Evidence-based medicine has led to the development of a multitude of clinical practice guidelines and treatment pathways that seek to standardize the care for many disorders. An example of a common clinical problem for otolaryngologists that has historically had a multitude of treatment options is the thyroid nodule. The American Thyroid Association (ATA) has published a comprehensive set of guidelines on the workup and management of thyroid nodules that has been revised to reflect updates in the literature 1. This valuable document, among others related to thyroid disease, is available to download at the ATA website.
In many ways, the workup of a thyroid nodule is straight forward, but the clinical information obtained can be challenging to integrate into a treatment plan. After a comprehensive history and physical exam, the standard diagnostic studies include thyroid function tests (TSH) and thyroid ultrasound. The ultrasound can be done by radiology, endocrinology or by the surgeon, with certain advantages and disadvantages to each. The size and sonographic features of the nodule — solid, hypoechoic, central blood flow, microcalcifications — will determine those that warrant biopsy with a fine needle aspiration (FNA). Numerous studies have demonstrated the accuracy and cost effectiveness of FNA in the workup of thyroid nodules. The addition of ultrasound guidance improves the accuracy of FNAs and is particularly useful for nodules that are non-palpable, partially cystic or posteriorly located in the gland.
In 2007, the National Cancer Institute sponsored a conference on thyroid nodule FNAs, which resulted in the publication of the Bethesda System of Reporting Thyroid Cytopathology. This standardized, six-tier reporting system has been widely adopted by pathologists and offers significant benefit as it relates to risk stratification for malignancy. The six diagnostic categories 2 include:
- nondiagnostic or unsatisfactory
- atypia of undetermined significance/follicular lesion of undetermined significance (FLUS)
- follicular neoplasm/“suspicious” for follicular neoplasm
- suspicious for malignancy
There is little debate on the management of the two extremes (benign and malignant) of this categorization. Benign nodules can be followed with serial ultrasounds (6 to 12 months) to demonstrate size stability, and malignant nodules warrant surgery with a total thyroidectomy or a thyroid lobectomy depending upon certain clinical features such as size.
The management of nodules that fall between the extremes of benign and malignant can be more challenging. The risk of malignancy of FLUS is typically quoted at 5-15% 3. In comparison, the risk of malignancy for an FNA that shows follicular neoplasm is 20-25%, and in general, the recommendation for these patients is to perform a thyroid lobectomy.
So what do you tell a patient who has an FNA finding of FLUS? Is the risk of malignancy really only 5-15%? The answer to this question depends upon the cytopathologist. Consistent with other published reports in the literature, the rate of malignancy for FLUS at the University of Wisconsin is approximately 30% 4. Management options for FLUS include surgery, repeat FNA and observation. The surgeon’s recommendation to the patient must be made with the knowledge of the institutional rate of malignancy for FNAs read as FLUS. If the institutional rate of malignancy for FLUS is only 5%, it is reasonable to observe with serial ultrasounds. However, if the rate of malignancy is greater than that of a follicular neoplasm, then surgery with a thyroid lobectomy or a total thyroidectomy should be undertaken.
Recent work published in The New England Journal of Medicine evaluated the use of a gene-expression classifier (Veracyte) to identify benign nodules among a group of indeterminate FNAs. The negative predictive value of Veracyte for FLUS was 95% 5. The application of this genetic test continues to evolve. It is now commercially available, but it is expensive and insurance coverage is variable. Clinical practice guidelines may become more complicated as our ability to stratify patients using molecular and genetic testing improves, but the obvious advantage to patients will be the avoidance of unnecessary surgery.
1 Cooper DS, Doherty GM, Haugen BR et al. Revised American Thyroid Association Management Guidelines for Patients with Thyroid Nodules and Differentiated Thyroid Cancer. Thyroid. 2009;19(11):11167-214.
2 Cibas ES, Sanchez MA. The National Cancer Institute Thyroid Fine-Needle Aspiration State-of-the-Science Conference: Inspiration for a uniform terminology linked to management guidelines. Cancer. 2008;2:71–73.
3 Baloch ZW, LiVolsi VA, Asa SL et al. Diagnostic terminology and morphologic criteria for cytopathologic diagnosis of thyroid lesions: a synopsis of National Cancer Institute Fine-Needle Aspiration State of Science Conference. Diagn Cytopathol. 2008 June;36:425-437.
4 Ho AS, Sarti EE, Jain KS et al. Malignancy rate in thyroid nodules classified as Bethesda Category III (AUS/FLUS). Thyroid. 2013 Dec 16 [Epub ahead of print].
5 Alexander EK, Kennedy GC, Baloch ZW et al. Preoperative Diagnosis of Benign Thyroid Nodules with Indeterminate Cytology. N Eng J Med. 2012;367(8):705-715.