Transcript: Johannes (Jan) Smit, MD, PhD: The difference between differentiated thyroid cancer and undifferentiated cancer is that in differentiated cancer, the cancer cells have retained many properties of normal thyroid cells. The most important property is uptake of iodide. In undifferentiated thyroid cancer, cancer cells have lost most of the properties of normal thyroid cells. However, the difference is not very strict because there are a spectrum of phenotypes ranging from differentiated thyroid cancer with modest aggressive behavior to undifferentiated thyroid cancer with very aggressive behavior. So, in fact, we see a spectrum.

Speaking about risks of thyroid cancer, there are a couple of factors. We have to consider environmental factors. The most important one is external radiation. Subjects who have received external radiation as medical treatment in the neck area are at increased risk for developing thyroid cancer. Also, environmental factors, like pollution with radioactive substances, contribute to the risk of thyroid cancer. There are also endogenous factors. A very important consideration is genetic factors. Although the prevalence of family thyroid cancer is very low, there are conditions in which certain families are affected by thyroid cancer. In most cases, thyroid cancer occurs sporadically without a well-known cause.

Speaking about prognosis of thyroid cancer, there are many factors involved. In recent years, we have understood that many of these factors are related to genetic events taking place in thyroid cancer. But if we speak about undifferentiated thyroid cancer—very aggressive thyroid cancer that does not take up iodide anymore, has a rapid progression rate, and tends to metastasize—the risk of dying of thyroid cancer is increased. Whereas, in differentiated thyroid cancer, as long as the tumor can be treated with radioactive iodide and doesn’t grow that fast, the risk of dying from thyroid cancer is very, very minimal.

Marcia S. Brose, MD, PhD: Most patients who are diagnosed with thyroid cancer come to our attention because they’ve noticed something. Many times they may have had a change in their voice, may have noticed a nodule in their throat, or may have felt something sticking when swallowing. They usually present to a general practitioner and, at that point, have a physical exam conducted. On the physical exam, a mass or nodule might be palpated. On rare occasions, if they already have a nodule, they might even present directly to a surgeon because they can feel that there’s something there.

At that point, they need to undergo a diagnostic workup. The primary diagnostic workup is ultrasound of the neck. The ultrasound usually evaluates the patient’s thyroid area, but it also evaluates the lateral lymph nodes. If there is a possibility of thyroid cancer, they also want to make sure that there aren’t any abnormal nodes laterally. Sometimes a fine needle aspirate is done at the time of the ultrasound. They will actually biopsy the areas that are suspicious.

Johannes (Jan) Smit, MD, PhD: During the initial workup for the diagnosis of thyroid cancer, there is not a specific blood test that will help you determine whether the lesion is malignant or benign. We always take blood for free T4 and TSH [thyroid stimulating hormone] measurements, but the levels of T4 and TSH will not tell you what the diagnosis is. We also take blood samples for measuring thyroglobulin, which is the most important tumor marker for thyroid cancer. However, it doesn’t help you make the diagnosis. There’s 1 exception: For medullary thyroid cancer, many experts think that measuring serum calcitonin levels will help you determine the risk for medullary thyroid cancer.

The most important test in the diagnosis of thyroid cancer is the fine needle aspiration. Most people present with a thyroid nodule. Fine needle aspirations can be taken to get an idea about the nature of the lesion.

Thyroid cancer is very low in prevalence, whereas people who present with thyroid nodules, well, this occurs frequently. It’s very important to discriminate between people with nodules that might not be malignant and people who present with nodules that may be malignant. For this reason, the fine needle aspiration is an important test. Then, within the group of patients who are suspected of thyroid cancer, it’s important to discriminate between low-risk and high-risk patients. This is very difficult before surgery has taken place because the initial risk stratification will take place after surgery. However, patients with a very rapidly growing thyroid nodule that is very big, who have complaints regarding their voice or have lymph node nodules are the subjects in whom we advise to do more extensive imaging, including CT scans of the neck and the lungs, to exclude metastases. But there is no general rule to determine what kind of workup you should do before surgery, except an ultrasound of the neck.

Transcript Edited for Clarity