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

Area of Science:

• Pediatric Endocrinology
• Thyroid Pathology
• Molecular Diagnostics

Background:

• Pediatric thyroid nodules have a high malignancy risk (20-26%).
• Hyperfunctioning thyroid nodules are rare in children and usually benign.
• This study presents a rare case of malignant hyperfunctioning thyroid nodule in a child.

Purpose of the Study:

• To report a rare case of a hyperfunctioning thyroid nodule in a prepubertal child diagnosed as angioinvasive follicular carcinoma.
• To review and analyze published pediatric cases of hyperfunctioning thyroid nodules with malignant histology.
• To highlight diagnostic challenges and potential molecular mechanisms.

Main Methods:

• Case presentation of a 12-year-old boy with a progressively enlarging thyroid nodule.
• Laboratory tests (TSH, fT4, fT3), ultrasound, thyroid scintigraphy, and fine-needle aspiration cytology (FNAC).
• Surgical excision followed by histopathological examination and comprehensive molecular analysis (GNAS, TSHR, BRAF, RAS, TERT, DICER1).

Main Results:

• The nodule was autonomously functioning with suppressed TSH, classified as TIR2 on FNAC.
• Histopathology revealed angioinvasive encapsulated follicular carcinoma with papillary features.
• Molecular analysis identified a pathogenic GNAS gene variant; other common oncogenic alterations were absent.

Conclusions:

• Integrated evaluation is crucial for pediatric thyroid nodules, especially with coexisting hyperfunction and suspicious imaging.
• Follicular-patterned neoplasms with papillary architecture present diagnostic challenges in pediatric patients.
• Molecular analysis can aid in risk stratification and understanding the pathogenesis of autonomous function and malignancy.