Background: Autonomously functioning (“hot”) thyroid nodules are overwhelmingly benign adenomas, and current guidelines recommend against biopsy due to the very low risk of malignancy. Rarely, differentiated thyroid carcinoma may arise within a hyperfunctioning nodule, creating a significant diagnostic challenge.
Case Presentation: We describe a 35-year-old woman initially diagnosed with hyperthyroidism in 2024. Previously, she had a 29 mm left thyroid nodule identified on ultrasound in 2022. Fine-needle aspiration (FNA) cytology performed at that time and cytology revealed atypia of undetermined significance (AUS). Afirma ® molecular testing was benign. As part of her hyperthyroidism evaluation in 2024, scintigraphy subsequently demonstrated a hyperfunctioning nodule consistent with a toxic adenoma with suppression of the surrounding gland. The patient preferred surgical intervention to radioactive iodine ablation and therefore underwent left hemithyroidectomy in March 2025. Surgical histopathology revealed minimally invasive follicular thyroid carcinoma without vascular invasion.
Conclusion: Follicular thyroid carcinoma arising in a toxic nodule is exceptionally rare. This case underscores the importance of maintaining suspicion for malignancy in toxic nodules despite currently recommended diagnostic algorithms. As well as in the setting of discordant diagnostic findings and highlights the limitations of cytology and molecular testing in follicular lesions. It suggests that clinically concerning hyperfunctioning nodules may still warrant surgical consideration.
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