The Current Status of Thyroid Cytology in the Era of New Classifications, Molecular Profiling, and Clinical Risk Stratification

In recognition of the 70th anniversary of Acta Cytologica, this review delineates the historical and conceptual evolution of thyroid cytology from its origins in descriptive morphologic interpretation to its contemporary function within a structured, risk stratified, and multimodality informed diagnostic framework. Over successive decades, the major international reporting systems have progressively aligned around a shared hierarchical architecture; nonetheless, meaningful differences persist in the definition, operationalization, and clinical integration of indeterminate ("grey zone") diagnostic categories across regions and practice settings. Concurrently, refinements in histopathologic classification, particularly the formal recognition of borderline and other low risk neoplastic entities have recalibrated reported risks of malignancy without altering the foundational cytomorphologic features. These developments underscore the necessity for explicit outcome definitions and transparent denominator selection when estimating malignancy risk for individual diagnostic categories. Advances in contemporary molecular profiling, now feasible across routine cytology preparations, introduce an additional, sequential layer of risk modification. When interpreted in conjunction with ultrasonographic findings and clinical context, molecular data increasingly inform the management of indeterminate diagnoses and facilitate selection between active surveillance and surgical intervention. Moreover, the influence of ultrasound based sampling strategies and partial surgical verification on observed malignancy rates highlights the conditional and context dependent nature of category specific risk estimates, supporting the adoption of a Bayesian approach rather than reliance on fixed universal risk values. Taken together, these developments reaffirm the central role of thyroid cytology as a precise diagnostic modality and as an essential communication interface within contemporary, individualized thyroid nodule management.