What’s the fuss about FLUS?

Thyroid fine needle aspiration is one of the most commonly performed cytologic procedures and is the standard diagnostic method for managing a patient with a thyroid nodule. Because most thyroid lesions are diagnosed using cytology, the terminology has evolved in recent years for the diagnosis of thyroid lesions to become a standardization of language that is used between doctors performing the procedures and those diagnosing the specimens, since often times these are not one in the same. In 2007, a large group of pathologists, endocrinologists, radiologists and surgeons met in Bethesda, Maryland with the goal to standardize the terminology used to describe thyroid cytology and the reporting of thyroid lesions. Published in 2008, this is known as The Bethesda System for Reporting Thyroid Cytolopathology.  This system has been widely adopted by cytopathologists as the standard reporting system, and anyone who deals with thyroid cytopathology on a routine basis is familiar with it.

The Bethesda System classifies thyroid cytology diagnoses into 6 categories: Non-diagnostic (I), Benign (II), Atypia of Undetermined Significance/Follicular Lesion of Undetermined Significance (AUS/FLUS, III), Follicular Lesion or Suspicious for Follicular Lesion (IV), Suspicious for Malignancy (V), and finally, Malignant (VI). All of these categories are pretty understandable by all who read them. The only category that gives many of us trouble is Category III, or AUS/FLUS. This category, combined with Category IV, are called “Indeterminate”, meaning that the lesion examined cannot be classified as benign or malignant by cytology alone. Category III is particularly troublesome the management of these lesions is unclear.

According to the American Thyroid Association 2014 Guidelines for the Diagnosis and Management of Thyroid Nodules and Differentiated Thyroid Cancer, patients with indeterminate thyroid nodules can undergo either additional testing using molecular methods, surveillance with repeat ultrasound or diagnostic surgical excision, depending on clinical factors and patient preference.

Molecular testing of indeterminate thyroid nodules can make a difference between surgery or surveillance in most cases, and has become fairly common in the practice of thyroid cytology. For example, using a certain molecular test called the “Gene Expression Classifier (GEC)”, an indeterminate nodule with a benign molecular result carries the same risk of malignancy as benign cytology alone (approximately 6%). These patients can avoid surgery and the risks that go along with it. However, an indeterminate nodule with a suspicious molecular result carries a 40% risk of malignancy. In these cases it should be pointed out that based on the molecular results the nodule cannot be put in the malignant category unequivocally, but cannot be classified as benign either. These patients are surgical candidates. That being said, not all of these patients will go to surgery, however, since every patients is different and these decisions are made on an individual basis.

The field of molecular cytology is still emerging. Technologies being developed now will have great utility in the near future to help correctly diagnose patients with treatable disease and safely rule out patients who do not have disease. These technologies will not replace the pathologist’s eyes when it comes to making a diagnosis. Without the pathologist performing triage of the specimens, testing will be over-utilized, and too much unnecessary testing will be performed.  Ultimately, testing should be performed on only those specimens that require it, and the pathologist is in the appropriate position to make those decisions together with the treating physician so that the patient is best served.