Department of Pathology, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan.
Departments of Pathology, Massachusetts General Hospital and Harvard Medical School, Pathology Service, WRN 219, 55 Fruit Street, MA, 02114, Boston, USA.
Endocr Pathol. 2022 Dec;33(4):421-435. doi: 10.1007/s12022-022-09739-9. Epub 2022 Oct 29.
The past decade has brought significant advances in our understanding of the molecular mechanisms of thyroid carcinogenesis. Among thyroid carcinomas, the most successful class of targeted therapeutics appears to be selective kinase inhibitors. Actionable kinase fusions arise in around 10-15% of cases of thyroid cancer, a significant subset. A cohort of molecular testing platforms, both commercial and laboratory-derived, has been introduced into clinical practice to identify patients with targetable tumors, requiring pathologists to develop an integrative approach that utilizes traditional diagnostic cytopathology and histopathology, immunohistochemistry, and cutting-edge molecular assays for optimal diagnostic, prognostic, and therapeutic efficiency. Furthermore, there has been increasing scrutiny of the clinical behavior of kinase fusion-driven thyroid carcinoma (KFTC), still regarded as papillary thyroid carcinomas, and in characterizing molecular predictors of kinase inhibitor resistance with an aim to establish standardized, evidence-based treatment regimens. This review presents an overview of the current literature on the clinicopathologic and molecular features of KFTC as well as the latest investigational progress and encountered challenges for this unique subset of thyroid neoplasias.
过去十年，我们对甲状腺癌发生的分子机制的理解取得了重大进展。在甲状腺癌中，靶向治疗最成功的一类似乎是选择性激酶抑制剂。大约有 10-15%的甲状腺癌病例存在可操作的激酶融合，这是一个重要的亚组。一系列的分子检测平台，包括商业和实验室衍生的平台，已经引入临床实践，以识别可靶向肿瘤的患者，这要求病理学家采用一种综合的方法，利用传统的诊断细胞学和组织病理学、免疫组织化学和最先进的分子检测，以实现最佳的诊断、预后和治疗效果。此外，人们对激酶融合驱动的甲状腺癌（KFTC）的临床行为进行了越来越多的审查，KFTC 仍被认为是甲状腺乳头状癌，并对激酶抑制剂耐药的分子预测因子进行了特征描述，目的是建立标准化的、基于证据的治疗方案。本文综述了 KFTC 的临床病理和分子特征的最新文献，以及这一独特甲状腺肿瘤亚组的最新研究进展和遇到的挑战。
