Thymic neuroendocrine tumours (NETs), also known as thymic carcinoid tumours, are a rare type of cancer that develop in the thymus gland, which sits in the mediastinum. The thymus gland is a part of the lymphatic system, which is a network of tissues and organs that help our bodies fight infection and disease.
The thymus gland is responsible for the production and maturation of T lymphocytes, a type of white blood cell that regulates the body’s immune response and helps protect the body from pathogens. Once developed, the T lymphocytes travel to the lymph nodessmall bean-shaped structures that filters harmful substances from lymph fluid in the body, which filter out damaged and potentially harmful cells.
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, blood pressure and metabolism. They most commonly develop in the gastro-intestinal tract, pancreas, and the lungs; however, they can develop anywhere in the body. These tumours develop from neuroendocrine cells, which are responsible for receiving signals from the nervous system and producing hormones and peptides (small proteins) in response.
Thymic NETs are more common in males, and tend to be diagnosed between the ages of 40-60. However, anyone can develop this disease.
Types of Thymic Neuroendocrine Tumours
Because of how rare thymic NETs are, there has been limited research done into the types of this disease. However, some distinct subtypes have been identified.
Neuroendocrine Carcinomas of the Thymus Gland
Neuroendocrine carcinomas of the thymus gland are a rare type of cancer that are characterised by abnormal looking cancer cells under the microscope. There are two primary subtypes of this disease.
Small Cell Carcinoma of the Thymus Gland
Small cell thymic NETs are a very rare form of cancer that is often classified as a type of extrapulmonary small cell lung cancer, as the cells present are identical under a microscope. Unfortunately, small cell thymic neuroendocrine carcinomas are often aggressive, and may not have as good of a prognosisto predict how a disease/condition may progress and what the outcome might be as other types of thymus gland cancers.
Large Cell Carcinoma of the Thymus Gland
Large cell thymic NETs are a very rare form of cancer that is often associated with large cell undifferentiated carcinomacancer arising from tissues that line organs of the lungs. Unfortunately, large cell thymic neuroendocrine carcinomas are often aggressive, and may not have as good of a prognosis as other types of thymus gland cancers.
Typical Carcinoid Tumour of the Thymus Gland
Typical carcinoid tumours of the thymus gland are a less common type of thymic NET that are generally classified as grade one (slow growing) neuroendocrine tumours. These tumours are less common than atypical carcinoid tumours of the thymus gland, and can have a good prognosis when caught early.
Atypical Carcinoid Tumour of the Thymus Gland
Atypical carcinoid tumours of the thymus gland are a more common type of thymic NET that are generally more aggressive than typical carcinoid tumours of the thymus gland. This subtype is more likely to metastasise, and may not have as good of a prognosis as other types of thymus gland cancers.
Treatment
If a thymic NET is detected, it will be staged and graded based on size, metastasis, and how the cancer cells look under the microscope. Staging 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 (node) 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 localised 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:
- Grade 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 thymic NETs may include:
- Surgery, potentially including:
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- Thymectomycomplete or partial removal of the thymus gland.
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- Lymphadenectomysurgical removal of lymph node(s).
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- Tumour debulkingremoval of as much of the tumour as possible when complete tumour removal is not possible, also known as cytoreduction.
- Radiation therapya treatment that uses controlled doses of radiation to damage or kill cancer cells, potentially including peptide receptor radionuclide therapy (PRRT)a targeted cancer treatment that uses radioactive substances (radionuclides) to deliver radiation directly to tumour cells.
- Chemotherapya cancer treatment that uses drugs to kill or slow the growth of cancer cells, while minimising damage to healthy cells.
- Somatostatin analogues (SSAs)medication used to inhibit excessive hormone production.
- 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
Because of how rare thymic NETs are, there has been little research done into the risk factors of this disease. However, there may be a potential link to the development of this disease and people with the genetic condition multiple endocrine neoplasia type 1 (MEN1).
Symptoms
Some patients with thymic NETs will appear asymptomatic in the early stages of disease. As the tumour progresses, some of the following symptoms may appear:
- Dyspnea.
- Persistent cough.
- Chest discomfort and/or pain.
- Hoarseness of the voice.
- Difficulty swallowing.
- Superior vena cava syndrome (caused by tumour pressing on the superior vena cava vessel), which carries its own set of symptoms:
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- Swelling of the face, neck, and/or upper chest.
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- A bluish complexion from the upper chest up.
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- Swelling of visible veins from the upper chest up.
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- Headaches.
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- Dizziness.
- Unexplained weight loss and/or loss of appetite.
- Carcinoid syndrome (rare), 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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- Diarrhoea.
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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 hormone production).
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- Faecal urgency.
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- Fatigue.
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- Skin changes, such as red or purple spots on the face, neck, and/or upper chest.
- Excess adrenocorticotropic hormone (ACTH) (Cushing’s syndrome), which carries its own set of symptoms:
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- Unexplained weight gain (particularly in face, chest and abdominal areas).
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- Exaggerated facial roundness.
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- Thinning of arms and legs with muscle weakness.
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- Pink or purple stretch marks on the chest and/or abdomen.
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- Easy bruising.
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- New or increased hair growth.
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- Acne.
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- Hyperglycaemiahigh blood sugar.
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- Hypertensionhigh blood pressure.
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- Weakening of bones, which may cause osteoporosis or easily broken bones.
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- Anxiety, irritability and/or depression.
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- Difficulties concentrating.
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- Delayed growth in children.
- Excess growth hormone (acromegaly), which carries its own set of symptoms:
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- Growth of skull, hands and feet. This may cause an increase in hat, shoe, glove and/or ring size.
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- Changes in vision and/or voice.
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- Changes in facial appearance (such as wider spacing of teeth and/or jawbone growth).
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- Joint pain.
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- Increased sweating.
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- Hyperglycaemia.
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- Kidney stones.
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- Heart disease.
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- Tingling and/or numbness in the hands and fingers.
- Paraneoplastic syndromesa group of rare disorders that occur when the immune system has a reaction to a cancerous tumour within the body.
- Hypercalcaemiaexcess levels of calcium in the blood.
- Hypophosphatemialow levels of phosphate in the blood.
- Hyponatraemialow levels of sodium in the blood.
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 thymic NET, they may order the following tests to confirm the diagnosis and refer you to a specialist for treatment:
- Physical examinationan examination of your current symptoms, affected area(s) and overall medical history.
- Imaging tests, potentially including:
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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.
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- Chest X-raya type of medical imaging that uses x-ray beams to create detailed images of the body .
- Blood teststesting done to measure the levels of certain substances in the blood.
- Exploratory surgerya surgical procedure used for conditions that cannot be confirmed by scans and tests alone.
- Biopsy.