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Jang-Hee Kim 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
DOI: https://doi.org/10.3803/EnM.2020.860
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  • 13 Web of Science
  • 13 Crossref
AbstractAbstract PDFPubReader   ePub   
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.

Citations

Citations to this article as recorded by  
  • Differentiating BRAF V600E- and RAS-like alterations in encapsulated follicular patterned tumors through histologic features: a validation study
    Chankyung Kim, Shipra Agarwal, Andrey Bychkov, Jen-Fan Hang, Agnes Stephanie Harahap, Mitsuyoshi Hirokawa, Kennichi Kakudo, Somboon Keelawat, Chih-Yi Liu, Zhiyan Liu, Truong Phan-Xuan Nguyen, Chanchal Rana, Huy Gia Vuong, Yun Zhu, Chan Kwon Jung
    Virchows Archiv.2024; 484(4): 645.     CrossRef
  • Clinicopathologic Features and Cytologic Correlation of ALK-Rearranged Papillary Thyroid Carcinoma: A Series of Eight Cases
    Kun-Ping Shih, Yu-Cheng Lee, Jia-Jiun Tsai, Shu-Hui Lin, Chih-Yi Liu, Wan-Shan Li, Chien-Feng Li, Jen-Fan Hang
    Endocrine Pathology.2024; 35(2): 134.     CrossRef
  • Small Multi-Gene DNA Panel Can Aid in Reducing the Surgical Resection Rate and Predicting the Malignancy Risk of Thyroid Nodules
    Moon Young Oh, Hye-Mi Choi, Jinsun Jang, Heejun Son, Seung Shin Park, Minchul Song, Yoo Hyung Kim, Sun Wook Cho, Young Jun Chai, Woosung Chung, Young Joo Park
    Endocrinology and Metabolism.2024; 39(5): 777.     CrossRef
  • Diagnostic challenges in the assessment of thyroid neoplasms using nuclear features and vascular and capsular invasion: a multi-center interobserver agreement study
    Agnes Stephanie Harahap, Mutiah Mutmainnah, Maria Francisca Ham, Dina Khoirunnisa, Abdillah Hasbi Assadyk, Husni Cangara, Aswiyanti Asri, Diah Prabawati Retnani, Fairuz Quzwain, Hasrayati Agustina, Hermawan Istiadi, Indri Windarti, Krisna Murti, Muhammad
    Journal of Pathology and Translational Medicine.2024; 58(6): 299.     CrossRef
  • 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
  • Could Oxidative Stress Play a Role in the Development and Clinical Management of Differentiated Thyroid Cancer?
    Maria Kościuszko, Angelika Buczyńska, Adam Jacek Krętowski, Anna Popławska-Kita
    Cancers.2023; 15(12): 3182.     CrossRef
  • Pitfalls in thyroid pathology and the medicolegal aspects of error
    David N Poller
    Diagnostic Histopathology.2023; 29(11): 495.     CrossRef
  • Developing Models to Predict BRAFV600E and RAS Mutational Status in Papillary Thyroid Carcinoma Using Clinicopathological Features and pERK1/2 Immunohistochemistry Expression
    Agnes Stephanie Harahap, Imam Subekti, Sonar Soni Panigoro, Asmarinah, Lisnawati, Retno Asti Werdhani, Hasrayati Agustina, Dina Khoirunnisa, Mutiah Mutmainnah, Fajar Lamhot Gultom, Abdillah Hasbi Assadyk, Maria Francisca Ham
    Biomedicines.2023; 11(10): 2803.     CrossRef
  • The Asian Thyroid Working Group, from 2017 to 2023
    Kennichi Kakudo, Chan Kwon Jung, Zhiyan Liu, Mitsuyoshi Hirokawa, Andrey Bychkov, Huy Gia Vuong, Somboon Keelawat, Radhika Srinivasan, Jen-Fan Hang, Chiung-Ru Lai
    Journal of Pathology and Translational Medicine.2023; 57(6): 289.     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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