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Large-scale genomic analyses such as The Cancer Genome Atlas have shown the need to understand thyroid tumor molecular genetics. The WHO 5th was revised with systematic classification based on cell of origin and clinical risk, highlighting driver mutations, updated benign lesion categories, revised low-risk and histologic subtype concepts, the introduction of high-grade carcinomas, and genetic-prognostic reclassification of entities to support accurate diagnosis and early therapy selection, including molecular targeted options.",{"@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/molecular-pathology-of-thyroid-tumors-essential-points-to-comprehend-regarding-the-latest-who-classification/336196/",{"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/molecular-pathology-of-thyroid-tumors-essential-points-to-comprehend-regarding-the-latest-who-classification/336196.png","ImageObject",300,407,{"name":92,"@type":93},"Emma Wilson","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-22","2026-09-21",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",11,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119],{"name":110,"@type":111,"acceptedAnswer":112},"What key principle drives the WHO 5th classification of thyroid tumors?","Question",{"text":113,"@type":114},"The WHO 5th emphasizes classification based on both the cell of origin and clinical risk, integrating genetic abnormalities with histomorphology.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"Which genetic pathways and mutations are highlighted in follicular cell-derived neoplasms (FDNs)?",{"text":118,"@type":114},"Driver mutations in the MAP kinase pathway are emphasized, including RET, RAS, and BRAF, which help explain carcinogenesis and correlate with morphological categories.",{"name":120,"@type":111,"acceptedAnswer":121},"What major updates does the WHO 5th make to benign lesions and tumor risk groups?",{"text":122,"@type":114},"The framework for benign lesions is revised with a new category of developmental abnormalities, and low-risk tumors such as NIFTP, TT-UMP, and HTT are defined as having extremely low malignant potential or uncertain malignant potential.","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},336196,1790109605,{"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":41},3848291630094,"https://eur-avatar.wpscdn.com/davatar_085a072bc5b1113ac321206ff7593b45","biomedicines  \nReview  \nMolecular Pathology of Thyroid Tumors: Essential Points to Comprehend Regarding the Latest WHO Classification  \nTomohiro Chiba 1,2  \nCitation: Chiba, T. Molecular Pathology of Thyroid Tumors:  \nEssential Points to Comprehend Regarding the Latest WHO Classification. Biomedicines 2024, 12, 712. [https://doi.org/10.3390/](https://doi.org/10.3390/)[ ](https://doi.org/10.3390/)biomedicines12040712  \nAcademic Editor: Zhilong Ai  \nReceived: 26 February 2024  \nRevised: 16 March 2024  \nAccepted: 20 March 2024  \nPublished: 22 March 2024  \nCopyright: © 2024 by the author. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) .  \n1 Department of Cytology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo 135-8550, Japan; [tomohiro.chiba@jfcr.or.jp](tomohiro.chiba@jfcr.or.jp); Tel.: +81-3-3520-0111; Fax: +81-3-3570-0558  \n2 Department of Pathology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo 135-8550, Japan  \nAbstract: In 2022, the new WHO Classification of Endocrine and Neuroendocrine Tumors, Fifth Edition (beta version) (WHO 5th), was published. Large-scale genomic analyses such as The Cancer Genome Atlas (TCGA) have revealed the importance of understanding the molecular genetics of thyroid tumors. Consequently, the WHO 5th was fundamentally revised, resulting in a systematic classification based on the cell of origin of tumors and their clinical risk. This paper outlines the following critical points of the WHO 5th. 1. Genetic mutations in follicular cell-derived neoplasms (FDNs) highlight the role of mutations in the MAP kinase pathway, including RET, RAS, and BRAF, as drivers of carcinogenesis. Differentiated thyroid cancers such as follicular thyroid carcinoma (FTC) and papillary thyroid carcinoma (PTC) have specific genetic alterations that correlate with morphological classifications: RAS-like tumors (RLTs) and BRAF p.V600E-like tumors (BLTs), respectively.  \n2. The framework for benign lesions has been revised. The WHO 5th introduces a new category: “developmental abnormalities”. Benign FDNs comprise “thyroid follicular nodular disease”, follicular thyroid adenoma (FTA), FTA with papillary architecture, and oncocytic adenoma (OA) .“Hürthle cell adenoma/carcinoma” is renamed oncocytic adenoma/carcinoma of the thyroid (OA/OCA), which can be distinguished from FTA/FTC by its unique genetic background. 3. Low-risk tumors include NIFTP, TT-UMP, and HTT, and they have an extremely low malignant potential or an uncertain malignant potential. 4. PTC histological variants are reclassified as “subtypes” in the WHO 5th.  \n5. The concept of high-grade carcinomas is introduced, encompassing poorly differentiated thyroid carcinoma (PDTC), differentiated high-grade thyroid carcinoma (DHGTC), and high-grade medullary thyroid carcinoma (MTC) . 6. Squamous cell carcinoma is included in anaplastic thyroid carcinoma (ATC) in the WHO 5th due to their shared genetic and prognostic features. 7. Other miscellaneous tumors are categorized as salivary-gland-type carcinomas of the thyroid, thyroid tumors of uncertain histogenesis, thymic tumors within the thyroid, and embryonal thyroid neoplasms. The WHO 5th thus emphasizes the importance of classifying tumors based on both genetic abnormalities and histomorphology. This approach aids in achieving accurate pathological diagnosis and facilitates the early selection of appropriate treatment options, including molecular targeted therapies.  \nKeywords: thyroid cancer; genomic alterations; pathological diagnosis; WHO classification  \n1. Introduction  \nThyroid cancer diagnoses, particularly in women, are on the rise. Improved ","cbCaimND1Zw5rzif","https://ap.wps.com/l/cbCaimND1Zw5rzif","pdf",3630758,12,"English","# Abstract\n# Introduction\n# WHO 5th classification framework\n## Follicular cell-derived neoplasms and genetic drivers\n## Benign lesions and developmental abnormalities\n## Low-risk tumors and histological subtypes\n## High-grade carcinomas and anaplastic lineage reclassification\n## Other thyroid tumor categories\n# Keywords","[{\"question\":\"What key principle drives the WHO 5th classification of thyroid tumors?\",\"answer\":\"The WHO 5th emphasizes classification based on both the cell of origin and clinical risk, integrating genetic abnormalities with histomorphology.\"},{\"question\":\"Which genetic pathways and mutations are highlighted in follicular cell-derived neoplasms (FDNs)?\",\"answer\":\"Driver mutations in the MAP kinase pathway are emphasized, including RET, RAS, and BRAF, which help explain carcinogenesis and correlate with morphological categories.\"},{\"question\":\"What major updates does the WHO 5th make to benign lesions and tumor risk groups?\",\"answer\":\"The framework for benign lesions is revised with a new category of developmental abnormalities, and low-risk tumors such as NIFTP, TT-UMP, and HTT are defined as having extremely low malignant potential or uncertain malignant potential.\"}]","Molecular Pathology of Thyroid Tumors: Essential Points to Comprehend Regarding the Latest WHO Classification | PDF",1790014069]