Riascos Maria Cristina, Barletta Justine A
Department of Pathology, Mass General Brigham, Harvard Medical School, Boston, MA, USA.
Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA, 02115, USA.
Endocr Pathol. 2025 Sep 4;36(1):32. doi: 10.1007/s12022-025-09876-x.
Although a diagnosis of anaplastic thyroid carcinoma (ATC) can be rendered on fine needle aspiration (FNA), a core needle biopsy is often performed to provide sufficient material for immunohistochemical and molecular analysis. Rendering an ATC diagnosis on core biopsy can be challenging due to limited material. It is crucial that other diagnostic entities in the differential, such as poorly differentiated thyroid carcinoma, medullary thyroid carcinoma, lymphoma, metastases, and NUT carcinoma (among others), are considered and that immunohistochemistry (IHC) is employed judiciously to support the diagnosis. IHC for BRAF V600E should also be performed for ATC to expeditiously assess BRAF V600E mutation status because BRAF-targeted therapy is a critical treatment option for patients with BRAF V600E-mutant ATC. Molecular testing utilizing next-generation sequencing (NGS) should also be initiated at the time of an ATC diagnosis both to confirm BRAF V600E mutation status and to evaluate for other actionable alterations in BRAF-wild-type ATC (such and NTRK or RET fusions or mismatch repair deficiency) and to assess tumor mutation burden. Additionally, IHC for PD-L1 is increasingly being utilized given the results of studies demonstrating the efficacy of checkpoint inhibitors in some ATC patients with PD-L1 expression in tumor cells (especially when utilized along with BRAF inhibitors in patients with BRAF V600E-mutant ATC). In this review, the morphologic and immunophenotypic features of ATC are outlined, the differential diagnosis is reviewed, and the therapeutic implications of key biomarkers are highlighted.
虽然细针穿刺活检（FNA）可用于诊断间变性甲状腺癌（ATC），但通常会进行粗针活检以提供足够的材料用于免疫组织化学和分子分析。由于材料有限，在粗针活检上做出ATC诊断可能具有挑战性。至关重要的是要考虑鉴别诊断中的其他实体，如低分化甲状腺癌、髓样甲状腺癌、淋巴瘤、转移瘤和NUT癌（等等），并且要明智地使用免疫组织化学（IHC）来支持诊断。对于ATC，还应进行BRAF V600E的IHC检测，以便快速评估BRAF V600E突变状态，因为BRAF靶向治疗是BRAF V600E突变型ATC患者的关键治疗选择。在诊断ATC时，也应启动利用下一代测序（NGS）的分子检测，以确认BRAF V600E突变状态，并评估BRAF野生型ATC中的其他可操作改变（如NTRK或RET融合或错配修复缺陷），并评估肿瘤突变负荷。此外，鉴于研究结果表明检查点抑制剂在一些肿瘤细胞中表达PD-L1的ATC患者中有效（特别是在BRAF V600E突变型ATC患者中与BRAF抑制剂联合使用时），PD-L1的IHC检测越来越多地被采用。在本综述中，概述了ATC的形态学和免疫表型特征，回顾了鉴别诊断，并强调了关键生物标志物的治疗意义。
