Tests for Pancreatic Neuroendocrine Tumor

Certain signs and symptoms might suggest that a person could have a pancreatic neuroendocrine tumor (NET), but tests are needed to confirm the diagnosis.

Medical history and physical exam

In taking your medical history, the doctor will ask you questions about your general health, lifestyle habits, symptoms, and risk factors. The doctor will also probably ask about symptoms related to excess hormone production such as diarrhea, abdominal (belly) pain, or rash.  

Your doctor will also examine you to look for signs of pancreatic NET or other health problems. The exam will probably focus mostly on your belly. Pancreatic NETs can sometimes cause the liver or gallbladder to swell, which the doctor might be able to feel during the exam.

If the results of the exam are abnormal, your doctor will probably order tests, such as imaging, labs, or other procedures, to help find the problem. You might also be referred to a gastroenterologist (a doctor who treats digestive system diseases) for further tests and treatment.

Imaging tests

Computed tomography (CT) scan

A CT scan uses x-rays taken from different angles, which are combined by a computer to make detailed pictures of the organs. This test is most often used to look at the chest and/or belly (abdomen) to see the pancreas clearly and if the pancreatic NET has spread to nearby lymph nodes or other organs such as the liver. It can also be used to guide a biopsy needle into an area of concern.

Magnetic resonance imaging (MRI)

Like CT scans,  MRI scans show detailed images of soft tissues in the body. But MRI scans use radio waves and strong magnets instead of x-rays. A dye called gadolinium may be injected into a vein before the scan to see details better. A MRI scan sometimes can see cancer spread to the liver better than a CT scan.

MR cholangiopancreatography (MRCP), is a special type of MRI scan, which can be used to look at the pancreatic and bile ducts, and is described below in the section on cholangiopancreatography.

Ultrasound

Ultrasound tests use sound waves to create images of organs such as the pancreas.

Abdominal ultrasound: For this test, a wand-shaped probe is moved over the skin of the abdomen. It gives off sound waves and detects the echoes as they bounce off organs. If it’s not clear what might be causing a person’s abdominal symptoms, this might be the first test done because it is easy to do and it doesn’t expose a person to radiation.

Endoscopic ultrasound (EUS): This test uses an endoscope with a small ultrasound probe on the end. The scope is then passed through your mouth or nose, down through the stomach, and into the first part of the small intestine. It is then pointed toward the pancreas, which is next to the small intestine. The probe on the tip of the endoscope can get very close to the pancreas, so this is a very good way to look at it. If a tumor is seen, a small, hollow needle can be passed down the endoscope to get biopsy samples of it.

Cholangiopancreatography

This is an imaging test that looks at the pancreatic ducts and bile ducts to see if they are blocked, narrowed, or dilated. These tests can help show if someone might have a pancreatic neuroendocrine tumor that is blocking a duct. They can also be used to help plan surgery. The test can be done in different ways, each of which has pros and cons.

Endoscopic retrograde cholangiopancreatography (ERCP): For this test, an endoscope (a thin, flexible tube with a tiny video camera on the end) is passed down the throat, through the esophagus and stomach, and into the first part of the small intestine. This is usually done while you are sedated (given medicine to make you sleepy).

The doctor can see through the endoscope to find the ampulla of Vater (where the common bile duct empties into the small intestine). The doctor guides a catheter (a very small tube) through the tip of the endoscope and into the common bile duct. A small amount of dye is then injected into the common bile duct, and x-rays are taken. This dye outlines the bile and pancreatic ducts. The x-rays can show narrowing or blockage in these ducts that might be due to pancreatic neuroendocrine tumor. The doctor doing this test can also put a small brush through the tube to remove cells for a biopsy (see below).

ERCP can also be used to place a stent (small tube) into a bile or pancreatic duct to keep it open if a nearby tumor is pressing on it.

Magnetic resonance cholangiopancreatography (MRCP): This is a non-invasive way to look at the pancreatic and bile ducts using the same type of machine used for standard MRI scans. Unlike ERCP, it does not require an injection of a dye. Because this test is non-invasive, doctors often use MRCP if the purpose is just to look at the pancreatic and bile ducts. But this test can’t be used to get biopsy samples of tumors or to place stents in ducts.

Percutaneous transhepatic cholangiography (PTC): In this procedure, the doctor puts a thin, hollow needle through the skin of the belly and into a bile duct within the liver. A dye is then injected through the needle, and x-rays are taken as it passes through the bile and pancreatic ducts. As with ERCP, this approach can also be used to take fluid or tissue samples or to place a stent into a duct to help keep it open. Because it is more invasive (and might cause more pain), PTC is not usually used unless ERCP has already been tried or can’t be done for some reason.

