Evolving Pathology of Anaplastic Thyroid Carcinoma: Integrating Morphology, Immunohistochemistry, and Molecular Insights

Anaplastic thyroid carcinoma (ATC) is a rare malignancy characterized by an extremely aggressive clinical course, in contrast to the typically indolent behavior of most thyroid carcinomas. Recent advances in high-throughput sequencing technologies have markedly enhanced our understanding of the genetic alterations underlying ATC. These molecular insights have also influenced current clinical management and pathologic classification. In diagnostic pathology, squamous cell carcinoma arising in the thyroid is now recognized as a histologic variant of ATC. The BRAF p.V600E mutation, detected in approximately half of ATCs, represents a clinically significant genetic alteration, as targeted therapies directed against this mutation have been associated with improved clinical outcomes. In addition to advances in molecular pathology, progress has also been made in diagnostic pathology, including expanded recognition of the histologic spectrum of ATC and the development of novel immunohistochemical markers. In this review, we summarize recent advances in the diagnostic and molecular pathology of ATC, aiming to provide both fundamental and practical insights for clinical practice. In diagnostic pathology, ATC often presents significant challenges because of its marked histologic heterogeneity and a broad differential diagnosis. Accordingly, this review provides an overview of both classical knowledge and recent molecular findings related to ATC and integrates these insights to present an updated framework for differential diagnosis and diagnostic approach. In addition, we discuss recent advances in immunohistochemistry, including mutation-specific antibodies and novel diagnostic markers, and highlight their relevance in the context of contemporary diagnostic pathology and evolving therapeutic strategies.