# Artificial Intelligence in Thyroid Cytopathology: Diagnostic and Technical Insights

**Authors:** Mariachiara Negrelli, Chiara Frascarelli, Fausto Maffini, Elisa Mangione, Clementina Di Tonno, Mariano Lombardi, Francesca Maria Porta, Mario Urso, Vincenzo L’Imperio, Fabio Pagni, Claudio Bellevicine, Mariantonia Nacchio, Umberto Malapelle, Giancarlo Troncone, Antonio Marra, Giuseppe Curigliano, Konstantinos Venetis, Elena Guerini-Rocco, Nicola Fusco

PMC · DOI: 10.3390/cancers17213525 · 2025-10-31

## TL;DR

This paper explores how artificial intelligence, specifically deep learning, can improve the accuracy and consistency of thyroid cancer diagnosis by analyzing cytology slides.

## Contribution

The paper provides a technical overview of deep learning applications in thyroid cytopathology and highlights challenges and requirements for clinical deployment.

## Key findings

- Deep learning can assist in Bethesda category classification and reduce diagnostic uncertainty in thyroid cytology.
- Preanalytical variability and annotation bias limit the generalizability of deep learning models across institutions.
- Multicenter trials and standardized datasets are needed for safe clinical adoption of these technologies.

## Abstract

Thyroid nodules are very common, and fine-needle aspiration cytology is the main test used to decide whether a nodule is benign or not. While this test is reliable in most cases, many samples fall into an “indeterminate” category, often leading to unnecessary operations or delays in treatment. New computer-based methods, known as deep learning, can analyze digital images of thyroid cytology slides and may help reduce this uncertainty. By learning patterns that even experienced specialists may overlook, these systems could support pathologists in making faster and more accurate decisions, especially in difficult cases. In this article, we discuss how deep learning has been applied to thyroid cytology, the technical and practical challenges it faces, and how it could eventually help make thyroid cancer diagnosis more precise, consistent, and accessible worldwide.

Fine-needle aspiration cytology (FNAC) is the cornerstone of thyroid nodule evaluation, standardized by the Bethesda System. However, indeterminate categories (Bethesda III–IV) remain a major challenge, often leading to unnecessary surgery or delayed molecular testing. Deep learning (DL) has recently emerged as a promising adjunct in thyroid cytopathology, with applications spanning triage support, Bethesda category classification, and integration with molecular data. Yet, routine adoption is limited by preanalytical variability (staining, slide preparation, Z-stack acquisition, scanner heterogeneity), annotation bias, and domain shift, which reduce generalizability across centers. Most studies remain retrospective and single-institution, with limited external validation. This article provides a technical overview of DL in thyroid cytology, emphasizing preanalytical sources of variability, architectural choices, and potential clinical applications. We argue that standardized datasets, multicenter prospective trials, and robust explainability frameworks are essential prerequisites for safe clinical deployment. Looking forward, DL systems are most likely to enter practice as diagnostic co-pilots, Bethesda classifiers, and multimodal risk-stratification tools. With rigorous validation and ethical oversight, these technologies may augment cytopathologists, reduce interobserver variability, and help transform thyroid cytology into a more standardized and data-driven discipline.

## Linked entities

- **Diseases:** thyroid cancer (MONDO:0002108)

## Full-text entities

- **Diseases:** thyroid nodule (MESH:D016606)

## Figures

1 figure with captions in the complete paper: https://tomesphere.com/paper/PMC12610226/full.md

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Source: https://tomesphere.com/paper/PMC12610226