walnuts, and some medicines can raise it, so you may be asked to avoid them for a few days before the test.

Chromogranin A and other hormone tests

Chromogranin A is a protein many NETs release into the blood. It can help track the tumor, but stomach acid pills and kidney problems can raise it falsely. Other blood tests, such as insulin, gastrin, or glucagon, are done if a functional tumor is suspected.

Endoscopy and endoscopic ultrasound

A thin tube with a camera looks inside the stomach, intestine, or colon. With a small ultrasound on the tip, the doctor can see the pancreas up close and take a sample. You are sedated.

Echocardiogram

An ultrasound of the heart. People with carcinoid syndrome get this to check for carcinoid heart disease, which can damage the heart valves.

Genetic testing

A blood or saliva test for inherited conditions that raise NET risk, such as MEN1, von Hippel-Lindau (VHL), and others. It is often advised for people with pancreatic NETs, young people, and people with a family history.

Grade and stage

For NETs, two things matter most: the grade and the stage. The grade tells how fast the tumor cells are growing. The stage tells where the tumor is and how far it has spread.

Grade is based on the Ki-67 number and how many cells are dividing under the microscope. A lower grade usually means a slower tumor. Stage uses numbers from 1 to 4, and the details differ by where the tumor started. The liver is the most common place NETs spread.

Your care team also looks at whether the tumor lights up on a somatostatin receptor scan and whether it makes hormones. All of these together guide treatment.

Grade 1 (G1)

Ki-67 below 3%. The cells grow very slowly. Many people can be watched or treated gently for a long time.

Grade 2 (G2)

Ki-67 from 3% to 20%. The cells grow a little faster. Treatment depends on the stage and how quickly the tumor is changing.

Grade 3 (G3) NET

Ki-67 above 20%, but the cells still look fairly normal (well-differentiated). These grow faster and may need stronger treatment. They are not the same as neuroendocrine carcinoma.

Localized

The tumor is only where it started. Surgery or removal with a scope can often cure it.

Regional

The tumor has spread to nearby lymph nodes or tissue. Surgery is still often the main treatment.

Metastatic

The tumor has spread to distant places, most often the liver, and sometimes bones or lungs. It is usually not curable, but it can often be controlled for many years with treatment.

Hormones, receptors, and gene tests

NETs are unusual because the tumor itself can make hormones. These hormones can cause symptoms even when the tumor is small. Treating the hormones is often as important as treating the tumor.

Your care team also checks whether the tumor has somatostatin receptors. This matters because several key treatments, including somatostatin analog shots and PRRT, work by attaching to these receptors. Ask your care team what your scan and test results show.

Somatostatin receptor positive

The tumor lights up on a somatostatin receptor PET scan. This means somatostatin analog drugs and PRRT may work well. Most well-differentiated NETs are positive.

Serotonin and carcinoid syndrome

Many small intestine NETs make serotonin and other chemicals. When the tumor has spread to the liver, these can reach the rest of the body and cause flushing, diarrhea, wheezing, and heart valve damage. This is called carcinoid syndrome.

Insulin, gastrin, glucagon, and VIP

Hormones made by some pancreatic NETs. Too much insulin causes low blood sugar. Too much gastrin causes stomach ulcers and diarrhea. Too much glucagon causes a rash, weight loss, and high blood sugar. Too much VIP causes severe watery diarrhea.

Ki-67

A marker of how many tumor cells are dividing. It sets the grade and helps choose treatment. It can change over time, so a new biopsy is sometimes done if the tumor starts acting differently.

MEN1 and other inherited syndromes

Inherited changes in genes such as MEN1, VHL, NF1, and TSC raise the risk of NETs and other tumors. A positive result may change your care and can help your relatives get checked. A genetic counselor can explain what it means.

Tumor gene testing

Broad gene testing of the tumor is sometimes done, more often for higher-grade tumors or carcinomas. It rarely changes treatment for slower NETs, but it may point to a clinical trial.

Main treatments

Surgery

Surgery is the main way to cure a NET that has not spread far. Small NETs in the rectum or stomach can sometimes be removed with a scope. For small intestine NETs, the surgeon also removes nearby lymph nodes. When the tumor has spread to the liver, removing as much as possible can sometimes help control symptoms and growth. The gallbladder may be taken out at the same time, because long-term somatostatin analog shots can cause gallstones.

Watching closely

Some small, slow-growing NETs, like small pancreatic NETs that cause no symptoms, can be watched with regular scans instead of treated right away.

Somatostatin analogs

Octreotide and lanreotide are man-made versions of somatostatin. They are given as a shot about once a month. They calm hormone symptoms like flushing and diarrhea, and they slow tumor growth. They are often the first treatment for spread NETs that have somatostatin receptors. Short-acting octreotide shots can be used for breakthrough symptoms.

