Diagnostic thresholds in thyroid cytopathology: toward biological risk stratification

Thyroid cytopathology has traditionally been interpreted within a binary diagnostic framework in which lesions are classified as benign or malignant. However, increasing recognition of borderline thyroid neoplasms, indolent carcinomas, and biologically heterogeneous tumors has challenged this paradigm and highlights the need for a more biologically informed approach. This review outlines conceptual developments reshaping thyroid cytopathology, with particular emphasis on the limitations of the binary paradigm and the emerging concept of diagnostic threshold theory. Variations in diagnostic thresholds influence the distribution of cytologic categories, resection rates, and reported risks of malignancy across institutions and health care systems. Within this framework, thyroid cytology is better understood as a method of biologic risk stratification rather than a definitive diagnosis of malignancy. Cytologic findings can help distinguish indolent lesions from clinically significant disease and may also identify tumors with aggressive behavior requiring prompt intervention. Integration of cytomorphology with ultrasound findings, molecular testing, and clinical factors is increasingly recognized as essential for risk stratification. This biology-based approach aligns diagnostic interpretation with tumor behavior and supports proportional clinical management, including active surveillance for selected low-risk thyroid cancers.