Types of Neuroendocrine Cancer
Neuroendocrine tumors are rare and can be found in most organs, including the lungs and pancreas. They are more common in people aged 50 to 60 years old. There is no way to prevent the disease as its cause is unknown. Learn more.
What are neuroendocrine tumors?
Neuroendocrine tumors (NETs) are rare types of cancer that originate in the cells of the neuroendocrine system. These cells are spread throughout the body and are found in most organs, including the gastrointestinal tract, pancreas, thyroid, and lungs.
Neuroendocrine cells are like nerve cells, but they also produce hormones, like the cells of the endocrine system.
When neuroendocrine cells change and do not grow or function normally, they can lead to the formation of neuroendocrine tumors. Some are detected and treated quickly, while others can spread to other parts of the body. They can grow slowly (indolent) or rapidly (aggressive).
With an incidence of seven in every 100,000 people, neuroendocrine tumors are more common in men and women aged 50 to 60 years old.
Subtypes of neuroendocrine tumors
Firstly, it’s important to highlight that neuroendocrine tumors that produce hormonal symptoms are called “functioning,” while those that are asymptomatic regarding hormonal symptoms are called “non-functioning.”
There are three main types of neuroendocrine tumors. They are:
Gastrointestinal neuroendocrine tumors (GI NETs) – this is the most common type. As the name suggests, these tumors are found in the gastrointestinal tract, developing in organs such as the small intestine, rectum, stomach, colon, esophagus, and appendix. Most are indolent, meaning they progress slowly. The most common are in the small intestine and primarily release serotonin when they metastasize to the liver.
GI NETs are subdivided into two categories, related to comparison with normal cells:
- Well-differentiated GI NETs: composed of cells that look and act like normal cells. They can be either indolent or aggressive; they are classified as grade 1 and 2 tumors in the most indolent cases, and grade 3 in cases of faster growth with higher proliferation rates;
- Poorly differentiated GI neuroendocrine carcinomas: aggressive tumors composed of very abnormal cells, they have a behavior and treatment completely different from other tumors.
Neuroendocrine lung tumors – accounting for a quarter of NETs, they develop in the lungs or airways, often in the bronchi. There are four subtypes of lung NETs:
- Typical carcinoid tumors: they are indolent and have cells that look and act like normal cells;
- Atypical carcinoid tumors: they are similar to typical carcinoids but have a greater ability to spread to other parts of the body;
- Large cell and small cell neuroendocrine lung carcinomas: they are composed of very abnormal cells, tend to be aggressive, and spread to other parts of the body more quickly;
- Pancreatic neuroendocrine tumors: these tumors closely resemble the pancreatic islets (a group of cells in the pancreas that produce the hormones glucagon, insulin, and somatostatin). They are subdivided into two groups: functional pancreatic neuroendocrine tumors and non-functional pancreatic neuroendocrine tumors. They may release hormone but do not cause a syndrome associated with it.
Other rare NETs include those that originate in or affect:
- Thyroid gland – medullary thyroid tumors;
- Skin – Merkel cell carcinoma;
- Adrenal glands – pheochromocytoma;
- Thymus;
- Other organs, such as breasts, prostate, and kidneys.
In approximately 10% of cases, it is not possible to determine where the NET originated. When this happens, it is called carcinoma of unknown primary origin (CUP).
Symptoms and signs of neuroendocrine tumors
Neuroendocrine cancer can be asymptomatic when indolent. Symptoms and signs tend to appear when tumors are aggressive and functional, and they vary according to the subtype of the disease.
Symptoms of gastrointestinal neuroendocrine tumors:
- Abdominal discomfort or pain;
- Sudden hot flashes with facial flushing;
- Chronic diarrhea;
- Rectal bleeding or blood in stool;
- Anemia and fatigue;
- Heartburn or indigestion;
- Stomach ulcers, causing heartburn, indigestion, and chest or abdominal pain;
- Unexplained weight loss;
Symptoms of pulmonary neuroendocrine tumors:
- Persistent cough;
- Asthma attacks;
- Coughing up blood;
- Difficulty breathing;
- Fatigue;
- Pneumonias.
