Introduction: Who Should Undergo Diagnostics

Neuroendocrine carcinomas are rare cancers that can develop in many places throughout the body, most commonly in the digestive tract, lungs, and pancreas. Because these cancers start in cells that make hormones and respond to signals from the brain, they can affect many different body functions depending on where they are located and what hormones they produce.^[1]

You should consider seeking medical evaluation if you experience persistent symptoms that don’t improve over time. These symptoms can be quite varied and often resemble less serious conditions, which is one reason why neuroendocrine carcinomas can be challenging to identify. Common warning signs include ongoing fatigue that doesn’t go away with rest, stomach pain that persists, diarrhea that continues for weeks, nausea and vomiting, shortness of breath, or coughing that sometimes produces blood.^[2]

It’s important to remember that having these symptoms doesn’t necessarily mean you have cancer. Many other conditions can cause similar problems. However, if you notice symptoms that last for several weeks without improvement, or if they worsen over time, talking to a healthcare provider is advisable. Early diagnosis can make a significant difference in treatment outcomes.^[3]

Certain people may need to be more vigilant about screening. If you have a family history of rare inherited conditions such as multiple endocrine neoplasia (a condition that causes overactive tumors to form in various organs and glands), your risk of developing neuroendocrine tumors increases. People with these genetic syndromes should discuss regular monitoring with their healthcare team even if they don’t have symptoms.^[2]

Diagnostic Methods for Identifying Neuroendocrine Carcinoma

Diagnosing neuroendocrine carcinoma typically begins with a physical examination. Your healthcare provider will check your body for signs of cancer, such as swollen lymph nodes, and look for evidence that a tumor might be producing excess hormones. They will ask detailed questions about your symptoms, when they started, and how they’ve changed over time.^[10]

Blood and Urine Tests

Blood and urine tests are often the next step in diagnosis. These tests look for signs of excess hormones that some neuroendocrine tumors produce. When neuroendocrine cells become cancerous, they sometimes make large amounts of hormones or similar substances that shouldn’t be present at high levels in your body. By measuring these substances in your blood or urine, doctors can get clues about whether a neuroendocrine tumor might be present and where it might be located.^[10]

Blood tests can also reveal other important information, such as whether you’re anemic (have low red blood cells) or have elevated liver enzymes, which might indicate that the cancer has affected your liver. These findings can prompt doctors to investigate further with additional tests.^[3]

Imaging Tests

Imaging tests create pictures of the inside of your body to help doctors see where tumors are located and how large they are. If there’s concern that cancer may have spread to other parts of the body, imaging tests can detect that as well. Several types of imaging may be used to diagnose neuroendocrine carcinoma.^[10]

Ultrasound uses sound waves to create images of internal organs. It’s painless and doesn’t use radiation. Ultrasound can be particularly helpful for looking at organs like the liver or pancreas.^[10]

A computed tomography scan, or CT scan, uses X-rays taken from many angles to create detailed, three-dimensional images of your body. The machine moves around you while you lie still on a table. CT scans can show tumors in many different parts of the body and help determine their size and location.^[10]

Magnetic resonance imaging, or MRI, uses powerful magnets and radio waves instead of X-rays to create detailed images of your body’s soft tissues. This test can be especially useful for seeing certain types of tumors more clearly than other imaging methods.^[10]

A specialized type of positron emission tomography scan, or PET scan, is particularly valuable for neuroendocrine tumors. This scan uses a radioactive tracer that attaches to cells with receptors for a chemical called somatostatin, which neuroendocrine tumor cells often have on their surface. The tracer contains a medicine called dotatate, so this kind of scan is also called a dotatate PET scan or somatostatin receptor PET scan. This test can find neuroendocrine tumors throughout the body, even small ones that other imaging tests might miss.^[10]

Biopsy

A biopsy is the most definitive way to diagnose neuroendocrine carcinoma. During a biopsy, a small sample of tissue is removed from the suspected tumor and examined under a microscope in a laboratory. The laboratory tests can definitively show whether cancer cells are present and what type of cancer it is.^[10]

How a biopsy is performed depends on where the tumor is located in your body. Some biopsies can be done with a needle inserted through the skin, guided by ultrasound or CT imaging. Others might require a more involved procedure, such as an endoscopy (where a flexible tube with a camera is inserted through your mouth or rectum) or even surgery to reach the tumor.^[10]

Once the tissue sample is obtained, a specialist doctor called a pathologist examines the cells under a microscope. They look at how abnormal the cells appear and how quickly they are dividing and growing. This information helps determine whether the cancer is a neuroendocrine tumor that grows slowly or a neuroendocrine carcinoma that grows quickly. Neuroendocrine carcinomas look very different from normal neuroendocrine cells and are considered high-grade, fast-growing cancers.^[6]

Distinguishing Between Tumor Types

It’s crucial for doctors to distinguish between different types of neuroendocrine cancers because they behave very differently and require different treatments. There are two main groups: neuroendocrine tumors, which can be slow, moderate, or fast growing, and neuroendocrine carcinomas, which are all fast growing. The cells in tumors still look somewhat similar to normal neuroendocrine cells, while the cells in carcinomas look very abnormal and not like normal cells at all.^[6]

The pathologist assigns a grade to the cancer based on how the cells look and how fast they’re growing. Neuroendocrine tumors may be grade 1, 2, or 3. Neuroendocrine carcinomas are typically not assigned a grade because they are all considered high-grade by definition. Carcinomas may be described as small cell or large cell in appearance.^[6]

Diagnostics for Clinical Trial Qualification

Clinical trials test new treatments for neuroendocrine carcinoma and often have specific requirements for which patients can participate. To determine if you qualify for a clinical trial, doctors use many of the same diagnostic tests described above, but they apply them with specific criteria in mind.^[4]

Standard blood tests are typically required to ensure your organs, particularly your liver and kidneys, are functioning well enough to handle the experimental treatment being studied. Blood counts are checked to make sure you have enough red blood cells, white blood cells, and platelets. These tests help researchers understand your overall health status before you begin a trial.^[10]

Imaging tests such as CT scans, MRI scans, or specialized PET scans are used to precisely measure the size and location of your tumors before starting a clinical trial. These baseline measurements are critical because researchers need to be able to compare how your tumors respond to the experimental treatment over time. Follow-up scans are performed at regular intervals during the trial to see if tumors are shrinking, staying the same size, or growing.^[10]

Tissue samples from your biopsy may need to be tested for specific biomarkers, which are biological characteristics of the tumor cells. Some clinical trials are designed for patients whose tumors have certain genetic changes or express particular proteins on their surface. For example, trials might require that your tumor cells have somatostatin receptors or specific genetic mutations. These biomarker tests help match patients to the treatments most likely to benefit them.^[4]

The stage of your cancer—meaning how far it has spread—is also important for clinical trial eligibility. Some trials are designed for patients with cancer that is confined to one area and can potentially be removed with surgery, while others are specifically for patients whose cancer has spread to multiple organs. Doctors use imaging tests and sometimes surgical exploration to accurately determine the stage of your disease.^[10]

Performance status is another factor considered for clinical trials. This refers to how well you are able to carry out daily activities. Doctors assess whether you are active and able to do most things on your own, or whether you need significant help with daily tasks. Most clinical trials require that participants are well enough to tolerate the experimental treatment being studied.^[14]