Interpretation of the 5th edition of WHO classification of endocrine and neuroendocrine tumors: update and progress on follicular cell-derived thyroid tumors

The 2022 WHO classification of endocrine and neuroendocrine tumors (5th edition) categorizes thyroid follicular cell-derived tumors into benign, low-risk, and malignant types. Benign tumors now include thyroid follicular nodular lesions. A newly added category previously termed "borderline tumors" have been revised to low-risk follicular cell-derived tumors, which encompass non-invasive follicular thyroid neoplasm with papillary-like nuclear features, thyroid tumors of uncertain malignant potential, and hyalinizing trabecular tumors. The new WHO classification stratifies malignant follicular cell-derived tumors based on molecular characteristics and invasiveness: papillary thyroid carcinoma (PTC) with various histological subtypes represents BRAF-like malignancies; invasive encapsulated follicular variant PTC and follicular thyroid carcinoma represent RAS-like malignancies. Oncocytic carcinoma is now recognized as a distinct entity, specifically referring to tumors composed of ≥75% oncocytic follicular cells lacking PTC nuclear features and high-grade characteristics (necrosis and mitotic figures ≥3/2 mm²). A new category termed "high-grade follicular cell-derived thyroid carcinoma" has been added, encompassing traditional poorly differentiated thyroid carcinoma and differentiated high-grade thyroid carcinoma. Anaplastic thyroid carcinoma(ATC) remains the most undifferentiated type, with thyroid squamous cell carcinoma now classified as a subtype of ATC. The term "papillary thyroid microcarcinoma" is no longer recommended as a distinct subtype. Cribriform-morular thyroid carcinoma is no longer classified as a subtype of PTC, but is instead categorized as a tumor of uncertain histogenesis.