Most anaplastic thyroid carcinomas (ATCs) arise from papillary thyroid carcinoma (PTC). This process is also called anaplastic transformation, and the morphological harbingers of this phenomenon in nodal recurrence have not been assessed systematically. For this reason, the current study focused on features of 10 PTCs with regional lymph node recurrence that was accompanied with disease progression due to anaplastic transformation in at least one of the nodal recurrences. The findings of additional 19 PTCs which recurred without anaplastic transformation after ≥ 10 years of follow-up served as the control group. There were no clinicopathological differences between the two groups at initial surgery including age, gender, tumor size, lymph node metastasis, distant metastasis, extrathyroidal extension, histologic subtype, and treatment. The median time from the initial thyroid surgery to anaplastic transformation in the nodal recurrence was 106 months (range 6 to 437 months). Mutational analyses showed recurrent PTCs with anaplastic transformation had a high prevalence of BRAF^V600E mutation (8/9) and TERT promoter mutation (9/9), both of which were detected in primary tumors. PIK3CA^H1047R mutation was detected in one case. No case had RAS mutation. Nineteen recurrent PTCs without anaplastic transformation harbored BRAF^V600E mutation and seventeen of these had TERT promoter mutation. Unlike primary tumors with subsequent nodal anaplastic transformation, TERT promoter mutation was only present in the metastatic nodal recurrence from 4 patients without transformation. No patients had neither high-grade features (necrosis and increased mitotic activity) nor solid/insular growth or hobnail cell features in their primary tumors. In the group of patients with transformation, 3 had solid/insular growth in the lymph node metastasis at the time of primary tumor resection (one displaying nuclear features of PTC and solid growth with increased mitotic activity, one with insular component consistent with poorly differentiated carcinoma component, and one displaying nuclear features of PTC and solid growth), and additional 2 patients had solid/insular growth with no high-grade features or poorly differentiated carcinoma component at the time of subsequent nodal recurrence prior to anaplastic transformation. Hobnail cell features were exclusively seen in subsequent metastatic lymph nodes prior to anaplastic transformation. The control group lacked solid/insular growth and hobnail cell features in the metastatic nodal disease. Aberrant p53 expression and loss of TTF-1 featured tumor components with anaplastic transformation. This series identified a subset of recurrent PTCs with TERT promoter mutation was prone to undergo anaplastic transformation, and that solid/insular growth and hobnail cell features were morphological predictors of anaplastic transformation in the nodal recurrence.

大多数甲状腺未分化癌 (ATC) 起源于甲状腺乳头状癌 (PTC)。这个过程也被称为间变性转化，这种现象在淋巴结复发中的形态学预兆尚未得到系统的评估。出于这个原因，目前的研究集中在 10 个 PTC 的特征上，这些 PTC 在至少一个淋巴结复发中伴有由于间变性转化导致的疾病进展。随访 ≥ 10 年后，另外 19 例 PTC 复发且无间变性转化的结果作为对照组。两组在初次手术时在年龄、性别、肿瘤大小、淋巴结转移、远处转移、甲状腺外扩散、组织学亚型和治疗等方面均无临床病理学差异。从最初的甲状腺手术到淋巴结复发的间变性转化的中位时间为 106 个月（范围 6 至 437 个月）。突变分析显示具有间变性转化的复发性 PTC 的患病率很高BRAF ^V600E突变 (8/9) 和TERT启动子突变 (9/9)，两者均在原发性肿瘤中检测到。1例检测到PIK3CA ^H1047R突变。没有病例有RAS突变。19 个没有间变性转化的复发性 PTC 携带BRAF ^V600E突变，其中 17 个具有TERT启动子突变。与随后发生淋巴结间变性转化的原发性肿瘤不同，TERT启动子突变仅存在于 4 名未转化的转移性淋巴结复发患者中。没有患者在其原发肿瘤中既没有高级特征（坏死和有丝分裂活动增加）也没有实体/岛状生长或钉状细胞特征。在发生转化的患者组中，3 例在原发肿瘤切除时淋巴结转移出现实性/岛状生长（1 例显示 PTC 的核特征和实性生长，有丝分裂活性增加，1 例具有岛状成分与低分化癌一致）部分，1 例显示 PTC 和实性生长的核特征），另外 2 名患者在间变性转化之前的随后淋巴结复发时有实性/岛状生长，没有高级别特征或低分化癌成分。在间变性转化之前，仅在随后的转移性淋巴结中看到了钉状细胞特征。对照组在转移性淋巴结病中缺乏实体/岛状生长和钉状细胞特征。异常的 p53 表达和 TTF-1 的缺失以具有间变性转化的肿瘤成分为特征。该系列确定了一部分复发性 PTCTERT启动子突变容易发生间变性转化，并且实体/岛状生长和钉状细胞特征是淋巴结复发中间变性转化的形态学预测因子。