Understanding the path to diagnosis can feel overwhelming when you first hear about gastrointestinal neuroendocrine tumors, but knowing what tests you might need and why they matter can help you feel more prepared and in control of your healthcare journey.

Introduction

Gastrointestinal neuroendocrine tumors, often called GI NETs, are unusual growths that develop in specialized cells scattered throughout the digestive system. These cells normally help control digestion by releasing hormones and responding to signals from the nervous system. When something goes wrong and these cells begin to multiply abnormally, they can form tumors^[1].

Many people wonder when they should seek diagnostic testing for GI NETs. The truth is that these tumors often grow very slowly and may not cause any symptoms in their early stages. Some people only discover they have a GI NET when they undergo imaging tests or procedures for completely unrelated health issues^[2]. This means the tumor might have been present for months or even years before anyone noticed it.

If you experience persistent symptoms such as stomach pain, ongoing diarrhea, unexplained weight loss without trying to lose weight, nausea and vomiting that won’t go away, or notice bright red blood in your stool or dark tarry stools, it’s important to talk to your doctor^[2]. Another sign that might prompt testing is jaundice, which is when your skin and the whites of your eyes take on a yellowish color. Some people also experience extreme fatigue that goes beyond normal tiredness.

Certain individuals have a higher chance of developing GI NETs and might benefit from earlier or more frequent monitoring. If you have a family history of conditions called multiple endocrine neoplasia type 1 (MEN1) syndrome or neurofibromatosis type 1 (NF1) syndrome, your doctor may recommend screening even without symptoms^[1]. Additionally, people with stomach conditions that reduce acid production, such as atrophic gastritis, pernicious anemia, or Zollinger-Ellison syndrome, face increased risk.

Diagnostic Methods

Once you and your doctor decide that testing is needed, several different approaches can help identify whether a GI NET is present and determine its characteristics. The diagnostic process typically begins with simpler tests and may progress to more detailed examinations depending on what doctors find.

Physical Examination

Your doctor will start with a thorough physical examination. During this exam, they will feel your abdomen to check for any unusual masses or tenderness. They will also examine your lymph nodes to see if any feel swollen or enlarged, which can sometimes indicate that a tumor has spread^[13]. Your doctor will ask detailed questions about your symptoms, including when they started, how often they occur, and whether anything makes them better or worse. This conversation helps guide which additional tests might be most helpful.

Blood and Urine Tests

Laboratory testing plays a crucial role in detecting GI NETs, especially because some of these tumors produce excess hormones that can be measured. Blood tests can reveal whether your tumor is releasing hormones into your bloodstream^[1]. For example, doctors might check your blood for elevated levels of specific substances that GI NETs commonly produce.

Urine tests serve a similar purpose. Some hormones and their breakdown products pass from your blood into your urine, where they can be detected and measured. Collecting urine over a 24-hour period sometimes provides more accurate information than a single sample^[13].

These tests are particularly important when doctors suspect carcinoid syndrome, a collection of symptoms that occurs when certain GI NETs release large amounts of hormones into the bloodstream. This syndrome is more common when tumors have spread to the liver or other parts of the body^[1].

Imaging Studies

Creating pictures of the inside of your body helps doctors locate tumors, determine their size, and see whether they have spread. Several types of imaging studies are used for GI NETs.

X-rays are sometimes the first imaging test performed. While they may not always show a GI NET clearly, they can provide useful preliminary information^[2]. More detailed imaging usually follows.

Ultrasound uses sound waves to create pictures of organs and structures inside your body. For GI NETs, doctors might perform a regular abdominal ultrasound or a specialized transvaginal or pelvic ultrasound depending on where the tumor is suspected^[13]. Ultrasound is painless and doesn’t involve radiation.

Computed tomography scans, often called CT scans, combine multiple X-ray images taken from different angles to create detailed cross-sectional views of your body. A CT scan can show the tumor itself as well as whether it has spread to nearby lymph nodes or other organs^[13]. Sometimes you will be asked to drink a contrast liquid or receive an injection that helps certain tissues show up more clearly on the images.

Magnetic resonance imaging, or MRI, uses powerful magnets and radio waves instead of radiation to create detailed pictures of soft tissues. MRI scans are particularly good at showing detail in certain body areas and can help doctors evaluate the tumor’s characteristics^[13].

A specialized type of scan called a somatostatin receptor PET scan, sometimes referred to as a dotatate PET scan, is especially useful for GI NETs. Many neuroendocrine tumor cells have receptors on their surface that attach to a chemical called somatostatin. During this scan, you receive an injection containing a small amount of radioactive material that binds to these receptors. The scan then detects where this material has concentrated, revealing the location of tumor cells throughout your body^[13]. This test is excellent at finding both the primary tumor and any spots where the cancer may have spread.

