Chiba, T. Molecular Pathology of Thyroid Tumors: Essential Points to Comprehend Regarding the Latest WHO Classification. Biomedicines2024, 12, 712.
Chiba, T. Molecular Pathology of Thyroid Tumors: Essential Points to Comprehend Regarding the Latest WHO Classification. Biomedicines 2024, 12, 712.
Chiba, T. Molecular Pathology of Thyroid Tumors: Essential Points to Comprehend Regarding the Latest WHO Classification. Biomedicines2024, 12, 712.
Chiba, T. Molecular Pathology of Thyroid Tumors: Essential Points to Comprehend Regarding the Latest WHO Classification. Biomedicines 2024, 12, 712.
Abstract
In 2022, the new WHO Classification of Endocrine and Neuroendocrine Tumors, Fifth Edition (beta version) (WHO 5th) was published. The importance of understanding the molecular genetics of thyroid tumors as revealed by large-scale genomic analyses such as The Cancer Genome Atlas (TCGA). Consequently, the WHO 5th was fundamentally revised, resulting in a systematic classification based on tumor cell-of-origin and clinical risk. This paper outlines following critical points of the WHO 5th.
1. Genetic mutations in follicular cell-derived neoplasms (FDN) 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.
2. The Framework for benign lesions have revised. The WHO 5th introduces new categories such as "developmental abnormalities" and "thyroid follicular nodular disease" in benign FDN.
3. Low-Risk Tumors include NIFTP, TT-UMP, and HTT.
4. PTC histological variants are reclassified as "subtypes" in the WHO 5th.
5. 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 shared genetic and prognostic features.
7. Hürthle cell adenoma/carcinoma is renamed oncocytic thyroid adenoma/carcinoma.
8. Other miscellaneous tumors are classified into salivary gland-type carcinomas of the thyroid, thyroid tumours of uncertain histogenesis, thymic tumours within the thyroid, and embryonal thyroid neoplasms.
The WHO 5th thus emphasizes the importance of classifying tumors based on genetic abnormalities together with histomorphology, aiding in accurate pathological diagnosis and treatment selection, including molecular-targeted therapies.
Keywords
thyroid cancer; genomic alterations; pathological diagnosis; WHO classification
Subject
Biology and Life Sciences, Endocrinology and Metabolism
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
