Medullary Thyroid Cancer

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What is Medullary Thyroid Cancer?

Medullary thyroid carcinoma (MTC) is a special type of thyroid cancer distinct from differentiated thyroid cancers. This cancer starts in the parafollicular C cells of the thyroid gland. These cells make a hormone called calcitonin. Calcitonin is not made from iodine unlike other thyroid hormones.

MTC is very rare in children. Most often, pediatric MTC is associated with a genetic predisposition: familial MTC or type 2 multiple endocrine neoplasias (MEN syndromes).

Graphic of an adult female body with layover of organs visible and the thyroid gland is highlighted and labeled. — The thyroid gland is a butterfly-shaped organ located at the base of the throat in the front of the neck. It is arranged in two lobes, one on the right side and one on the left side.

Risk Factors and Causes of Medullary Thyroid Cancer

Hereditary or familial MTC is caused by a germline mutation of the RET gene. RET gene mutations can also lead to multiple endocrine neoplasia (MEN). These conditions affect the endocrine system and may include pheochromocytoma and hyperparathyroidism. The specific type of mutation can influence the management of MTC and related health conditions. Family members of patients with RET mutations should receive genetic counseling and testing.

Signs and Symptoms of Medullary Thyroid Cancer

The main symptom of thyroid cancer is a nodule, or lump, in the thyroid gland. Sometimes, lymph nodes in the neck will appear swollen. Other possible symptoms include problems breathing, difficulty or pain swallowing, and hoarseness. However, often thyroid cancer does not cause any symptoms and may be found as part of a routine exam.

In children, medullary thyroid cancer is most often seen as part of a genetic syndrome. In certain cases, the thyroid gland may be removed before there are any signs of cancer as a way to prevent MTC.

Diagnosis of Medullary Thyroid Cancer

Doctors test for thyroid cancer in several ways. These tests include:

A health history and physical exam helps doctors learn about symptoms, general health, past illness, and risk factors. Family history is important to find out whether there may be an inherited risk. With certain forms of thyroid cancer, genetic testing and genetic counseling is recommended for the child and family. Doctors will test for certain gene changes (RET mutation) that increase risk for cancer.
Lab studies will look at substances in the blood that give information about the thyroid and tumor (tumor markers).
- Calcitonin, a hormone produced by the thyroid gland. It helps regulate the building of bone. Calcitonin may be higher in medullary thyroid cancer.
- Carcinoembryonic antigen (CEA), a protein which is normally very low in the blood. Higher levels of CEA may be seen in medullary thyroid cancer.
Imaging tests help identify the tumor, see how big the tumor is, and find out if it has spread to other places.
- Ultrasound uses sound waves to create an image of the organs and tissues within the body. A neck ultrasound is often one of the main tests doctors use to see if there is a tumor in the thyroid gland. Imaging of both sides of the neck is used to check for abnormally enlarged lymph glands. A high quality ultrasound by an experienced sonographer is important for evaluation of thyroid nodules and neck lymph glands. This information will be used to plan the next steps for diagnosis and treatment. Many times, the neck and thyroid ultrasound is the main imaging used prior to surgery.
In some circumstances for patients with signs/symptoms of advanced disease that has spread beyond the thyroid gland, additional imaging may include:
- Computed tomography (CT scan) uses X-rays to create cross-sectional images of the organs and tissues inside the body. The machine takes many pictures to make a very detailed image. The images are taken as a series of “slices” of the body and are saved to a computer. These slices or sections can allow very small tumors to be seen. In more advanced cases, a CT scan can help doctors get a better view of the tumor and plan treatment. A CT scan may be used to look for spread of the cancer to the lungs or liver.
- Magnetic resonance imaging (MRI) makes detailed pictures of the neck using radio waves and magnets. In advanced disease, MRI of the liver and axial skeleton may be used to look for metastases.
- A bone scan, also called nuclear bone scintigraphy, uses a special scanner to take pictures of the bones. In this test, the patient receives an injection with small amount of radioactive material, or tracer, which travels throughout the body in the blood. After the tracer is absorbed by the bones, the scanner detects radiation to create images. The tracer highlights places in the bones where cells divide quickly and can show areas where cancer has spread.
Biopsy of the some of the tissue from the tumor to check for signs of cancer in the cells and learn more about the histology. Ultrasound guided fine needle aspiration allows doctors to take a sample of thyroid tissue using a thin needle inserted through the skin. A pathologist looks at the tissue samples using a microscope to see if there are cancer cells. The way cells look under a microscope is important to make a diagnosis.

