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KMID : 1141520210360010123
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Endocrinology and Metabolism
2021 Volume.36 No. 1 p.123 ~ p.133
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Molecular Correlates and Nuclear Features of Encapsulated Follicular-Patterned Thyroid Neoplasms
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Jung Chan-Kwon
Bychkov Andrey
Song Dong-Eun
Kim Jang-Hee
Zhu Yun
Liu Zhiyan
Keelawat Somboon
Lai Chiung-Ru
Hirokawa Mitsuyoshi
Kameyama Kaori
Kakudo Kennichi
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Abstract
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Background: Assessing nuclear features is diagnostically challenging in the aspect of thyroid pathology. The aim of this study was to determine whether pathologists could distinguish BRAF-like and RAS-like nuclear features morphologically and identify morphological features to differentiate thyroid tumors with RAS-like mutations from encapsulated papillary thyroid carcinoma (PTC) with predominant follicular growth and BRAFV600E mutation.
Methods: Representative whole slide images of 16 encapsulated thyroid tumors with predominant follicular growth were reviewed by 12 thyroid pathologists using a web browser-based image viewer. Total nuclear score was calculated from semi-quantitatively scored eight nuclear features. The molecular profile of RAS and BRAF genes was determined by Sanger sequencing.
Results: Total nuclear score ranging 0 to 24 could differentiate BRAF-like tumors from RAS-like tumors with a cut-off value of score 14. The interobserver agreement was the highest for the assessment of nuclear pseudoinclusions (NPIs) but the lowest for nuclear elongation and sickle-shaped nuclei. NPIs were found in tumors with BRAFV600E mutation, but not in tumors with RAS-like mutations. Total nuclear scores were significantly higher for tumors with BRAFV600E than for those with RAS-like mutations (P<0.001).
Conclusion: Our results suggest that NPIs and high nuclear scores have diagnostic utility as rule-in markers for differentiating PTC with BRAFV600E mutation from benign or borderline follicular tumors with RAS-like mutations. Relaxation of rigid criteria for nuclear features resulted in an overdiagnosis of PTC. Immunostaining or molecular testing for BRAFV600E mutation is a useful adjunct for cases with high nuclear scores to identify true PTC.
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KEYWORD
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Thyroid cancer, papillary, Proto-oncogene proteins B-raf, Genes, ras, Thyroid neoplasms, Mutation, Medical overuse, Pathologists, Observer variation
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