The process of diagnosing thyroid cancer typically follows a number of key steps.
1. Detection of a nodule or lump
You may feel or see a lump in your neck. Your doctor may also detect a nodule manually or visually during a routine examination. In some cases, your nodule or lump may be felt by someone else such as a family member, hairdresser, or massage therapist who handles your neck. Sometimes, a nodule is accidentally detected during an X-ray or imaging test performed for another purpose, such as a dental X-ray, or a magnetic resonance imaging (MRI) test, computerized tomography (CT) scan, or ultrasound of your head and neck to diagnose pain.
2. Initial consultation and evaluation with your doctor
Once a nodule is detected, you should see your doctor for a medical history and thorough clinical examination. Your doctor should review your personal and family history, your risk factors for thyroid cancer, and any possible symptoms you may be experiencing. During your clinical examination, your doctor should manually evaluate your thyroid, looking for characteristics, size, firmness, and shape of the nodule, as well as evidence of any enlarged cervical lymph nodes.
3. Blood tests
Blood tests may be done at this stage to help evaluate your thyroid function. These tests typically include thyroid stimulating hormone (TSH), thyroxine (T4) and triiodothyronine (T3). Even in the presence of thyroid cancer, however, these tests can be normal, so they are not considered diagnostic for thyroid cancer.
If there is any possibility that you have medullary thyroid cancer, or you have a family history of this cancer, your doctor will order tests for calcitonin and carcinoembryonic antigen (CEA) levels. Calcitonin and CEA levels are typically elevated in medullary thyroid cancer. The doctor should also recommend a genetic test to look for RET proto-oncogenes, a marker for medullary cancer.
Imaging tests can’t conclusively rule out or positively diagnose thyroid cancer. They are, however, helpful in identifying which nodules are suspicious and warrant further investigation.
Most doctors first perform an ultrasound imaging test. Ultrasound can detect the size of your thyroid gland, and identify the number, location, and size of your thyroid nodules. It can also detect your nodules are fluid-filled cysts (less likely to be cancerous), or higher-risk solid nodules. Ultrasound can also identify the specific location of your nodules to aid in subsequent biopsy of those nodules.
In some cases, radionuclide scanning is done to evaluate the nodules further. In this test, you take a small tracer dose of radioactive iodine. Your thyroid absorbs the iodine, and the scan can then detect whether the nodules are considered “functioning” (normal) or “cold” (inactive or underactive). Inactive or cold nodules are more likely to be cancerous.
CT scans or positron emission tomography (PET) scans may be performed to look at areas of the thyroid that can’t be seen on an ultrasound, or to detect any spread of thyroid cancer to other organs and areas of the body.
5. Fine Needle Aspiration (FNA) biopsy
If your nodule is large, cold, or has other characteristics such as rapid growth that make it suspicious, the next step is a fine needle aspiration (FNA) biopsy. This test is performed by inserting a thin needle into your skin, directly into the thyroid nodule. In some cases, the area of the biopsy will be numbed prior to the biopsy. In many cases, however, the biopsy is performed without numbing. Usually, two to three samples of tissue and fluid are taken from the nodule during the procedure. The samples are then analyzed by a cytopathologist to identify cancer.
In some cases, your doctor will also use ultrasound during the biopsy procedure in order to ensure the most accurate sampling of the nodule. This is called ultrasound-guided fine needle aspiration biopsy.
According to the American Thyroid Association’s 2015 guidelines, nodules larger than 2 cm in diameter should almost always be biopsied. Those smaller than 2 cm may be monitored if ultrasound testing does not show any suspicious characteristics. Nodules of any size that have any suspicious features are always biopsied.
FNA biopsy can definitively diagnose or rule out thyroid cancer in many cases.
Most FNA biopsies show that a nodule is benign. It's rare, but occasionally a cancerous nodule is identified by FNA as benign because the biopsy sample was not taken from an area where the cancer was present.
A smaller percentage of FNA biopsy results show cancer or are "suspicious" for cancer. Some experts estimate that one in 20 FNA biopsy results positively diagnose thyroid cancer.
Finally, some FNA biopsy results are considered indeterminate or inconclusive. This means that the cytopathologist is unable to clearly determine if your nodule is benign or cancerous.
6. Molecular evaluation
When your FNA biopsy result is inconclusive or indeterminate, molecular testing — called gene expression classification — can be performed to make a more accurate assessment of the nodule’s potential for cancer. A molecular test such as Veracyte’s Afirma Thyroid FNA Analysis can rule out a significant number of inconclusive biopsy results. Molecular evaluation is not 100 percent accurate, but it can dramatically reduce the number of inconclusive or indeterminate nodules.
7. Surgical biopsy
In some cases, your doctor may recommend what’s known as a surgical or open biopsy. This is a procedure in which the nodule or half of your thyroid gland — known as a lobe — is surgically removed. The surgically removed tissue is then sent to a pathologist for further evaluation, and to diagnose or rule out thyroid cancer.