ABSTRACT Introduction: BRAFV600E mutations have been associated with papillary thyroid carcinoma histological types including Tall-cell and Classical, peritumoral infiltration, and nuclear signs, whereas cytological features such as plump cells and sickle nuclei have also been associated with favorable thyroid FNA results for this tumor. BRAF and RAS are considered early driver mutations that contribute to the development of BRAF-like PTCs and RAS-like PTCs. Our aim was to assess the possible association between all Bethesda System cytological features and thyroid FNAs for papillary thyroid carcinoma and their potential predictive value for future BRAF V600E related biopsies. Methods: Our study analyzed 63 cases of PTCs operated on at our hospital over a five-year period between 2005 and 2017 that had previously undergone FNA and had been classified by the Bethesda System. BRAFV600E was identified by pyrosequencing paraffin-embedded tissues and comparing the cytological signs with the Bethesda System. In addition, a statistical and predictive study of the diagnostic factors “non-follicular”, “non-round nuclei” and “non-clear chromatin” was performed to discriminate BRAF-like signs from other hypothetical RAS-like follicular signs. Results: BRAFV600E was detected in 43/63 cases (68.2%). Histological types were significant (p<0.001), with the classical variant being the most prevalent 31/63 (49.2%) and independent by multivariate analysis Odd-Ratio 10.58 [2.67; 41.97]. Follicular cytological signs are negatively associated with BRAFV600E: follicular structure (p<0.001), round nuclei (p=0.015) and clear chromatin (p=0.049), while the diagnostic factors: “non follicular” (PPV 82.9, Sensitivity 79.1, negative predictive value 59.1, Specificity 65.0), “non-round nuclei” positive predictive value 76.6, Sensitivity 83.7, negative predictive value 56.3, Specificity 45.0 and “non-clear chromatin” positive predictive value 75.6, Sensitivity 79.1, negative predictive value 50.0, Specificity 45.0) have predictive value for the mutation. There was no individual significance for the remaining cytological features. Conclusions: Our study found no association between cytomorphological signs of thyroid FNA and BRAFV600E mutation. Considering the Bethesda System, there is an association (p=0.045) with numerous cases of mutated PTC in categories V and VI. Our results indicate, however, that the presence of signs referred to as "non-follicular", "non-round nuclei" and "non clear chromatin" in biopsy of Papillary Thyroid Carcinoma is predictive of BRAF type mutation, whereas follicular signs indicate a RAS type PTC, according to published literature. These results need to be confirmed or modified by further research.


中文翻译：

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甲状腺细针抽吸、Bethesda 系统和甲状腺乳头状癌中的 BRAFV600E 突变。活检的关联和预测。

摘要 简介：BRAFV600E 突变与甲状腺乳头状癌组织学类型（包括高细胞型和经典型）、瘤周浸润和核体征相关，而细胞学特征（如肥大细胞和镰状核）也与该肿瘤的良好甲状腺 FNA 结果相关。BRAF 和 RAS 被认为是早期驱动突变，有助于 BRAF 样 PTC 和 RAS 样 PTC 的发育。我们的目的是评估所有 Bethesda 系统细胞学特征与甲状腺乳头状癌甲状腺 FNA 之间可能的关联及其对未来 BRAF V600E 相关活检的潜在预测价值。方法：我们的研究分析了 2005 年至 2017 年五年间在我院接受手术的 63 例 PTC 病例，这些病例之前接受过 FNA，并已由 Bethesda 系统分类。通过对石蜡包埋组织进行焦磷酸测序并与 Bethesda 系统比较细胞学特征来鉴定 BRAFV600E。此外，对诊断因素“非滤泡”、“非圆形核”和“染色质不清晰”进行了统计和预测研究，以区分 BRAF 样体征和其他假设的 RAS 样滤泡体征。结果：43/63例（68.2%）检出BRAFV600E。组织学类型具有显着性（p<0.001），其中经典变异最为常见，为 31/63 (49.2%)，并且通过多变量分析，比值比是独立的，为 10.58 [2.67；2.67]。41.97]。滤泡细胞学体征与 BRAFV600E 呈负相关：滤泡结构 (p<0.001)、圆形细胞核 (p=0.015) 和清晰的染色质 (p=0.049)，而诊断因素：“非滤泡”（PPV 82.9，灵敏度 79.1，阴性）预测值 59.1，特异性 65.0)，“非圆形细胞核”阳性预测值 76.6，敏感性 83.7，阴性预测值 56.3，特异性 45.0，“染色质不清晰”阳性预测值 75.6，敏感性 79.1，阴性预测值 50.0，特异性45.0）对突变具有预测价值。其余细胞学特征没有个体意义。结论：我们的研究发现甲状腺 FNA 的细胞形态学体征与 BRAFV600E 突变之间没有关联。考虑到 Bethesda 系统，V 类和 VI 类中的大量 PTC 突变病例存在关联 (p=0.045)。然而，我们的结果表明，甲状腺乳头状癌活检中出现“非滤泡性”、“非圆形核”和“染色质不清晰”迹象可预测 BRAF 型突变，而滤泡性迹象表明根据已发表的文献，RAS 型 PTC。这些结果需要通过进一步的研究来证实或修改。