Pathology and new insights in thyroid neoplasms in the 2022 WHO classification

The assessment of thyroid nodules is a common clinical problem, linked to the high incidence of thyroid nodules in the population and the low incidence of aggressive thyroid carcinoma. The screening is therefore one of the strengths of our patient care. Recently, the 2023 Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) and 2022 WHO classification of thyroid neoplasms have been released based on the definition of new entities and the growing impact of molecular testing. The aim of this review is to analyze how these upgrades can help us in the daily routine practice diagnosis of thyroid cancer.

Our review is focused on the most frequent thyroid tumors derived from thyroid follicular cell. Fine needle aspiration (FNA) is the gold standard for the screening of thyroid nodules with very high levels of sensitivity and specificity. These sensitivity and specificity are improved by molecular testing, which refines the risk of malignancy. The 2023 TBSRTC integrates molecular data and the upgrades integrated in the 2022 WHO classification such as the 'low-risk neoplasms' and the 'high-grade follicular-cells derived carcinoma'. The morphological examination remains crucial since the capsular and/or vascular invasion are key features of malignancy in the follicular thyroid neoplasms. Low-risk neoplasms represent a clinical challenge since no specific guidelines are available. Challenges remain regarding oncocytic thyroid lesions, which are not associated with specific diagnostic molecular biomarkers. Molecular testing can help not only in deciphering the prognosis but also in the targeted therapeutic strategy.

While molecular testing has succeeded to substantially improve the pre and postoperative diagnosis and risk stratification of thyroid tumors, the morphological examination is still central in the daily routine diagnosis of thyroid pathology. Future is the integrated diagnosis of clinical, morphological, molecular and epigenetic features with the help of artificial intelligence algorithms.