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Papillary Thyroid Cancer

Symptoms, Treatments, and Prognosis for Papillary Thyroid Carcinoma

Papillary thyroid cancer (also sometimes called papillary thyroid carcinoma) is the most common type of thyroid cancer. You may have even heard your doctor talk about metastatic papillary thyroid cancer ("metastatic" means that it has spread beyond your thyroid gland). This article will focus on papillary thyroid cancer basics, including papillary thyroid cancer symptoms, treatments, and prognosis. You can read a general overview of thyroid cancer in our Introduction to Thyroid Cancer article.

Visit our Patients' Guide to Thyroid Cancer for complete information on all types of thyroid cancer, including papillary thyroid cancer.

Papillary thyroid carcinoma is the most common thyroid cancer. About 80% of all thyroid cancers cases are papillary thyroid cancer.

Most commonly, papillary thyroid cancers are totally asymptomatic. However, the most common symptom is a mass in the neck. Papillary carcinoma typically arises as a solid, irregular or cystic mass that comes from otherwise normal thyroid tissue. This type of cancer has a high cure rate—10-year survival rates for all patients with papillary thyroid cancer estimated at over 90%. Cervical metastasis (spread to lymph nodes in the neck) are present in 50% of small papillary carcinomas and in more than 75% of the larger papillary thyroid carcinomas.

The presence of lymph node metastasis in the neck area typically has a more frequent recurrence rate but not a higher mortality rate. Distant spread of papillary thyroid cancer is called metastasis. Distant metastasis of papillary thyroid cancer is uncommon, but when it does occur, it may spread to the lungs, liver, and bone. Papillary thyroid cancers that invade the surrounding tissues next to the thyroid gland have a much worse prognosis because of a high local recurrence rate.

But what do doctors look for in diagnosing papillary thyroid cancer?

Characteristics of Papillary Thyroid Cancer

  •  Peak onset ages are 30 to 50 years old.
  • Papillary thyroid cancer is more common in females than in males by a 3:1 ratio.
  • The prognosis is directly related to tumor size. Less than 1.5 cm [1/2 inch] is a good prognosis.
  • The prognosis is also directly related to age. Patients under 55 years of age do much better than patients who are over 55 years of age.
  • The prognosis is directly related to gender.  Women have a much better prognosis than do similarly aged men.
  • This cancer accounts for 85% of thyroid cancers due to radiation exposure.
  • In more than 50% of cases, it spreads to lymph nodes of the neck.
  • Distant spread (to lungs, liver or bones) is uncommon.
  • The overall cure rate is very high (approaching 100% for small lesions in young patients).Management of Papillary Thyroid Cancer

Thyroid gland has 2 lobes connected by an isthmus.Considerable controversy exists when discussing the management of well-differentiated thyroid carcinomasboth papillary thyroid cancer and even follicular thyroid cancer.

Some experts contend that if these tumors are small and not invading other tissues (the usual case) then simply removing the lobe (one side) of the thyroid that harbors the tumor (and the small central portion called the isthmus) will provide as good a chance of cure as removing the entire thyroid.

These proponents of conservative surgical therapy relate the low rate of clinical tumor recurrence (5% to 20%) despite the fact that small amounts of tumor cells can be found in up to 88% of the opposite lobe thyroid tissues. They also cite some studies showing an increased risk of and recurrent laryngeal nerve injury in patients undergoing total thyroidectomy (since it is an operation on both sides of the neck).

Proponents of total thyroidectomy (more extensive surgery) cite several large studies that show that in experienced hands, the incidence of recurrent laryngeal nerve injury and permanent hypoparathyroidism are quite low (about 2%). More importantly, these studies show that patients with total thyroidectomy followed by radioiodine therapy and thyroid suppression, have a significantly lower recurrence rate and lower mortality when tumors are greater than 1.5 cm.  Survival rates (prognosis) do not appear to be affected by the extent of thyroid surgery. Remember that it is also desirable to reduce the amount of normal gland tissue that will take up radioiodine.

