Related Experiment Video
Updated: Oct 21, 2025
Spontaneous Murine Model of Anaplastic Thyroid Cancer
Published on: February 3, 2023
Kinase fusion-related thyroid carcinomas: distinct pathologic entities with evolving diagnostic implications
Ying-Hsia Chu1, Peter M Sadow2
1Fellow, Molecular Genetic Pathology, Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Abstract:
Activating genomic alterations in protein kinases represent a major driving force in thyroid carcinogenesis. Recently, oncogenic kinase fusions have been a central subject of pharmaceutical development, with a rapidly growing number of inhibitors validated for treating molecularly matched malignancies. Thyroid carcinomas harbor actionable kinase fusions in 10-15% of cases, occupying an increasingly recognized subpopulation of thyroid carcinomas with enhanced attention to molecular profiling. With advances in kinase-based cancer therapy, several challenges have emerged for pathologists. To interrogate an expanding list of targetable genes, the diagnostic paradigm has shifted from conventional single-gene methods toward high-throughput nucleic acid sequencing. Considering the relatively low incidence of most kinase fusions, a selective approach for molecular testing that utilizes histologic and immunohistochemical findings in triaging cases becomes essential for laboratory resource management. Moreover, kinase inhibitor resistance inevitably evolves, requiring a multimodal approach to optimal therapy, despite targeted therapies showing an enhanced, durable response. In this review, we assess the current clinicopathologic understanding and ongoing investigational topics in kinase fusion-related thyroid carcinomas.
Insights
Activating kinase fusions drive thyroid cancer. This review covers their pathology, diagnosis using molecular profiling, and challenges like drug resistance in targeted therapy.
Area of Science:
- Oncology
- Genetics
- Pathology
Background:
- Activating genomic alterations in protein kinases are key drivers of thyroid carcinogenesis.
- Oncogenic kinase fusions are a focus of pharmaceutical development for targeted cancer therapies.
- Thyroid carcinomas exhibit actionable kinase fusions in 10-15% of cases, highlighting the importance of molecular profiling.
Purpose of the Study:
- To review the clinicopathologic understanding of kinase fusion-related thyroid carcinomas.
- To discuss the evolving diagnostic paradigm and challenges for pathologists in the era of targeted therapy.
- To explore ongoing investigational topics in this specific subset of thyroid cancer.
Main Methods:
- Review of current literature on kinase fusions in thyroid cancer.
- Analysis of diagnostic shifts towards high-throughput nucleic acid sequencing.
- Discussion of histologic and immunohistochemical approaches for case triaging.
Main Results:
- Kinase fusions represent an important, targetable subpopulation of thyroid carcinomas.
- High-throughput sequencing is replacing conventional methods for interrogating targetable genes.
- Challenges include managing low incidence of fusions and evolving kinase inhibitor resistance.
Conclusions:
- Molecular profiling is crucial for identifying patients with actionable kinase fusions in thyroid cancer.
- Pathologists face challenges in adapting diagnostic workflows and managing targeted therapy resistance.
- A multimodal approach is necessary for optimal patient management despite advances in kinase-based therapies.
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