College of American Pathologists
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  What is the role of fine needle aspiration in
  evaluating thyroid nodules?





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May 2007
PAP/NGC Programs Review

Patricia G. Wasserman, MD

A review of the new American Thyroid Association guidelines

The American Thyroid Association, or ATA, has updated its guidelines for evaluating and managing thyroid nodules and differentiated thyroid cancer and has published its new recommendations in the January 2006 issue of Thyroid. This is a summary of main points regarding the value and limitations of fine needle aspiration as a diagnostic tool in evaluating and managing thyroid nodules, as recommended by this panel of experts (Cooper D, et al. American Thyroid Association Guidelines Taskforce. Management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid. 2006;16:109–141).

Thyroid nodules are a widespread clinical problem. Palpable thyroid nodules are found in about five percent of women and one percent of men in iodine-sufficient parts of the world. On the contrary, thyroid nodules detected by ultrasound can be found in 19 percent to 67 percent of a random sample of individuals, with higher frequencies in women and the elderly. The challenge is to identify the five percent to 10 percent of thyroid cancers within this large number of thyroid nodules in the general population. In the United States, approximately 23,500 cases of differentiated thyroid cancer are diagnosed each year.

The task force appointed by the ATA developed clinical guidelines using principles of evidence-based medicine regarding the best methods for diagnostic evaluation of thyroid nodules, in terms of laboratory tests, imaging modalities, and fine needle aspiration; the most appropriate methods for long-term followup and treatment of thyroid nodules; the extent of surgery needed for small thyroid cancers; the role of medical therapy for benign thyroid nodules; and management of thyroid nodules in children and pregnant women.

A thyroid nodule is defined as a discrete lesion within the thyroid gland that is palpably or ultrasonographically distinct, or both, from the surrounding thyroid parenchyma. Nodules larger than 1 cm have the potential to harbor clinically significant cancers. Accordingly, only nodules 1 cm in size or greater should be evaluated, unless there are suspicious ultrasound findings, a history of head and neck irradiation, a positive family history of thyroid cancer in a first-degree relative, exposure to fallout from Chernobyl (under the age of 14), and rapid growth and hoarseness. Physical findings that suggest the possibility of malignancy include vocal cord paralysis, ipsilateral cervical lymphadenopathy, and nodule fixation to surrounding tissues.

Fine needle aspiration is the most accurate, cost-effective method for evaluating thyroid nodules, and the procedure of choice. FNA diagnostic categories include non-diagnostic, benign, malignant, and indeterminate or suspicious for neoplasm.

The authors recommend the following management guidelines for these diagnostic categories (Related article: Algorithm for the evaluation of patients with one or more thyroid nodules):

  • Non-diagnostic biopsies should be repeated using ultrasound guidance.
  • Repeatedly non-diagnostic aspirates of cystic lesions should be closely followed up or surgically excised. Excision should be strongly advised in those cases of solid nodules yielding non-diagnostic aspirations.
  • Surgical management is recommended for aspirates diagnostic for malignancy.
  • The incidence of indeterminate aspirates (“suspicious,” “follicular neoplasm,” or “follicular lesion”) is approximately 15 percent to 30 percent of thyroid FNAs. Currently, there are no good clinical or morphological predictive factors or specific molecular markers that help improve diagnostic accuracy. If a radioiodine thyroid scan does not demonstrate a concordant separate functioning nodule, a nodule yielding a diagnosis of indeterminate should be surgically excised, either with lobectomy or total thyroidectomy.
  • Aspirates interpreted as “suspicious for papillary carcinoma or Hurthle cell neoplasm” should undergo surgical treatment. In these cases, a radionuclide scan is not necessary.
  • Benign aspirates do not require further immediate diagnostic studies or treatment. Patients with multinodular goiters should undergo a diagnostic ultrasound to identify the nodule or nodules with the highest risk of harboring significant lesions. Suspicious sonographic characteristics include the presence of microcalcifications, hypoechogenicity of a solid nodule, and intranodular hypervascularity. These sonographically atypical nodules, especially those larger than 1 cm to 1.5 cm, should be preferentially aspirated.

What is the best method of long-term followup of patients with thyroid nodules?

Fine needle aspiration is the method of choice for evaluating thyroid lesions. However, it is not a perfect test. FNAs have a well-documented false-negative rate of approximately five percent. The false-negative rate is higher in those FNA cases performed with palpation (one percent to three percent) compared with those done under ultrasound guidance (0.6 percent). This is the basis for recommending followup even in nodules diagnosed as benign. Clinically significant nodular growth, preferably documented by serial ultrasounds (defined as 20 percent increase in diameter), is an indication for repeat aspiration.

Noticeably palpable benign nodules should undergo clinical followup at six- to 18-month intervals and do not require sonographic monitoring. All other benign nodules should be followed with serial ultrasounds at six- to 18-month intervals. Any clinical or sonographic evidence of nodular growth should generate a sonographically guided FNA.

What is the management of thyroid nodules in children?

Thyroid nodules are less prevalent in children than in adults, occurring in approximately 20 per 1,000 children. However, some studies show a higher rate of malignancy in children than in adults (15 percent to 20 percent). FNA biopsy is an accurate diagnostic method for childhood thyroid nodules. The diagnostic and therapeutic approach to one or more thyroid nodules in a child should be the same as in an adult.

What is the management of thyroid nodules in pregnant women?

Evaluation during pregnancy is the same as for a patient who is not pregnant except that a radionuclide scan is contraindicated. If the FNA is malignant, surgery should be considered before 24 weeks of gestation to minimize the risk of miscarriage.

Studies have shown that thyroid cancers in pregnant women have a similar biologic behavior to those diagnosed in a similar-aged group of non-pregnant women. There appears to be no difference in recurrence or survival rates between women operated on during or after pregnancy. In addition, there is evidence that treatment delays of less than one year do not adversely affect patient outcome. Therefore, it is wise to wait until after delivery for definitive surgery if the nodule remains stable by midgestation or if it is diagnosed in the second half of pregnancy.

Dr. Wasserman, a member of the CAP Cytopathology Committee, is with Long Island Jewish Medical Center, New Hyde Park, NY.

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