Department of Pathology, Yale School of Medicine, 310 Cedar Street, LH-108, New Haven, CT, 06520, USA.
Virchows Arch. 2014 Apr;464(4):435-42. doi: 10.1007/s00428-014-1552-3. Epub 2014 Feb 19.
Papillary thyroid carcinomas (PTC) with BRAF (V600E) mutation are morphologically distinctive. They are typically classic or tall cell variants, show infiltrative borders, and are associated with desmoplasia/fibrosis, psammoma bodies, and well-developed nuclear features of papillary carcinoma. We hypothesize that morphologic features of PTC can help in the prediction of BRAF (V600E) mutation, and we evaluate the accuracy and the interobserver reproducibility of such prediction. Hematoxylin and eosin-stained sections from 50 PTCs comprising of 26 mutation-positive and 24 mutation-negative tumors were examined. BRAF (V600E) mutation was predicted correctly in 42/50 tumors (accuracy, 84 %) with 96 % sensitivity, 71 % specificity, and 78 % positive and 94 % negative predictive values (NPV). Subtle nuclear features of PTC (n = 10) had the highest (100 %) negative predictive value followed by well-circumscribed non-infiltrative tumor borders (17/22 mutation-negative tumors, 95 % NPV). The positive predictive value of infiltrative tumor borders (21/28 [75 %] mutation-positive), desmoplasia/fibrosis (23/31 [74 %] mutation-positive), and psammoma bodies (13/20 [65 %] mutation-positive) increased to 100 % when all three features were present (n = 8/8 mutation-positive). To assess interobserver reproducibility, two pathologists blinded to the mutational status evaluated 30 PTCs (15 mutation-positive and 15 mutation-negative) after self-training on 10 PTCs with known BRAF (V600E) mutational status (five mutation-positive and five mutation-negative). The prediction of the mutation was achieved with substantial agreement (κ value, 0.79) and accuracy (25/30, 83 %). This study demonstrates that BRAF (V600E) mutation in papillary thyroid carcinoma can be predicted on morphology with accuracy and with substantial interobserver agreement.
甲状腺乳头状癌（PTC）伴 BRAF（V600E）突变在形态学上具有特征性。它们通常为经典型或高细胞型变体，表现为浸润性边界，并与纤维变性/纤维化、砂粒体和乳头状癌的发育良好的核特征相关。我们假设 PTC 的形态特征有助于预测 BRAF（V600E）突变，我们评估了这种预测的准确性和观察者间的可重复性。检查了 50 例 PTC 的苏木精和伊红染色切片，包括 26 例突变阳性和 24 例突变阴性肿瘤。正确预测了 50 例肿瘤中的 42 例（准确性为 84%），具有 96%的敏感性、71%的特异性、78%的阳性预测值和 94%的阴性预测值（NPV）。PTC 的细微核特征（n=10）具有最高的（100%）阴性预测值，其次是边界清晰的非浸润性肿瘤（22 例突变阴性肿瘤中的 17 例，95%NPV）。浸润性肿瘤边界（28 例中的 21 例[75%]突变阳性）、纤维变性/纤维化（31 例中的 23 例[74%]突变阳性）和砂粒体（20 例中的 13 例[65%]突变阳性）的阳性预测值增加到 100%，当所有三个特征均存在时（n=8/8 例突变阳性）。为了评估观察者间的可重复性，两位病理学家在对 10 例已知 BRAF（V600E）突变状态的 PTC（5 例突变阳性和 5 例突变阴性）进行自我培训后，对 30 例 PTC（15 例突变阳性和 15 例突变阴性）进行了盲法评估。突变的预测具有显著一致性（κ 值，0.79）和准确性（25/30，83%）。这项研究表明，PTC 中 BRAF（V600E）突变可以通过形态学准确且具有显著观察者间一致性进行预测。
