Thyroid Cancer  Medullary
Medullary thyroid cancer is completely different than the more common papillary and follicular types.
Medullary thyroid cancer is usually not classified in terms of differentiation because it does not arise from the thyroid cells themselves, but rather from the specialized "C-cells" that are in between the thyroid cells.
These C-cells are also sometimes referred to as parafollicular cells.
They are found mostly in the upper and middle parts of the thyroid and they produce a substance called calcitonin which can serve as a marker for medullary thyroid cancer.
Although we know that calcitonin is somehow involved in the body's regulation of calcium, we do not know its exact function.
We do know that people who have had their thyroids removed surgically, do not require replacement of calcitonin for normal function and a healthy life.
Types of Medullary Thyroid Cancer
Sporadic
Sporadic medullary thyroid cancer is a non-hereditary type of medullary cancer, since there is no family history of medullary thyroid cancer.
This means that the patient who develops this disease will not pass it on to their children.
MEN associated
The second and third types are called MEN associated medullary thyroid cancer.
MEN stands for multiple endocrine neoplasia, which are a group of tumors affecting hormone glands that are passed on from one generation to the next.
Although there are several different types of MENs, MEN2A and MEN 2B are the ones associated with medullary thyroid cancer.
MEN 2A is a hereditary syndrome in which affected patients suffer from medullary thyroid cancer, tumors of the adrenal gland (the adrenal glands are specialized endocrine glands located on top of each kidney) and tumors of the parathyroid glands (four glands that sit near the thyroid gland and control the level of calcium in the bloodstream).
MEN 2B patients usually have medullary thyroid cancer and tumors of the adrenal gland, but do not have problems with their parathyroid glands.
Instead, these patients all have characteristic bumps on the end of their tongue, called mucosal neuromas.
These bumps are also found on the undersurface of the eyelid and throughout the gut.
These patients also have thickened lips and eyelids.
Familial
The fourth type of medullary thyroid cancer is called familial type, which means that the thyroid cancer is passed genetically through a family, but not in association with the other endocrine tumors that occur in the MEN syndromes.
Because there are so many different types of medullary thyroid cancers, they can occur in people of different ages.
The MEN associated type usually occurs in younger patients, while the non-MEN familial and the sporadic types occur usually in patients in their 40s or 50s.
Unlike differentiated thyroid cancer which usually affects women, medullary thyroid cancer affects women and men equally.
Diagnosis
As with the more common papillary and follicular types of thyroid cancer, most patients with medullary thyroid cancer do not have any idea that they have the disease until their doctor notices a painless lump in their thyroid.
A few people with more advanced forms of the disease can have hoarseness, difficulty swallowing (especially solid foods) and difficulty breathing.
Other people have enlarged neck lymph nodes, indicating spread of the tumor to these nodes.
Occasionally some patients will also have diarrhea, possibly due to the elevated calcitonin levels in the blood produced by the tumor.
Sometimes people with the hereditary form for medullary thyroid cancer have hypertension, increased heart rate, headaches and/or other endocrine disease.
The diagnosis of medullary thyroid cancer is usually suggested by abnormal cells obtained from a fine needle aspiration biopsy.
These cells can then be specially stained for calcitonin in order to confirm the diagnosis.
Fine needle aspirates taken from medullary cancer tumors usually show that the tumor is malignant but cannot always determine the type, since the architecture of the cells are important to make a more definitive diagnosis.
Blood tests showing an elevated calcitonin and CEA level also help in identifying this cancer.
Once the diagnosis is made, it is important to search for other associated tumors such as adrenal and parathyroid.
A careful family history should be obtained and special importance given to relatives who died from unknown causes at an early age, perhaps an aunt died during childbirth or a brother died while undergoing anesthesia for a routine operation.
Often a rare adrenal tumor called pheochromocytoma can cause massive elevations in blood pressure and sudden death, especially with external stress such as childbirth or anesthesia.
If an adrenal tumor is found, it will require operation prior to thyroid surgery in order to ensure safe blood pressure levels during the thyroid cancer operation.
In the past, we have used a special test called a calcium/pentagastrin stimulation test in order to identify an early form of medullary thyroid cancer or the precursor to this type of cancer, called C-cell hyperplasia.
This test involves the intravenous injection of two substances, calcium gluconate and pentagastrin, two agents which stimulate the C-cells of the thyroid to produce calcitonin. Serial blood tests to check for calcitonin levels are obtained prior to the test and at 1,2,3, and 5 minutes after the injection.
Family members with elevated calcitonin levels are considered to be at risk for medullary thyroid cancer and prophylactic thyroid surgery is recommended.
Currently, we have a better way to determine which family members are at risk for medullary thyroid cancer.
A special genetic test called direct DNA testing is available. This is a blood test which identifies a change in the genetic material which causes medullary cancer to form.
Although we have identified many defects or mutations that cause medullary thyroid cancer, we have not identified all of them.
Therefore this test is only useful if you have a family member with medullary thyroid cancer who tests positively.
Then, your family can be screened for this mutation. Family members who test positively are candidates for prophylactic thyroid surgery.
If a patient with known medullary thyroid cancer tests negatively for these mutations, then their family members must be screened with the calcium/pentagastrin test as described above.
If you have a history of medullary thyroid cancer or other endocrine tumors, it is important to be screened for medullary thyroid cancer with a simple blood test. By discovering the disease in its earliest forms, total cure is possible.
Treatment
Because this disease tends to involve both lobes of the thyroid gland with multiple tumors in the hereditary forms of the disease, the operation of choice is a total thyroidectomy plus lymph node dissection both in the center of the neck as well as the side(s).
This operation is described in the section on papillary thyroid cancer.
The best prognosis is associated with the familial form of the disease, the worst with the MEN 2B associated form, while the MEN 2A and sporadic forms have prognoses somewhere in between.
There is an 80% 10 year survival for the very earliest forms of disease that are confined to the thyroid gland without metastasis, but that figure drops to about 25% for patients whose disease has spread to lymph nodes or distant sites such as the lung, liver and bone.
For people who undergo thyroid surgery for C-cell hyperplasia (which is the precursor to medullary thyroid cancer), the survival is 100%.
An important issue in the discussion of medullary thyroid cancer is the question of whether future family members may develop this form of cancer, since three out of the four types of medullary thyroid cancer are hereditary.
After your operation, you will be followed by careful physical examination, as well as blood tests to determine your calcitonin and CEA levels.
If these levels rise, some surgeons would advocate a repeat operation to clear out any new neck lymph nodes that have been invaded by cancer.
The location of these lymph nodes (either right or left side) may be determined preoperatively by obtaining an ultrasound of the neck looking for enlarged lymph nodes or a special test measuring blood samples for possible elevated calcitonin levels from both the right and left sides of the neck through a small tube inserted in the groin (femoral) vein which is threaded up to the neck area.
Somatostatin scanning and sestamibi scanning may also be useful.
Occasionally, if you cannot undergo re-operation because the tumor has spread to many different organs in the body, additional therapy with radiation or chemotherapy is used to improve symptoms.
However, these forms of non-operative treatments are not curative, and the disease will eventually spread further and become lethal.
Unfortunately, radioactive iodine therapy, which is so helpful in other cases of thyroid cancer, does not work with medullary thyroid cancer.
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