Diagnosing Thyroid Lesions Through A Morphology–Molecular Lens: Four Case‐Based Lessons From 22nd International Congress of Cytology—Florence 2025

Imaging‐driven detection of thyroid nodules has expanded the role of fine‐needle aspiration (FNA) while demanding integration of molecular data into routine cytologic assessment. We present four illustrative cases spanning the contemporary diagnostic spectrum: (1) an Atypia of Undetermined Significance (AUS) nodule with dual low‐level PTEN mutations managed by active surveillance; (2) an oncocytic follicular neoplasm upgraded to total thyroidectomy by concurrent HRAS and TERT promoter mutations; (3) an oncocytic subtype poorly differentiated thyroid carcinoma (O‐PDTC) highlighting subtle high‐grade cytologic cues and a distinct genomic profile; and (4) a pediatric poorly differentiated carcinoma harboring a DICER1 hotspot mutation, underscoring age‐specific biology and the need for genetic consideration. These cases emphasize that morphology remains foundational, but mutation context, single versus co‐alterations, allelic burden, and patient age ultimately direct management. Harmonized reporting that clearly conveys molecular findings is essential to translate limited cytology material into precise, patient‐specific care.