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Summaries for the Public from recent articles in Clinical Thyroidology
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THYROID NODULE
Unnecessary surgery is performed in the majority of indeterminate cytology thyroid nodules managed without molecular testing

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BACKGROUND
Thyroid nodules are very common and may be found in up to 50% of individuals that have imaging of the neck. The concern of a thyroid nodule is whether it is a cancer. Fortunately, only 5-6% of nodules are cancerous. Evaluation of a thyroid nodule includes an ultrasound to characterize the nodule as to the risk of cancer followed by a thyroid biopsy of the higher risk nodules to make a diagnosis. About 15-20% of thyroid biopsies fall into the indeterminate category, meaning that the cells obtained by the biopsy are not entirely normal nor abnormal. Prior to the development of molecular marker testing, the only way to make a diagnosis in an indeterminate nodule was surgery to remove the nodule. This meant that many benign nodules were removed by surgery.

The major breakthrough to identify which indeterminate nodules are benign and do not require surgery was the development of molecular marker analysis on biopsy specimens. Molecular markers test for genes that are associated with cancer. If molecular marker testing is negative, the nodule is considered benign and does not require surgery. Thus, one of the main advantages of molecular testing in indeterminate thyroid nodules is the possibility of reducing the use of unnecessary thyroid surgery to make a diagnosis. However, these tests are costly and not widely available, particularly in Europe, and their cost-effectiveness has been challenged. The authors of this study aimed to evaluate the frequency of unnecessary thyroid surgery for indeterminate nodules without the aid of molecular tests in Europe.

THE FULL ARTICLE TITLE
 Mavromati M et al. Unnecessary thyroid surgery rate for suspicious nodule in the absence of molecular testing. Eur Thyroid J. 2023;12(6):e230114; doi: 10.1530/ETJ-23- 0114. PMID: 37855426.

SUMMARY OF THE STUDY
This was a single-center study of consecutive patients undergoing thyroid biopsy under ultrasound guidance between January 2017 and December 2021 in the endocrinology and radiology division of Geneva University Hospital. The European Thyroid Imaging and Reporting Data System (EU-TIRADS) score and the Bethesda System for Reporting Thyroid Cytopathology were assessed. Patients were referred to surgery if the patient have symptoms or if results were indeterminate or cancer. Unnecessary surgery was defined as benign pathology after initial surgery for a nodule with indeterminate cytology in the absence of local compressive symptoms. Indeterminate categories were Bethesda 3 (Atypia of Unknown Significance, AUS) , Bethesda 4 (Follicular Neoplasm, FN) and Bethesda 5 (Suspicious for Malignancy, SFM). Descriptive analysis was performed, and the association between EU-TIRADS score and rate of cancer in indeterminate nodules was evaluated.

Out of 1010 nodules in 862 patients (average age, 54.2 years), 1189 biopsies were performed. EU-TIRADS indeterminate scores 3 (33.5%) and 4 (41.9%) were the most frequent ultrasound findings. Surgery was indicated in 33.3% of all patients, and 56.8% underwent lobectomy. According to cytology, 36% of all AUS, 74% of all FN, and 97% of all SFM nodules were referred for surgery. For AUS, FN, and SFM nodules, the benign rate was 81%, 76%, and 21%, respectively. Combining the EU-TIRADS score with the Bethesda classification did not yield a significantly higher cancer rate. Surgery was considered unnecessary in 56%, 68%, and 21% of patients with Bethesda 3, 4, and 5.

WHAT ARE THE IMPLICATIONS OF THIS STUDY?
This study confirms that the majority of nodules with indeterminate cytology are indeed benign. What is not known is how many of the benign nodules with indeterminate cytology would also have negative molecular markers. However, it is likely that many of the benign nodules would also have negative molecular marker analysis. In this study, 56 to 68% of nodules with AUS/ FN cytology and 21% with SFM cytology did not harbor cancer. These cases reveal the real-life number of unnecessary thyroidectomies in indeterminate nodules and provides that case for more widespread use of molecular marker analysis.

— Alan P. Farwell, MD

ABBREVIATIONS & DEFINITIONS

Thyroid nodule: an abnormal growth of thyroid cells that forms a lump within the thyroid. While most thyroid nodules are non-cancerous (Benign), ~5% are cancerous.

Thyroid Ultrasound: a common imaging test used to evaluate the structure of the thyroid gland. Ultrasound uses soundwaves to create a picture of the structure of the thyroid gland and accurately identify and characterize nodules within the thyroid. Ultrasound is also frequently used to guide the needle into a nodule during a thyroid nodule biopsy.

Molecular markers: genes and microRNAs that are expressed in benign or cancerous cells. Molecular markers can be used in thyroid biopsy specimens to either to diagnose cancer or to determine that the nodule is benign. The two most common molecular marker tests are the AfirmaTM Gene Expression Classifier and Thyroseq™

Indeterminate thyroid biopsy: this happens a few atypical cells are seen but not enough to be abnormal (atypia of unknown significance (AUS) or follicular lesion of unknown significance (FLUS)) or when the diagnosis is a follicular or hurthle cell lesion. Follicular and hurthle cells are normal cells found in the thyroid. Current analysis of thyroid biopsy results cannot differentiate between follicular or hurthle cell cancer from noncancerous adenomas. This occurs in 15-20% of biopsies and often results in the need for surgery to remove the nodule..

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