Clinical Thyroidology® for the Public
Summaries for the Public from recent articles in Clinical Thyroidology
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THYROID NODULES
Molecular tests for thyroid nodules: unintended consequences
BACKGROUND
Thyroid nodules are very common, occurring in up to 50% of individuals. Ultrasound is the best way to evaluate a nodule. Nodules that are concerning on ultrasound are then recommended to proceed to a biopsy. In up to 25% of biopsies, the results are indeterminate, meaning that the cells cannot be clearly identified as either normal or abnormal. Prior to being able to test for molecular markers (tests to determine if any gene mutations associated with cancer are present), indeterminate nodules were usually sent to surgery. Now, by measuring molecular markers, those nodules with negative results (ie mutations are absent) are considered benign/not cancer and surgery can be avoided.
Despite their relatively high cost, molecular markers have been found to be cost-effective by virtue of ~50% decrease in thyroid surgery for indeterminate nodules. Molecular markers are now covered by most insurers in the United States and are widely used. In this study, the authors examined how these tests have changed clinical practices in real life.
THE FULL ARTICLE TITLE
Stillman MD et al. Molecular testing for Bethesda III thyroid nodules: Trends in implementation, cytopathology call rates, surgery rates, and malignancy yield at a single institution. Thyroid 2024;34(4):460-466; doi: 10.1089/ thy.2023.0664. PMID: 38468547.
SUMMARY OF THE STUDY
This study reports on an analysis of the effect of the availability of molecular testing on the interpretation of thyroid biopsy samples. The authors analyzed almost 9000 thyroid biopsies collected in a variety of settings that included both an academic medical center and an affiliated community site. Both an in-house molecular markers and all commercially available molecular markers were used during the study period. The use of molecular markers for indeterminate biopsies increased steadily during the study period and eventually became standard operating procedure. During the observation period, the rate of biopsies classified as indeterminate rose sharply, from 7.6% to 18.2%. Most of the change occurred at the expense of the benign results, which dropped from 73.5% to 62.1%. The frequency of positive molecular markers in indeterminate samples decreased from 23.6% to 20.4%, but the differences was not statistically significant. The cancer rate in indeterminate nodules submitted to surgery decreased from 57.1% to 50.0%, also not statistically significant.
WHAT ARE THE IMPLICATIONS OF THIS STUDY?
These data suggest that the use of molecular markers to confirm the absence or presence of gene mutations associated with cancer resulted in a decrease of reporting benign biopsy results and a corresponding increase in indeterminate results. Thus, cytopathologists appeared to have a lower threshold to call a biopsy indeterminate knowing that the molecular markers will measured because molecular markers are objective instrumental tests designed to improve the cancer risk stratification of thyroid nodules. As a result of these changes, the clinical performance of molecular markers in determining cancer may need to be revisited.
— Alan P. Farwell, MD
ATA RESOURCES
Thyroid Nodules: https://www.thyroid.org/thyroid-nodules/
Biopsy of Thyroid Nodules: https://www.thyroid.org/fna-thyroid-nodules/
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.
Thyroid biopsy: a simple procedure that is done in the doctor’s office to determine if a thyroid nodule is benign (non-cancerous) or cancer. The doctor uses a very thin needle to withdraw cells from the thyroid nodule. Patients usually return home or to work after the biopsy without any ill effects.
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.
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 Afirma™ Gene Expression Classifier and Thyroseq™
Mutation: A permanent change in one of the genes.
Genes: a molecular unit of heredity of a living organism. Living beings depend on genes, as they code for all proteins and RNA chains that have functions in a cell. Genes hold the information to build and maintain an organism’s cells and pass genetic traits to offspring.
Cancer-associated genes: these are genes that are normally expressed in cells. Cancer cells frequently have mutations in these genes. It is unclear whether mutations in these genes cause the cancer or are just associated with the cancer cells. The cancer-associated genes important in thyroid cancer are BRAF, RET/PTC, TERT and RAS.
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