Papillary Thyroid Cancer

Papillary thyroid is a form of differentiated thyroid cancer. It is the most common type of thyroid cancer accounting for 80% of cases.  The rate of papillary thyroid cancer is increasing, and about 20,000 new cases are expected in the United States this year alone.

The prognosis for patients with papillary thyroid cancer is excellent.  When the disease is identified early and treated appropriately, the majority of patients are cured.  The disease is more common among women and generally affects younger people (age less than 45).  The disease can spread to regional lymph nodes, but unlike many other cancers, lymph node involvement does not decrease survival.

Signs and Symptoms

Today, in the era of easy access to high quality imaging, most papillary thyroid cancers are identified long before they become symptomatic.  In fact, many of these cancers are identified on imaging studies that are done for another indication.  Other patients will present with an asymptomatic nodule palpated within the thyroid on physical exam performed by the patient’s primary care physician or gynecologist.  Occasionally, a papillary thyroid cancer will be large enough to cause compressive symptoms such as difficulty breathing or swallowing.  Even a small papillary cancer can invade the nerve to the voice box (recurrent laryngeal nerve) and cause hoarseness.

Papillary thyroid cancers generally do not over produce thyroid hormones, so patients are typically euthyroid (normal thyroid function).  Some patients will present initially with an enlarged lymph node in the neck which ultimately turns out to be a site of regional spread from a papillary thyroid cancer.

Diagnosis

The diagnosis of papillary thyroid cancer is determined using the algorithm outlined above for the work up of a thyroid nodule.  On physical exam, these tumors tend to be hard and sometimes fixed or immobile.  There may be palpable lymph nodes within the side of the neck along the jugular vein.  Ultrasound will allow your physician to accurately measure and locate the tumor.  There are also several characteristics on ultrasound that, when present, are worrisome for malignancy.  These include calcifications, irregular borders, and hypervascularity (increased number of blood vessels).  The ultrasound is also used to map the lymph node basins that drain the thyroid to identify possible spread of the disease which will also need to be addressed at the time of surgery.

Once a nodule greater than 1 cm or with worrisome ultrasound characteristics is identified, the next step is a fine needle aspiration biopsy.  This procedure can be performed by an endocrinologist, and endocrine surgeon or a radiologist.  Under ultrasound guidance, a 21 to 25 gauge needle is advanced into the nodule which is aspirated to obtain cellular material.  The obtained material is place on glass slides and then put into fixative for review by the cytopathologist.  The needle used for the biopsy is a little smaller than the one typically used to draw blood.  Sometimes the nodule needs to be aspirated more than once to obtain adequate material.

The cytopathologist will review the slides and score the biopsy using the Bethesda classification system. If nuclear changes (pallor, inclusions, grooves) and papillary formations are detected on the slides, this will yield a diagnosis of papillary thyroid cancer (Bethesda VI). If some, but not all of these features are seen, then the impression will be suspicious for thyroid cancer (Bethesda V).

Treatment

The successful management of papillary thyroid cancer requires surgery, thyroid hormone suppression and sometimes radioactive iodine ablation.

Surgery for Papillary Thyroid Cancer

For several reasons, the treatment for papillary thyroid cancer at most centers is total thyroidectomy (removal of the entire thyroid).  First, although the nodule that has been diagnosed as papillary thyroid cancer can be removed by taking out just half of the thyroid, up to 30 percent of patients will have another focus of cancer within the other lobe that was not recognized before the surgery.  Second, if radioactive iodine ablation is necessary, it is only effective if the entire gland has been removed. This is because normal thyroid tissue absorbs radioiodine much more efficiently than papillary thyroid cancer cells.  So, to effectively deliver the radioiodine to the cancer cells, the entire normal thyroid needs to be absent.  Third, removing the entire thyroid makes the identification of recurrent tumor much easier to detect.  Patients with papillary thyroid cancer are followed lifelong with a blood test for a tumor marker called thyroglobulin (Tg).  Tg is made by both normal thyroid cells and by papillary thyroid cancer cells.  If the entire thyroid has been removed, then the Tg level in the blood should be undetectable.  If however, part of the thyroid remains, the Tg will be elevated and it will be more difficult to determine that the cancer has not recurred.  Also, a radioiodine body scan will not be able to identify recurrent disease if part of the normal thyroid is left behind, because all of the dye will be absorbed by the thyroid remnant.  Fourth, it is well known that the risk of recurrence is higher among patients who only have part of the thyroid removed.  Finally, there is really no advantage to keeping half of the thyroid when papillary thyroid cancer has been diagnosed.  The complication rates of the two operations (removing the entire thyroid or just half) are essentially the same.  And all patients with papillary thyroid cancer are treated with thyroid hormone suppression.

