Tests for Pancreatic Neuroendocrine Tumors (pNET)

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

Medical history and physical exam

In taking your medical history, the doctor will ask 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 rashes.

Your doctor will also examine you to look for signs of a pancreatic neuroendocrine tumor (pNET) or other health problems. The exam will probably focus mostly on your belly. PNETs can sometimes cause the liver or gallbladder to swell, which might be able to be felt during the exam.

If the exam results 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 to diagnose pNETs

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. An iodine-based dye may be injected into your vein before the scan to show details better. This test is most often used to look at the belly (abdomen) to see the pancreas clearly and if the pNET 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 show details better. An MRI scan sometimes can see cancer that has spread to the liver better than a CT scan.

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 picks up 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 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 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.

Cholangiopancreatography tests

These imaging tests look at the pancreatic ducts and bile ducts to see if they are blocked, narrowed, or dilated. They can help show if someone might have a pancreatic neuroendocrine tumor blocking a duct. They can also be used to help plan surgery. These tests can be done in different ways; each has benefits and risks.

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 drugs to make you sleepy).

The doctor can see the ampulla of Vater (where the common bile duct empties into the small intestine) through the endoscope. 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 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 caused by a pNET. 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 duct 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 they just need 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 on 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 put a stent into a duct to help keep it open. Because it is more invasive (and might cause more pain), PTC is not usually done unless ERCP has already been tried or can’t be done for some reason.

Radionuclide scans to diagnose pNETs

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

Somatostatin receptor targeted PET-CT (SSTR-PET/CT): This test can be very helpful in finding pNETs, except those that overproduce insulin or are high-grade tumors. The somatostatin receptor (SSTR) is commonly found on pNETs. Somatostatin is a natural hormone in the body that binds to the receptor (SSTR). When somatostatin binds to SSTR on the cancer cell, it typically slows its growth and hormone-making abilities.

A combination of an SSTR agonist (man-made molecule that binds to the SSTR) linked to a radioactive tracer is used to identify pancreatic NETs. The SSTR agonist, dotatate, brings the tracer directly to the cancer cells. The radioactive tracer, gallium-68 or copper-64, shows up on a PET scan. Combining these two parts (SSTR agonist and radioactive tracer), 68Ga-DOTATATE, 64Cu-DOTATATE, and 68Ga-DOTATOC are the agents used for somatostatin receptor-based imaging

Somatostatin receptor-based imaging (like Octreoscan), can be helpful in two ways:

• It can show the location of the pNET
• It can show doctors if treating the pNET with a somatostatin analog (i.e., octreotide or lanreotide) or PRRT would be helpful. 

The SSTR-PET scan can be done with a CT scan to give clearer images. You might have a dye injected into your vein before the CT scan to show details better.

Somatostatin Receptor Targeted PET-MRI (SSTR-PET/MRI): The SSTR-PET also can be done with a MRI scan, instead of a CT scan. The decision on which scan to use is based on which organ is of concern. For example, if it is thought cancer cells have spread to the liver, a SSTR-PET/MRI may be a preferred option.

Blood tests to diagnose pNETS

Certain blood tests may help diagnose and check the response to treatment.

Tests might be done to check blood levels of:

• Hormones made by different types of pancreatic NET cells, such as insulin, gastrin, glucagon, and VIP (vasoactive intestinal peptide)
• Chromogranin A (CgA)
• Pancreatic polypeptide (PP)

Biopsies used to diagnose pNET

In many cases, the only way to know for sure if a person has a pNET is to remove cells from the tumor and look at them in the lab. This procedure is called a biopsy. Biopsies are done in different ways.

Percutaneous (through the skin) biopsy: For this type of biopsy, 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 pancreatic NETs 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 biopsy 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 directly with surgery, and 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.