Staging of Medullary Thyroid Cancer

The stage, or extent of disease, of medullary thyroid cancer depends on the size of the tumor and whether the cancer has spread to lymph nodes or other parts of the body.

Stage	Extent of disease
Stage 1	Tumor is 2 centimeters or less across and limited to the thyroid. There is no spread of disease.
Stage 2	Tumor is larger than 2 centimeters across. It is primarily limited to the thyroid with no spread to lymph nodes or other sites.
Stage 3	The tumor may have grown slightly outside the thryoid gland, and there is spread of disease to nearby lymph nodes in the neck.
Stage 4	There is evidence of morderate or advanced disease. The tumor has spread beyond the thyroid into other tissue; there is spread to regional lymph nodes; and/or the tumor has spread to distant sites.

Prognosis for Medullary Thyroid Cancer

In children with known predisposition to have MTC, a major goal is to plan for safe removal of the thyroid before MTC develops, and particularly before distant spread of MTC. Prognosis is related to the extent (stage) of disease.

Factors that influence prognosis include:

Stage of disease at diagnosis.
Extent of initial surgery.
Whether the disease has spread to other places such as the lungs or bones.
Gene mutations or hereditary factors that increase risk for other cancers.
Calcitonin levels after surgery.

Treatment of Medullary Thyroid Cancer

A multidisciplinary team is needed for the evaluation and treatment of medullary thyroid cancer (MTC). Care decisions are focused on survival while lowering risk of continued disease and unwanted treatment effects. Because of the risk of recurrence and other considerations (e.g., hormone function, secondary cancers, genetic predisposition), long-term follow-up is needed for all patients. Total thyroidectomy to remove the thyroid gland is the recommended treatment for MTC. Unlike differentiated thyroid cancers, medullary thyroid cancer does not take up iodine. Therefore, radioactive iodine is not used for imaging and treatment of MTC. After surgery to remove the thyroid, patients need lifelong thyroid hormone replacement medication (levothyroxine). TSH is monitored and maintained in normal range. TSH suppression is not needed in medullary thyroid cancer.

Surgery

Surgery to remove the thyroid gland (thyroidectomy) is the main treatment for medullary thyroid cancer. A total thyroidectomy is recommended. Complete removal of the thyroid helps to lower the risk of metastasis or continued disease. Neck dissection to remove lymph nodes and other tissues may also be performed to reduce the risk of recurrence. Assessment and care by a multidisciplinary pediatric team is important including a surgeon who is experienced in thyroid cancer surgeries.

Preventive Surgery for MEN Syndromes
The best chance of treating MTC is to prevent it from spreading. A prophylactic thyroidectomy is recommended for children with known genetic mutations. This means that the thyroid gland is surgically removed before cancer is detected because of the high risk of developing cancer. For children with a MEN2A mutation, prophylactic thyroidectomy is recommended before 5 years of age. Children with a MEN2B mutation should have a thyroidectomy before 1 year of age. MTC in patients with the MEN2B mutation has an early onset and is very aggressive.

Thyroidectomy should be done by an experienced surgeon who regularly performs these procedures on pediatric patients. Treatment guidelines recommend that surgery be performed by a high-volume thyroid surgeon who does at least 30 similar procedures each year. This reduces the risk of surgical complications. Risks of surgery include damage to structures in the neck region such as nerves and parathyroid glands.

