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Kennichi Kakudo 3 Articles
Thyroid
Update from the 2022 World Health Organization Classification of Thyroid Tumors: A Standardized Diagnostic Approach
Chan Kwon Jung, Andrey Bychkov, Kennichi Kakudo
Endocrinol Metab. 2022;37(5):703-718.   Published online October 4, 2022
DOI: https://doi.org/10.3803/EnM.2022.1553
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AbstractAbstract PDFPubReader   ePub   
The fifth edition of the World Health Organization (WHO) histologic classification of thyroid neoplasms released in 2022 includes newly recognized tumor types, subtypes, and a grading system. Follicular cell-derived neoplasms are categorized into three families (classes): benign tumors, low-risk neoplasms, and malignant neoplasms. The terms “follicular nodular disease” and “differentiated high-grade thyroid carcinoma” are introduced to account for multifocal hyperplastic/neoplastic lesions and differentiated thyroid carcinomas with high-grade features, respectively. The term “Hürthle cells” is replaced with “oncocytic cells.” Invasive encapsulated follicular and cribriform morular variants of papillary thyroid carcinoma (PTC) are now redefined as distinct tumor types, given their different genetic alterations and clinicopathologic characteristics from other PTC subtypes. The term “variant” to describe a subclass of tumor has been replaced with the term “subtype.” Instead, the term “variant” is reserved to describe genetic alterations. A histologic grading system based on the mitotic count, necrosis, and/or the Ki67 index is used to identify high-grade follicular-cell derived carcinomas and medullary thyroid carcinomas. The 2022 WHO classification introduces the following new categories: “salivary gland-type carcinomas of the thyroid” and “thyroid tumors of uncertain histogenesis.” This review summarizes the major changes in the 2022 WHO classification and their clinical relevance.

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Close layer
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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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.

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Thyroid
Updates in the Pathologic Classification of Thyroid Neoplasms: A Review of the World Health Organization Classification
Yanhua Bai, Kennichi Kakudo, Chan Kwon Jung
Endocrinol Metab. 2020;35(4):696-715.   Published online December 2, 2020
DOI: https://doi.org/10.3803/EnM.2020.807
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AbstractAbstract PDFPubReader   ePub   
Advances in medical sciences and evidence-based medicine have led to momentous changes in classification and management of thyroid neoplasms. Much progress has been made toward avoiding overdiagnosis and overtreatment of thyroid cancers. The new 2017 World Health Organization (WHO) classification of thyroid neoplasms updated the diagnostic criteria and molecular and genetic characteristics reflecting the biology and behavior of the tumors, and newly introduced the category of borderline malignancy or uncertain malignant potential. Some neoplasms were subclassified, renamed, or redefined as a specific entity. This review introduces changes in the fourth edition WHO classification of thyroid tumors and updates the contemporary diagnosis and classification of thyroid tumors. We also discuss several challenges with the proposal of new diagnostic entities, since they have unique histopathologic and molecular features and clinical relevance.

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