{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T02:46:04Z","timestamp":1774579564294,"version":"3.50.1"},"reference-count":57,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2024,4,24]],"date-time":"2024-04-24T00:00:00Z","timestamp":1713916800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,9,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>Few cytologically indeterminate thyroid fine-needle aspirations (FNAs) harbor BRAF V600E. Here, we assess interobserver agreement for The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) category III (atypia of undetermined significance [AUS]) FNAs harboring BRAF V600E and contrast their features with those harboring non-BRAF V600E alterations, with attention to cytopathology experience.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Seven reviewers evaluated 5 AUS thyroid FNAs harboring BRAF V600E. To blind reviewers, cases were intermixed with 19 FNAs falling within other TBSRTC categories and in which genetic alterations other than BRAF V600E had been identified (24 FNAs total). Interobserver agreement against both \u201cindex\u201d and most popular (\u201cmode\u201d) diagnoses was calculated. Four additional BRAF V600E cases were independently reviewed.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Reviewers included 3 trainees and 3 American Board of Pathology (board)\u2013certified cytopathologists. Board-certified cytopathologists, whose experience ranged from 2 to more than 15 subspecialty practice years, had known AUS rates. BRAF V600E was identified in 5 of 260 (2%) AUS FNAs. Interobserver agreement was higher among cytopathologists with more experience. Mode diagnosis differed from index diagnosis in 6 of 11 cases harboring RAS-like alterations; mode diagnosis was AUS in 4 of 5 BRAF V600E FNAs.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Atypia of undetermined significance of thyroid FNAs harboring BRAF V600E is uncommon yet relatively reproducible, particularly among pathologists with experience. It is advisable to sequence BRAF across V600 in such cases.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ajcp\/aqae043","type":"journal-article","created":{"date-parts":[[2024,4,24]],"date-time":"2024-04-24T13:59:06Z","timestamp":1713967146000},"page":"302-313","source":"Crossref","is-referenced-by-count":4,"title":["Diagnostic interobserver agreement for thyroid fine-needle aspirates: Effects of reviewer experience and molecular diagnostics"],"prefix":"10.1093","volume":"162","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8782-9908","authenticated-orcid":false,"given":"Hamza N","family":"Gokozan","sequence":"first","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, NewYork-Presbyterian Hospital\/Weill Cornell Medical College , New York, NY , US"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Mostyka","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, NewYork-Presbyterian Hospital\/Weill Cornell Medical College , New York, NY , US"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Theresa","family":"Scognamiglio","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, NewYork-Presbyterian Hospital\/Weill Cornell Medical College , New York, NY , US"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James P","family":"Solomon","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, NewYork-Presbyterian Hospital\/Weill Cornell Medical College , New York, NY , US"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shaham","family":"Beg","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, NewYork-Presbyterian Hospital\/Weill Cornell Medical College , New York, NY , US"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Evan","family":"Stern","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, NewYork-Presbyterian Hospital\/Weill Cornell Medical College , New York, NY , US"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abha","family":"Goyal","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, NewYork-Presbyterian Hospital\/Weill Cornell Medical College , New York, NY , US"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Momin T","family":"Siddiqui","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, NewYork-Presbyterian Hospital\/Weill Cornell Medical College , New York, NY , US"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6624-7116","authenticated-orcid":false,"given":"Jonas J","family":"Heymann","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, NewYork-Presbyterian Hospital\/Weill Cornell Medical College , New York, NY , US"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2024,4,24]]},"reference":[{"key":"2024090305550026300_CIT0001","first-page":"27","article-title":"Overview of the 2022 WHO classification of thyroid neoplasms","volume-title":"Endocr Pathol.","author":"Baloch","year":"2022"},{"key":"2024090305550026300_CIT0002","first-page":"676","article-title":"Integrated genomic characterization of papillary thyroid