Follicular and Hurthle Cell Thyroid Cancer

Follicular and Hurthle cell thyroid cancer makes up about 15 to 20% of all cases of thyroid cancer.

These cancers are actually two separate types of cancer, but they are often discussed together because they present and behave similarly. Follicular and Hurthle cell thyroid cancers are somewhat more aggressive than the more common papillary type. Similar to papillary cancer, they are most often discovered as a painless lump in the thyroid. They usually occur after the age of 40 and are more common in women than in men. Although risk factors for follicular and Hurthle cell thyroid cancer include radiation exposure and a family history of thyroid cancer, it is important to note that the majority of patients have no risk factors at all. Fortunately, most patients can be cured if treated appropriately and early enough. Follicular cancer tends to spread through the bloodstream and although it is common, can spread (i.e. metastasize) to the liver, lungs, bones, and brain. Hurthle cell cancers can spread through the blood or to the lymph nodes, but fortunately, metastasis is uncommon.

Signs and Symptoms

Most follicular and Hurthle cell thyroid cancers do not cause symptoms (i.e. they are asymptomatic). In fact, many patients will not know that they are there. Patients with large nodules may notice a palpable mass (i.e. a mass they can feel) or a visible mass (i.e. a mass they can see). Very large nodules may cause compressive symptoms which include difficulty swallowing, food or pills getting "stuck" when they swallow, and pressure or shortness of breath when lying flat. In cases of advanced cancer that are growing (i.e. invading) into surrounding structures, patients may develop hoarseness or difficulty swallowing. Enlarged neck lymph nodes that are concerning for cancer include those that are non-tender, firm, growing, and/or do not shrink over time. Patients with compressive symptoms, enlarged lymph nodes, hoarseness, and/or a rapidly growing nodule should seek medical evaluation right away.

Diagnosis

When a thyroid nodule is discovered, a complete history and physical examination should be performed.

In particular, the doctor is looking for risk factors for cancer that include: a family history of thyroid cancer, a history of radiation exposure to the head, neck, and/or chest, age less than 20, age greater than 70, male gender, very hard nodules, enlarged lymph nodes, and/or hoarseness. After the history and physical exam, a TSH level should be checked to see if the patient is euthyroid (i.e. normal thyroid function), hyperthyroid (i.e. hyperactive or overactive thyroid), or hypothyroid (i.e. underactive thyroid). In general, it is unusual for hyperthyroid patients to have cancer while patients who are hypothyroid may have a slightly higher rate of cancer. Most patients with thyroid cancer are euthyroid.

The next step in the work-up of a thyroid cancer is an ultrasound (USG) of the neck. There is no radiation associated with an USG. An USG is the best test to look at the thyroid and will allow the doctor to see the size of the thyroid and specific features of the nodule(s) including: size, number of nodules, if there are calcifications (calcium deposits), echotexture (i.e. how bright or dark it looks on USG), borders, shape, and if it is solid or cystic (i.e. fluid-filled). In general, USG findings that are concerning for thyroid cancer include microcalcifications (i.e. microcalcifications), hypoechoic nodules, hypervascularity (i.e. more blood vessels than normal), irregular borders, and enlarged suspicious lymph nodes.

The best test to determine if a thyroid nodule is benign or cancer is a fine-needle aspiration biopsy (FNAB). In this test, a small needle (like the needles used for drawing blood) is placed into the nodule either by USG or feeling the nodule with the fingers. Cells are removed from the nodule into the needle (i.e. aspirated) and looked at under the microscope by a specially trained doctor called a cytologist. There are a number of different guidelines as to which nodules should be biopsied, but in general, nodules over 1 cm should be biopsied. If a patient has risk factors for thyroid cancer (especially a family history of thyroid cancer or exposure to radiation therapy) or suspicious findings on USG, then nodules over 0.5 cm should be biopsied. The FNAB may give one of 4 results:

  • Non-diagnostic:

    This means that not enough cells were removed to make a diagnosis. Even in the best of hands, this happens in 5 to 10% of FNAB. Typically the FNAB will be repeated. If the nodule grows, then a repeat biopsy will usually be performed. In certain cases, a patient may go straight to an operation to make a diagnosis, especially if the risk of cancer is high or if the patient has had two or more non-diagnostic FNAB in the past.

