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EWSR1 rearrangement is a frequent event in papillary thyroid carcinoma and in carcinoma of the thyroid with Ewing family tumor elements (CEFTE)

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Carcinomas of the thyroid with Ewing family tumor element (CEFTEs) are small-cell thyroid tumors with epithelial differentiation that disclose p63 expression and EWSR1-FLI1 rearrangement, carry a favorable prognosis and may co-exist with papillary thyroid carcinoma (PTC) foci. Two histogenetic hypotheses have been advanced regarding the origin of CEFTEs: arising in PTCs or in solid cell nests (SCN). A total of 3 CEFTEs, 54 PTCs, and 10 SCNs were reviewed, and fluorescence in situ hybridization (FISH) technique was performed in all cases to search for the presence of EWSR1 rearrangements. The three CEFTEs disclosed the EWSR1-FLI1 rearrangement both in the small cell and in the PTC component. Out of the 54 PTC cases, 28 (51.9%) were positive, 20 (37.0%) were negative, and 6 (11.1%) were inconclusive for EWSR1 rearrangement; in two of the positive PTC cases, the EWSR1-FLI1 rearrangement was detected. Classic PTC disclosed more often the EWSR1 rearrangement than other PTC variants (p = 0.031). PTCs with EWSR1 rearrangement disclosed a lower percentage of nuclei with EWSR1 polysomy than those without EWSR1 rearrangement (p = 0.001). Out of the 10 SCNs, 7 (70.0%) were negative and 3 (30.0%) were inconclusive for the EWSR1 rearrangement. Monosomic nuclei were more frequent (mean of 44.3%) in SCNs than in PTCs (p < 0.001). The presence of the EWSR1-FLI1 rearrangement in PTC component of all studied CEFTEs and the existence of the EWSR1 rearrangement in some PTCs favor the origin of CEFTE from PTC. The high frequency of EWSR1 rearrangements in PTC may represent a new diagnostic marker of these tumors.

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The authors thank A.Menarini® Diagnósticos Portugal and ZytoVision® for providing the FISH probes and microscope filter for FISH analysis. This work has been partially supported by grant PI15/01501-FEDER to JMC-T from the Instituto de Salud Carlos III, the Ministry of Economy and Competitiveness, Spain.

Authors’ contributions

Oliveira G wrote the manuscript and performed the lab work. Polónia A wrote the manuscript and performed the statistical analysis. Leitão D performed part of the lab work. Cameselle-Teijeiro JM determined the BRAF status of the tumors and revised the manuscript. Sapia S provided external consultation. Sobrinho-Simões M revised the manuscript. Eloy C wrote the manuscript and made the design of the project.

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Correspondence to C. Eloy.

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This work was performed in archived paraffin tissue that remained from the diagnosis of the thyroid samples of patients that were anonymized. The materials used for the work are not needed for diagnosis in the present nor in the future.

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The authors declare that they have no conflict of interest.

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Oliveira, G., Polónia, A., Cameselle-Teijeiro, J.M. et al. EWSR1 rearrangement is a frequent event in papillary thyroid carcinoma and in carcinoma of the thyroid with Ewing family tumor elements (CEFTE). Virchows Arch 470, 517–525 (2017).

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