Pediatric thyroid nodules: A comprehensive study of cytology, histology, molecular findings, and risk of malignancy with emphasis on atypia of undetermined significance category.

Objective: Pediatric thyroid nodules are more challenging in clinical practice than in adults. Herein, we report our comprehensive experience with pediatric thyroid nodules, including cytology, histology, and molecular correlation.

Methods: Pediatric thyroid fine needle aspiration (FNA) performed from 2014 to 2024 was identified. Patients' demographics, FNA site, number and size of nodules, Bethesda category diagnosis, molecular studies, and surgical diagnoses were recorded.

Results: In 310 reports, 378 nodules from 302 patients were included. Patients' mean age was 17.0 years (range, 1-21 years). Applying the Bethesda system, benign diagnoses were most common (198/378, 52.4%), while the indeterminate category of atypia of undetermined significance (AUS) was the most prevalent (51/378, 13.5%). Surgical resection was performed in 36.8% (139/378) of cases, revealing malignancy in 50.0% of AUS, 45.4% of follicular neoplasms, and 93.8% of suspicious-for-malignancy cases. Among AUS subtypes, nuclear atypia was most frequently noted (16/30, 53.3%) and linked to papillary thyroid carcinoma in half of these cases (8/16, 50.0%). The risk of malignancy (ROM) increased with age and showed a female predominance (81.9%), with 86.1% of malignancies in the 16- to 21-year age group and no malignant histology in ages 0 to 5 years. Molecular testing, including Afirma (34/38, 89.5%) and Thyroseq (4/38, 10.5%), often returned suspicious (16/34, 47.1%) or intermediate (3/4, 75.0%) results.

Conclusions: Indeterminate diagnoses in pediatrics posed a significant ROM, particularly in female adolescents and early adulthood (ages 16-21 years). The AUS category was the most common among indeterminate categories, with AUS nuclear highly associated with malignancy. No malignancy was seen in ages 0 to 5 years.