PRRT with Lu-177 dotatate

PRRT means peptide receptor radionuclide therapy. A radioactive medicine (Lutathera) travels through the blood and sticks to somatostatin receptors, giving radiation right to the tumor cells. It is usually given as 4 infusions about 8 weeks apart. It is used when NETs grow despite somatostatin analogs, and sometimes earlier for higher-grade tumors. You will get instructions to protect others from radiation for a short time afterward.

Everolimus

A daily pill that blocks a growth signal (mTOR) inside tumor cells. It slows growth of NETs from the pancreas, lungs, and digestive tract.

Sunitinib and cabozantinib

Daily pills that block blood vessel growth and other signals tumors need. Sunitinib is used for pancreatic NETs. Cabozantinib can be used for pancreatic and other NETs after earlier treatment.

Chemotherapy

Capecitabine with temozolomide (CAPTEM) is often used for pancreatic NETs and some faster-growing NETs. Platinum chemotherapy with etoposide is used for neuroendocrine carcinoma.

Liver-directed treatments

When NETs have spread to the liver, doctors can treat liver spots directly. Options include blocking the blood supply to the tumor (embolization), sometimes with tiny radioactive beads, and burning or freezing the spots (ablation).

Treating hormone symptoms

Telotristat is a pill added to somatostatin analogs to help carcinoid syndrome diarrhea. People with insulinoma may need diet changes and medicines to keep blood sugar up. Stomach acid pills treat ulcers from gastrinoma.

Clinical trials

NETs are rare, so research studies are an important way to get new treatments. Many newer radioactive medicines and targeted drugs are being tested. Ask about them at any stage.

Symptoms, side effects, and what helps

Flushing and diarrhea from carcinoid syndrome

Somatostatin analog shots help most people. Alcohol, spicy foods, large meals, and stress can trigger flushing, so a diary can help you find your triggers. Tell your care team if diarrhea is getting worse, since medicines can be added.

Carcinoid crisis

A rare, sudden flare of severe flushing, low blood pressure, fast heartbeat, or wheezing. It can happen during surgery or procedures. Your care team will give octreotide before procedures to prevent it. Make sure every doctor knows you have a NET.

Side effects of somatostatin analog shots

These can include soreness at the shot site, loose or greasy stools, belly cramps, and gas. Over time they can cause gallstones and changes in blood sugar. Most side effects are mild and often ease after the first few months.

Side effects of PRRT

Nausea is common on the day of treatment and is treated with medicine. PRRT can lower blood counts for a while. Rarely, it can affect the kidneys or, years later, the bone marrow. Your care team checks your blood and kidneys before each dose and afterward.

Mouth sores and other everolimus effects

Everolimus often causes mouth sores. A steroid mouth rinse can help prevent them. It can also cause rash, tiredness, higher blood sugar and cholesterol, infections, and lung swelling that causes a dry cough. Report a new cough or shortness of breath.

High blood pressure, hand-foot problems, and diarrhea

Sunitinib and cabozantinib can raise blood pressure, cause sore, red skin on the hands and feet, and cause diarrhea and tiredness. Check your blood pressure at home if asked. Thick lotion and comfortable shoes help your feet.

Low blood sugar

Insulinomas can cause shakiness, sweating, confusion, or fainting. Eat small, frequent meals and keep a sugar source with you. Your care team may give medicines to help.

Carcinoid heart disease

Long-term high serotonin can thicken heart valves, often on the right side of the heart. Watch for leg swelling, belly swelling, and getting short of breath. Regular heart ultrasounds help find it early. Valve surgery can help some people.

Vitamin and nutrition problems

Long-term diarrhea and somatostatin analogs can lower some vitamins. Carcinoid syndrome can also lower niacin (vitamin B3). A dietitian can help, and your care team may check vitamin levels.

Fatigue

Feeling tired is common. Gentle daily activity, good sleep habits, and pacing yourself can help. Tell your care team, since tiredness can come from low blood counts, hormones, or medicine.

Living with and after a NET

For many people, a NET is a long-term condition managed over years, a bit like other chronic illnesses. There may be long stretches of stable disease with only regular shots and scans.

You will have scans and blood tests on a regular schedule, often every 3 to 12 months. How often depends on the grade and how the tumor is behaving. Keep a copy of your reports, since NET care often spans many years and several doctors.

Because NETs are rare, it helps to be seen at least once at a center that treats many of them. A team of surgeons, oncologists, nuclear medicine doctors, and radiologists can plan care together.

Carry a card or note that says you have a NET, especially if you have carcinoid syndrome. Before any surgery, dental work under sedation, or procedure, tell the team so they can give octreotide if needed.

If you have an inherited syndrome like MEN1, your blood relatives may want genetic testing. Some will need regular checkups for related tumors.

Living with a rare tumor can feel lonely. Patient groups such as the Neuroendocrine Tumor Research Foundation and the Healing NET Foundation offer education and support. Social workers and counselors can help you and your family too.