To add to the controversy, clinical studies in Tokyo, Japan and in New York City, have investigated the safety of just observing the much smaller papillary thyroid cancers that do not have any evidence of lymph node spread in patients who have had no prior treatment for this type of cancer. The most extensive, long-term study was performed in Japan; the findings suggest that in well-selected patients with small papillary thyroid cancers, few patients progress by evidence of the growth of cancer or experience spread to lymph nodes in the neck during periods of observation. Whether these findings would have similar results in the US population needs to be confirmed. However, even the American Thyroid Association guidelines suggest that small tumors (less than 1 centimeter in size) should not be routinely biopsied unless there is evidence of abnormal lymph nodes in the neck.

Based on these studies and the known natural history of papillary carcinoma, surgery is the most commonly proposed treatment for papillary thyroid cancer worldwide. The extent and type of operation indicated for papillary thyroid cancer are based upon expert evaluation and the experience of your surgeon. The following is a commonly proposed plan for treating papillary thyroid cancer: Papillary carcinomas that are well-circumscribed, isolated, and less than 2.5 cm in young patients (20 to 40 years old), without a history of radiation exposure, may be treated with thyroid lobectomy (also called hemithyroidectomy, removal of half of the thyroid gland).

What are some other papillary thyroid cancer treatments? The other surgical option for patients with papillary thyroid cancer is a total thyroidectomy (complete removal of the thyroid gland). An expert pre-operative evaluation of the papillary thyroid cancer patient is required to determine whether there is any involvement of the lymph nodes in the neck. In most circumstances, the involvement of neck lymph nodes can be determined prior to the thyroid surgery procedure. When there is evidence that the papillary thyroid cancer has spread to lymph nodes in the neck, surgical approaches to the central and lateral neck lymph nodes should be performed.

When neck lymph nodes are involved with papillary thyroid cancer, either during the evaluation of the papillary thyroid cancer or during surgery for the papillary thyroid cancer, the recommended operation is a total thyroidectomy.

Often, other characteristics of the tumor that can be seen under the microscope which may have an influence on whether the surgeon should remove the entire thyroid (such as vascular invasion, nerve invasion, soft tissue invasion or growth of the papillary thyroid cancer outside of the confines of the thyroid gland, and capsule invasion).

The surgical options are covered in greater detail (with drawings) in our article on surgical options for thyroid cancer.  A more detailed discussion of thyroid surgery for the thyroid gland and lymph nodes of the neck can be found here. 

Undergoing Evaluation for Papillary Thyroid Cancer

Your doctor may order a variety of tests in order to diagnose the type of node and stage of cancer. Common procedures are noted below:

  • Thyroid Ultrasound

Endocrinology specialist may order an ultrasound to evaluate neck and thyroid gland.High resolution ultrasound machine for evaluation of the neck and thyroid.

The thyroid ultrasound uses sound waves to create pictures inside the neck. This ultrasound will not only examine the thyroid gland but will include a comprehensive examination of the lymph nodes in the neck. For this test, a small transducer (wand-like instrument) is placed on the skin in front of your thyroid and around the neck. The sound waves pick up echoes as they bounce off the thyroid and neck tissues, which are converted into a black and white image on the computer screen. There is no radiation used during this test.

Image of the thyroid gland produced by ultrasound soundwaves.View of an actual ultrasound of the thyroid gland.

The image created by an ultrasound test shows the thyroid gland. The green arrow points to the breathing tube in the neck (trachea). The yellow arrow points to a nodule in the right side of the thyroid gland (the ultrasound pictures are a mirror image: meaning left side of the image is on the patient’s right side and vice versa) which a biopsy then confirmed it as papillary thyroid cancer.

Other Reasons that Might Necessitate an Ultrasound
Expert ultrasound may also help confirm a diagnosis of papillary thyroid cancer which has spread to the lymph nodes of the neck. The ultrasonographer will look for multiple changes. Although unskilled observers might believe that size is a major issue, in fact, it is not. High-resolution ultrasound is able to detect a diagnosis of papillary thyroid cancer in the lymph nodes as small as 1-2 mm (the size of a tip of a ballpoint pen).

When looking at the lymph nodes in the neck with ultrasound, the following criteria are important considerations in confirming the presence of thyroid cancer:

  • enlarged or cystic lymph nodes
  • changes in the normal “architecture” of a lymph nodes
  • small calcifications within lymph nodes
  • disorganized or irregular blood flow to the lymph node
  • asymmetric lymph nodes when comparing one side of the neck to the other

In the end, the most important factor will be location, location, location. A  diagnosis of papillary thyroid cancer that has spread to neck lymph nodes is quite predictable.