carcinoma","volume-title":"Cell.","author":"Cancer Genome Research Atlas Network","year":"2014"},{"key":"2024090305550026300_CIT0003","first-page":"618","article-title":"BRAF mutation associated with other genetic events identifies a subset of aggressive papillary thyroid carcinoma","volume-title":"Clin Endocrinol 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correlation","volume-title":"Mod Pathol","author":"Virk","year":"2013"},{"key":"2024090305550026300_CIT0008","first-page":"1256","article-title":"Molecular alterations in partially-encapsulated or well-circumscribed follicular variant of papillary thyroid carcinoma","volume-title":"Thyroid.","author":"Howitt","year":"2013"},{"key":"2024090305550026300_CIT0009","first-page":"1191","article-title":"Molecular genotyping of papillary thyroid carcinoma follicular variant according to its histological subtypes (encapsulated vs infiltrative) reveals distinct BRAF and RAS mutation patterns","volume-title":"Mod Pathol.","author":"Rivera","year":"2010"},{"key":"2024090305550026300_CIT0010","doi-asserted-by":"crossref","DOI":"10.1007\/978-3-319-60570-8","volume-title":"The Bethesda System for Reporting Thyroid Cytopathology: Definitions, Criteria, and Explanatory Notes.","author":"Ali","year":"2018","edition":"2"},{"key":"2024090305550026300_CIT0011","first-page":"259","article-title":"Combining 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Cytopathol.","author":"Padmanabhan","year":"2017"},{"key":"2024090305550026300_CIT0018","first-page":"850","article-title":"Analysis of intra-observer and inter-observer variability of pathologists for non-benign thyroid fine needle aspiration cytology according to Bethesda system categories","volume-title":"Diagn Cytopathol.","author":"Kuzan","year":"2021"},{"key":"2024090305550026300_CIT0019","first-page":"1471","article-title":"Malignancy risk and reproducibility associated with atypia of undetermined significance on thyroid cytology","volume-title":"Surgery.","author":"Mathur","year":"2014"},{"key":"2024090305550026300_CIT0020","first-page":"152083","article-title":"Interobserver variability in inconclusive diagnostic categories of thyroid fine needle aspiration cytology: an urban-based tertiary hospital experience","volume-title":"Ann Diagn Pathol.","author":"Sripodok","year":"2023"},{"key":"2024090305550026300_CIT0021","first-page":"355","article-title":"Low reproducibility of 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carcinoma: results and review of a pilot study","volume-title":"Cancer Cytopathol","author":"Kim","year":"2022"},{"key":"2024090305550026300_CIT0025","first-page":"1","article-title":"2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer: The American Thyroid Association Guidelines Task Force on Thyroid Nodules and Differentiated Thyroid Cancer","volume-title":"Thyroid.","author":"Haugen","year":"2016"},{"key":"2024090305550026300_CIT0026","first-page":"306","article-title":"Fine-needle aspiration of thyroid nodules: a study of 4703 patients with histologic and clinical correlations","volume-title":"Cancer.","author":"Yang","year":"2007"},{"key":"2024090305550026300_CIT0027","first-page":"298","article-title":"Thyroid fine-needle aspiration with atypia of undetermined significance: a necessary or optional 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multi-institutional study on 4651 FNAs with a focus on the role of the interventional cytopathologist","volume-title":"Cancer Cytopathol","author":"Nacchio","year":"2023"},{"key":"2024090305550026300_CIT0035","first-page":"313","article-title":"Risk stratification of cytologically indeterminate thyroid nodules with nondiagnostic or benign cytology on repeat FNA: implications for molecular testing and surveillance","volume-title":"Cancer Cytopathol","author":"Hall","year":"2023"},{"key":"2024090305550026300_CIT0036","first-page":"355","article-title":"Development and analytical validation of an expanded mutation detection panel for next-generation sequencing of thyroid nodule aspirates","volume-title":"J Mol Diagn.","author":"Ablordeppey","year":"2020"},{"key":"2024090305550026300_CIT0037","first-page":"1682","article-title":"Analytical performance of the ThyroSeq v3 genomic classifier for cancer diagnosis in thyroid nodules","volume-title":"Cancer.","author":"Nikiforova","year":"2018"},{"key":"2024090305550026300_CIT0038","first-page":"817","article-title":"Performance of a genomic sequencing classifier for the preoperative diagnosis of cytologically indeterminate thyroid nodules","volume-title":"JAMA Surg","author":"Patel","year":"2018"},{"key":"2024090305550026300_CIT0039","first-page":"1217","article-title":"Impact of the multi-gene ThyroSeq next-generation sequencing assay on cancer diagnosis in thyroid nodules with atypia of undetermined significance\/follicular lesion of undetermined significance cytology","volume-title":"Thyroid.","author":"Nikiforov","year":"2015"},{"key":"2024090305550026300_CIT0040","first-page":"356","article-title":"Molecular