Neuroendocrine Tumors of the Lung

Neuroendocrine tumors are tumors that begin in cells of the neuroendocrine system. These cells are found in all organs and help control many bodily functions. They receive messages from neurons (nerve cells) and release hormones.

Because neuroendocrine cells exist throughout the body, neuroendocrine tumors can form anywhere. They most commonly form in the gastrointestinal tract.

There are several types of neuroendocrine tumors, including carcinoid tumors. This is a subset of neuroendocrine tumors that are low or intermediate grade.

Because they start in hormone-producing cells, some lung neuroendocrine tumors can make hormone-like substances called neuropeptides and amines. This can lead to a potentially serious condition called carcinoid syndrome.

There are four types of lung neuroendocrine tumors, which are generally classified by:

• tumor cell size and shape
• the size and shape of cell nuclei
• the number of cells dividing in the tumor
• whether there’s necrosis (cell death) in the tumor

The four types of lung neuroendocrine tumors are:

Small-cell lung cancer

Small-cell lung cancer accounts for about 10% to 15% of lung cancers. SCLC is the most common type of lung neuroendocrine tumor.

Not all cases of SCLC have neuroendocrine markers. About 5% to 10% of SCLC tumors are neuroendocrine-negative. But these tumors still behave similarly to neuroendocrine-positive tumors.

SCLC is aggressive, grows quickly, and doesn’t have well-defined borders. By the time doctors diagnose it, SCLC has usually spread beyond the lungs. It usually responds well to initial treatment but often returns later.

Smoking is a major risk factor for this SCLC.

Large cell neuroendocrine lung carcinoma

Large cell neuroendocrine lung carcinoma is a subset of large cell carcinoma that’s similar in many ways to SCLC. It grows and spreads quickly and is difficult to treat. It’s relatively rare, making up about 3% of all lung cancers.

Large cell neuroendocrine lung carcinomas have large, quickly-dividing cells. There’s often necrosis in the tumors, and they can appear in any part of the lung.

Smoking is also a major risk factor for this type of cancer.

Typical carcinoid

Typical carcinoids make up around 1% of lung cancers. Most develop in the major bronchi, which carry air into the lungs.

This type of tumor grows slowly, has well-defined borders, and rarely metastasizes. It usually doesn’t have a lot of cells actively dividing and doesn’t cause necrosis. It’s not linked to smoking or any environmental hazards.

Atypical lung carcinoid

This type of lung cancer is very rare, making up about 0.1% of all lung cancers. It’s more common in smokers, but smoking isn’t as significant a risk factor as it is for other types of lung cancer.

Most atypical carcinoids develop in the major bronchi. They grow more quickly than typical carcinoids but still slower than other types of cancer. These tumors have well-defined borders, have a moderate number of dividing cells, and may or may not feature necrosis.

Common signs and symptoms of a lung neuroendocrine tumor include:

• cough
• bloody phlegm
• chest pain
• wheezing
• pneumonia

In rare cases, neuroendocrine tumors can cause a condition called carcinoid syndrome, which can be the first symptoms of the tumor. Signs of carcinoid syndrome include:

• facial flushing
• diarrhea
• sweating
• shortness of breath
• fast heartbeat
• weakness
• high blood pressure
• heart murmur

Lung neuroendocrine tumors are most common in:

• females
• white people
• people who are 45 to 55 years old

Researchers don’t fully understand the reasons for these, especially as other forms of lung cancer are more common in males and people 65 years and older.

Other risk factors include:

• a family history of lung carcinoid tumors
• multiple endocrine neoplasia type 1
• smoking

Although smoking is still a risk factor, carcinoids are usually not related to smoking.

Diagnosis of neuroendocrine tumors of the lung involves several steps. Your doctor will first diagnose lung cancer and then determine the specific type.

Your doctor will first review your medical history. They’ll ask about your symptoms, when they started, your risk factors for lung cancer, and your family history. They’ll also do a full physical exam.