  • Benign:

    This means that there is a 97% chance that the nodule is not cancer. In most cases, patients with a benign biopsy are watched with an USG and physical exam 6 months later, and then at regularly scheduled times. A patient with a benign nodule may still have an operation if the nodule is large, causing symptoms, or cosmetically unappealing.

  • Malignant:

    This means that there is a 97% chance that the nodule is cancer, usually a papillary thyroid cancer. Much less commonly, the FNAB can show a medullary or anaplastic thyroid cancer. Sometimes the cytologist reports that the nodule is "suspicious for thyroid cancer" which means that there is an 80 to 90% chance of cancer, again usually papillary thyroid cancer. Most patients with a FNAB of cancer will have a total thyroidectomy (i.e. removal of the entire thyroid) with or without removal of certain lymph nodes.

  • Indeterminate:

    This category includes different readings like: follicular lesion, follicular neoplasm, Hurthle cell lesion, Hurthle cell neoplasm, and atypical cells or atypical lesions. This means that the cytologist cannot tell if the nodule is cancer, but the cells do not look normal. There is a 15 to 20% chance of having thyroid cancer with an indeterminate biopsy. Said another way, 1 out of 5 people with an indeterminate biopsy will have cancer. (See Follicular and Hurthle Cell Cancer »)

    The only way to make a clear diagnosis of cancer or no cancer is to remove half or all of the thyroid and see if the cells in the nodule are invading (i.e. growing) outside of the nodule into the surrounding thyroid or outside of the thyroid. (See Thyroid Surgery »)

Unlike papillary thyroid cancer, it can be difficult to diagnose follicular and Hurthle cell thyroid cancer without performing surgery, because there are no characteristic changes in the way the thyroid cells look on FNAB. Rather, the only way to tell if an indeterminate lesion is a cancer is to look at the entire capsule around the nodule and see if there is any sign of invasion. Surgery is usually the only way of making a deinifitve diagnosis and patients typically require removal of at least half or all of the thyroid gland. If there is a cancer and only half of the thyroid has been removed, removal of the other half of the thyroid will be performed in an operation called a "completion thyroidectomy." (See Follicular and Hurthle Cell Thyroid Cancer Treatment »)


Ultrasound guided fine needle biopsy demonstrating the needle (white line) sampling the nodule

Of note, radioactive iodine (RAI) scans used to be performed routinely for patients with thyroid nodules because "hot" (i.e. hyperactive nodules) were rarely cancer (less than 1%) while "cold" (i.e. underactive nodules) carried a 10% risk of cancer. However, FNAB is far more accurate for determining the risk of cancer and RAI scans are mostly only used in cases of hyperthyroidism.

Treatment

Fortunately, patients with follicular and Hurthle cell cancer rarely need chemotherapy or traditional external beam radiation therapy. There are three main parts to the treatment of follicular and Hurthle cell cancer:

Surgery:

The best treatment for thyroid cancer is almost always total thyroidectomy (i.e. removal of the entire thyroid). However, the most common way in which patients with follicular and Hurthle cell thyroid cancer present is with an indeterminate biopsy (i.e. atypical cells, follicular lesion, follicular neoplasm, Hurthle cell lesion, or Hurthle cell neoplasm). With an indeterminate biopsy, the risk of having a follicular or Hurthle cell cancer is 15 to 20%. In this scenario, the patient has two choices — Thyroid lobectomy (i.e. remove the half of the thyroid with the nodule) or total thyroidectomy (i.e. remove the entire thyroid). The decision to remove half or the entire thyroid can be difficult. Columbia Thyroid Center physicians will help explain the risks and benefits for each treatment, but this ends up being a very personal decision and is ultimately a risk-benefit analysis for each individual patient. Factors that can help patients make this decision include:

  1. Need for thyroid hormone replacement: If only half of the thyroid is removed there is approximately a 60 to 70% chance of not needing to take thyroid hormone replacement pills. This percentage goes down if patients have Hashimoto's thyroiditis, a personal or family history of hypothyroidism (i.e. an underactive thyroid), and/or other autoimmune problems. This issue may not be relevant for patients who are already taking thyroid hormone pills.
  2. Contralateral nodules: If a patient has nodules in the other side of the thyroid, those nodules may need to be biopsied and/or removed in the future.
  3. Need for a second operation: If the patient is one of the 15 to 20% of people who have thyroid cancer and they have removed only half of the thyroid, they will need a second operation to remove the other half of the thyroid. Said another way, 1 of 5 people who have half of their thyroid removed for an indeterminate biopsy will need a second operation.