There is one important weakness in relying on ultrasound findings—it cannot distinguish cancerous from inflammatory lymph nodes. Both conditions—enlarged and inflammatory lymph nodes—may appear very similar on ultrasound. Therefore, ultrasound-guided fine needle aspiration (FNA) biopsy would be a necessary next step to confirm or rule out a diagnosis of papillary thyroid cancer.

The quality of the ultrasound will depend upon four critical and equally important factors. The best quality will be determined by:

  • The quality of the ultrasound machine
  • The device that is held in the hand of the technician (the transducer) producing the sound waves
  • The experience and the skill of the ultrasound technician
  • The experience of the radiologist or diagnostician who is interpreting the study.

Actual ultrasound of neck lymph nodes in papillary thyroid cancer.

Ultrasound of the neck lymph nodes. CCA is the common carotid artery, IJV is the internal jugular vein. The red arrow points to an 8 mm lymph node which FNA confirms a diagnosis of papillary thyroid cancer spread (metastatic) to a lymph node.

  • Computed Tomography (CT) Scan 

CT scan (also called a CAT scan, is an x-ray that produces detailed images from the base of the skull to the middle of the chest) of a patient with a diagnosis of papillary thyroid cancer:

Taking a CT scan of the neck is done to help determine the location and size of possible thyroid cancer, and to assess whether thyroid cancer has invaded nearby structures. or spread to lymph nodes. Also, a CT scan may be used to look for the spread of cancer into distant organs such as the lungs.

 The CAT scan is a mirror image of the patient. Therefore, objects on the left side of the x-ray are actually on the right side of the body. A CT scan designed for a diagnosis of papillary thyroid cancer is sliced in 1mm increments. It is an incredibly detailed study that creates very exquisite images.  Although not ordered as a usual standard of evaluation, as of yet, this author recommends a CT scan for any patient with papillary thyroid cancer has spread to lymph nodes of the neck as confirmed on biopsy. 

The CT scan will examine the thyroid and neck but also examine areas that the ultrasound is unable to visualize.  CT scans of the neck should only be given with IV (intravenous) contrast dye. This helps better outline structures in your body. This CAT scan shows very typical abnormal lymph nodes common in papillary thyroid cancer. The lymph node seen on the left side of this x-ray is called a carotid/vertebral lymph node. It is located between these two critically important blood vessels in the neck. The lymph node seen on the right side of the x-ray is a lymph node of the central compartment of the neck. These are also commonly called paratracheal lymph nodes. These lymph nodes can be readily biopsied with ultrasound-guided FNA biopsy to confirm that the papillary thyroid cancer has spread to these lymph nodes.

Clarifying Use of Iodine—There is a theoretical problem with using CT scans for a diagnosis of papillary thyroid cancer because the CT contrast dye contains iodine, which interferes with radioiodine scans. This should not be a concern whatsoever. The iodine used for a CT scan will be eliminated from the body in approximately two months. Therefore, at most, there may just be a slight delay in the timing of any radioactive iodine procedure if this is thought to be potentially indicated in the management of the particular diagnosis of papillary thyroid cancer. As such, the added information obtained from a CT scan may merely just delay the evaluation of radioactive iodine by a month or so.

Information Gained on CT Scan. The CT scan for the diagnosis of papillary thyroid cancer provides different information to your doctor than the ultrasound. The ultrasound tells the doctor if there is something abnormal. The CT scan tells the doctor where the abnormality is located. Both studies complement each other. Ultimately, findings from all of these studies will determine the extent of required surgery.

In patients over 55 years of age with advanced papillary thyroid cancer in the thyroid gland or spread to lymph nodes, a CT scan of the chest should be obtained. The CT scan of the chest provides an excellent baseline examination of the lungs and the lymph nodes in the chest as both of these sites the highest risk of distant spread in patients with a diagnosis of papillary thyroid cancer.

  • Magnetic Resonance Imaging (MRI) Scan

MRI scans use radio waves and strong magnets instead of x-rays, therefore there is no radiation exposure. A contrast material called gadolinium is often injected into a vein before the scan to better show details.

MRI of thyroid, neck and chest to evaluate for papillary thyroid cancer.

