The Journal of clinical endocrinology and metabolism · 2026
Age-specific risk of malignancy in pediatric thyroid cytology: Reframing ROM based on pre-test probability.
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Canberk Sule, Baloch Zubair W, Isaza Amber, Bojarsky Mya, Vigliar Elena, Carillo Anna Maria, Dello Iacovo Filippo, Bellevicine Claudio, Troncone Giancarlo, Simplício Mariana, Barroca Helena, Akkoyunlu Serra Zeynep, Günver Mehmet Güven, Rodrigues Elisabete, Capela João, Weiss Vivian L, Wang Huiying, Aydin Ozlem, Thodou Eleni, Gücer Hasan, Schmitt Fernando, Bauer Andrew J
Аннотация
OBJECTIVE: Pediatric thyroid nodules are uncommon but have a higher malignancy rate than adult nodules. Existing Bethesda risk-of-malignancy (ROM) estimates are not age-stratified and are affected by verification bias. We aimed to generate age-specific ROM, likelihood ratios (LRs), and post-test malignancy probabilities for pediatric and young adult thyroid cytology.
METHODS: We analysed 2728 thyroid fine-needle aspirations (FNAs) from patients aged 0-25 years across multiple tertiary centers (2000-2023). All cases were classified or reclassified using the 2023 Bethesda System and grouped into four age bands (0-8, 9-14, 15-18, and 19-25 years). We calculated lower-bound ROM (ROM overall; assuming nonoperated FNAs were benign) and surgery-only upper-bound ROM (ROM surgery; 991 of 2728 cases with histology). Age-specific pretest probabilities and Bethesda-category LRs were used to compute post-test malignancy probabilities with Bayes' theorem.
RESULTS: Among operated nodules, malignancy prevalence decreased with age (84.2% at 0-8 years to 64.6% at 19-25 years). Verification bias was substantial: malignancy prevalence was 24.6% (671/2728) under the lower-bound assumption but 67.7% (671/991) among surgical cases. Upper-bound ROM values were 2-10 times higher than lower-bound values across categories. Benign cytology showed low LRs (0.07-0.15), reducing post-test malignancy probability to 0-25%. Indeterminate categories showed age-related variation; for example, a follicular neoplasm diagnosis carried a ∼71% post-test risk in a 9-year-old versus ∼49% in a 24-year-old. AUS subtyping (nuclear vs other atypia) did not consistently separate ROM.
CONCLUSION: Age substantially modifies both pretest and post-test malignancy probabilities in pediatric thyroid cytology. An age-stratified LR framework helps quantify verification bias and provides individualized risk estimates to guide decisions about surgery, molecular testing, and follow-up.
METHODS: We analysed 2728 thyroid fine-needle aspirations (FNAs) from patients aged 0-25 years across multiple tertiary centers (2000-2023). All cases were classified or reclassified using the 2023 Bethesda System and grouped into four age bands (0-8, 9-14, 15-18, and 19-25 years). We calculated lower-bound ROM (ROM overall; assuming nonoperated FNAs were benign) and surgery-only upper-bound ROM (ROM surgery; 991 of 2728 cases with histology). Age-specific pretest probabilities and Bethesda-category LRs were used to compute post-test malignancy probabilities with Bayes' theorem.
RESULTS: Among operated nodules, malignancy prevalence decreased with age (84.2% at 0-8 years to 64.6% at 19-25 years). Verification bias was substantial: malignancy prevalence was 24.6% (671/2728) under the lower-bound assumption but 67.7% (671/991) among surgical cases. Upper-bound ROM values were 2-10 times higher than lower-bound values across categories. Benign cytology showed low LRs (0.07-0.15), reducing post-test malignancy probability to 0-25%. Indeterminate categories showed age-related variation; for example, a follicular neoplasm diagnosis carried a ∼71% post-test risk in a 9-year-old versus ∼49% in a 24-year-old. AUS subtyping (nuclear vs other atypia) did not consistently separate ROM.
CONCLUSION: Age substantially modifies both pretest and post-test malignancy probabilities in pediatric thyroid cytology. An age-stratified LR framework helps quantify verification bias and provides individualized risk estimates to guide decisions about surgery, molecular testing, and follow-up.