Lung neuroendocrine tumours (NETS), also known as bronchopulmonary NETS, pulmonary NETs or lung carcinoid tumours, are a group of neuroendocrine tumours that develop in within the lungs, which are the primary organs of our respiratory system and allow us to breathe. The lungs are a pair of cone-shaped organs that are located under our ribcage.
The respiratory system is composed of the nose, mouth, tracheathe tube that connects your voicebox (larynx) to the lungs, also known as a windpipe (windpipe) and airways (bronchi and bronchioles) that lead to the lungs, which is where the breathing process primarily occurs. Each lung is made up of lobes, with the right lung being composed of three lobes and the left only having two lobes to accommodate room for the heart. The lungs sit on top of a muscle called the diaphragm, which separates the abdomenstomach, stomach area, belly from the chest. The diaphragm works by contracting/flattening when we inhale, pulling air into the lungs. When we exhale, the diaphragm relaxes and pushes air out of the lungs. The space between the lungs is called the mediastinumthe space between the lungs that holds many important structures, including the heart, trachea and oesophagus, and holds several important structures, including the heart, trachea, oesophagus and lymph nodessmall bean-shaped structures that filters harmful substances from lymph fluid. Each lung is covered by a layer of tissuea group of cells that work together to perform a function called the pleuraa thin layer of tissue covering the lungs and the wall of the interior chest cavity.
Neuroendocrine cancers are a complex group of tumours that develop in the neuroendocrine system, which is responsible for regulating important bodily functions such as heart rate, bloodthe red bodily fluid that transports oxygen and other nutrients around the body pressure and metabolism. They most commonly develop in the gastro-intestinal tract, pancreasa long, flat organ that sits between the stomach and the spine that plays a key role in digestion and blood sugar regulation, and the lungs; however, they can develop anywhere in the body. These tumours develop from neuroendocrine cellsthe basic structural and functional unit of all living things, which are responsible for receiving signals from the nervous system and producing hormones and peptides (small proteins) in response.
Lung NETs are slightly more common in males, and tend to be diagnosed between the ages of 40-60. However, anyone can develop this disease.
Types of Lung NETs
There are four primary types of lung NETs, including typical carcinoid lung NETS, atypical lung NETS, small cell carcinomacancer arising from tissues that line organs and large cell neuroendocrine carcinoma. Lung NETs are categorised based on cell type and tumoura tissue mass that forms from groups of unhealthy cells behaviour.
Carcinoid Lung NETs
Typical Lung NETs
Typical carcinoid lung NETs are the most common form of lung NETs, and rarely spread beyond the lungs. They have not been linked to smoking, are generally slow growing, and can have a good prognosisto predict how a disease/condition may progress and what the outcome might be when caught early.
Atypical Carcinoid Lung NETs
Atypical carcinoid lung NETs are a less common form of lung NET that can be more aggressive than typical carcinoid lung NETs. They have also not been linked to smoking, however they have a higher riskthe possibility that something bad will happen of metastasiswhen the cancer has spread to other parts of the body, also known as mets than typical carcinoid lung NETs. Atypical carcinoid lung NETs can have a good prognosis when found early.
Diffuse Idiopathic Pulmonary Neuroendocrine Cell Hyperplasia (DIPNECH)
Diffuse intrapulmonary neuroendocrine cell hyperplasia (DIPNECH) is a rare and poorly understood condition that occurs when neuroendocrine cells of the lungs start to grow uncontrollably. It is thought to be a precursor to the development of typical and atypical carcinoid lung NETs.
Small Cell Carcinoma
Small cell lung cancera disease where abnormal cells split without control and spread to other nearby body tissue and/or organs (SCLC), or oat cell carcinoma, is the less common type of lung NET that generally starts in the bronchi of the lungs. SCLC has been linked to smoking, are generally diagnosed at a later stage of disease, and may not have as good of a prognosis as other types of lung NETs.
Large Cell Neuroendocrine Carcinoma
Large cell neuroendocrine carcinomas are the rarest form of lung NET that generally originates from the bronchi of the lungs. It has features of both small cell lung cancer and non-small cell lung cancer, and has been linked to smoking. Large cell neuroendocrine carcinomas can be aggressive, are likely to metastasise, and may not have as good of a prognosis as other types of lung NETs.
Treatment
If a lung NET is detected, it will be staged and graded based on size, metastasis, and how the cancer cells look under the microscope. Stagingthe process of determining how big the cancer is, where it started and if it has spread to other areas and grading helps your doctors determine the best treatment for you.
Cancers can be staged using the TNM staging system:
- T (tumour) indicates the size and depth of the tumour.
- N (nodea small lump or mass of tissue in your body) indicates whether the cancer has spread to nearby lymph nodes.
- M (metastasis) indicates whether the cancer has spread to other parts of the body.
This system can also be used in combination with a numerical value, from stage 0-IV:
- Stage 0: this stage describes cancer cells in the place of origin (or ‘in situ’) that have not spread to nearby tissue.
- Stage I: cancer cells have begun to spread to nearby tissue. It is not deeply embedded into nearby tissue and had not spread to lymph nodes. This stage is also known as early-stage cancer.
