Kinase Fusion–Related Thyroid Carcinomas: Towards Predictive Models for Advanced Actionable Diagnostics

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.