The 5th edition of WHO classification of tumors of endocrine organs: changes in the diagnosis of follicular-derived thyroid carcinoma

Sep 24, 2026

Uploaded by Miles

The 5th edition of the World Health Organization (WHO) classification of endocrine tumors was released in 2022, introducing updates to the nomenclature and histopathological diagnosis of follicular-derived thyroid neoplasms. Tumor types are restructured into benign tumors, low-risk neoplasms, and malignant neoplasms based on prognostic risk categories. A grading system for differentiated thyroid carcinomas is implemented to improve tumor stratification, with particular focus on molecular profiles of well-differentiated histotypes. This review presents the major changes and critically discusses practical diagnostic effects and expected clinical implications of the new scheme.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages7

Reading Time18 min

AccessFree to download

Abstract

Introduction

Benign tumors

Multinodular goiter and thyroid follicular nodular disease

Follicular adenoma with papillary architecture

Oncocytic adenoma

Endocrine (2023) 80:470–476 [https://doi.org/10.1007/s12020-023-03336-4](https://doi.org/10.1007/s12020-023-03336-4) REVIEW The 5th edition of WHO classiﬁcation of tumors of endocrine organs: changes in the diagnosis of follicular-derived thyroid carcinoma Fulvio Basolo 1 ● Elisabetta Macerola1 ● Anello Marcello Poma1 ● Liborio Torregrossa1 Received: 20 January 2023 / Accepted: 21 February 2023 / Published online: 25 March 2023 © The Author(s) 2023 Abstract The 5th edition of the World Health Organization (WHO) classiﬁcation of endocrine tumors was released in 2022 . Several novelties have been introduced concerning the nomenclature and histopathological diagnosis of follicularderived thyroid neoplasms. Tumor types have been sharply classiﬁed according to prognostic risk categories into benign tumors, low-risk neoplasms and malignant neoplasms. A grading system for differentiated thyroid carcinomas has been implemented with the aim of improving the stratiﬁcation of tumors. Particular attention has been paid to the molecular proﬁle of well-differentiated histotypes. In this review, the main changes introduced by the latest edition of the WHO system are presented. The practical effects on the diagnostic pathology of thyroid tumors, along with the clinical implications expected with the new classiﬁcation scheme, are critically discussed. Keywords Endocrine pathology ● Follicular-derived thyroid cancer ● WHO classiﬁcation system ● Diagnostic pathology Introduction The 4th edition of the WHO classiﬁcation of tumors of endocrine organs was published in 2017 [1] . After only 5 years, a re-edited version of this important reference guide for pathologists and clinicians came to light [2] . Follicular-derived thyroid tumors were categorized into“Benign tumors”,“Low-risk neoplasms” and “Malignant neoplasms” (Fig. 1); this clear-cut subdivision appears far more linear than the previous one, where a list of histotypes rather than a real categorization was present. The new version seems to give more importance to the integration of morphological and molecular characteristics of tumors. In this brief review, the main novelties of the 5th edition of the WHO classiﬁcation of follicularderived thyroid tumors are summarized, discussing the expected consequences for pathologists and clinicians in real-world practice. * Fulvio Basolo [fulvio.basolo@unipi.it](fulvio.basolo@unipi.it) 1 Department of Surgical, Medical, Molecular Pathology and Critical Area -University of Pisa, via Savi 10, Pisa 56126, Italy Benign tumors In the 5th edition of the WHO classiﬁcation, more space is given to the group of benign thyroid lesions. The follicular adenoma, an encapsulated tumor with follicular architecture characterized by clonal expansion and RASlike alterations, was already present in the previous edition. The novelty is represented by a more detailed deﬁnition of the well-known multinodular goiter. Multinodular goiter is a clinical condition characterized by multiple, non-malignant thyroid nodules originated by the proliferation of follicular cells. So far, the histological appearance of these lesions has determined various deﬁnitions: micro- and/or macro-follicular nodules, hyperplastic nodules, colloidal nodules, and adenomatous nodules. However, the nature of these nodules can be both hyperplastic and neoplastic, as demonstrated by the occurrence of clonal molecular alterations. To uniform the terminology, the deﬁnition of thyroid follicular nodular disease has been introduced in the new WHO classiﬁcation scheme [2] . Two other entities have been included in the category of benign tumors, namely the follicular adenoma with papillary architecture and the oncocytic adenoma. These neoplasms were already present in the 4th edition of the WHO and their histopathological characteristics have not been subject to signiﬁcant modiﬁcations. The follicular adenoma Fig. 1 The World Health Organization classiﬁcation of follicular cell-

FAQs

What key changes does the 5th edition introduce for follicular-derived thyroid neoplasms?

It updates the nomenclature and histopathological diagnosis, with tumor types reclassified into benign, low-risk, and malignant categories based on prognostic risk.

How are tumor types categorized in the 5th WHO edition?

Tumors are sharply classified into benign tumors, low-risk neoplasms, and malignant neoplasms using prognostic risk categories.

Why does the review emphasize molecular profiling in the new classification scheme?

The review highlights increased importance of integrating morphological and molecular characteristics, particularly the molecular profile of well-differentiated histotypes, to support more accurate diagnostic stratification.

Sep 24, 2026

Uploaded by Miles