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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. 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 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 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 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 tests

These imaging tests look 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. These tests 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 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 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 caused by a 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 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 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.

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

To identify the presence of pancreatic NETs, a substance is used that is a combination of a SSTR agonist (man-made molecule that binds to the SSTR) linked to a radioactive tracer. The SSTR agonist, dotatate, acts like a homing signal by attaching to the SSTR on cancer cells, bringing the tracer directly to them. The radioactive tracer, gallium-68 or copper-64, can be seen 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.

S?omatostatin receptor-based imaging, can be helpful in two ways:

• It can show doctors the location of the pancreatic NET.?
• It can show doctors if treating the pancreatic NET with a somatostatin angalog (i.e., octreotide or lanreotide) would be helpful. ?

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

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

Blood tests

Certain blood tests may be used to 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)

Biopsy

In many cases, the only way to know for sure if a person has 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 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 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 directly 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.