Surgical Removal of Lymph Nodes in Thyroid Cancer

Surgery to remove lymph nodes in the neck is called neck dissection. Central neck dissections are typically done when the primary thyroid tumor is larger than 4 cm or when the tumor has spread beyond the tissue that covers the thyroid gland (thyroid capsule).

Lateral neck dissections are most often done when the thyroid cancer has spread to the lymph nodes in the neck. Both types of neck dissections involve removing the lymph nodes that are most likely to communicate with the thyroid gland and are most likely to contain cancer cells which have spread.

Risks of Surgery

Each individual has 4 parathyroid glands, which are very small structures located behind the thyroid and are responsible of maintaining normal levels of calcium in the body. Even in the absence of surgical damage, the parathyroid glands frequently get “stunned” after thyroidectomy; affected patients experience symptoms of low calcium (or hypocalcemia) including numbness and tingling in the hands, feet, and face and muscle cramps. Treatment requires the use of a potent form of vitamin D (calcitriol) and calcium supplementation until the resolution of this condition (“Transient post-surgical hypo-parathyroidism”). When the parathyroid glands are removed or permanently damaged, hypo-parathyroidism becomes permanent and patients require lifelong treatment for it.

Damage to Nerves after Thyroidectomy

Another risk of thyroid surgery is injury to the recurrent laryngeal nerve. This nerve allows the vocal cords to move and function for speech. Sometimes, the recurrent laryngeal nerve may have to be removed due to the tumor itself.

Before surgery, otolaryngologists typically perform a “scope” in the office to check vocal cord function. This procedure involves placing a flexible camera through the nose to visualize the vocal cords and to make sure that they are they are working properly. The procedure is repeated after surgery to evaluate vocal cord function.

To reduce the risk of injury to the nerve during surgery, a special endotracheal tube (breathing tube) can be used. This breathing tube has an electrode that detects and monitors the nerves during surgery.

If a vocal cord is injured during surgery, it is often temporary. However, it may take up to a year and a half to recover. If a patient has a change in voice or difficulty breathing or swallowing, the vocal cords can be injected with a temporary material to improve those functions. A re-innervation procedure may be needed if the nerve does not recover. This procedure connects the non-working recurrent laryngeal nerve with a working nerve to improve the function of the affected vocal cord.

These nerve complications due to thyroidectomy are rare and occur at a rate from 1.4% - 14%. The more experienced the surgeon, the lower the risk of complications.
Targeted Therapies

Targeted therapies are being studied in the treatment of thyroid cancer. These drugs act on specific targets of cancer cells to stop them from growing. Kinase inhibitors may be helpful for some patients.

Patients with advanced or recurrent disease may consider enrolling in a clinical trial.

Life after Medullary Thyroid Cancer

Monitoring for recurrence and follow-up care

Patients need lifelong monitoring and follow-up care by an interdisciplinary medical team after treatment for thyroid cancer. Specific recommendations for frequency and types of tests differ according to patient needs and thyroid cancer type and stage. Additional considerations include support for adherence to thyroid hormone replacement therapy.

Ongoing monitoring includes physical exams, measurement of calcitonin levels, and neck ultrasound. Patients should also be examined for signs of other cancers related to known genetic mutations.

Key Aspects of Long-Term Care:

Regular physical exams
Neck ultrasound imaging
Thyroid hormone replacement (levothyroxine)
TSH monitoring; maintain in normal ranges
Measurement of calcitonin and carcinoembryonic antigen (CEA)

Care after thyroid and neck surgery

Patients can benefit from psychosocial support during treatment and survivorship. Care team members representing Psychology, Child Life, Social Work, and other disciplines can assist with coping and adherence to treatments that may affect quality of life. Possible issues include adjustment to daily medication use, body image concerns due to surgical scars, and other adjustment needs.

Patients may also need physical therapy after surgery to assist with neck mobility and range of motion.

Health after cancer

For general health and disease prevention, all cancer survivors should adopt healthy lifestyle and eating habits, as well as continue to have regular physical checkups and screenings by a primary physician at least annually.

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Reviewed: June 2018

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