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

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.