Medullary Thyroid Cancer: Overview

A rare form of thyroid cancer.

Written by Gary Clayman, DMD, MD, FACS

This article will discuss common medullary thyroid cancer symptoms, common characteristics, how it is diagnosed as well as the how it is treated. Medullary thyroid cancer is rare, making up about 3% of all thyroid cancer cases.

If a nodule is found on your thyroid, your doctor will want to evaluate the node to rule out cancer. The nodule may be benign, but when it is determined to be cancerous, there are four types of thyroid cancer: papillary, follicular, Hurthle cell, or medullary. Is It Medullary Thyroid Cancer?

Medullary Thyroid Cancer: Distinctive Symptoms 

Early in the course of medullary thyroid cancer, there are usually no symptoms. It almost never causes hyperthyroidism (increased thyroid function) or hypothyroidism (decreased thyroid function). It doesn't make people feel tired or any different.

As such, the early detection of sporadic (non-hereditary) medullary thyroid cancer typically is found by the patient or someone else noticing an unusual lump in the neck or throat, or by a doctor feeling a lump or nodule when examining a patient's thyroid gland. Because sporadic early medullary thyroid cancer doesn’t present with any symptoms, it is difficult to assess how long the tumor has been growing.

Although rare among thyroid cancers, medullary thyroid tumors may be tender to the touch and can even be painful either where they originated in the thyroid or where they spread to in the lymph nodes of the neck. But, almost all cancers that spread to the neck lymph nodes do not produce any noticeable discomfort.  

Medullary thyroid cancer produces many proteins and sheds other substances that may lead to another common symptom of advanced medullary thyroid cancer—diarrhea. Diarrhea might arise from an interaction of several factors including increased calcitonin, prostaglandins, and the presence of several other substances. This diarrhea can be managed either by surgical removal of the tumor (and any involved lymph nodes) and/or appropriate medications.

Medullary Thyroid Cancer: How Is It Diagnosed?

Medullary thyroid cancer starts as a growth of abnormal cancer cells within the thyroid. These special cells are the parafollicular C cells. In the hereditary form of medullary thyroid cancer, the growth of these cells is due to a mutation in the RET gene which was inherited. This mutated gene may first produce a premalignant condition called C cell hyperplasia. The parafollicular C cells of the thyroid begin to have unregulated growth. In the inherited forms of medullary thyroid cancer, the growing C cells may form a bump or nodule in any portion of the thyroid gland. With this type of cancer, patients may not be diagnosed unless the cancer has spread to the lymph nodes of the neck and presented with a “lump in the neck.

For patients with a sporadic (non-hereditary) form of medullary thyroid cancer, they may form a bump or "nodule" within the thyroid that often sticks out of the side or front of the thyroid gland. For this reason, most medullary thyroid cancers, like all thyroid cancers, are diagnosed after a doctor feels the neck of a patient or an ultrasound or other x-ray notices a lump within a thyroid gland. In examining a thyroid gland, most doctors stand behind the patient to feel the thyroid for nodules or bumps.

Sometimes, these growths and nodules can be seen when looking at the neck of thin women as a small bump under the skin that moves when the person swallows. Sometimes people are undergoing scans or x-rays of the neck for some other reason and a nodule or worrisome area of the thyroid is seen. Either way, your physician feeling this mass or seeing it as a surprise on some other scan will typically order a thyroid ultrasound to look at the thyroid closely and take pictures of the mass or nodule.

Why Is My Doctor Recommending an Ultrasound?
Ultrasound for medullary thyroid cancer is far more sensitive than even the most experienced of hands. It is critically important when trying to determine the extent of the medullary thyroid cancer to have the most accurate information available.

Since medullary thyroid cancer commonly spreads to the lymph nodes of the central neck and sides of the neck, very close examination of these areas is required in every ultrasound for medullary thyroid cancer. If there are any suspicious lymph nodes on the side(s) of the neck, a needle biopsy isbe performed.

This will assist the thyroid cancer surgeon in knowing the exact extent of surgery required to address all the medullary thyroid cancer requiring removal in a single operation. Failure to have a high quality (resolution) ultrasound and an expert thyroid cancer surgeon to assess the finding may increase the patient’s risk for persistent or recurrent medullary thyroid cancer.

In medullary thyroid cancer patients, the patient often is diagnosed with a lump in the neck that is actually due to spread of the cancer to the neck lymph nodes. In this instance, a fine needle aspiration biopsy of a neck lymph node can adequately provide a diagnosis to avoid any further need for a biopsy of the thyroid gland.

Medullary Thyroid Cancer: Distinguishing Characteristics 

Unlike papillary and follicular thyroid cancers, which arise from thyroid hormone-producing cells, medullary thyroid cancer originates in the parafollicular cells (also called C cells) of the thyroid. These cancer cells make a different hormone called calcitonin, which has nothing to do with the control of metabolism like thyroid hormone does.  

