Clinical meaning
Thyroid nodules are present in 4-7% of the population by palpation and up to 67% by ultrasound, but only 5-15% are malignant. Thyroid carcinomas arise from two cell types: follicular cells (producing papillary, follicular, and anaplastic carcinomas) and parafollicular C-cells (producing medullary thyroid carcinoma). Papillary thyroid carcinoma (PTC) is the most common (80-85%), driven by RET/PTC rearrangements and BRAF V600E mutations; it spreads via lymphatics to cervical nodes, has an excellent prognosis, and characteristically displays psammoma bodies and Orphan Annie nuclei on histology. Follicular thyroid carcinoma (10-15%) is driven by RAS mutations and PAX8-PPARgamma rearrangements; it spreads hematogenously (bone, lung metastases) and requires histological demonstration of capsular or vascular invasion for diagnosis (cannot be diagnosed by FNA alone). Medullary thyroid carcinoma (3-5%) arises from calcitonin-producing C-cells, associated with MEN2A/2B (RET proto-oncogene mutations); calcitonin serves as tumor marker. Anaplastic carcinoma (<2%) is one of the most aggressive human cancers with near-100% mortality, typically arising from dedifferentiation of existing differentiated thyroid cancer, often with TP53 mutations. The Bethesda System for Reporting Thyroid Cytopathology standardizes FNA results into six categories with implied malignancy risk and management recommendations.