analysis of residual ThinPrep material from thyroid FNAs increases diagnostic sensitivity","volume-title":"Cancer Cytopathol","author":"Krane","year":"2015"},{"key":"2024090305550026300_CIT0041","first-page":"238","article-title":"Differences in surgical resection rate and risk of malignancy in thyroid cytopathology practice between Western and Asian countries: a systematic review and meta-analysis","volume-title":"Cancer Cytopathol","author":"Vuong","year":"2020"},{"key":"2024090305550026300_CIT0042","first-page":"368","article-title":"Follicular epithelial dysplasia as Hashimoto thyroiditis-related atypia: a series of 91 specimens","volume-title":"Endocr Pathol.","author":"Kholov\u00e1","year":"2021"},{"key":"2024090305550026300_CIT0043","first-page":"587","article-title":"ACR thyroid imaging, reporting and data system (TI-RADS): white paper of the ACR TI-RADS committee","volume-title":"J Am Coll Radiol.","author":"Tessler","year":"2017"},{"key":"2024090305550026300_CIT0044","first-page":"64","article-title":"Can cytomorphology differentiate between benign nodules and tumors arising in Graves\u2019 disease","volume-title":"Diagn Cytopathol.","author":"Anderson","year":"2004"},{"key":"2024090305550026300_CIT0045","first-page":"67","article-title":"Molecular testing results as a quality metric for evaluating cytopathologists\u2019 utilization of the atypia of undetermined significance category for thyroid nodule fine-needle aspirations","volume-title":"J Am Soc Cytopathol","author":"VanderLaan","year":"2022"},{"key":"2024090305550026300_CIT0046","first-page":"109","article-title":"Molecular-derived risk of malignancy and the related positive call rate of indeterminate thyroid cytology diagnoses as quality metrics for individual cytopathologists","volume-title":"Cancer Cytopathol","author":"Ohori","year":"2023"},{"key":"2024090305550026300_CIT0047","first-page":"451","article-title":"Use of molecular testing results to analyze the overuse of atypia of undetermined significance in thyroid cytology","volume-title":"J Am Soc Cytopathol.","author":"Martinez Coconubo","year":"2023"},{"key":"2024090305550026300_CIT0048","first-page":"100124","article-title":"Successful integration of thyroid cytopathology and surgical pathology education in an E-module format","volume-title":"J Pathol Inform","author":"Rohr","year":"2022"},{"key":"2024090305550026300_CIT0049","first-page":"23742895211006819","article-title":"Using dynamic virtual microscopy to train pathology residents during the pandemic: perspectives on pathology education in the age of COVID-19","volume-title":"Acad Pathol","author":"Christian","year":"2021"},{"key":"2024090305550026300_CIT0050","first-page":"325","article-title":"A prospective assessment defining the limitations of thyroid nodule pathologic evaluation","volume-title":"Ann Intern Med.","author":"Cibas","year":"2013"},{"key":"2024090305550026300_CIT0051","first-page":"1336","article-title":"Observer variation in the diagnosis of follicular variant of papillary thyroid carcinoma","volume-title":"Am J Surg Pathol.","author":"Lloyd","year":"2004"},{"key":"2024090305550026300_CIT0052","first-page":"736","article-title":"Interobserver and intraobserver variation among experts in the diagnosis of thyroid follicular lesions with borderline nuclear features of papillary carcinoma","volume-title":"Am J Clin Pathol.","author":"Elsheikh","year":"2008"},{"key":"2024090305550026300_CIT0053","first-page":"17","article-title":"Interinstitutional variation in predictive value of the ThyroSeq v2 genomic classifier for cytologically indeterminate thyroid nodules","volume-title":"Surgery.","author":"Marcadis","year":"2019"},{"key":"2024090305550026300_CIT0054","first-page":"947","article-title":"Combined molecular and histologic end points inform cancer risk estimates for thyroid nodules classified as atypia of undetermined significance","volume-title":"Cancer Cytopathol","author":"Onken","year":"2021"},{"key":"2024090305550026300_CIT0055","doi-asserted-by":"crossref","DOI":"10.1007\/978-3-031-28046-7","volume-title":"The Bethesda System for Reporting Thyroid Cytopathology: Definitions, Criteria, and Explanatory Notes.","author":"Ali","year":"2023","edition":"3"},{"key":"2024090305550026300_CIT0056","first-page":"2019","article-title":"Tiny but mighty: use of next generation sequencing on discarded cytocentrifuged bile duct brushing specimens to increase sensitivity of cytological diagnosis","volume-title":"Mod Pathol","author":"Harbhajanka","year":"2020"},{"key":"2024090305550026300_CIT0057","first-page":"208","article-title":"Cytologic diagnosis of \u201catypical\u201d in serous fluid cytopathology: approach of the international system for reporting serous fluid cytopathology","volume-title":"Diagn Cytopathol.","author":"Chandra","year":"2022"}],"container-title":["American Journal of Clinical 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