MRI of a patient with papillary thyroid cancer of the left thyroid lobe. (MRI's show mirror images therefore what you see on the right is actually on the patient's left). The arrow points to the thyroid cancer which is more invasive and aggressive than the usual papillary thyroid cancer. This cancer has spread to the overlying muscles.

Like CT scans, MRI scans can be used to look for a diagnosis of papillary thyroid cancer in the thyroid, for cancer that has spread to nearby or distant parts of the body. But ultrasound is usually the first choice for looking at the thyroid and neck structures. 

MRI scans are very sensitive to movement and moving during the scanning process produces artifacts that make interpretation difficult. Because people are constantly swallowing and unconsciously moving their voice box and swallowing structures (and therefore their thyroid gland and surrounding lymph nodes, CT of the neck is the preferred cross-sectional study of the neck in patients with a diagnosis of papillary thyroid cancer.

  • Positron Emission Tomography (PET)/CT Scan

Scan showing thyroid cancer that has spread to the lungs.This shows a PET/CT scan of a patient with recurrent papillary thyroid cancer.

PET/CT scan of a patient with recurrent papillary thyroid cancer. The patient had already undergone three surgeries to treat cancer. The bright orange circle on the left is a lymph node where the papillary thyroid cancer has spread. The black area to the left of the bright spot is the lungs. This view of thyroid cancer with metastatic lymph node involvement is located next to the trachea, which should only be removed by a highly skilled surgeon. It will take about 15 minutes with a nearly 98% chance that it will never recur.

What to Expect When Having a PET Scan?

In preparing foa PET scan, a radioactive substance (usually a type of sugar known as FDG) is injected into the blood. The amount of radioactivity used is low. Because cancer cells in the body generally utilize sugar as their energy source to grow, they absorb more of the sugar than normal cells.

This test can be very useful for physicians to make a diagnosis of papillary thyroid cancer that has:

  • Come back (recurred) following prior surgery
  • Spread to other sites in the body
  • Diagnosed as papillary thyroid cancer but didn't take up radioactive iodine (a condition called non-iodine avid)

The PET/CT scan for a diagnosis of papillary thyroid cancer combines images of both PET and CT scans at the same time. This is because PET images alone are not very detailed. The computer shows the relative amount of radioactivity in a particular area and where the sugar is localized, appearing red or “hot”. The combination of these two images lets the doctor compare an abnormal area on the PET scan with its detailed appearance and location on the CT scan.

PET/CT scanning is not always positive in patients with a diagnosis of papillary thyroid cancer.

Blood Tests to Monitor Thyroid Function

  • Thyroid-stimulating hormone (TSH)
Tests of blood levels of thyroid-stimulating hormone (TSH or thyrotropin) may be used to check the overall activity of the thyroid gland. In previously untreated patients with a diagnosis of papillary thyroid cancer, their TSH level is usually normal. 
  • T3 and T4 (thyroid hormones)
These are the two main hormones made by the thyroid gland. Levels of these hormones may be measured to get a sense of overall thyroid gland function. The T3 and T4 levels are usually normal in patients with a previously untreated papillary thyroid cancer. Papillary thyroid cancer rarely produces either T3 or T4 hormones. 
  • Blood Thyroglobulin Level
Thyroglobulin is a protein made by the thyroid gland that can be measured in the blood. However, monitoring the thyroglobulin level in the blood is not used to make a diagnosis of papillary thyroid cancer, but it can be helpful after treatment to determine whether the patient has (or does not) have cancer. In patients with a diagnosis of papillary thyroid cancer, which have undergone total thyroidectomy with or without radioactive iodine treatment, their blood marker for thyroglobulin should be very low within several weeks of their surgery.
If the blood test for thyroglobulin is not low, there are only two possible explanations:
  • Papillary thyroid cancer cells remain in the body.
  • Excess thyroid tissue is producing thyroglobulin that has not been removed and/or which was not fully destroyed by radioactive iodine treatment.
Most importantly, in patients with a diagnosis of papillary thyroid cancer who have undergone total thyroidectomy, if the thyroglobulin level rises again after being low, it is a sign that cancer has almost certainly recurred.
  • Thyroglobulin Antibodies
Some patients have an inflammatory condition of their thyroid gland called thyroiditis. The most common cause of thyroiditis is a condition where the body produces an immune reaction to normal thyroid tissue. The body’s immune reaction is the production of an antibody and in autoimmune thyroiditis, this can result in an antibody to the protein normally produced by thyroid cells called thyroglobulin. These thyroglobulin antibodies directly bind (grab onto thyroglobulin).
Very importantly, in patients with a diagnosis of papillary thyroid cancer who also have thyroiditis, their antibodies to thyroglobulin directly bind to thyroglobulin and make the blood level of thyroglobulin appear to be zero (because the antibodies are clumped with the thyroglobulin protein and then not detected in the blood test).
Whenever the marker thyroglobulin is checked in the blood, the antibody to thyroglobulin must also be measured. If the antibody to thyroglobulin is detected, measuring thyroglobulin in the blood is not an effective marker in patients with a diagnosis of papillary thyroid cancer.
  • Other Tests
Vocal cord exam (laryngoscopy)
Thyroid tumors can sometimes affect the function of your voice box. Even if your voice sounds normal, this does not mean that the vocal cords are functioning properly. A procedure called a laryngoscopy will probably be done first to see if the vocal cords are moving normally. For this exam, the doctor will look through the nose or down the throat to view the larynx (voice box) with a special thin tube that has a light and a lens on the end. This special tiny scope is inserted through the nose and does not cause any noticeable discomfort during the exam. 

