The Role of Cytology, Histology and Molecular Pathology in the Diagnostic Process of Thyroid Nodules

Sep 22, 2026

Uploaded by Grenda

Thyroid nodule diagnosis and classification have evolved through updated cytologic and histologic frameworks and broader molecular testing. Recent progress includes the 2022 fifth edition of the WHO Classification of Endocrine and Neuroendocrine Tumors and the 2023 third edition of the Bethesda System for Reporting Thyroid Cytopathology, which converge in shared terminology to strengthen clinicopathologic correlation between FNAC and surgical pathology. Molecular testing increasingly informs indeterminate FNA categories. The 2025 American Thyroid Association guidelines recalibrate postoperative risk stratification in differentiated thyroid cancer by re-centering histopathology, while the review synthesizes practical integration of these advances for evaluation and management of thyroid nodules.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages18

Reading Time45 min

AccessFree to download

Introduction

Management of Thyroid Nodules in Children

Review The Role of Cytology, Histology and Molecular Pathology in the Diagnostic Process of Thyroid Nodules Mathilde Ribeiro 1, Sule Canberk 1,2 and Massimo Bongiovanni 3, * Academic Editor: Michael Bouvet Received: 28 February 2026 Revised: 21 May 2026 Accepted: 24 May 2026 Published: 1 June 2026 Copyright: © 2026 by the authors. 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. 1 Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal; [up202305227@edu.med.up.pt](up202305227@edu.med.up.pt) (M.R.); [sulecanberk@med.up.pt](sulecanberk@med.up.pt) (S.C.) 2 RISE-Health, Department of Pathology, Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal 3 Unilabs Pathology, 1003 Lausanne, Switzerland * [Correspondence: massimo.bongiovanni@unilabs.com](Correspondence: massimo.bongiovanni@unilabs.com) Simple Summary The updated cytologic (The Bethesda System for Reporting Thyroid Cytopathology) and histologic (World Health Organization Classification of Endocrine and Neuroendocrine Tumors) classifications of thyroid neoplasms, together with the expanding use of molecular tests in thyroid nodules, have enhanced preoperative malignancy risk stratification and optimized patient management. The 2025 American Thyroid Association guidelines further refine postoperative risk stratification in differentiated thyroid carcinoma by integrating histologic classification and tumor histotype, underscoring the central role of histology in assessing recurrence risk, predicting radioactive iodine responsiveness, and tailoring follow-up strategies. Abstract In recent years, thyroid nodule diagnosis and classification have been updated by two major developments: the fifth edition of the World Health Organization (WHO) Classification of Endocrine and Neuroendocrine Tumors classification 2022), which includes thyroid neoplasms, and the third edition of The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) (2023) . Importantly, these classification systems converge in terminology, improving clinicopathologic correlation between fine-needle aspiration cytology (FNAC) and surgical pathology and supporting more consistent risk-based management. In parallel, molecular testing has assumed a growing role, particularly for indeterminate FNA categories, as reflected in contemporary practice recommendations. Moreover, the 2025 American Thyroid Association guidelines recalibrate postoperative risk stratification in differentiated thyroid cancer by reasserting histopathology as the cornerstone of clinical decision-making. In this review, we summarize key updates in thyroid FNAC reporting, histopathologic classification, and the practical application of molecular pathology for the evaluation and management of thyroid nodules. Keywords: thyroid; fine-needle aspiration cytology; The Bethesda System for Reporting Thyroid Cytopathology; histological classification; diagnostic accuracy; molecular cytopathology 1. Introduction The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) is a categorization system for providing uniform and standardized diagnosis in thyroid cytology that has proven its efficiency over the years [1] . It is widely used all over the world and has now reached its third edition, published in 2023 . It has improved communication between cytopathologist and doctors implicated in the management of thyroid nodules to improve care of patients with thyroid diseases. The quantity of literature production and data over the years since its first edition in 2007 has permitted us to refine and ameliorate its purposes: to provide reliable diagnostic criteria associated with robust risk-of-malignancy rates for each diagnostic category and propose management actions based on scientific evidence [2] . Contemporarily, in 2023, the World Health Organization (WHO) publish

FAQs

What are the main updates in thyroid cytology and histology discussed in this review?

The review summarizes updates to the Bethesda System for Reporting Thyroid Cytopathology and the WHO histologic classification of endocrine and neuroendocrine tumors, which include thyroid neoplasms. It highlights how the systems converge in terminology to improve clinicopathologic correlation between FNAC and surgical pathology.

How does molecular testing contribute to evaluating thyroid nodules?

Molecular testing plays an expanding role, particularly for indeterminate FNA categories. It supports improved diagnostic yield and helps clinicians select appropriate management and therapeutic options.

Why do the 2025 American Thyroid Association guidelines emphasize histopathology in postoperative risk stratification?

The review states that the 2025 ATA guidelines recalibrate postoperative risk stratification in differentiated thyroid cancer by reasserting histopathology as the cornerstone of decision-making. This supports assessment of recurrence risk, prediction of radioactive iodine responsiveness, and follow-up tailoring.

Sep 22, 2026

Uploaded by Grenda