Key factors about this type of cancer:

Medullary thyroid cancer has a much lower cure rate than the more well-differentiated type of thyroid cancers (ie, papillary and follicular), but the cure rate is higher than for anaplastic thyroid cancer. Overall, 10-year survival rates are 90% when all the disease is confined to the thyroid gland, is 70% when the cancer has spread to cervical lymph nodes and 20% when the cancer is found in distant sites.

If the results of your biopsy indicate that medullary thyroid tumor is likely,  it is highly recommended that you seek out a thyroid cancer surgeon who has had experience with this specific type of cancer.  Here is why:

Medullary Thyroid Cancer: Treatment and Management  

Medullary Thyroid Cancer Treatment
In contrast to papillary and follicular type thyroid cancers, there is little discussion as to the best way to treat medullary thyroid cancer: the answer is surgery. After you have been assessed and treated for any associated endocrine conditions, such as pheochromocytomas, (if present) all patients undergo a total thyroidectomy in which all lymph nodes and fatty tissues in the central area of the neck are removed. Just the presence of enlarged lymph nodes does not mean medullary thyroid cancer has spread. The lymph nodes on the side of the neck will only be removed if there is confirmed cancerous cells or a very large tumor.

Medullary Thyroid Cancer Surgery
The precise procedure will depend upon staging of the cancer (its size and spread), the patient's overall health, and surgeon's expertise. Since the goal of surgery is to achieve a comprehensive removal of the entire thyroid gland and all of the affected and high at-risk lymph nodes of the neck, this requires an expert thyroid cancer surgeon who is capable of accomplishing the procedure by addressing all of the neck disease while maintaining the patient's appearance, function, and quality of life. In this way, all critical structures, including the nerves to the voice box and all parathyroid glands which are not directly affected by cancer are preserved.

In a total thyroidectomy, a small incision is made at the lower neck. Even patients with a known RET mutation but without ultrasound evidence of medullary thyroid cancer or elevated calcitonin levels may opt for this procedure; this is considered a prophylactic thyroidectomy, which offers the individual a lifetime cure of medullary thyroid cancer.  

When the medullary thyroid tumor is small, surgery is not only the first treatment but is commonly the only treatment needed.

If medullary thyroid cancer should recur or persist due to an incomplete surgery, a secondary surgery of the central compartment may be required.

Extended or Complicated Thyroidectomy
Medullar thyroid cancer may sometimes be more aggressive than ultrasound or CT imaging suggested prior to undergoing surgery. In these cases, the surgeon will recognize these unanticipated aggressive intraoperative findings such as growth or extension of the cancer outside of the thyroid gland or invasion of the cancer into adjacent structures such as the nerve to the voice box (recurrent laryngeal nerve), breathing tube (trachea), voice box, or esophagus-must adapt the surgery to adequately address the complete removal of the cancer. A highly skilled thyroid surgeon will be prepared to make the necessary adjustments to perform a complete surgical resection of all cancerous tissue.

Radioactive Iodine in Medullary Thyroid Cancer
Although thyroid cells have the cellular mechanism to absorb iodine, medullary thyroid cancer does not arise from this type of thyroid cell.Therefore, radioactive iodine therapy has no role in the treatment of medullary thyroid cancer. Similarly, if medullary cancer spreads to distant sites, it cannot be found by iodine scanning the way cancer metastasis of papillary or follicular thyroid cancer can.

For those individuals which are interested in seeing what these operations look like, you can go to the following link and see what a thyroidectomy with central neck dissection and anterolateral neck dissection look like. There is no bleeding or blood loss during these operations. Blood loss averages on a teaspoon level. These are real videos of real operations, therefore if you feel uncomfortable with seeing such an operation, then do not go to this link. 

Four Clinical Situations Behind This Rare Form of Thyroid Cancer

What Kind of Long-term Follow-Up Is Necessary?

In addition to the usual cancer monitoring, patients should receive an annual chest x-ray as well as blood checks for calcitonin and carcinoembryonic antigen (CEA) levels. Serum calcitonin is very useful in the follow up of medullary thyroid cancer because no other cells of the body make this hormone. A high serum calcitonin level that had previously been low following total thyroidectomy is indicative of recurrence.

Carcinoembryonic antigen is a protein that is usually found in the blood at a very low level but might rise in certain cancers, such as medullary thyroid cancer. There is no direct relationship between serum calcitonin levels and extent of medullary thyroid cancer.  However, trending serum calcitonin and CEA levels can be a useful tool for doctors to consider in determining the pace of change of a patient’s medullary cancer. 

Under the best circumstances, medullary thyroid cancer surgery will remove all of the thyroid and all lymph nodes in the neck that harbor metastatic spread. In this case, post-operative calcitonin levels will go to zero. This is often not the case, and calcitonin levels frequently remain elevated, but less than pre-operatively.

These levels should still be checked every six months, and when they begin to rise, a more diligent examination is in order to find the source.For a general overview of the different types of thyroid cancer, read our Introduction to Thyroid Cancer article, and you can also visit our Patient Guide to Thyroid Cancer to learn about thyroid cancer diagnosis and treatments. 

We want to acknowledge and thank James Norman, MD, who wrote the original content on this topic for EndocrineWeb.

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