Clinical Thyroidology® for the Public
Summaries for the Public from recent articles in Clinical Thyroidology
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THYROID NODULES
Are thyroid nodules in the isthmus different from nodules in the thyroid lobes?
BACKGROUND
Thyroid nodules are very common and found in up to 50% of individuals with imaging studies that include the neck. The concern about any thyroid nodule is whether they are a thyroid cancer. Fortunately, only 5-6% of thyroid nodules are cancers and the most common cancer by far is papillary thyroid cancer. The best way to determine if a nodule is a cancer is to perform a biopsy of nodules. The analysis of the cells in the biopsy sample (cytology) can make a diagnosis of benign (no cancer), at risk for cancer and cancer and help determine which patients should undergo thyroid surgery.
The thyroid is separated into right and left lobes connected by the isthmus. Some studies suggest that isthmus nodules, while less frequent than nodules within the thyroid lobes, may carry a higher risk of cancer than nodules in either thyroid lobe. There may be several reasons for this based on the anatomy of the thyroid. However, recently a study suggested potential differences in gene mutations found in thyroid cancer between the isthmus and the lobes. These gene mutations are identified using molecular marker analysis that is done on thyroid biopsies to determine the risk for a nodule being a cancer.
This study examines the cytologic and molecular marker differences between nodules and papillary thyroid cancer based on whether the cancer is in the isthmus or the thyroid lobes.
THE FULL ARTICLE TITLE
Jasim S, et al. Cytologic and molecular assessment of isthmus thyroid nodules and carcinomas. Thyroid. Epub 2024 Nov 11; doi: 10.1089/thy.2024.0254. PMID: 39527399.
SUMMARY OF THE STUDY
This study examined two groups of thyroid biopsy results obtained from a molecular marker company’s thyroid nodule data base (Afirma™). The molecular marker group included 177,227 samples while the thyroid pathology group included 583 samples of classic papillary thyroid cancer and 194 of a follicular subtype of papillary thyroid cancer.
There were 8527 (4.8%) isthmus nodules identified in the AfirmaTM database, with the remainder from the thyroid lobes. Isthmus nodules were twice as likely to have cytology that was suspicious for cancer or cancer (8.2% vs. 4.3%) and had twice the frequency of the molecular marker BRAF V600E (21% vs. 10.6%), an increased frequency of the more aggressive ALK/NTRK/RET fusions (4.6% vs. 2.5%) and a decreased frequency of the less aggressive NRAS mutations (7.8% vs. 13.2%). Despite these differences, analysis of clinical outcomes from 454 samples did not show differences in the aggressiveness of the cancers on pathology analysis or spread of the cancer to the lymph nodes.
WHAT ARE THE IMPLICATIONS OF THIS STUDY?
This study shows that isthmus nodules were more likely to be cancer and to have increased rates of higher-risk molecular mutations compared to nodules in the lobes. Despite these changes, the cancers identified did not appear to be more aggressive in the isthmus vs the lobes. While interesting, more studies are needed to confirm these findings before changing recommendations for the management of isthmus thyroid nodules.
— Alan P. Farwell, MD
ATA RESOURCES
Thyroid Cancer (Papillary and Follicular): https://www.thyroid.org/thyroid-cancer/
Fine Needle Aspiration Biopsy of Thyroid Nodules: https://www.thyroid.org/fna-thyroid-nodules/
Thyroid Nodules: https://www.thyroid.org/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 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.
Suspicious thyroid biopsy: this happens when there are atypical cytological features suggestive of, but not diagnostic for malignancy. Surgical removal of the nodule is required for a definitive diagnosis.
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.
Mutation: A permanent change in one of the genes.
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 ThyroseqTM
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, ALK/NTRK/RET fusions and RAS.
BRAF gene: this is gene that codes for a protein that is involved in a signaling pathway and is important for cell growth. Mutations in the BRAF gene in adults appear to cause cancer.
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