Diagnostic Evaluation of Anaplastic Thyroid Carcinoma in Core Biopsy Specimens: Morphologic, Immunohistochemical, Molecular, and Therapeutic Considerations.

Although a diagnosis of anaplastic thyroid carcinoma (ATC) can be rendered on fine needle aspiration (FNA), a core needle biopsy is often performed to provide sufficient material for immunohistochemical and molecular analysis. Rendering an ATC diagnosis on core biopsy can be challenging due to limited material. It is crucial that other diagnostic entities in the differential, such as poorly differentiated thyroid carcinoma, medullary thyroid carcinoma, lymphoma, metastases, and NUT carcinoma (among others), are considered and that immunohistochemistry (IHC) is employed judiciously to support the diagnosis. IHC for BRAF V600E should also be performed for ATC to expeditiously assess BRAF V600E mutation status because BRAF-targeted therapy is a critical treatment option for patients with BRAF V600E-mutant ATC. Molecular testing utilizing next-generation sequencing (NGS) should also be initiated at the time of an ATC diagnosis both to confirm BRAF V600E mutation status and to evaluate for other actionable alterations in BRAF-wild-type ATC (such and NTRK or RET fusions or mismatch repair deficiency) and to assess tumor mutation burden. Additionally, IHC for PD-L1 is increasingly being utilized given the results of studies demonstrating the efficacy of checkpoint inhibitors in some ATC patients with PD-L1 expression in tumor cells (especially when utilized along with BRAF inhibitors in patients with BRAF V600E-mutant ATC). In this review, the morphologic and immunophenotypic features of ATC are outlined, the differential diagnosis is reviewed, and the therapeutic implications of key biomarkers are highlighted.