Kinase fusion-related thyroid carcinomas: distinct pathologic entities with evolving diagnostic implications.

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.