Endoscopy Procedures

Sometimes doctors need to look directly inside your digestive tract to find and examine suspicious areas. Endoscopy is a procedure where a thin, flexible tube with a light and camera on the end is inserted into your body. The type of endoscopy depends on which part of your digestive system needs examination.

Upper endoscopy, also called esophagogastroduodenoscopy or EGD, involves passing the scope through your mouth, down your esophagus, and into your stomach and the first part of your small intestine. This allows doctors to look for tumors in these upper areas of the digestive tract.

Colonoscopy examines the large intestine and rectum. The scope enters through the anus and travels through the colon. This procedure can detect tumors in the lower digestive tract^[13].

During these procedures, if doctors see anything suspicious, they can use small instruments passed through the endoscope to take tissue samples for further examination. This brings us to one of the most definitive diagnostic tools.

Biopsy

A biopsy involves removing a small sample of tissue so it can be examined under a microscope. This is the only way to know for certain whether cells are cancerous and, if so, what type of cancer they represent^[13]. For GI NETs, biopsies can be obtained in several ways.

Sometimes the tissue sample is collected during an endoscopy, as mentioned above. In other cases, doctors might use imaging guidance such as ultrasound or CT scans to direct a needle to the tumor through the skin. Once the tissue is obtained, specialists called pathologists examine it in detail.

The pathology report provides crucial information. It confirms whether cancer is present and describes characteristics of the tumor cells, including how abnormal they look and how quickly they appear to be growing. Pathologists determine the grade of the tumor, which reflects how aggressive it is. They also check for specific features of the cells, such as whether they have somatostatin receptors, which can influence treatment decisions^[3].

Diagnostics for Clinical Trial Qualification

Clinical trials are research studies that test new treatments or different ways of using existing treatments. Participating in a clinical trial can sometimes give patients access to cutting-edge therapies not yet widely available. However, clinical trials have specific entry requirements, and certain diagnostic tests are typically needed to determine if someone qualifies.

Most clinical trials for GI NETs require confirmation through biopsy that you actually have a neuroendocrine tumor. The biopsy report must document specific features of your tumor, including its grade and how well the cells are differentiated. Trials often specify whether they accept only low-grade tumors, only high-grade tumors, or tumors of any grade^[3].

Imaging studies form another essential part of trial qualification. Researchers need to establish a baseline measurement of your tumor’s size and location before starting any experimental treatment. This allows them to accurately measure whether the treatment is working by comparing future scans to the initial ones. Typical baseline imaging includes CT scans or MRI scans of the chest, abdomen, and pelvis. Some trials also require somatostatin receptor PET scans, especially if the treatment being studied targets these receptors.

Blood tests help ensure that trial participants are healthy enough to receive experimental treatments. Standard tests measure your kidney function, liver function, and blood cell counts. These tests identify people whose organ function might be too compromised to safely handle the study treatment. Specific tumor marker tests, which measure hormones or other substances released by GI NETs, are often required at baseline and will be repeated during the study to track treatment response.

Functional status assessment is another qualification criterion. Doctors use standardized scales to evaluate how well you can perform daily activities. Most trials only accept patients who can care for themselves and are not bedridden for large portions of the day. This ensures that participants are likely to tolerate the experimental treatment.

Previous treatment history matters too. Some trials only accept patients who have never received treatment for their GI NET, while others specifically look for patients whose cancer has progressed despite previous therapies. You’ll need documentation of all treatments you’ve received, including dates and how your cancer responded.

Heart function testing, such as an electrocardiogram (ECG or EKG) or echocardiogram, may be required for trials testing certain types of drugs. These tests ensure your heart is strong enough for the treatment being studied^[13].

Genetic testing is increasingly becoming part of clinical trial screening. Some trials target specific genetic changes found in certain tumors. Researchers may test your tumor tissue for these genetic markers to see if you’re likely to benefit from the experimental treatment^[13].

The stage of your cancer, determined through the combination of imaging and sometimes surgical findings, influences trial eligibility. Staging tells doctors whether the cancer is confined to its original site, has spread to nearby lymph nodes, or has spread to distant organs. Different trials focus on different stages of disease.

Understanding these qualification requirements helps you and your doctor identify which clinical trials might be appropriate for your situation. Your medical team can help you navigate the screening process and gather the necessary diagnostic information if you’re interested in participating in research.