Radionuclide scans

Scans using small amounts of radioactivity and special cameras can be helpful in looking for pancreatic NETs. They can help find tumors or look for areas of cancer spread if doctors aren’t sure where it is in the body.

Positron emission tomography (PET) scan: For most types of cancer, PET scans use a form of radioactive glucose (sugar) to find tumors. This type of PET scan is useful in finding poorly differentiated pancreatic neuroendocrine carcinomas (NECs), but a newer type of PET scan, called a Gallium-68 PET/CT Dotatate scan is being used for pancreatic NETs. It uses the radioactive agent gallium-68 dotatate which attaches to the somatostatin protein on neuroendocrine tumor cells. A special camera can detect the radioactivity. This Gallium-68 PET/CT scan is slowly becoming more widely available since it was approved by the FDA in 2016 and is able to find neuroendocrine tumors better than an OctreoScan (described below).

Somatostatin receptor scintigraphy (SRS or OctreoScan): This test can be very helpful in finding pancreatic NETs.  It uses a drug called octreotide joined to radioactive indium-111. Octreotide is a hormone-like substance that attaches to pancreatic NET cells. A small amount of the octreotide-radioactive substance is injected into a vein and travels though the blood where it attaches to the tumor types of many types of pancreatic NET cells (although it is less helpful for insulinomas).  A few hours after the injection, a special camera can be used to show where the radioactivity has collected in the body. More scans may be done over the next few days as well. Along with showing where tumors are, this test can also tell whether treatment with certain drugs such as octreotide and lanreotide is likely to be helpful.  

Blood and urine tests

Several types of blood and urine tests can be used to help diagnose pancreatic NET or to help determine treatment options if it is found.

Blood tests looking at the levels of certain pancreatic hormones can often help diagnose pancreatic NETs. Tests might be done to check blood levels of:

• Hormones made by different types of pancreatic NET cells, such as insulin, gastrin, glucagon, somatostatin, pancreatic polypeptide, and VIP (vasoactive intestinal peptide)
• Chromogranin A (CgA)
• Glucose and C-peptide (for insulinomas)

Carcinoid tumors: For carcinoids, a blood test may be done to look for serotonin, which is made by many of these tumors. The urine might also be tested for serotonin and for related chemicals such as 5-HIAA and 5-HTP.

Other common tests to look for carcinoids include blood tests for chromogranin A (CgA), neuron-specific enolase (NSE), substance P, and gastrin.

Depending on where the tumor might be located and the patient’s symptoms, doctors might do other blood tests as well.

Some of these tests can also be used to show how well treatment is working, since the levels of these substances tend to go down as tumors shrink.

Biopsy

In many cases, the only way to know for sure if a person has some type of pancreatic NET is to remove cells from the tumor and look at them in the lab. This procedure is called a biopsy. Biopsies can be done in different ways.

Percutaneous (through the skin) biopsy: For this test, a doctor inserts a thin, hollow needle through the skin over the abdomen and into the pancreas to remove a small piece of a tumor. This is known as a fine needle aspiration (FNA). The doctor guides the needle into place using images from ultrasound or CT scans.

Endoscopic biopsy: Doctors can also biopsy a tumor during an endoscopy. The doctor passes an endoscope (a thin, flexible, tube with a small video camera on the end) into the throat, down the esophagus, and into the small intestine near the pancreas. At this point, the doctor can either use endoscopic ultrasound (EUS) to pass a needle into the tumor or endoscopic retrograde cholangiopancreatography (ERCP) to remove cells from the bile or pancreatic ducts. These tests are described in more detail above.

Surgical biopsy: In rare cases, an endoscopic biopsy or a CT-guided needle biopsy will not be able to get enough tissue to identify the type of tumor. In such cases, surgery may be needed to remove a tissue sample. Surgical biopsies are done much less often now than in the past since PNETs are mostly diagnosed using imaging (CT or MRI scans), somatostatin receptor-based imaging, EUS biopsy, and checking for excessive levels of hormones.

Some people might not need a biopsy

Rarely, the doctor might not do a biopsy on someone who has a neuroendocrine tumor in the pancreas if imaging tests, blood tests, and somatostatin receptor-based imaging show the tumor is very likely to be cancer and if it looks like surgery can remove all of it. Instead, the doctor will proceed with surgery, at which time the tumor cells can be looked at in the lab to confirm the diagnosis. During surgery, if the doctor finds that the cancer has spread too far to be removed completely, only a sample of the cancer may be removed to confirm the diagnosis, and the rest of the planned operation may be stopped.

See Testing Biopsy and Cytology Specimens for Cancer to learn more about different types of biopsies, how the biopsy samples are tested in the lab, and what the results will tell you.