Many patients, especially those with contralateral nodules, will choose a total thyroidectomy in order to "be done with it once and for all" and will choose to take the thyroid hormone pills. Others want to avoid taking a pill a day for the rest of their lives and are willing to take the risk of needing a second operation and therefore choose a thyroid lobectomy. Ultimately, if a patient has a follicular or Hurthle cell cancer, they will need to have their entire thyroid removed.

Thyroid Hormone Suppression:

After removal of the entire thyroid, patients will need to take thyroid hormone replacement pills (usually one pill a day for the rest of their lives) in order to replace the hormone that the thyroid would normally make. Patients with thyroid cancer are typically given a slightly higher dose than patients without thyroid cancer in order to suppress or block any stimulation for thyroid cancer cells to grow. The thyroid hormone tricks the brain into thinking that enough thyroid hormone is being manufactured by the thyroid gland, therefore shutting down the brain's production of TSH (thyroid stimulating hormone which normally encourages the thyroid to make thyroid hormone). This is important because if TSH is left at high levels, it will stimulate both the remaining normal thyroid as well as any thyroid cancer and metastases to grow and enlarge. The thyroid hormone suppression dose for cancer is usually calculated to be 2 mcg/kg. In order to maintain a dose of thyroid hormone that is right for you, blood tests for thyroid function will need to be checked periodically. Generally, these blood tests are done every two months after surgery until a stable dose has been achieved, after which they may be done less frequently. Ask your doctor what is your correct individual dose.

Radioactive Iodine (RAI) Ablation:

Depending on the final pathology, the patient may need RAI ablation or what some doctors call remnant ablation. RAI ablation is not like the traditional external beam radiation which can be difficult on patients. RAI ablation is a pill that is taken once and usually causes few side effects. In this therapy, radioactive iodine is given to destroy any remaining thyroid cells (both cancer and benign) after total thyroidectomy. RAI ablation does not improve the overall excellent prognosis, but rather, it decreases the recurrence rate (i.e. chance of cancer coming back). Patients with lymphatic invasion (growth into the lymph channels), vascular invasion (i.e. growth into blood vessels), extrathyroid invasion (i.e. thyroid cancer that grows outside of the thyroid into surrounding tissue), thyroid cancer in lymph nodes (i.e. positive nodes), and/or thyroid cancer that has spread to other parts of the body (i.e. metastases) should have RAI ablation after total thyroidectomy. In general, follicular and Hurthle cell thyroid cancers with minimal capsular invasion (i.e. growth through the shell of the nodule but not outside the thyroid) do not require RAI ablation. It is important to note that Hurthle cell cancers tend not to absorb RAI very well and therefore these cancers are less responsive to RAI ablation. Having said that, thyroid specialists will often recommend RAI ablation for Hurthle cell cancers because

  1. some Hurthle cell cancers will respond to RAI ablation and
  2. by destroying any remaining normal thyroid tissue (i.e. remnant ablation) following post-operative thyroglobulin levels is more accurate in looking for recurrences. 
    See RAI ablation »

Fortunately, patients with follicular and Hurthle cell thyroid cancer rarely need chemotherapy or traditional external beam radiation therapy. External beam radiation is typically used in cases where the cancer has invaded into surrounding structures like the esophagus or windpipe (i.e. trachea). Finally, many people want to take an active role in their recovery from thyroid cancer. The Thyroid Center advises a healthy lifestyle and diet, including regular exercise, decreased alcohol consumption, avoiding cigarette smoking, and eating a diet which is low in fat and high in fiber. These changes are recommended to reduce many types of cancers, not just thyroid.

Follow-up

After surgery for follicular or Hurthle cell thyroid cancer, it is important to be examined regularly for signs that the cancer may have recurred. In general, patients should have a thyroglobulin blood test, TSH level, and USG of the neck every 6 months to a year. If the thyroglobulin level starts to go up, there are suspicious physical exam findings, or there are concerning nodules on USG, a RAI scan and/or FNAB may be done to determine if there is a recurrence.

Recurrence of Thyroid Cancer

Although thyroid cancer recurrence is not common, there are many treatment options available if it happens. If a cancer recurrence is detected in the neck lymph nodes, the best course of action is usually an operation to remove the affected node(s) or additional treatment with RAI ablation. In order to determine the best treatment for recurrent thyroid cancer, it is critical to work with an experienced team of thyroid specialists.