{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T17:09:32Z","timestamp":1772730572666,"version":"3.50.1"},"reference-count":16,"publisher":"The Endocrine Society","license":[{"start":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T00:00:00Z","timestamp":1771977600000},"content-version":"am","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"The Children\u2019s Hospital of Philadelphia Frontier Program"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>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\u2019 theorem.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>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 \u223c71% post-test risk in a 9-year-old versus \u223c49% in a 24-year-old. AUS subtyping (nuclear vs other atypia) did not consistently separate ROM.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1210\/clinem\/dgag073","type":"journal-article","created":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T12:43:48Z","timestamp":1771937028000},"source":"Crossref","is-referenced-by-count":0,"title":["Age-specific risk of malignancy in pediatric thyroid cytology: Reframing ROM based on pre-test probability"],"prefix":"10.1210","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3736-1323","authenticated-orcid":false,"given":"Sule","family":"Canberk","sequence":"first","affiliation":[{"name":"Department of Pathology, Faculty of Medicine, RISE-Health, University of Porto (FMUP) , 4200-319 Porto ,","place":["Portugal"]}]},{"given":"Zubair W","family":"Baloch","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, University of Pennsylvania , Philadelphia, PA 19104 ,","place":["USA"]}]},{"given":"Amber","family":"Isaza","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Diabetes, The Thyroid Center, Children's Hospital of Philadelphia , Philadelphia, PA 19104 ,","place":["USA"]}]},{"given":"Mya","family":"Bojarsky","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Diabetes, The Thyroid Center, Children's Hospital of Philadelphia , Philadelphia, PA 19104 ,","place":["USA"]}]},{"given":"Elena","family":"Vigliar","sequence":"additional","affiliation":[{"name":"Department of Public Health, University of Naples Federico II , 80131 Naples ,","place":["Italy"]}]},{"given":"Anna Maria","family":"Carillo","sequence":"additional","affiliation":[{"name":"Department of Public Health, University of Naples Federico II , 80131 Naples ,","place":["Italy"]}]},{"given":"Filippo","family":"Dello Iacovo","sequence":"additional","affiliation":[{"name":"Department of Public Health, University of Naples Federico II , 80131 Naples ,","place":["Italy"]}]},{"given":"Claudio","family":"Bellevicine","sequence":"additional","affiliation":[{"name":"Department of Public Health, University of Naples Federico II , 80131 Naples ,","place":["Italy"]}]},{"given":"Giancarlo","family":"Troncone","sequence":"additional","affiliation":[{"name":"Department of Public Health, University of Naples Federico II , 80131 Naples ,","place":["Italy"]}]},{"given":"Mariana","family":"Simpl\u00edcio","sequence":"additional","affiliation":[{"name":"Department of Pathology, Faculty of Medicine, RISE-Health, University of Porto (FMUP) , 4200-319 Porto ,","place":["Portugal"]}]},{"given":"Helena","family":"Barroca","sequence":"additional","affiliation":[{"name":"Department of Pathology, Unidade Local de Sa\u00fade de S\u00e3o Jo\u00e3o , 4200-319 Porto ,","place":["Portugal"]}]},{"given":"Serra Zeynep","family":"Akkoyunlu","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, Istanbul Medical Faculty, Basic Medical Sciences , 34093 Istanbul, T\u00fcrkiye"}]},{"given":"Mehmet G\u00fcven","family":"G\u00fcnver","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, Istanbul Medical Faculty, Basic Medical Sciences , 34093 Istanbul, T\u00fcrkiye"}]},{"given":"Elisabete","family":"Rodrigues","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, ULS S\u00e3o Jo\u00e3o and Faculty of Medicine, University of Porto , 4200-319 Porto, Portugal"}]},{"given":"Jo\u00e3o","family":"Capela","sequence":"additional","affiliation":[{"name":"Endocrine and Neck Surgery Division, Department of Surgery, ULS S\u00e3o Jo\u00e3o and Faculty of Medicine, University of Porto , 4200-319 Porto, Portugal"}]},{"given":"Vivian L","family":"Weiss","sequence":"additional","affiliation":[{"name":"Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center , Nashville, TN 37232 ,","place":["USA"]}]},{"given":"Huiying","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center , Nashville, TN 37232 ,","place":["USA"]}]},{"given":"Ozlem","family":"Aydin","sequence":"additional","affiliation":[{"name":"Department