Thymic Neuroendocrine Tumours

Thymic neuroendocrine tumours (NETs), also known as thymic carcinoid tumours, are a rare type of cancera disease where abnormal cells split without control and spread to other nearby body tissue and/or organs that develop in the thymus gland, which sits in the mediastinumthe space between the lungs that holds many important structures, including the heart, trachea and oesophagus. The thymus gland is a part of the lymphatic systema network of tissues and organs that help our bodies fight infection and disease, which is a network of tissues and organs that help our bodies fight infectiona condition where harmful pathogens, such as bacteria, viruses or parasites, have entered the body and disease.

The thymus gland is responsible for the production and maturation of T lymphocytes, a type of white bloodthe red bodily fluid that transports oxygen and other nutrients around the body cell that regulates the body’s immune response and helps protect the body from pathogensany substance or organism that has the potential to cause disease (e.g. bacteria, viruses, fungi, parasites etc.). 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 cellsthe basic structural and functional unit of all living things.

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, 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 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 gradea description of how abnormal cancer cells and tissue look under a microscope when compared to healthy cells 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, metastasiswhen the cancer has spread to other parts of the body, also known as mets, 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 (tumoura tissue mass that forms from groups of unhealthy cells) 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 tissuea group of cells that work together to perform a function.

• 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:

• 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:

• Surgerytreatment involving removal of cancerous tissue and/or tumours and a margin of healthy tissue around it to reduce recurrence, potentially including:

• • Thymectomycomplete or partial removal of the thymus gland.

• • Lymphadenectomysurgical removal of lymph node(s).

• • 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 riskthe possibility that something bad will happen 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:

• Dyspneadifficulty breathing, shortness of breath.

• 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 vessela tube that carries bodily fluid, such as blood or lymph fluid, around the body), which carries its own set of symptoms:

• • Swelling of the face, neck, and/or upper chest.

• • A bluish complexion from the upper chest up.

• • Swelling of visible veins from the upper chest up.

• • Headaches.

• • Dizziness.

• Unexplained weight loss and/or loss of appetite.

• Carcinoid syndrome (rare), which carries its own set of symptoms:

• • Facial flushing (usually red or purple in the face, neck, and/or upper chest).

• • Diarrhoeafrequent discharge of watery or loose stools from the body.

• • Wheezing.

• • Abdominal pain.

• • 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).

• • Faecal urgency.

• • Fatiguea state of extreme tiredness or exhaustion, can be physical or mental.

• • 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:

• • Unexplained weight gain (particularly in face, chest and abdominal areas).

• • Exaggerated facial roundness.

• • Thinning of arms and legs with muscle weakness.

• • Pink or purple stretch marks on the chest and/or abdomenstomach, stomach area, belly.

• • Easy bruising.

• • New or increased hair growth.

• • Acne.

• • Hyperglycaemiahigh blood sugar.

• • Hypertensionhigh blood pressure.

• • Weakening of bones, which may cause osteoporosis or easily broken bones.

• • Anxiety, irritability and/or depression.

• • Difficulties concentrating.

• • Delayed growth in children.

• Excess growth hormone (acromegaly), which carries its own set of symptoms:

• • Growth of skull, hands and feet. This may cause an increase in hat, shoe, glove and/or ring size.

• • Changes in vision and/or voice.

• • Changes in facial appearance (such as wider spacing of teeth and/or jawbone growth).

• • Joint pain.

• • Increased sweating.

• • Hyperglycaemia.

• • Kidneya pair of bean-shaped organs in the abdomen that are responsible for filtering excess water and waste products from the blood and converting them into urine to be removed from the body stones.

• • Heart disease.

• • 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 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:

• • 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.

• • CT (computed tomography) scana type of medical imaging that uses x-rays and computer technology to create detailed images of the body.

• • PET (positron emission tomography) scana type of medical imaging that uses radioactive tracers to create detailed images of the body.

• • 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 surgeryan exploratory surgical procedure used for conditions that cannot be confirmed by scans and tests alone.

• Biopsy.

References

• Neuroendocrine Cancer UK
• Pathology Outlines
• Radiopaedia
• UpToDate