What Is Medullary Thyroid Cancer? Symptoms, Diagnosis and Treatment

What Is Medullary Thyroid Cancer?

Medullary thyroid cancer (MTK) is a rare type of cancer arising in the thyroid. It differs from other forms of thyroid cancer because it originates in a different type of cell. MTK develops in a distinct cell known as the parafollicular C cell.

The thyroid is a small gland at the front of the neck that plays an important role in producing hormones that regulate the body. Thyroid cancer occurs when abnormal cells begin growing uncontrollably in the thyroid. The types of thyroid cancer vary according to the cell in which the cancer develops.

The rarest type of thyroid cancer is medullary thyroid cancer. MTK accounts for 3-4% of all thyroid cancers. Approximately 1000 people in the US are diagnosed with MTK each year.

• Related topic: Other Types of Thyroid Cancer

The thyroid gland is a butterfly-shaped gland at the front of the neck that produces thyroid hormones, which help regulate the body's metabolic rate. It contains 2 main types of cells: follicular cells and C cells, also known as parafollicular cells.

Follicular cells produce thyroid hormones, while parafollicular cells produce the hormone calcitonin. This hormone helps control how the body uses calcium. MTK differs from other thyroid cancers because it develops in parafollicular cells.

There are two types of medullary thyroid cancer:

• Sporadic: The most common type of MTK, usually occurring in older people and affecting a single thyroid lobe.
• Hereditary: Usually develops in childhood or early adulthood. People with this type may have cancer in both thyroid lobes and may also be at high risk of other types of cancer.

This type of thyroid cancer is called medullary because the cancer is located in the medulla region of the thyroid. MTK is also generally more difficult to detect and treat than other types of cancer.

What Are the Symptoms of Medullary Thyroid Cancer?

MTK tends to grow slowly. People may have no symptoms in the early stages. When symptoms develop, they usually appear as a lump or nodule in the neck, corresponding to masses of cells growing in the thyroid. If a nodule is large enough, it can cause difficulty breathing and swallowing, and hoarseness.

Less common symptoms include:

• Facial flushing
• Weight loss
• Diarrhea

Stages of Medullary Thyroid Cancer

Like most cancers, MTK has 4 stages. Staging depends on many factors, including tumor size and whether it has spread to lymph nodes or distant organs. Although age is a factor in staging other types of thyroid cancer, it plays no role in MTK. Stage 1 is the earliest stage, when the tumor is smallest and has not yet spread. Severity increases with each stage up to stage 4. At stage 4, the cancer may be any size, may grow and may spread to nearby structures or distant sites.

Causes of Medullary Thyroid Cancer

MTK results from changes in parafollicular cells. However, the exact cause is unknown because most cases are sporadic. For 25% of hereditary MTK cases, studies report that these individuals carry an alteration in the RET gene. This gene, which plays a role in cell signaling, is located on chromosome 10. Scientists associate changes in this gene with several sporadic cancers, including MTK.

Alterations in the gene known as RET can pass from parent to child. Almost everyone carrying an altered RET gene may develop medullary thyroid cancer. When the disease develops alone, it is called medullary thyroid cancer; when it develops together with other cancers, it is termed Multiple Endocrine Neoplasia (MEN) Syndrome.

Diagnosing Medullary Thyroid Cancer

People with medullary thyroid cancer usually have a lump in their neck. Initial diagnosis typically involves examining this lump. Imaging such as ultrasound, CT or MRI will be used to scan the thyroid.

If a doctor suspects thyroid cancer, a fine-needle aspiration biopsy of the nodule will probably be performed. This procedure uses a very small needle to take a tiny amount of tissue from the nodule. A pathologist examines the tissue to determine whether cancer cells are present.

Specialists may also request further tests to confirm the diagnosis and provide more information to help plan treatment. Examples include blood tests that check calcitonin, calcium and carcinoembryonic antigen (CEA) levels.

How Is Medullary Thyroid Cancer Treated?

• Medullary thyroid cancers (MTK) are neuroendocrine tumors of the thyroid's parafollicular cells, which do not concentrate iodine. The primary treatment for MTK is comprehensive, meticulous surgery that also removes lymph nodes in the neck. External radiotherapy has a limited role.
• For patients with asymptomatic metastatic tumors, usually less than 1 to 2 cm in diameter, whose diameter grows by less than 20 percent per year, disease progression continues to be monitored. Known sites of metastatic disease should be imaged by computed tomography (CT) or magnetic resonance imaging (MRI) every 6 to 12 months, with screening for potential new disease sites every 12 to 24 months. The frequency of imaging within the recommended interval can be guided by serial measurements of carcinoembryonic antigen (CEA) and calcitonin.
• Patients with metastatic tumors at least 1-2 cm in diameter, growing by at least 20 percent per year, or with symptoms related to multiple metastatic sites that cannot be relieved by local intervention (surgery or adyoterapi), should receive systemic treatment.
• For patients with metastatic tumors at least 1-2 cm in diameter, growing by at least 20 percent per year, or symptoms related to multiple metastatic sites who cannot take part in a clinical trial, an oral tyrosine kinase inhibitor is more appropriate than conventional chemotherapy.
• RET-mutated tumors: for initial treatment in these patients, either selpercatinib or prasetinib, among the new generation of targeted drugs, is recommended.
• RET germline or somatic mutations absent: kabozantinib or vandetanib is recommended first. Sorafenib, sunutinib or lenvatinib are reasonable options for patients in whom either or both cabozantinib and candetanib have failed.
• Complete responses to these kinase inhibitors are rare, but these treatments may provide potentially long-term disease stabilization and delay cancer progression in selected patients; no study has yet reported their effects on improving survival.
• Although probably less life-threatening than those of cytotoxic chemotherapy, toxicities of many of these new treatments are common and may limit the dose. Doctors planning to use these agents should be familiar with recognizing and managing their side effects.
• Cytotoxic chemotherapy, preferably dacarbazine-based regimens such as cyclophosphamide-vincristine-dacarbazine, is an alternative for patients who cannot tolerate or have failed multiple kinase inhibitors.

Preventing Medullary Thyroid Cancer

Most forms of thyroid cancer cannot be prevented because they usually arise sporadically. However, people with a family history of MTK can undergo genetic testing to identify particular genetic alterations that may confer a risk of this disease. If a person is at high risk, thyroidectomy may be performed to prevent cancer from developing.

Recurrence of Medullary Thyroid Cancer

Studies indicate that MTK may recur even years after the initial diagnosis. Routine follow-up and screening should generally continue for years after diagnosis.

Some tests can identify recurrence or metastasis. Ongoing screening will include blood tests measuring calcitonin levels. Calcitonin levels are usually undetectable after surgery to remove the thyroid. Rising levels, however, may indicate that the cancer has returned.

Disease Course and Overall Survival

Outcomes, or the course of the disease, vary for MTK patients. Factors such as tumor stage at diagnosis, treatment response and overall health affect recovery and prognosis.

Although the prognosis of MTK is generally not as good as that of other thyroid cancers, early diagnosis and treatment can improve it optimally. In addition, routine monitoring of biomarkers such as calcitonin or CEA for a year after surgery may be a good indicator of survival.

MTK is rarer than other types of thyroid cancer, so fully accurate survival data may not be available. Although there is no definitive cure, people can live with MTK for years. Research into treatment options that may improve survival also continues. According to 2017 research, 10-year survival rates for MTK are:

• 95% for early-stage cancer localized to the thyroid gland only
• 75% for regionally advanced disease that has not spread to distant organs
• 20% for disease that has spread to distant organs such as the lungs or liver