THADA-IGF2BP3 fusions detected in fine-needle aspiration specimens of thyroid nodules: An institutional experience

Introduction: Though the clinical significance of THADA-IGF2BP3 fusions detected in thyroid nodules preoperatively is still under investigation, the limited literature suggests these lesions are clinically low-risk. Methods: The pathology archives were searched from 2018 to 2022 for all thyroid nodules with a THADA-IGF2BP3 fusion detected via ThyroSeqV3® analysis. Patient demographics and tumor characteristics were collected. Statistical analyses were performed and p <.05 was considered statistically significant. This study was approved by the institutional review board. Results: The case cohort included 34 thyroid nodules with THADA-IGF2BP3 fusions from 32 patients (average age—56.1 years, range: 30–86, male to female ratio—10:22). The average nodule size was 3.2 cm (range: 1.3–7.3 cm). At the time of biopsy, 21 cases were diagnosed as atypia of undetermined significance/follicular lesion of undetermined significance, 12 as follicular neoplasm/suspicious for follicular neoplasm and 1 as suspicious for malignancy. Surgical resection was performed in 29 patients (13 partial and 16 total thyroidectomies) to give a total of 31 nodules. Papillary thyroid carcinoma was diagnosed in 19/31 (61%) cases. No cases showed extrathyroidal extension or lymphovascular invasion. The remaining cases were considered either a low-risk neoplasm or benign. Four cases of NIFTP on final surgical pathology harbored concurrent incidental papillary thyroid microcarcinoma. One patient had the THADA-IGF2BP3 fusion detected in bilateral nodules. Conclusions: THADA-IGF2BP3 fusions can occur in malignant, low-risk and benign thyroid neoplasms, where malignant neoplasms show lack of aggressive features. Therefore, such entities can be classified as clinically low risk.