Department of Pathology and Laboratory Medicine, NewYork-Presbyterian Hospital/Weill Cornell Medical College, New York, NY, US.
Am J Clin Pathol. 2024 Sep 3;162(3):302-313. doi: 10.1093/ajcp/aqae043.
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.
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 "index" and most popular ("mode") diagnoses was calculated. Four additional BRAF V600E cases were independently reviewed.
Reviewers included 3 trainees and 3 American Board of Pathology (board)-certified 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.
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.
少数细胞学不确定的甲状腺细针抽吸（FNA）中存在 BRAF V600E。在此，我们评估了报告甲状腺细胞学病理的 Bethesda 系统（TBSRTC）类别 III（意义未确定的不典型性[AUS]）中存在 BRAF V600E 的 FNA 的观察者间一致性，并对比了它们与非 BRAF V600E 改变的特征，同时注意细胞学经验。
7 位审阅者评估了 5 例存在 BRAF V600E 的 AUS 甲状腺 FNA。为了使审阅者保持盲态，病例与其他 TBSRTC 分类中的 19 例 FNA 混合，这些 FNA 中除了 BRAF V600E 以外还存在其他基因改变（总共 24 例）。计算了针对“索引”和最常见（“模式”）诊断的观察者间一致性。另外独立审查了 4 例 BRAF V600E 病例。
审阅者包括 3 名受训者和 3 名美国病理学会（board）认证的细胞病理学家。board 认证的细胞病理学家的经验从 2 年到超过 15 年的亚专科实践经验不等，其知晓 AUS 发生率。在 260 例 AUS FNA 中，有 5 例（2%）发现了 BRAF V600E。经验更丰富的细胞病理学家之间的观察者间一致性更高。在存在 RAS 样改变的 11 例中有 6 例模式诊断与索引诊断不同；在 5 例 BRAF V600E FNA 中有 4 例模式诊断为 AUS。
存在 BRAF V600E 的甲状腺 FNA 的 AUS 并不常见，但具有相对可重复性，尤其是在有经验的病理学家中。在这种情况下，建议对 BRAF 进行 V600 测序。
