Diagnosing small intestine neuroendocrine tumours requires careful attention, as these cancers often hide behind common symptoms and grow silently for years before being discovered.

Introduction: Who Should Undergo Diagnostics

Small intestine neuroendocrine tumours, also known as small bowel NETs, present a unique challenge when it comes to diagnosis. These rare cancers develop in the special cells of the small intestine that produce hormones to help with digestion. Because they typically grow very slowly and their symptoms often mirror those of much less serious conditions, many people live with these tumours for years without knowing they have them.^[8]

You should consider seeking diagnostic testing if you experience persistent symptoms that don’t go away or worsen over time. Common warning signs include ongoing abdominal pain, particularly in the lower abdomen, chronic diarrhea, unexplained weight loss, or unusual fatigue that leaves you exhausted all the time. Some people notice blood in their stool, which may appear bright red or dark and tarry, indicating possible intestinal bleeding. Others experience nausea and vomiting that doesn’t resolve with standard treatments.^[1][3]

It’s important to understand that not everyone with a small bowel NET experiences symptoms, especially in the early stages. Many people discover they have these tumours completely by accident. A doctor might spot the cancer on a CT scan or other imaging test performed for an entirely different reason. This is why these tumours often go undiagnosed for extended periods, and many patients already have spread to other parts of the body, particularly the liver, by the time they receive their diagnosis.^[4][8]

Certain individuals may be at higher risk and should be particularly attentive to symptoms. If you have a family history of cancer, especially neuroendocrine tumours, you face an increased risk. Rare inherited conditions can also raise your chances of developing small bowel NETs. These include multiple endocrine neoplasia type 1 (MEN1) syndrome, which causes certain glands to become overactive or form tumours, and neurofibromatosis type 1 (NF1) syndrome, where tumours grow on skin and nerves. People with conditions that reduce stomach acid production, such as certain types of gastritis or pernicious anemia, may also face elevated risk.^[4][5]

Diagnostic Methods

Identifying small intestine neuroendocrine tumours requires a combination of different tests and procedures. Doctors use these methods not only to confirm the presence of a tumour but also to distinguish it from other conditions that might cause similar symptoms. The diagnostic process can involve blood tests, urine tests, imaging studies, and sometimes direct examination of the intestine itself.

Blood and Urine Tests

One of the first steps in diagnosing small bowel NETs involves analyzing blood and urine samples. These tests look for specific substances that might indicate the presence of a neuroendocrine tumour. Your doctor may check for elevated liver enzymes, which could suggest that the tumour has spread to the liver. Blood tests might also reveal anemia, which means your body doesn’t have enough healthy red blood cells to carry oxygen properly. This can happen when a tumour causes bleeding in the intestines.^[8]

Many small bowel NETs produce hormones and other substances that can be measured in the blood and urine. Doctors often test for a substance called chromogranin A, which is a protein marker that neuroendocrine cells release. When levels of chromogranin A are elevated, it may suggest the presence of a NET. Another important test measures 5-HIAA (5-hydroxyindoleacetic acid) in a 24-hour urine collection. This substance is a breakdown product of serotonin, a hormone that many small bowel NETs produce in excess. Elevated 5-HIAA levels can help confirm a diagnosis, especially in patients with carcinoid syndrome.^[8]

Imaging Studies

Imaging tests create pictures of the inside of your body, allowing doctors to see tumours and determine whether they have spread. Several different imaging methods may be used to evaluate small bowel NETs, and each provides different types of information.

CT scans (computed tomography scans) use X-rays taken from multiple angles to create detailed cross-sectional images of your body. These scans are particularly useful for identifying tumours in the small intestine and checking whether cancer has spread to the liver or lymph nodes in the abdomen. The procedure is painless and typically takes less than an hour. You may need to drink a contrast liquid or receive an injection of contrast dye to make the images clearer.^[5][8]

MRI scans (magnetic resonance imaging) use powerful magnets and radio waves instead of X-rays to create detailed pictures of soft tissues in your body. MRI can be especially helpful for examining the liver in great detail, as it can sometimes detect small tumour deposits that other imaging methods might miss. Like CT scans, MRI is painless, though some people find the enclosed space of the MRI machine uncomfortable, and the machine makes loud noises during the scan.^[8]

Nuclear medicine scans represent a specialized type of imaging particularly valuable for detecting neuroendocrine tumours. These scans involve injecting a small amount of radioactive material that attaches to specific receptors on NET cells. The most common types include somatostatin receptor imaging, also called OctreoScan or DOTATATE PET scan. Because many neuroendocrine tumours have receptors for somatostatin on their surface, the radioactive tracer concentrates in areas where tumour cells are present. This makes these scans extremely sensitive for finding both the primary tumour and any spread throughout the body.^[8]

Plain X-rays are less commonly used for diagnosing small bowel NETs, as they don’t provide as much detail as CT or MRI scans. However, they might reveal complications such as bowel obstruction if a tumour has grown large enough to block the intestine.^[5]

Endoscopic Procedures

Sometimes doctors need to look directly inside the digestive tract to identify or confirm a tumour. Endoscopy involves inserting a thin, flexible tube with a light and camera on the end through your mouth or rectum to examine the lining of your digestive system. For small bowel NETs, doctors may use specialized types of endoscopy.

