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Despite its rarity, HGDTC creates major diagnostic and therapeutic difficulties, often overlapping with poorly differentiated or anaplastic thyroid carcinoma. This review synthesizes histopathologic recognition, molecular characteristics, prognostic determinants, and evolving treatment strategies.",{"@graph":69,"@context":123},[70,84,106],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/diagnostic-challenges-prognostic-assessment-and-treatment-strategies-in-high-grade-differentiated-thyroid-carcinoma/434024/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/diagnostic-challenges-prognostic-assessment-and-treatment-strategies-in-high-grade-differentiated-thyroid-carcinoma/434024.png","ImageObject",300,407,{"name":92,"@type":93},"Rowan","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-31","2026-09-29",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",13,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119],{"name":110,"@type":111,"acceptedAnswer":112},"What criteria define high-grade differentiated thyroid carcinoma (HGDTC) in the 2022 WHO classification?","Question",{"text":113,"@type":114},"HGDTC is defined by a mitotic count of ≥5 mitoses per 2 mm² and/or unequivocal tumor necrosis, while maintaining architectural and cytologic features of differentiated thyroid carcinoma without anaplastic morphology.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"Why is the diagnosis of HGDTC considered challenging?",{"text":118,"@type":114},"It is uncommon and can overlap with poorly differentiated thyroid carcinoma or be misdiagnosed as anaplastic thyroid carcinoma. Pattern-specific pitfalls and interpretation issues can further reduce diagnostic reproducibility.",{"name":120,"@type":111,"acceptedAnswer":121},"How does the review suggest improving clinical management of HGDTC?",{"text":122,"@type":114},"It proposes an integrated, stepwise diagnostic approach to enhance histopathologic reproducibility, refine risk stratification, and optimize multidisciplinary management.","https://schema.org",{"og:url":83,"og:type":125,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":127,"canonical":83},"index,follow",{"doc_id":129,"site_id":62},434024,1790822554,{"code":4,"msg":5,"data":132},{"doc_id":129,"user_id":133,"nickname":92,"user_avatar":134,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":105,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":140,"language":141,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":142,"faqs":143,"seo_title":144,"seo_description":67,"update_tm":145,"read_time":146,"preview_page_count":4},1099514067415,"https://ap-avatar.wpscdn.com/avatar/100002539d78ffe74a7?x-image-process=image/resize,m_fixed,w_180,h_180&k=1779092875211072502","Review Article  \nEndocrinol Metab 2025;40:830-850 [https://doi.org/10.3803/EnM.2025.2725](https://doi.org/10.3803/EnM.2025.2725)[ ](https://doi.org/10.3803/EnM.2025.2725)[pISSN 2093-596X](pISSN 2093-596X) · eISSN 2093-5978  \nDiagnostic Challenges, Prognostic Assessment, and Treatment Strategies in High-Grade Differentiated Thyroid Carcinoma  \nChan Kwon Jung 1,2, Agnes Stephanie Harahap3  \n1Department of Hospital Pathology, 2Cancer Research Institute, College of Medicine, The Catholic University of Korea, Seoul, Korea; 3Department of Anatomical Pathology, Universitas Indonesia, Dr. Cipto Mangunkusumo Hospital, Jakarta, Indonesia  \nHigh-grade differentiated thyroid carcinoma (HGDTC) is a recently codified entity in the 2022 World Health Organization Classification of Endocrine Tumors, defined by a mitotic count of ≥5 mitoses per 2 mm² and/or tumor necrosis in a carcinoma that retains papillary, follicular, or oncocytic differentiation without anaplastic morphology. Although uncommon, HGDTC presents significant diagnostic and therapeutic challenges. This review summarizes current evidence regarding histopathologic recognition, molecular features, prognostic determinants, and evolving treatment paradigms. Particular attention is given to pattern-specific pitfalls such as high-grade papillary thyroid carcinoma, the diffuse sclerosing subtype, and the prognostic influence of the invasion phenotype (encapsulated versus infiltrative) . Subcentimeter papillary carcinomas exhibiting increased mitotic activity alone should not be overinterpreted as HGDTC. An integrated, stepwise approach is proposed to enhance diagnostic reproducibility, refine risk stratification, and optimize multidisciplinary management in clinical practice.  \n\n| Keywords: Thyroid neoplasms; Phenotype; World Health Organization; Risk assessment; Prognosis; Necrosis |  |\n| --- | --- |\n| INTRODUCTION\u003Cbr>Differentiated thyroid carcinomas (DTC) represent one of the most common types of thyroid cancer and are generally associated with favorable outcomes and an excellent prognosis [1-4] . However, a subset of these tumors acquires histologically highgrade features linked to significantly poorer outcomes. These cases have long been inconsistently classified, frequently overlapping with poorly differentiated thyroid carcinoma (PDTC) or being misdiagnosed as anaplastic thyroid carcinoma (ATC) . Poor differentiation and high-grade features have emerged as independent prognostic indicators of adverse outcomes in a sub- | set of thyroid carcinomas situated between well-differentiated and anaplastic types [5-7]. After decades of research and clinical refinement, the World Health Organization (WHO) in 2022 introduced these criteria into a newly designated group within the thyroid carcinoma classification, representing tumors with intermediate prognoses [8-10] . This group encompasses PDTC anda newly defined subtype, high-grade differentiated thyroid carcinoma (HGDTC) [6,11,12] .\u003Cbr>The concept of this aggressive form of follicular cell-derived thyroid carcinoma was first introduced in the early 1980s by Sakamoto et al. [13] and Carcangiu et al. [14], based on its distinctive solid, trabecular, or insular (STI) growth patterns. Two |\n| Received: 19 October 2025, Revised: 22 October 2025, Accepted: 24 October 2025\u003Cbr>Corresponding author: Chan Kwon Jung\u003Cbr>Department of Hospital Pathology, College of Medicine, The Catholic University\u003Cbr>of Korea, 222 Banpo-daero, Seocho-gu, Seoul 06591, Korea\u003Cbr>Tel: +82-2-2258-1622, Fax: +82-2-2258-1627, E-mail: [ckjung@catholic.ac.kr](ckjung@catholic.ac.kr) | Copyright © 2025 Korean Endocrine Society\u003Cbr>This is an Open Access article distributed under the terms of\u003Cbr>the Creative Commons Attribution Non-Commercial License ([https://creativecommons.org/licenses/by-nc/4.0/](https://creativecommons.org/licenses/by-nc/4.0/)) which permits unrestricted\u003Cbr>non-commercial use, distribution, and reproduction in any medium, provided\u003Cbr>the original work is ","cbCainWJhjeOEiEu","https://ap.wps.com/l/cbCainWJhjeOEiEu","pdf",9444567,21,"English","# Introduction\n# Diagnostic Spectrum and WHO Criteria\n## Definitions and Key Pathologic Features\n# Prognostic Determinants\n# Treatment Paradigms\n# Practical Diagnostic Approach\n## Pattern-specific Pitfalls","[{\"question\":\"What criteria define high-grade differentiated thyroid carcinoma (HGDTC) in the 2022 WHO classification?\",\"answer\":\"HGDTC is defined by a mitotic count of ≥5 mitoses per 2 mm² and/or unequivocal tumor necrosis, while maintaining architectural and cytologic features of differentiated thyroid carcinoma without anaplastic morphology.\"},{\"question\":\"Why is the diagnosis of HGDTC considered challenging?\",\"answer\":\"It is uncommon and can overlap with poorly differentiated thyroid carcinoma or be misdiagnosed as anaplastic thyroid carcinoma. Pattern-specific pitfalls and interpretation issues can further reduce diagnostic reproducibility.\"},{\"question\":\"How does the review suggest improving clinical management of HGDTC?\",\"answer\":\"It proposes an integrated, stepwise diagnostic approach to enhance histopathologic reproducibility, refine risk stratification, and optimize multidisciplinary management.\"}]","Diagnostic Challenges, Prognostic Assessment, and Treatment Strategies in High-Grade Differentiated Thyroid Carcinoma | PDF",1790666588,53]