Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Histopathology. 2020 Aug;77(2):314-320. doi: 10.1111/his.14144. Epub 2020 Jul 23.
Treatment with a BRAF inhibitor, alone or in combination with a MEK inhibitor, may be considered for BRAF-mutant anaplastic thyroid carcinoma (ATC). The purpose of this study was to characterise the histology of BRAF V600E-mutant ATC.
We identified 28 ATC that were consecutively resected between 2003 and 2019. All tumour slides for each case were evaluated for the presence of a precursor tumour and for ATC morphology (sarcomatoid, pleomorphic giant cell, epithelioid or squamous). BRAF V600E mutation status was determined by BRAF V600E IHC or molecular analysis (OncoPanel NGS). Eighteen (64%) ATC had an associated well-differentiated precursor, including 10 (36%) with associated papillary thyroid carcinoma (PTC) and eight (29%) with associated follicular thyroid carcinoma (FTC) or Hürthle cell carcinoma (HCC). Most ATC (19 cases, 68%) demonstrated a mixed anaplastic morphology. Squamous morphology was present in four cases. Ten (36%) ATC had a BRAF V600E mutation. All ATC that had a PTC precursor had a BRAF V600E mutation (and all ATC with a BRAF V600E mutation had a PTC precursor), whereas no ATC with an FTC or HCC precursor had a BRAF V600E mutation. All four cases of ATC with a squamous morphology had a PTC precursor and a BRAF V600E mutation.
In our cohort, the presence of a PTC precursor predicted the presence of the BRAF V600E mutation, whereas ATC with an FTC or HCC precursor lacked a BRAF V600E mutation. A squamous morphology was associated with the presence of a PTC precursor and a BRAF V600E mutation.
对于 BRAF 突变的间变性甲状腺癌（ATC），可单独使用 BRAF 抑制剂或联合 MEK 抑制剂进行治疗。本研究的目的是描述 BRAF V600E 突变型 ATC 的组织学特征。
我们连续纳入了 2003 年至 2019 年间切除的 28 例 ATC。对每个病例的所有肿瘤切片进行了存在前驱肿瘤和 ATC 形态（肉瘤样、多形性巨细胞、上皮样或鳞状）的评估。通过 BRAF V600E IHC 或分子分析（OncoPanel NGS）确定 BRAF V600E 突变状态。18 例（64%）ATC 存在相关的高分化前驱肿瘤，包括 10 例（36%）与甲状腺乳头状癌（PTC）相关，8 例（29%）与滤泡状甲状腺癌（FTC）或 Hurthle 细胞癌（HCC）相关。大多数 ATC（19 例，68%）表现为混合性间变性形态。4 例存在鳞状形态。10 例（36%）ATC 存在 BRAF V600E 突变。所有存在 PTC 前驱肿瘤的 ATC 均存在 BRAF V600E 突变（并且所有存在 BRAF V600E 突变的 ATC 均存在 PTC 前驱肿瘤），而不存在 FTC 或 HCC 前驱肿瘤的 ATC 则不存在 BRAF V600E 突变。4 例存在鳞状形态的 ATC 均存在 PTC 前驱肿瘤和 BRAF V600E 突变。
在我们的队列中，存在 PTC 前驱肿瘤预测存在 BRAF V600E 突变，而存在 FTC 或 HCC 前驱肿瘤的 ATC 则不存在 BRAF V600E 突变。鳞状形态与存在 PTC 前驱肿瘤和 BRAF V600E 突变相关。