Upper endoscopy, also called esophagogastroduodenoscopy (EGD), allows examination of the upper portion of the small intestine called the duodenum. The doctor passes the endoscope through your mouth, down your esophagus, through your stomach, and into the duodenum. If a suspicious area is found, small tissue samples called biopsies can be taken for analysis under a microscope.^[8]

Because most small bowel NETs occur in the lower parts of the small intestine, particularly in the section called the ileum, they may not be visible with standard endoscopy. In these cases, doctors might use capsule endoscopy, where you swallow a pill-sized camera that takes thousands of pictures as it travels through your digestive system. These images are transmitted to a recorder you wear on your belt, and your doctor reviews them later to look for abnormalities.

Biopsy and Tissue Analysis

Ultimately, the definitive diagnosis of a small bowel NET requires examining actual tumour tissue under a microscope. This is done through a biopsy, where a small sample of tissue is removed for analysis. Biopsies can be obtained during endoscopy if the tumour is accessible, or sometimes during surgery if the tumour has already been identified through imaging.^[8]

When tissue is examined under the microscope by a specialist called a pathologist, they can confirm whether the growth is indeed a neuroendocrine tumour and determine important characteristics. The pathologist looks at how the cells are organized and how abnormal they appear. They also perform special stains and tests to identify markers that are typical of neuroendocrine cells. This helps distinguish NETs from other types of intestinal tumours that might look similar on imaging studies but behave very differently and require different treatments.

The pathologist also determines the grade of the tumour, which indicates how fast the cells are dividing and growing. This is done by counting how many cells are actively dividing in a certain area of the tissue sample. Lower-grade tumours grow more slowly and generally have a better outlook, while higher-grade tumours grow more rapidly and may require more aggressive treatment.^[8]

Diagnostics for Clinical Trial Qualification

Clinical trials are research studies that test new treatments or combinations of treatments for small bowel NETs. These trials help advance medical knowledge and may offer patients access to promising new therapies before they become widely available. However, to ensure patient safety and obtain accurate research results, clinical trials have specific requirements that patients must meet before they can enroll.

The diagnostic tests required for clinical trial enrollment are often more extensive than those used for standard diagnosis. Trial organizers need detailed information about each participant’s tumour to ensure the experimental treatment is appropriate for their specific situation and that results can be properly interpreted.

Confirming Diagnosis and Tumour Characteristics

Nearly all clinical trials for small bowel NETs require tissue confirmation that you actually have this specific type of cancer. This means you must have undergone a biopsy, and a pathologist must have examined the tissue and confirmed the diagnosis. The pathology report needs to clearly state that the tumour is a neuroendocrine tumour originating from the small intestine, rather than a different type of cancer that may require different treatment approaches.^[8]

Trials typically specify the grade of tumour they will accept. Some studies focus on slow-growing, well-differentiated NETs (lower grade), while others may study more aggressive, poorly differentiated tumours (higher grade). You’ll need documentation of your tumour’s grade from the pathology report. This grading is usually based on the Ki-67 index, which measures the percentage of tumour cells that are actively dividing, or on the mitotic count, which looks at how many cells are dividing in a specific area of tissue.

Staging and Disease Extent

Clinical trials usually require precise information about where the cancer is located and whether it has spread. You’ll need recent imaging studies that document the extent of your disease. This typically includes CT scans or MRI scans of your chest, abdomen, and pelvis. Many trials also require specialized nuclear medicine scans, particularly somatostatin receptor imaging, to identify all sites where tumour might be present.^[8]

Trials often specify whether they accept patients with localized disease (cancer only in the original site), regional disease (cancer has spread to nearby lymph nodes), or metastatic disease (cancer has spread to distant organs like the liver or lungs). Some trials specifically focus on patients whose cancer has spread, while others might only accept those with earlier-stage disease. The imaging studies must be recent, usually performed within a few weeks to a few months before trial enrollment, to ensure the information accurately reflects your current situation.

Functional Status and Biomarkers

Many clinical trials measure specific blood markers to track how well a treatment is working. Before you can enroll, baseline measurements of these markers must be taken. For small bowel NETs, this typically includes chromogranin A levels in your blood. If your tumour produces hormones that cause symptoms, trials may also measure serotonin levels or 5-HIAA in urine collections. These baseline measurements provide a comparison point to see if the experimental treatment affects these markers.^[8]

Some trials require that certain markers be elevated above normal levels for you to qualify. This is particularly true for studies testing drugs designed to target specific molecules or receptors. For example, trials testing treatments that work through somatostatin receptors may require proof through imaging that your tumour cells actually have these receptors on their surface.

General Health Assessment

Beyond cancer-specific tests, clinical trials require comprehensive assessment of your overall health. Standard blood tests check your kidney function, liver function, and blood cell counts to ensure you’re healthy enough to tolerate the experimental treatment. These include tests measuring creatinine and blood urea nitrogen for kidney function, liver enzyme tests, and complete blood counts. Heart function may be evaluated through an electrocardiogram or echocardiogram if the experimental treatment could potentially affect the heart.^[8]

Trials typically exclude patients with certain other medical conditions that might complicate interpretation of results or increase risks. You’ll undergo testing to rule out conditions specified in the trial’s exclusion criteria. This might include tests for infectious diseases, pregnancy tests for women of childbearing age, or evaluations for other serious medical problems.

Documentation of Previous Treatments

If you’ve already received treatment for your small bowel NET, clinical trials need complete documentation of what treatments you’ve had and how your tumour responded. This includes surgical reports if you’ve had operations, treatment records for any medications you’ve taken, and imaging studies showing how the tumour changed with treatment. Some trials only accept patients who haven’t received certain types of prior therapy, while others specifically study patients whose cancer progressed despite previous treatments. You’ll need to provide medical records proving which treatments you’ve received and when.