Malignancy in Pediatric Hyperfunctioning Thyroid Nodules: A Case Report and Literature Review

ABSTRACT Background Thyroid nodules are rare in children but carry a markedly higher risk of malignancy compared to adults (20%–26% vs. 5%). Hyperfunctioning thyroid nodules are exceptionally uncommon in the pediatric population and are typically benign. We describe a rare case of a hyperfunctioning thyroid nodule in a prepubertal child that was ultimately diagnosed as an angioinvasive encapsulated follicular carcinoma, arising in the context of the WHO entity ‘follicular adenoma showing papillary architecture’. In addition, we provide a comprehensive review of published pediatric cases of hyperfunctioning thyroid nodules with malignant histology. Case Presentation A 12‐year‐old boy presented with a left‐sided thyroid nodule detected on ultrasound after cervical swelling. Laboratory evaluation revealed suppressed thyroid‐stimulating hormone (TSH), with free thyroxine (fT4) and free triiodothyronine (fT3) within the reference range. Serial ultrasound examinations revealed a progressively enlarging mildly hypoechoic nodule, autonomously functioning on thyroid scintigraphy. Fine‐needle aspiration cytology (FNAC) was classified as TIR2. Surgical excision showed a follicular‐patterned neoplasm showing papillary features, focal capsular and vascular invasion and no lymph node metastases. Comprehensive molecular analysis identified a pathogenic somatic variant in the GNAS gene, whereas no alterations were detected in TSHR , BRAF , RAS genes, the TERT promoter, or DICER1 . Conclusion This case highlights the importance of an integrated evaluation in pediatric thyroid nodules, particularly when hyperfunction coexists with indeterminate or suspicious imaging features. Follicular‐patterned thyroid neoplasms showing papillary architecture pose diagnostic challenges in children, and molecular analysis may assist risk stratification and elucidate pathogenetic mechanisms linking autonomous function and malignant transformation.