of Pathology, School of Medicine, Acibadem Mehmet Ali Aydinlar University , 34752 Istanbul ,","place":["Turkey"]}]},{"given":"Eleni","family":"Thodou","sequence":"additional","affiliation":[{"name":"Department of Pathology, Faculty of Medicine, School of Health Sciences, University of Thessaly , Larissa 41500 ,","place":["Greece"]},{"name":"Private Cytology Laboratory , Volos, Thessaly 38221 ,","place":["Greece"]}]},{"given":"Hasan","family":"G\u00fccer","sequence":"additional","affiliation":[{"name":"Department of Pathology, School of Medicine, Recep Tayyip Erdo\u011fan University , 53100 Rize, Turkiye"}]},{"given":"Fernando","family":"Schmitt","sequence":"additional","affiliation":[{"name":"Department of Pathology, Faculty of Medicine, RISE-Health, University of Porto (FMUP) , 4200-319 Porto ,","place":["Portugal"]}]},{"given":"Andrew J","family":"Bauer","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Diabetes, The Thyroid Center, Children's Hospital of Philadelphia , Philadelphia, PA 19104 ,","place":["USA"]},{"name":"Department of Paediatrics, Perelman School of Medicine, Children's Hospital of Philadelphia , Philadelphia, PA 19104 ,","place":["USA"]}]}],"member":"80","published-online":{"date-parts":[[2026,2,25]]},"reference":[{"key":"2026030511114017900_dgag073-B1","doi-asserted-by":"crossref","first-page":"1270518","DOI":"10.3389\/fendo.2023.1270518","article-title":"Global incidence and prevalence of differentiated thyroid cancer in childhood: systematic review and 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comparison of clinical characteristics and long-term outcomes in 14 years and younger and 15-18 years age groups","volume":"70","author":"Satapathy","year":"2023","journal-title":"Pediatr Blood Cancer"},{"issue":"3","key":"2026030511114017900_dgag073-B11","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1007\/s00383-022-05069-3","article-title":"Incidence and prognosis of thyroid cancer in children: based on the SEER database","volume":"38","author":"Zhang","year":"2022","journal-title":"Pediatr Surg Int"},{"issue":"3","key":"2026030511114017900_dgag073-B12","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1016\/S2213-8587(20)30401-0","article-title":"; IICC-3 contributors. Global patterns and trends in incidence and mortality of thyroid cancer in children and adolescents: a population-based study","volume":"9","author":"Vaccarella","year":"2021","journal-title":"Lancet Diabetes Endocrinol"},{"issue":"8","key":"2026030511114017900_dgag073-B13","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1002\/cncy.22809","article-title":"Risks of malignancy in the major nongynecologic cytopathology reporting systems: critiques and discussions","volume":"132","author":"Pusztaszeri","year":"2024","journal-title":"Cancer Cytopathol"},{"issue":"1","key":"2026030511114017900_dgag073-B14","doi-asserted-by":"crossref","first-page":"207","DOI":"10.2307\/2530820","article-title":"Assessment of diagnostic tests when disease verification is subject to selection bias","volume":"39","author":"Begg","year":"1983","journal-title":"Biometrics"},{"issue":"4","key":"2026030511114017900_dgag073-B15","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1177\/096228029800700403","article-title":"Correcting for verification bias in studies of a diagnostic test's accuracy","volume":"7","author":"Zhou","year":"1998","journal-title":"Stat Methods Med Res"},{"issue":"5","key":"2026030511114017900_dgag073-B16","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1002\/cncy.22544","article-title":"Subtype of atypia on cytology and risk of malignancy in pediatric thyroid nodules","volume":"130","author":"Cherella","year":"2022","journal-title":"Cancer Cytopathol"}],"container-title":["The Journal of Clinical Endocrinology &amp; Metabolism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jcem\/advance-article-pdf\/doi\/10.1210\/clinem\/dgag073\/67112236\/dgag073.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jcem\/advance-article-pdf\/doi\/10.1210\/clinem\/dgag073\/67112236\/dgag073.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T16:11:54Z","timestamp":1772727114000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jcem\/advance-article\/doi\/10.1210\/clinem\/dgag073\/8497622"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,25]]},"references-count":16,"URL":"https:\/\/doi.org\/10.1210\/clinem\/dgag073","relation":{},"ISSN":["0021-972X","1945-7197"],"issn-type":[{"value":"0021-972X","type":"print"},{"value":"1945-7197","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,25]]},"article-number":"dgag073"}}