Follicular and Hurthle Cell Cancer


Follicular and Hurthle cell thyroid cancer are forms of differentiated thyroid cancer that are less common than papillary thyroid cancer.  These tumors do have a similar presentation to papillary thyroid cancer.  Women predominate and these tumors tend to affect a slightly older patient population.  Risk factors include a family history of thyroid cancer and exposure to radiation.  The follicular cancers are often cured with surgery, however, they do have the ability to metastasize.  When this happens, the tumor often travels in the blood stream to distant organs like the lungs, liver and bone rather than to the lymph nodes as is more typically seen in papillary thyroid cancer.

Hurtle cell cancers behave similarly to follicular cancers.  However, when they spread, the disease often affects the lymph nodes.  An important feature of Hurthle cell cancers is that they do not take up radioactive iodine very well, making this form of therapy less effective.

Signs and Symptoms

While some patients may present with a large tumor causing difficulty swallowing or breathing, most patients have an asymptomatic nodule that is discovered on physical exam or on an imaging study done for some other purpose.  These tumors do not overexpress thyroid hormone, so the thyroid function blood tests are typically normal.


The diagnosis of follicular or Hurthle cell thyroid cancer is determined using the algorithm outline 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 (seen in Hurthle cell, but not follicular thyroid cancer).  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 (Hurthle cell cancer).

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 the cytopathologist sees a highly cellular specimen of monotonous, atypical follicular cells sometimes arranged in a microfollicular patter, it will be classified as a follicular neoplasm (Bethesda IV).  A needle biopsy cannot distinguish between a benign follicular adenoma and a malignant follicular carcinoma (which is why a Bethesda IV is sometimes called an “indeterminate” biopsy).  This determination can only be made by the pathologist once the nodule has been surgically removed.


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

Surgery for Follicular and Hurthle cell thyroid cancer

Most patients with follicular or Hurthle cell thyroid cancer initially have an “indeterminate” biopsy (Bethesda IV, follicular neoplasm, Hurthle cell neoplasm).  The biopsy results are often confusing and frustrating for patients who expected a clear diagnosis from the needle biopsy.  However, distinguishing between a benign follicular or Hurthle cell “adenoma” and a malignant “carcinoma” is not possible by preoperative needle biopsy or by intraoperative frozen section.  The reason for this is that the individual cells within both the benign and malignant tumors look the same under the microscope.  What defines a cancer is the behavior of those cells.  These tumors have a capsule around their entire circumference.  If the tumor cells remain within that capsule, then the tumor is benign (having not yet achieved the ability to metastasize).  If however, the tumor cells have broken through the capsule, then the tumor is malignant (cancer).  So, to distinguish between benign and malignant, the pathologist must evaluate the entire circumference of the tumor.  This is why surgical removal is required to make this determination and this is also why needle biopsy and frozen section at the time of surgery are not able to yield a reliable diagnosis.

Patients with an indeterminate biopsy have a 15 to 20% chance of harboring a cancer.  The treatment for follicular and Hurthle cell cancer is a total thyroidectomy (removal of the entire gland), while the treatment for a benign tumor is removing just the half of the thyroid that contains the tumor.  Together a patient and her surgeon must decide preoperatively how much thyroid to remove.  Several factors contribute to this decision making process.  First, 80% to 85% of patients will be done after having half the thyroid removed (final pathology benign).  But, about 1 in 5 patient (those whose final pathology is cancer) will have to return to the operating room for a second operation to remove the remaining thyroid.  Second, all patients who have their entire thyroid removed will need to take thyroid hormone replacement therapy, while only about a third of patients who have half of their thyroid removed will have to take thyroid hormone.  Third, patients who have nodules on the other side of their thyroid, will likely need needle biopsies that may lead to further surgery in the future.  And fourth, the complication rate from having half versus all of the thyroid removed is about the same.

Thyroid Hormone Suppression

One of the mainstays of treatment of follicular 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 the 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 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 reduce the risk of recurrence of the disease.  Hurthle cell cancers do not absorb radioiodine as well as the other forms of differentiated thyroid cancer.  However, some of these cancers do respond to radioiodine and ablation of the any remaining normal gland can be helpful when screening for potential recurrence in the future.


Patient diagnosed with follicular or Hurthle cell cancer are seen in follow up every 6 to 12 months.  To screen for potential recurrence, patients undergo physical examination and ultrasound of the neck and blood is drawn to determine the thyroglobulin level.  Patients with worrisome ultrasound findings typically will undergo a fine needle aspiration of the new target lesion to confirm or rule out the presence of recurrent disease.  Patients with a rising thyroglobulin level will also undergo further testing to identify the site of recurrent disease and to determine if it has the ability to absorb radioactive iodine.