Shanghai Center of Thyroid Diseases, Shanghai, China.
Department of Endocrinology and Metabolism, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.
Front Endocrinol (Lausanne). 2022 Feb 7;13:822423. doi: 10.3389/fendo.2022.822423. eCollection 2022.
To investigate the clinical characteristics of papillary thyroid cancer (PTC) classified as Bethesda category III [atypia of undetermined significance (AUS)/follicular lesion of undetermined significance (FLUS)] by fine-needle aspiration (FNA) for precision treatment.
A total of 1,739 patients diagnosed with Bethesda category III (AUS/FLUS) by FNA were investigated, and 290 patients diagnosed with PTC were analyzed.
The rate of papillary thyroid microcarcinoma (PTMC) was 82.1% (238/290). The rates of lymph node metastases were 44.9% (22/49) and 25.2% (56/222) for PTC and PTMC, respectively (p = 0.006). The rates of extra-thyroid extension were 46.2% (24/52) and 19.8% (47/237) (p < 0.001). Compared with PTMC, PTC had significantly higher odds ratios (ORs) of 3.41 (1.81-6.44, p < 0.001), 2.19 (1.16-4.13, p = 0.016), and 2.51 (1.29-4.88, p = 0.007) for extra-thyroid extension, multifocality, and lymph node metastases, respectively, after adjustment for age and gender. The larger size and BRAF V600E mutation had a robust synergistic effect for invasive features. The rates of lymph node metastases, multifocality, and extra-thyroid extension were significantly increased with larger sizes harboring BRAF V600E mutation. Compared with PTMC harboring wild type (WT)-BRAF, PTC harboring BRAF V600E mutation had adjusted higher ORs of 3.01 (1.26-8.68, p = 0.015), 3.20 (1.22-8.42, p = 0.018), and 5.62 (2.25-14.01, p < 0.001) for lymph node metastases, multifocality, and extra-thyroid extension, respectively.
In this study, risk stratification was recommended for patients with Bethesda category III (AUS/FLUS) nodules with a size under 1 cm harboring WT-BRAF being regarded as low risk and should be recommended for active surveillance. Nodules with a size over 1 cm harboring WT-BRAF or those under 1 cm harboring BRAF V600E mutation could be regarded as moderate risk, and molecular testing should be recommended. However, those with a size over 1 cm harboring BRAF V600E mutation should be regarded as high risk, and a diagnostic surgery should be recommended.
研究通过细针穿刺（FNA）诊断为 Bethesda 类别 III（不明确意义的滤泡性病变/不典型性）的甲状腺乳头状癌（PTC）的临床特征，以便进行精准治疗。
对 1739 例通过 FNA 诊断为 Bethesda 类别 III（不明确意义的滤泡性病变/不典型性）的患者进行了研究，并对 290 例诊断为 PTC 的患者进行了分析。
甲状腺微小乳头状癌（PTMC）的比例为 82.1%（238/290）。PTC 和 PTMC 的淋巴结转移率分别为 44.9%（22/49）和 25.2%（56/222）（p=0.006）。甲状腺外侵犯率分别为 46.2%（24/52）和 19.8%（47/237）（p<0.001）。与 PTMC 相比，PTC 的甲状腺外侵犯、多灶性和淋巴结转移的优势比（OR）分别显著升高，为 3.41（1.81-6.44，p<0.001）、2.19（1.16-4.13，p=0.016）和 2.51（1.29-4.88，p=0.007），这些差异在调整年龄和性别后仍然存在。较大的肿瘤大小和 BRAF V600E 突变对侵袭性特征具有强大的协同作用。携带 BRAF V600E 突变的肿瘤体积越大，淋巴结转移、多灶性和甲状腺外侵犯的发生率越高。与携带野生型（WT）-BRAF 的 PTMC 相比，携带 BRAF V600E 突变的 PTC 的淋巴结转移、多灶性和甲状腺外侵犯的调整后 OR 分别为 3.01（1.26-8.68，p=0.015）、3.20（1.22-8.42，p=0.018）和 5.62（2.25-14.01，p<0.001）。
在这项研究中，建议对 Bethesda 类别 III（不明确意义的滤泡性病变/不典型性）结节进行风险分层，对于直径<1cm 且携带 WT-BRAF 的结节，建议进行积极监测。对于直径>1cm 且携带 WT-BRAF 或直径<1cm 且携带 BRAF V600E 突变的结节，建议进行分子检测。然而，对于直径>1cm 且携带 BRAF V600E 突变的结节，应视为高危，建议进行诊断性手术。
