Types of neuroendocrine tumors

Various types of neuroendocrine tumors (NET) may form in many places in the body and grow differently. Many NETs first appear in the lungs or the gastrointestinal tract, including the stomach, pancreas, appendix, intestines, colon and rectum. NETs may also appear in the thymus, thyroid gland, adrenal gland and pituitary gland.

Functional vs. nonfunctional NETs

Neuroendocrine tumors may be functional or nonfunctional, depending on their hormone secretion. Functional NETs produce excess hormones, while nonfunctional tumors don’t produce hormones or enough of them to cause noticeable symptoms. Which hormone or hormones the cancer cells secrete depends on where the cancer develops. About 60 percent of NETs are categorized as nonfunctional, according to the American Society of Clinical Oncology (ASCO). The symptoms of the NET—if you have any—and your treatment plan will likely depend on whether the tumor is functional or nonfunctional.

Indolent vs. aggressive NETs

As your cancer care team learn more about the NET through testing, they may be able to classify it as either indolent or aggressive.

• An indolent NET is a slow-growing tumor, with cells that look somewhat similar (well-differentiated) to normal, noncancerous cells. This is also called a low-grade NET. As research on NETs evolves, the naming of these types of tumors has changed. You may hear them referred to as carcinoid tumors, which means “cancer-like,” describing their slow rate of growth as compared with other types of tumors. There’s a lower risk of spread, or metastasis, with indolent NETs.
• An aggressive NET is a fast-growing tumor, with cells that are poorly differentiated, meaning they look very different from normal, noncancerous cells. While an aggressive NET may be associated with a worse prognosis and faster growth, both indolent and aggressive NETs have the ability to spread and metastasize to other parts of the body.

Interestingly, because aggressive NET cells are so different from normal cells, chemotherapy may be more successful against them. Indolent NET cells may not respond as well to treatment due to their similarity to normal cells.

NETs may be classified by the site of origin. Doctors may use terms such as GI NET, pancreatic NET or lung NET to describe the tumor. Although NETs vary in size and how quickly they grow, almost all NETs are considered malignant, or cancerous.

Because NETs begin in certain cells that have properties of both endocrine and nerve cells, they’re unique compared with other cancers. They can start in many different areas of the body. These cells play a critical role in controlling many of your body’s functions. They control hormone production and nerve function.

Gastrointestinal (GI) NETs

NETs most commonly develop in the gastrointestinal tract, which includes the stomach, large intestine, small intestine and appendix. The majority of GI NETs (39 percent) begin in the small intestine, with the rectum (15 percent) as the second most common area, according to the ASCO. About 7 percent of GI NETs begin in the appendix, presenting symptoms that may closely mimic appendicitis.

Lung NETs

The second most common area for NETs to develop is in the airways of the lungs. There are different types based on exactly where they start growing, how fast they grow, and other characteristics of the cancerous cells. These NETs are less likely to be functional tumors, so they don’t tend to cause symptoms based on hormone production as compared with gastrointestinal NETs.

Lung NETs may be central, based in the main airway or airways to the lungs, or peripheral, meaning they develop in the smaller airways toward the outer edges of the lungs.

They may be classified as typical or atypical. This corresponds to the grade, or how different the cancer cells appear compared with normal cells. A typical carcinoid lung NET is low-grade and well-differentiated. It’s the least aggressive form of a lung NET. An atypical carcinoid is an intermediate-grade tumor, with cells that are less similar to normal cells.

Lung NETs also may be classified as small cell neuroendocrine carcinoma, more often called small cell lung cancer. Large cell neuroendocrine carcinoma, a type of non-small cell lung cancer, is another form of lung NET. It tends to grow quickly and, despite its name, is quite similar to small cell lung cancer.

Pancreatic NETs

Pancreatic neuroendocrine tumors are more rare than GI or lung NETs. About 7 percent of NETs develop in the pancreas, according to the ASCO. Most pancreatic NETs are nonfunctional and don’t cause symptoms.

Functional NETs may be classified into subtypes depending on the specific hormones they produce, though they may overproduce more than one hormone at a time. Subtypes of functional pancreatic NETs include:

• Gastrinoma, which produces too much of the hormone gastrin, possibly leading to overproduction of stomach acid
• Somatostatinoma, which produces a hormone called somatostatin, which may interfere with the production of other necessary hormones such as insulin
• Insulinoma, which makes excess insulin (this type of tumor may cause low blood sugar due to high levels of insulin, but only 10 percent of insulinomas become cancerous)
• Glucagonomas make too much of the hormone glucagon, which may lead to high blood sugar
• VIPomas may produce too much of a hormone called vasoactive intestinal peptide (VIP), possibly causing chronic, watery diarrhea as it moves more water than necessary into the intestines.

NETs in other parts of the body

Endocrine and nerve cells exist all throughout the body, so NETs can sometimes develop outside of the GI tract, lungs or pancreas.

• Merkel cell carcinoma: A rare type of NET that develops in the Merkel cells on the top layer of the skin. It’s also called neuroendocrine carcinoma of the skin or trabecular cancer. This type of NET often begins in areas of the skin most exposed to sunlight, such as the head, neck and arms.
• Medullary thyroid cancer (MTC): This NET is the rarest form of thyroid cancer. It develops in the thyroid, a small gland on the front of your neck that controls hormone signals throughout the rest of your body. According to the National Cancer Institute, 25 percent of MTC cases may be attributed to a genetic link passed down in families.
• Pheochromocytoma: This is a rare type of adrenal gland NET. One adrenal gland sits on top of each of your two kidneys. These glands produce hormones. Though they typically grow slowly, these tumors may cause surges of the hormones adrenaline and noradrenaline, leading to an increase in blood pressure and heart rate.
• Paraganglioma: This is another very rare type of NET that develops outside the adrenal gland. Because they develop in the abdomen or along nerve pathways in the head, neck, chest, pelvis or bladder, they’re often called extra-adrenal paragangliomas. They may be parasympathetic, meaning they develop within the parasympathetic nervous system that controls the body during times of rest, or they may be sympathetic, meaning they develop within the sympathetic nervous system that controls the body in times of stress or activity. Paragangliomas are most often slow-growing.

Next topic: What are the stages of neuroendocrine tumors?