Department of Pathology and Laboratory Medicine, Cleveland Clinic, Cleveland, Ohio, USA.
Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, Ohio, USA.
Diagn Cytopathol. 2024 Jun;52(6):295-302. doi: 10.1002/dc.25290. Epub 2024 Feb 19.
BRAF mutation is the most common molecular alteration found in papillary thyroid carcinoma (PTC) and has been linked to recurrent disease or possibly more aggressive behavior. Some studies have reported sickle-shaped nuclei (SSN) and plump pink cells (PPC) to be predictive markers of BRAF mutation in FNA cytology. We aimed to evaluate the reproducibility of the aforementioned cytologic features.
A computerized search for diagnosed PTC surgical pathology cases tested for BRAF mutation by Sanger DNA sequencing was performed. Blinded to BRAF results, the corresponding cytology was reviewed for presence of SSN and PPC. Classic nuclear PTC (CNPTC) features, cystic change, and psammoma bodies were also evaluated. The results were correlated with BRAF mutational status and histologic subtypes.
Study cohort consisted of 113 cases (74 BRAF mutated, 39 BRAF wild type). SSN and combined CNPTC /SSN had positive predictive value of 74% and 75%, respectively. CNPTC showed 92% sensitivity and 20% specificity. Psammoma bodies had 92% specificity and 5% sensitivity. The presence of combined PPC/SSN showed 80% specificity, 27% sensitivity, and diagnostic accuracy of 45%. CNPTC was seen in 60/61 (98%) SSN and 45/45 (100%) PPC. There was no significant statistical association between SSN, PPC, and CNPTC with specific histologic subtypes and BRAF mutational status.
CNPTC is sensitive but not specific for BRAF mutational status. SSN, PPC, and CNPTC are not predictive markers for the presence of BRAF mutation or histologic subtypes. Additional studies may be needed to further corroborate these findings.
BRAF 突变是甲状腺乳头状癌（PTC）中最常见的分子改变，与复发性疾病或可能更具侵袭性的行为有关。一些研究报告称，镰状核（SSN）和圆润的粉红色细胞（PPC）是 FNA 细胞学中 BRAF 突变的预测标志物。我们旨在评估上述细胞学特征的可重复性。
通过 Sanger DNA 测序对诊断为 PTC 手术病理病例进行 BRAF 突变检测，对计算机检索进行。在不了解 BRAF 结果的情况下，对相应的细胞学进行 SSN 和 PPC 的存在进行审查。还评估了经典核 PTC（CNPTC）特征、囊性变和砂粒体。结果与 BRAF 突变状态和组织学亚型相关。
研究队列包括 113 例（74 例 BRAF 突变，39 例 BRAF 野生型）。SSN 和合并的 CNPTC/SSN 的阳性预测值分别为 74%和 75%。CNPTC 的敏感性为 92%，特异性为 20%。砂粒体的特异性为 92%，敏感性为 5%。联合 PPC/SSN 的存在具有 80%的特异性、27%的敏感性和 45%的诊断准确性。61 例 SSN 中可见 CNPTC（98%），45 例 PPC 中可见 CNPTC（100%）。SSN、PPC 和 CNPTC 与特定组织学亚型和 BRAF 突变状态之间没有显著的统计学关联。
CNPTC 对 BRAF 突变状态敏感，但特异性不高。SSN、PPC 和 CNPTC 不是 BRAF 突变或组织学亚型存在的预测标志物。可能需要进一步的研究来进一步证实这些发现。
