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...