Anaplastic Thyroid Carcinoma With Kinase Gene Fusions: Report of 3 Cases With Corresponding Cytologic, Histologic, and Molecular Findings

Anaplastic thyroid carcinomas (ATCs) harboring oncogenic kinase fusion drivers are rare and highly aggressive malignancies that may benefit from targeted therapy. While fine needle aspiration (FNA) provides an opportunity for early diagnosis, the cytomorphologic features of these kinase fusion ATCs have not been specifically detailed in the literature. We present a focused analysis of three kinase fusion-positive ATCs with detailed cytologic, histologic, and molecular correlations. Our cases demonstrate cytologic features typical of conventional ATC, including marked nuclear atypia, sarcomatoid morphology, increased/atypical mitotic activity, and tumor necrosis. Although no microscopic features were identified cytologically or histologically that specifically distinguish kinase fusion-positive ATC from conventional ATC, negative immunohistochemistry for BRAF V600E and RAS Q61R may serve as an indication for early molecular testing that includes fusion analysis. Rapid genetic analysis would facilitate triage to optimal primary or neoadjuvant systemic therapy. This potentially allows for early patient triage for initiation of systemic and/or targeted therapies. The modest success observed with fusion-targeted therapy as part of a multimodal treatment strategy in our cohort is encouraging, although outcomes may be constrained by co-occurring oncogenic drivers, limited case numbers, and acquired resistance mechanisms.