Use of Radioactive Iodine and Papillary Thyroid Cancer

Thyroid cells are unique in that they have the cellular mechanism to absorb iodine. The iodine is used by thyroid cells to make thyroid hormone. No other cell in the body can absorb or concentrate iodine in a similar fashion than does the thyroid. Physicians can take advantage of this fact and give radioactive iodine to patients as a treatment option for papillary thyroid cancer.  The use of iodine as a cancer therapy was the first “targeted” therapy ever developed for any type of human cancer. 

There are several types of radioactive iodine, with one type being highly toxic to cells. Papillary thyroid cancer cells absorb iodine; therefore, they can be destroyed by giving the toxic isotope (I-131). Again, not everyone with papillary thyroid cancer needs this treatment, but those with larger tumors, tumors that have spread to lymph nodes or other areas including distant sites, tumors that are aggressive microscopically may benefit from this treatment.

Radioactive iodine therapy is particularly effective in children with thyroid cancer which has spread extensively to lymph nodes and even to distant sites in the body such as the lungs.  Although in theory, radioactive iodine is a very attractive treatment approach for papillary thyroid cancer, its use has decreased over the years except for the specific indications as described above.

Radioactive iodine is an extremely effective type of "targeted therapy" with little or no potential downsides regarding the common side effects of traditional types of chemotherapy (eg, no hair loss, nausea, or weight loss).

Radioactive iodine uptake is enhanced by high thyroid-stimulating hormone (TSH) levels. To raise TSH levels, patients can either stop taking their thyroid replacement medication or undergo 2 injections of Thyrogen® prior to undergoing radioactive iodine therapy (or radioiodine remnant ablation). In addition, patients need to be on a low iodine diet for at least 2 weeks before being treated with radioactive iodine. It is usually given 6-12 weeks after surgery (although it depends on the patient), and it can be repeated annually if necessary (within certain dose limits).

The effects of radioactive iodine therapy are not immediate.  Many patients with papillary thyroid cancer can be followed in their blood with the marker of thyroglobulin.  Before radioactive iodine is given, the thyroglobulin in the blood should be check with the TSH levels are very high. 

This is called a “stimulate” thyroglobulin level.  The stimulated thyroglobulin level tells treating physicians much about the patient’s likelihood of a cure.  Low stimulated thyroglobulin levels less than 3, have been shown to be highly predictive of long-term cure in papillary thyroid cancer patients.  Following radioactive iodine therapy, thyroglobulin levels have been shown to continue to drop and “respond to therapy” over years!

Toxicity and complications of radioactive iodine therapy are known as well.  Radioactive iodine can also localize within saliva glands, tear glands, breast tissue, and the bone marrow.  Repeat treatment with radioactive iodine increases the risk of complications from iodine therapy. 

Complaints and complications of dry mouth, increased risk for dental cavities, dry eyes, stricture of tear ducts and more are observed relatively often especially when patients are questioned.  Epidemiologic studies suggest there may be some increased risk of breast cancer and leukemias especially with repeated treatment suggesting some radioactive iodine dose relationships.