Dissecting Anaplastic Thyroid Carcinoma: A Comprehensive Clinical, Histologic, Immunophenotypic, and Molecular Study of 360 Cases
Top Cited Papers
- 1 October 2020
- journal article
- research article
- Published by Mary Ann Liebert Inc in Thyroid®
- Vol. 30 (10), 1505-1517
- https://doi.org/10.1089/thy.2020.0086
Abstract
Background: Anaplastic thyroid carcinoma (ATC) is nearly always fatal. Large studies on ATC are exceedingly rare. We aimed to study the clinical, genotypic and histologic characteristics of ATC in the largest retrospective cohort of ATC to date. Methods: Three hundred and sixty patients with ATC from 2 tertiary centers were studied. Molecular testing was performed in 126 cases including 107 using next generation sequencing. Results: The median patients’ age was 68 years old. Differentiated thyroid carcinoma (DTC) was present in 208 cases (58%), the most common being papillary carcinoma (n=150). The 1-year, 2-year, 3-year, and 5-year overall survival (OS) was 36%, 17%, 13%, and 11% respectively. On univariate analysis, age, resectability, chemotherapy, radiotherapy, margin status, encapsulation, gross residual disease (GRD), gross ETE, percentage and size of ATC in the primary tumor predicted OS (p<0.05). Age, resectability, chemotherapy, and GRD were independent prognostic factors in the entire cohort while GRD was the only independent predictor of OS in patients who had resection of their tumor. BRAF, RAS, TERT promoter, TP53, PIK3CA, E1F1AX, and PTEN mutations were detected in 45%, 24%, 75%, 63%, 18%, 14%, and 14% of ATC, respectively. Concomitant BRAF/RAS and TERT mutations were associated with worse outcome than mutation in only one of the genes. BRAF and RAS mutated-ATC had similar frequency of nodal and distant metastasis. Twelve cases were pure squamous cell carcinoma (SCC), 60% of which carried BRAF V600E mutation and showed a similar OS to other ATCs. Conclusions: 1) GRD remains the most crucial indicator of outcome in ATC. 2) Encapsulation, margin status, percentage and size of ATC in the primary were prognostically relevant. 3) Pure thyroid SCC may be considered as ATC given a BRAF V600E genotype and similar outcome. 4) In contrast to DTC, BRAF and RAS-mutated ATC have similar metastatic spread. 5) Concomitant mutations of BRAF or RAS with TERT confer a worse prognosis.Keywords
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