Artificial Intelligence in Thyroid Cytopathology: Diagnostic and Technical Insights
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.
Authors
- Clementina Di Tonno
- Konstantinos Venetis (ORCID: https://orcid.org/0000-0002-0163-879X)
- Giuseppe Curigliano (ORCID: https://orcid.org/0000-0003-1781-2518)
- Umberto Malapelle (ORCID: https://orcid.org/0000-0003-3211-9957)
- Elena Guerini‐Rocco (ORCID: https://orcid.org/0000-0003-2001-7582)
- Vincenzo L’Imperio (ORCID: https://orcid.org/0000-0002-9284-2998)
- Nicola Fusco (ORCID: https://orcid.org/0000-0002-9101-9131)
- Giancarlo Troncone (ORCID: https://orcid.org/0000-0003-1630-5805)
- Fausto Maffini (ORCID: https://orcid.org/0000-0002-4554-8956)
- Fabio Pagni (ORCID: https://orcid.org/0000-0001-9625-1637)
- Mariantonia Nacchio (ORCID: https://orcid.org/0000-0002-8528-5273)
- M Urso (ORCID: https://orcid.org/0000-0002-3444-1846)
- Chiara Frascarelli (ORCID: https://orcid.org/0009-0006-3077-8405)
- Francesca Porta (ORCID: https://orcid.org/0000-0003-2841-5024)
- Claudio Bellevicine (ORCID: https://orcid.org/0000-0002-7479-6457)
- Antonio Marra (ORCID: https://orcid.org/0000-0002-7310-7824)
- Elisa Mangione
- Mariachiara Negrelli (ORCID: https://orcid.org/0009-0003-0254-743X)
- M. Lombardi
Institutions
- University of Milan (IT)
- European Institute of Oncology (IT)
- University of Milano-Bicocca (IT)
- University of Naples Federico II (IT)
Publication Details
- Journal
- Cancers
- Published
- 2025-10-31
- DOI
- https://doi.org/10.3390/cancers17213525
- Primary Topic
- AI in cancer detection
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Ministero della Salute
- Fondazione Umberto Veronesi
- European Society for Medical Oncology