Neuroendocrine tumor

What is a NET?

A neuroendocrine tumor is a malignant neoplasm consisting of neuroendocrine cells that occur throughout the body. There are therefore different types of NET, which in the classic sense include gastrointestinal (in the gastrointestinal tract) and pancreatic (in the pancreas) NET as well as NET of the lungs.

As neuroendocrine cells are mainly found in the gastrointestinal tract and pancreas (stomach, small intestine, appendix, large intestine), NETs are most common here. For this reason, neuroendocrine tumors are also referred to as GEP-NET (= gastroenteropancreatic neuroendocrine tumors). Neuroendocrine tumors also occur in the lungs, thymus, thyroid gland and adrenal gland.

NET – frequency and age

NETs are rare tumors with an incidence of 2.5-5 new cases/100,000 inhabitants worldwide (0.2 % – 5 % of all tumors are NETs). However, the number of registered new cases has been increasing in recent years. One possible reason for this could be improved diagnostic procedures.

A neuroendocrine tumor occurs predominantly in older people (average age at diagnosis 50-60 years), although there are no gender differences. Men and women are therefore equally affected.

NET: Causes and risk factors

At present, it is still largely unknown what causes a neuroendocrine tumor to develop. The hormone-producing cells from which a NET develops can occur almost anywhere in the body. This also makes it difficult to identify risk factors.

As already mentioned, carcinoids are rare. This makes research into the causes even more difficult. Possible connections with environmental influences, viruses or hereditary factors are also difficult to recognize.

In very rare cases, genetic changes can play a role in the development of NET. In this case, we speak of multiple endocrine neoplasia syndrome (MEN 1 syndrome). In the context of MEN 1 syndrome, NETs also frequently occur in younger patients.

Symptoms: NET

In the early stages, NET often causes no symptoms. In about half of all cases, NETs do not produce any hormones that can be detected in the laboratory. NET is therefore often diagnosed relatively late. Unfortunately, by the time the diagnosis is made, more than 50% of cases have spread to other organs (metastasized).

Symptoms often only occur when the tumor grows, presses on neighboring tissue and organs or even displaces them. Depending on the location and the organ affected, NET can lead to the following symptoms:

• Abdominal pain
• Weight loss
• Jaundice
• Shortness of breath
• Coughing fits

If a NET releases large quantities of hormones or hormone-like messenger substances, it is also referred to as a functionally active neuroendocrine tumor (10-30% of all NETs). Depending on the type of hormone released, different symptoms are possible:

• If a neuroendocrine tumor produces the messenger substance serotonin, a carcinoid syndrome can occur. Only if the tumor has already spread to the liver or is primarily located in the lungs does increased serotonin production also lead to symptoms (carcinoid syndrome), as this is otherwise broken down in the liver. Such a carcinoid syndrome occurs in approx. 10 % of all NETs and is often characterized by
  • Paroxysmal reddening of the face (flushing)
  • Abdominal cramp
  • Diarrhea
  • Palpitations
  • Sweating
  • Breathing problems
  • Cardiac complaints, changes in the heart valves (insufficiencies, stenoses) with a long course of the disease

• Excessive insulin production can lead to hypoglycemia with sweaty skin, trembling, irritability and confusion (approx. 6-8% of NET).
• If the carcinoid produces increased gastrin, heartburn, stomach and small intestine ulcers can occur (Zollinger-Ellison syndrome) (approx. 4% of NET).
• If there is an increased release of VIP (= vasoactive intestinal polypeptide), diarrhea and increased urination are possible (< 1% of NET).

NET: Diagnosis with us

As there are usually no symptoms at the beginning of the disease, NET is often only detected late or by chance (see above).

The situation is different, however, if the neuroendocrine tumor produces large quantities of hormones or messenger substances, as described above. This can lead to early symptoms that lead to a suspected diagnosis. Some of these can be detected by examining the blood and urine. If a NET does not produce any hormones, a special tumor marker in the blood, chromogranin A (CgA), provides information about the disease. In carcinoid syndrome, 5-hydroxyindoleacetic acid (5HIES) can be determined as a tumor marker as a degradation product of serotonin in the urine. CgA and 5HIES are also useful progression parameters of the tumor disease in the evaluation of a therapy response.

NET: Imaging procedures

If NET is suspected, we will arrange for imaging procedures such as an ultrasound examination (sonography), computer tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET/CT or PET/MR) with somatostatin analogs or a gastrointestinal endoscopy (endoscopy) to make a definitive diagnosis.

If a carcinoid produces the hormone gastrin (gastrinoma), we can also use somatostatin receptor scintigraphy. In these tumors, binding sites for the messenger substance somatostatin are located on the cell surface. The cells of this tumor can be detected throughout the body.

NET: prevention, early detection, prognosis

You cannot prevent NET. There are also no generally recommended early detection examinations. In very rare cases, neuroendocrine tumors can be traced back to genetic changes. In the case of multiple endocrine neoplasia syndrome (MEN 1 syndrome), affected families are entitled to genetic counseling and regular early detection measures.

Progression and prognosis of NET

The course of the disease depends on various factors such as the type of tumor, its location (gastrointestinal tract versus pancreas) and the stage at which it is discovered. The earlier a NET is discovered and treated, the greater the chances of recovery.

The fact that NETs usually grow slowly also has a favorable effect on the prognosis.

Complications can occur if a NET remains untreated for a long time. In this case, the tumor can spread through the lymphatic and blood vessels in the body and form metastases, for example in the liver or bones. Metastases in the eye socket, in the heart muscle and, in women, in the breast are rarer.

NET in the area of the appendix hardly ever forms metastases and therefore has a very good prognosis.

But even with other types of NET or existing metastases, we can often positively influence the course of the disease for a longer period of time with the help of medication.

If a large NET or metastases displace the surrounding tissue, this can be life-threatening and result in a complete intestinal obstruction (ileus), for example, which must be treated immediately.

There is also a risk of complications if a NET releases large quantities of hormones. If the tumor produces gastrin, for example, gastric ulcers can occur as a result. This can lead to a gastric rupture or severe bleeding.

If a NET produces a lot of serotonin as part of a carcinoid syndrome, this can lead to severe diarrhea, shortness of breath, flushing and, in very severe cases of massive hormone release, a so-called carcinoid crisis with shock symptoms (drop in blood pressure and circulatory weakness). Somatostatin analogs are used as a good treatment option here.

NET: Treatment depending on the stage of the disease

If your doctor diagnoses a neuroendocrine tumor, he or she will arrange a therapy tailored to your individual case, depending on the type of tumor and the stage of the disease.

We discuss your case in our interdisciplinary neuroendocrine tumor board before starting treatment in order to offer you the best possible therapy from the perspective of all the different specialist disciplines involved.