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Updated: Aug 6, 2026
Spontaneous Murine Model of Anaplastic Thyroid Cancer
Published on: February 3, 2023
Anaplastic Thyroid Carcinoma With Kinase Gene Fusions: Report of 3 Cases With Corresponding Cytologic, Histologic,
Nicholas Jin Hong Tan1,2, Peter M Sadow1, Dora Dias-Santagata1
1Departments of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Abstract:
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.
Insights
Anaplastic thyroid carcinomas (ATCs) with kinase fusions are aggressive. Cytologic features are similar to conventional ATCs, but specific markers can guide molecular testing for targeted therapy.
Area of Science:
- Oncology
- Molecular Pathology
- Genetics
Background:
- Anaplastic thyroid carcinomas (ATCs) are rare, aggressive malignancies.
- Oncogenic kinase fusions are potential therapeutic targets in ATCs.
- Cytomorphologic features of kinase fusion-positive ATCs require detailed characterization.
Purpose of the Study:
- To analyze the cytologic, histologic, and molecular features of kinase fusion-positive ATCs.
- To identify potential diagnostic clues for kinase fusion-positive ATCs on fine needle aspiration (FNA).
- To correlate findings with treatment response and outcomes.
Main Methods:
- Case series analysis of three kinase fusion-positive ATCs.
- Detailed cytologic and histologic examination.
- Immunohistochemistry for BRAF V600E and RAS Q61R.
- Molecular testing including fusion analysis.
Main Results:
- Kinase fusion-positive ATCs showed cytologic features indistinguishable from conventional ATCs.
- Features included marked nuclear atypia, sarcomatoid morphology, atypical mitoses, and necrosis.
- Negative BRAF V600E and RAS Q61R immunohistochemistry may prompt molecular fusion analysis.
Conclusions:
- No specific cytologic or histologic features distinguish kinase fusion-positive ATCs from conventional ATCs.
- Early molecular testing, guided by negative BRAF/RAS IHC, is crucial for identifying fusion drivers.
- Targeted therapy shows modest success, but outcomes are influenced by co-occurring drivers and resistance mechanisms.
