Should there be a paradigm shift for the evaluation of isthmic thyroid nodules?

Purpose: Although the thyroid isthmus seems like a rudimentary structure that connects bilateral lobes, it is an undiscovered area that needs to be explored. Currently, the data is evolving that the increase in the risk of malignancy is higher in the isthmic nodules, and extrathyroidal extensions and lymph node metastases are more common in isthmic-derived malignant thyroid nodules. Therefore, we aimed to compare the malignancy rate of isthmic and lobar nodules, the ultrasonographic features of isthmic and lobar nodules, and presence of lymph node metastases, distant metastases, and extrathyroidal invasions in malignant isthmic nodules.

Methods: In this retrospective study, we enrolled patients between the ages of 18-80 years, who had thyroid nodule/nodules cytology and/or pathology results from January 2009 to November 2022. 9504 nodules were selected for the analysis of US findings, cytopathology results, and malignancy rates.

Results: A mean ± SD age of 55.3 ± 13.0 years with a female to male ratio of [7618 (80.2%)/1886(19.8%)] were included in the study. 962 of the nodules were at isthmic localization; whereas 8542 nodules were at lobar localization. 1188 nodules were resulted as malignant from histopathological evaluation. Of the 1188 malignant nodules, 986 nodules were (83.0%) PTC, 114 nodules (9.6%) were FTC, 55 nodules were (4.6%) MTC, 16 nodules 1.3% were Hurtle cell carcinoma, 8 nodules (0.7%) were anaplastic thyroid carcinoma, and 9 nodules (0.8%) were thyroid tumors of uncertain malignant potential (TT-UMP). 156 of the malignant nodules (13.1%) were located in the isthmus, whereas the majority of the malignant nodules (n = 1032, 86.9%) were located at the lobar parts (right or left) of the thyroid. When the metastasis patterns of isthmic and lobar thyroid cancers were examined, no significant relationship was found between isthmic and lobar cancers in terms of capsule invasion (p = 0.435), muscle invasion (p = 0.294), and lymph node metastasis (p = 0.633). A significant relation was found between nodule localization (isthmus-upper-middle and lower lobes) and malignancy (p < 0.001). In our logistic regression analysis, isthmic and upper pole nodule localizations, age and TI-RADS were evaluated as independent risk factors for malignancy (p < 0.001 for all factors).

Conclusion: We recommend nodule localization has to be considered an additional risk factor when performing a Fine Needle Aspiration Biopsy for the increased malignancy risk in this localization.