Symptoms of pancreatic neuroendocrine tumors:
- Hypoglycemia, which can cause sweating, tremors, dizziness, excessive hunger, and lack of concentration;
- Hyperglycemia, which can cause excessive thirst, frequent urination, and diarrhea;
- Stomach ulcers, causing heartburn, indigestion, and chest or abdominal pain;
- Unexplained weight loss;
- Reddish spots, sometimes causing itching and pain in the skin;
- Jaundice;
- Chronic, difficult-to-control diarrhea, which can lead to dehydration.
Diagnosis of Neuroendocrine Tumors
Due to their symptoms being very similar to those of other diseases, neuroendocrine tumors can be diagnosed late, sometimes months or even years after the onset of symptoms. It is not uncommon for patients to be told by doctors that what they are experiencing is related to Irritable Bowel Syndrome, gastritis, asthma, hypertension, or even menopause.
An accurate diagnosis is made by a doctor who is aware of the existence of neuroendocrine tumors. When suspecting the presence of the disease, tests such as:
- Physical examination and personal and family medical history;
- Biopsy (removal of a tissue sample from the suspected tumor site for analysis);
- Blood and urine tests;
- Imaging tests such as ultrasound, computed tomography (CT) scan, digestive endoscopy, endoscopic ultrasound, echocardiogram, and nuclear magnetic resonance imaging (MRI) (to look for clues of a medical condition in the body that may lead to tumors);
- Scintigraphy with octreotide or MIBG, PET CT (positron emission tomography) with somatostatin analogs (specific tests for cases already diagnosed with NET);
- Staging tests such as bone scintigraphy and CT scans (to determine where the NETs originated and if they have spread throughout the body);
- Additional tests such as bronchoscopy and pulmonary function tests (to confirm other suspicions related to NETs).
Treatment for Neuroendocrine Tumors
Treatment for neuroendocrine tumors depends on several factors, such as:
- Where the cancer originated;
- If the disease has spread throughout the body and where in the body;
- The characteristics of the disease (indolent or aggressive, functional or non-functional);
- Other health conditions of the patient.
- In most cases, surgery is the first choice of treatment. To alleviate symptoms and/or control tumor growth, specific medical treatments such as radiotherapy and chemotherapy are used.
If it is possible to completely remove the tumor with surgery, there may be no need for further treatment. Even if the tumor has spread (metastasized), surgery can still remove part of the tumor and any other secondary tumors – this is called tumor cytoreduction.
In cases where NETs are blocking an organ, such as the intestine, surgery may be helpful in relieving the blockage.
The most commonly used treatment for well-differentiated neuroendocrine tumors is somatostatin analogs, through an intramuscular or subcutaneous injection of a class of non-cytotoxic drugs, different from conventional chemotherapy. These drugs control both symptoms related to functional syndromes and the growth of tumor cells.
Radiotherapy is rarely used in treatments for NETs, but it can be used, for example, in some cases of controlling bone metastases.
Chemotherapy uses drugs applied to the bloodstream to destroy cancer cells, usually by interrupting the cancer cell’s ability to grow and divide. It can be used in cases of more aggressive or rapidly growing tumors with associated symptoms.
Immunotherapy is still being investigated for its role in combating NETs, but it already shows efficacy data in more aggressive subtypes.
Prevention of neuroendocrine cancer
Since the causes of neuroendocrine tumors are unknown, it’s not possible to take preventive actions against them.
However, in some rare cases, NETs may be associated with the following rare familial syndromes:
- Multiple endocrine neoplasia type 1 (MEN1);
- Neurofibromatosis type 1;
- Von Hippel-Lindau syndrome (VHL).
Keeping these conditions under control may help minimize the risk of developing neuroendocrine tumors.