- Stage II: cancer cells have grown deeper into nearby tissue. Lymph nodes may or may not be affected. This is also known as localisedaffecting only one area of body cancer.
- Stage III: the cancer has become larger and has grown deeper into nearby tissue. Lymph nodes are generally affected at this stage. This is also known as localised cancer.
- Stage IV: the cancer has spread to other tissues and organs in the body. This is also known as advancedat a late stage, far along or metastatic cancer.
Cancers can also be graded based on the rate of growth and how likely they are to spread:
- Gradea description of how abnormal cancer cells and tissue look under a microscope when compared to healthy cells I: cancer cells present as slightly abnormal and are usually slow growing. This is also known as a low-grade tumour.
- Grade II: cancer cells present as abnormal and grow faster than grade-I tumours. This is also known as an intermediate-grade tumour.
- Grade III: cancer cells present as very abnormal and grow quickly. This is also known as a high-grade tumour.
Once your tumour has been staged and graded, your doctor may recommend genetic testinga procedure that analyses DNA to identify changes in genes, chromosomes and proteins, which can be used to analyse tumour DNA to help determine which treatment has the greatest chance of success, which analyses your tumour DNA and can help determine which treatment has the greatest chance of success. This is often performed after a biopsyremoval of a section of tissue to analyse for cancer cells, and can help guide treatment options for you.
Treatment is dependent on several factors, including location, stage of disease and overall health.
Treatment options for lung NETs may include:
- Surgerytreatment involving removal of cancerous tissue and/or tumours and a margin of healthy tissue around it to reduce recurrence to remove as much of the tumour(s) as possible.
- Chemotherapya cancer treatment that uses drugs to kill or slow the growth of cancer cells, while minimising damage to healthy cells.
- Radiation therapya treatment that uses controlled doses of radiation to damage or kill cancer cells.
- Targeted therapymedication that targets specific molecular features of cancer cells.
- Hormone therapymedication that alters the levels of certain hormones in the body, such as oestrogen and progesterone, potentially including somatostatin analogues.
- Immunotherapya treatment that uses a person's immune system to fight cancer.
- Cryotherapythe process of freezing off cancerous tumours and/or lesions using liquid nitrogen.
- Watch and waitthe close monitoring of a cancer without giving treatment until symptoms appear or worsen (for early stage and slow-growing cancers).
- Clinical trialsresearch studies performed to test new treatments, tests or procedures and evaluate their effectiveness on various diseases.
- Palliative carea variety of practices and exercises used to provide pain relief and improve quality of life without curing the disease.
Risk factors
While the cause of lung NETs remains unknown, some of the following factors may increase the risk of disease.
- Genetic syndromes, such as multiple endocrine neoplasia syndrome type 1 (MENS1).
- History of smoking.
Not everyone with these risk factors will develop the disease, and some people who have the disease may have none of these risk factors. See your general practitioner (GP) if you are concerned.
Symptoms
Some patients with lung NETs will appear asymptomatic in the early stages of disease. As the tumour progresses, some of the following symptoms may appear.
- Carcinoid syndrome, which carries its own set of symptoms:
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- Facial flushing (usually red or purple in the face, neck, and/or upper chest).
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- Diarrhoeafrequent discharge of watery or loose stools from the body.
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- Wheezing.
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- Abdominal pain.
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- Carcinoid heart disease (plaques on the heart muscle caused by excess hormonea chemical substance produced by glands in the endocrine system that regulates various functions in the body production).
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- Faecal urgency.
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- Fatiguea state of extreme tiredness or exhaustion, can be physical or mental.
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- Skin changes, such as red or purple spots on the face, neck, and/or upper chest.
- Persistent cough.
- Wheezing.
- Breathlessness or difficulties breathing.
- Chest pain.
- Coughing or spitting up blood.
- Persistent chest infections.
- Fatigue.
- General weakness.
- Unexplained weight loss/loss of appetite.
Not everyone with the symptoms above will have cancer, but see your general practitioner (GP) if you are concerned.
Diagnosis
If your doctor suspects you have a lung NET, they may order the following tests to confirm the diagnosisthe process of identifying a disease based on signs and symptoms, patient history and medical test results and refer you to a specialist for treatment:
- Physical examinationan examination of your current symptoms, affected area(s) and overall medical history.
- Imagingtests that create detailed images of areas inside the body tests, potentially including:
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- Chest X-raya type of medical imaging that uses x-ray beams to create detailed images of the body .
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- MRI (magnetic resonance imaging)a type of medical imaging that uses radiowaves, a strong magnet and computer technology to create detailed images of the body.
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- CT (computed tomography) scana type of medical imaging that uses x-rays and computer technology to create detailed images of the body.
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- PET (positron emission tomography) scana type of medical imaging that uses radioactive tracers to create detailed images of the body.
- Blood teststesting done to measure the levels of certain substances in the blood.
- Bronchoscopyan examination of the trachea and lungs with a small, flexible instrument known as a bronchoscope.
- Biopsy.