The second component of surgery is assessment and possible removal of lymph nodes that may harbor cancer.  Prior to surgery, the lymph nodes are assessed by physical exam and ultrasound.  Malignant nodes (those containing cancer) are often larger and more round than normal nodes.  In some instances a needle biopsy of a suspicious node will be performed before the operation.  If no suspicious nodes are identified preoperatively, then the operation will be limited to the central compartment of the neck which is the area between the trachea and the carotid arteries.  The central compartment contains the thyroid and the level VI or central compartment lymph nodes.  Currently there is no consensus about whether the central compartment lymph nodes should be routinely removed (prophylactic central lymph node dissection) or only if the nodes are enlarged (therapeutic central lymph node dissection).  Proponents of performing a prophylactic dissection argue that disease will be found in some normal appearing nodes.  Proponents of performing only therapeutic central compartment lymph node dissections will point out that the recurrence rate and survival are the same without removing the nodes and that the complication rate from the additional surgery is too high to warrant their removal. Prophylactic neck dissections are associated with a 20% risk of temporary and 5% permanent risk of hypoparathyroidism. The risk is less than half that when only therapeutic dissections are performed.  Similarly, the risk of an injury to the nerve to the voice box is about three times higher when a prophylactic lymph node dissection is performed.

If the cancer has spread to the lymph nodes in the side of the neck (lateral compartment), then these nodes will need to be removed at the time of surgery also.  The is called a modified radical lymph node dissection and is designed to remove the lymph nodes around the jugular vein. Sometimes the jugular vein itself needs to be removed, which does not result in any clinical deficit.  Multiple vital structures are identified and preserved when performing this operation including the spinal accessory nerve (which allows you to shrug), the vagus nerve (which is partly responsible for the swallowing mechanism and for voice), the phrenic nerve (which enables the diaphragm to move up and down to breath), the hypoglossal nerve (which provides motor function to the tongue), the carotid artery (which supplies blood to your brain), and the thoracic duct (on the left side only).  Several small nerves to the skin are severed during this operation which is unavoidable.  Because of this, most patients will have some numbness along their jaw following the operation.

Thyroid Hormone Suppression:

One of the mainstays of treatment of papillary thyroid cancer is thyroid hormone suppression therapy.  The functional role of the thyroid is to make thyroid hormone.  This is regulated by the pituitary gland in the brain.  When thyroid hormone levels are low, the pituitary releases thyroid stimulating hormone (TSH).  TSH stimulates the thyroid to release more thyroid hormone.  TSH also can stimulate to growth of the thyroid and it can also stimulate the growth and spread of papillary thyroid cancer cells.  For this reason, patients with papillary thyroid cancer are placed on dose of thyroid hormone that is high enough to suppress release of TSH from the brain.  The dose of thyroid hormone prescribed is initially based on the weight of the patient and then adjusted based on the results of your blood tests.  It typically takes several weeks on a fixed dose of thyroid hormone before reliable changes in the blood work are seen.

Radioactive Iodine (RAI) Ablation

Following a total thyroidectomy for papillary or follicular thyroid cancer, your doctor may recommend radioactive iodine ablation. This, typically fairly low dose of radioiodine, is administered as a single oral pill which usually has limited side effects. Most of the radioiodine passes quickly through the body and is excreted in the urine.  The remainder is taken up by any remaining thyroid tissue or papillary thyroid cancer cells in an effort to eradicate them. Although a survival benefit has not been demonstrated, radioiodine dose reduces the risk of recurrence of the disease.  Most specialists would agree that patients with large tumors (greater than 4 cm), those with gross positive margins, and those with metastatic disease to the lymph nodes should be given radioactive iodine ablation therapy.  Patients with small tumors (less than 1 cm) and negative nodes and clear margins are generally not recommended to have radioiodine ablation.

Follow-up

Patients with papillary thyroid cancer require routine follow up every 6 months to a year. During this visit a physical examination is performed and blood work is sent for a TSH and thyroglobulin level.  An ultrasound of the lymph nodes in the neck is also performed. The most common site of tumor recurrence is in the lymph nodes in the neck and is often heralded by a rise in the thyroglobulin level.  A radioiodine scan may also be helpful in identifying the site of disease.  In this setting, patients are typically referred for a biopsy of the suspicious node and may benefit from further surgery to remove the involved lymph nodes. Other patients may benefit from additional doses of radioactive iodine.