Medullary thyroid carcinomacancer arising from tissues that line organs (MTC) is a rare type of cancera disease where abnormal cells split without control and spread to other nearby body tissue and/or organs that develops in the thyroid, a butterfly-shaped gland located in the neck below the larynx (voice box). The thyroid is responsible for producing the hormones thyroxine (T4) and triiodothyronine (T3), which control important bodily functions such as heart rate, digestion, and body temperature.
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.
MTCs generally develop from C cells (formerly known as parafollicular cells) in the thyroid, which are responsible for the production of the hormonea chemical substance produced by glands in the endocrine system that regulates various functions in the body calcitonin. Calcitonin is responsible for regulating the levels of calcium and potassium in the body.
The average age of diagnosisthe process of identifying a disease based on signs and symptoms, patient history and medical test results for MTC varies by subtype, and is generally diagnosed equally among the sexes. However, anyone can develop this disease.
Types of Medullary Thyroid Carcinoma
There are two primary types of MTC, which are classified by whether they occur sporadically or as a part of a genetic condition.
Sporadic Medullary Thyroid Carcinoma
Sporadic MTC is the most common subtype of this disease, and is not linked to any genetic mutations or syndromes. This subtype is generally diagnosed at an older age (between the ages of 40-60), and often presents as a singular nodule on the thyroid gland. Sporadic MTC is generally less aggressive than FMTC.
Familial Medullary Thyroid Carcinoma
Familial MTC (FMTC) is a less common subtype of disease, and is most commonly associated with the genetic condition multiple endocrine neoplasia syndrome type 2 (MEN2). It has also been associated with Von-Hippel Lindau (VHL) disease and neurofibromatosis type 1 (NF1). FMTC is caused by a mutation of the RET (rearranged during transfection) proto-oncogenea type of gene that normally regulates cell growth and division, but when mutated can cause uncontrollable cell growth and may lead to cancer. FMTC is generally diagnosed at a younger age (often under the age of 18), and often presents bilaterally on the thyroid gland. This type of tumoura tissue mass that forms from groups of unhealthy cells may be more aggressive than sporadic MTC.
Treatment
If a MTC 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 (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 nodessmall bean-shaped structures that filters harmful substances from lymph fluid.
- 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:
- 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 MTCs may include:
- Surgerytreatment involving removal of cancerous tissue and/or tumours and a margin of healthy tissue around it to reduce recurrence, potentially including:
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- Thyroidectomycomplete or partial removal of the thyroid gland.
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- Lymphadenectomysurgical removal of lymph node(s).
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- Neck dissectionsurgical removal of lymph nodes and surrounding tissue in the neck to remove and prevent the spread of cancer cells.
- Watch and waitthe close monitoring of a cancer without giving treatment until symptoms appear or worsen.
- Radiation therapya treatment that uses controlled doses of radiation to damage or kill cancer cells, such as external beam radiation therapy.
- Ablation therapya minimally invasive procedure that uses extremely high or low temperatures to destroy (ablate) abnormal tissue and/or cancer cells, potentially including:
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- Radiofrequency ablation (RFA)a minimally invasive procedure that uses heat to destroy abnormal tissue and/or cancer cells.
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- Cryotherapythe process of freezing off cancerous tumours and/or lesions using liquid nitrogen.
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- Embolisationa treatment that aims to reduce blood flow to the cancer and ultimately reduce cancer growth.
- 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 sporadic MTC remain unknown, FMTC has been linked to mutations in the RET proto-oncogene, and may occur as a result of any of the following conditions:
- Multiple endocrine neoplasia type 2 (MEN2).
- Von-Hippel Lindau disease (VHL).
- Neurofibromatosis type 1 (NF1).
Not everyone with these riskthe possibility that something bad will happen 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
Many people with a MTC may appear asymptomatic in the early stages of disease. As the tumour progresses, some of the following symptoms may appear:
- Painless lump in the neck.
- Difficulty swallowing.
- Dyspneadifficulty breathing, shortness of breath.
- Changes in the voice, such as hoarseness.
- Lymphadenopathyswollen lymph nodes/glands, also known as adenopathy in the neck.
- Excess calcitonin, which carries its own set of symptoms:
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- Diarrhoeafrequent discharge of watery or loose stools from the body.
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- Facial flushing.
- 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 abdomenstomach, stomach area, belly.
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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.
Patients with FMTC may have additional symptoms based on the genetic condition they have. For more information on your individual condition, please refer to the Rare Cancers Australia knowledgebase.
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 MTC, 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.
- Imagingtests that create detailed images of areas inside the body tests, potentially including:
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- Ultrasounda type of medical imaging that uses soundwaves 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, such as to check calcitonin level.
- Biopsy.