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Molecular Correlates and Nuclear Features of Encapsulated Follicular-Patterned Thyroid Neoplasms

Endocrinology and Metabolism 2021년 36권 1호 p.123 ~ 133
정찬권, Bychkov Andrey, 송동은, Kim Jang-Hee, Zhu Yun, Liu Zhiyan, Keelawat Somboon, Lai Chiung-Ru, Hirokawa Mitsuyoshi, Kameyama Kaori, Kakudo Kennichi,
소속 상세정보
정찬권 ( Jung Chan-Kwon ) - Catholic University College of Medicine Department of Hospital Pathology
 ( Bychkov Andrey ) - Kameda Medical Center Department of Pathology
송동은 ( Song Dong-Eun ) - University of Ulsan College of Medicine Asan Medical Center Department of Pathology
 ( Kim Jang-Hee ) - Ajou University School of Medicine Department of Pathology
 ( Zhu Yun ) - Jiangsu Institute of Nuclear Medicine Department of Pathology
 ( Liu Zhiyan ) - Shanghai Jiao Tong University Sixth People’s Hospital Department of Pathology
 ( Keelawat Somboon ) - Chulalongkorn University Faculty of Medicine Department of Pathology
 ( Lai Chiung-Ru ) - Taipei Veterans General Hospital Department of Pathology
 ( Hirokawa Mitsuyoshi ) - Kuma Hospital Department of Diagnostic Pathology and Cytology
 ( Kameyama Kaori ) - Keio University Hospital Division of Diagnostic Pathology
 ( Kakudo Kennichi ) - Izumi City General Hospital Department of Pathology

Abstract


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.

키워드

Thyroid cancer; papillary; Proto-oncogene proteins B-raf; Genes; ras; Thyroid neoplasms; Mutation; Medical overuse; Pathologists; Observer variation

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