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Endocrinol Metab : Endocrinology and Metabolism


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Somboon Keelawat 1 Article
Clinical Study
Molecular Correlates and Nuclear Features of Encapsulated Follicular-Patterned Thyroid Neoplasms
Chan Kwon Jung, Andrey Bychkov, Dong Eun Song, Jang-Hee Kim, Yun Zhu, Zhiyan Liu, Somboon Keelawat, Chiung-Ru Lai, Mitsuyoshi Hirokawa, Kaori Kameyama, Kennichi Kakudo
Endocrinol Metab. 2021;36(1):123-133.   Published online February 24, 2021
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AbstractAbstract PDFPubReader   ePub   CrossRef-TDMCrossref - TDM
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.
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.
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).
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.


Citations to this article as recorded by  
  • The Presence of Typical “BRAFV600E-Like” Atypia in Papillary Thyroid Carcinoma is Highly Specific for the Presence of the BRAFV600E Mutation
    John Turchini, Loretta Sioson, Adele Clarkson, Amy Sheen, Leigh Delbridge, Anthony Glover, Mark Sywak, Stan Sidhu, Anthony J. Gill
    Endocrine Pathology.2023; 34(1): 112.     CrossRef
  • Noninvasive Follicular Thyroid Neoplasm with Papillary-like Nuclear Features (NIFTP): Tumour Entity with a Short History. A Review on Challenges in Our Microscopes, Molecular and Ultrasonographic Profile
    Ivana Kholová, Elina Haaga, Jaroslav Ludvik, David Kalfert, Marie Ludvikova
    Diagnostics.2022; 12(2): 250.     CrossRef
  • Update from the 2022 World Health Organization Classification of Thyroid Tumors: A Standardized Diagnostic Approach
    Chan Kwon Jung, Andrey Bychkov, Kennichi Kakudo
    Endocrinology and Metabolism.2022; 37(5): 703.     CrossRef
  • Different Threshold of Malignancy for RAS-like Thyroid Tumors Causes Significant Differences in Thyroid Nodule Practice
    Kennichi Kakudo
    Cancers.2022; 14(3): 812.     CrossRef
  • The Incidence of Noninvasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features: A Meta-Analysis Assessing Worldwide Impact of the Reclassification
    Chanchal Rana, Huy Gia Vuong, Thu Quynh Nguyen, Hoang Cong Nguyen, Chan Kwon Jung, Kennichi Kakudo, Andrey Bychkov
    Thyroid.2021;[Epub]     CrossRef

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