If your doctor suspects lung cancer, they’ll do a chest X-ray, which is often enough to see a tumor. But if the chest X-ray doesn’t show anything, your doctor might request a CT scan. This can give your doctor more information about the size, shape, and position of a known tumor, and check if your cancer has spread to the lymph nodes.

Several other tests can help your doctor definitively diagnose lung cancer, including sputum cytology, in which your doctor examines your mucus for cancer cells, and a lung biopsy.

If your doctor suspects a neuroendocrine tumor, they’ll use blood and urine tests to look for hormone-like chemicals made by this type of tumor. They’ll also perform pulmonary function tests to see how well your lungs work.

Rarely, your doctor may use PET scans and other radionuclide scans to help diagnose cancer.

Treatment for lung neuroendocrine tumors depends on the stage at which doctors diagnose your cancer and your tumor type. Common treatments include:

• Surgery: Surgery can fully cure most localized lung neuroendocrine tumors, including carcinoids. Doctors can also use surgery in SCLC and more advanced cancer, but it’s unlikely to provide a cure.
• Somatostatin analogs: Doctors can use this medication to help lessen symptoms of neuroendocrine tumors that are making hormones. They may also slow the growth of tumors but won’t shrink them.
• Targeted therapy: Targeted therapy is medication that targets specific parts of cancer cells, such as proteins or genes, that allow the cells to grow. Everolimus (Afinitor) is the only type of targeted therapy FDA-approved to treat lung neuroendocrine tumors. Doctors can use it in advanced cancer to slow tumor growth.
• Chemotherapy: Doctors rarely use chemotherapy to treat carcinoid tumors, but may for SCLC or lung tumors that have spread to other parts of the body.
• Radiation therapy: Doctors often use radiation therapy to treat SCLC. They rarely use it to treat other lung neuroendocrine tumors, but it can help to manage symptoms of cancer that has metastasized.

Researchers are studying other types of treatment for lung neuroendocrine tumors, including other targeted therapies and peptide receptor radionuclide therapy, in clinical trials.

The outlook for lung neuroendocrine tumors varies depending on your specific tumor type.

Typical carcinoid

This type of tumor has a very positive outlook. Both the 5-year and 10-year survival rates are over 90%.

Atypical carcinoid

Atypical carcinoid tumors have a 5-year survival rate of about 70%. The 10-year survival rate is around 50%.

Small-cell lung cancer

The 5-year survival rate for SCLC depends on how far it has spread. But SCLC has a generally poor outlook, with an overall 5-year survival rate of 7%.

The 5-year survival rates are:

• 29% if the tumor is localized
• 18% if it has spread to nearby lymph nodes
• 3% if it has spread to distant parts of the body

Large cell neuroendocrine carcinoma

The 5-year survival rate of large cell neuroendocrine lung carcinoma also depends on your stage at diagnosis. However, because this cancer is hard to diagnose and stage, each stage has a wide range of survival rates:

• Stage 1: 33% to 62%
• Stage 2: 18% to 75%
• Stage 3: 8% to 45%

People who receive a diagnosis of stage 4 large cell neuroendocrine carcinoma are unlikely to survive 5 years after diagnosis.

Keep in mind that survival rates reflect data from previous years. As treatments emerge and improve, survival rates tend to increase. Talk with your doctor about any new information that might improve your outlook.

Lung neuroendocrine tumors are a less common type of lung cancer. SCLC accounts for about three-quarters of all lung neuroendocrine tumors and has a poorer outlook. But some lung neuroendocrine tumors, like carcinoids, are extremely treatable and have higher survival rates.

Because the different types of lung neuroendocrine tumors have different outlooks and treatments, it’s important to get a proper diagnosis.

Talk with your doctor if you have symptoms of lung cancer or hormonal problems, as these can be a sign of a neuroendocrine tumor.