The Morphologic and Immunohistochemical Profiling of Thyroid Nodules Submitted to Thermal Ablation  Avoids a Misdiagnosis of Carcinoma

Thermal ablation (TA) is a minimally invasive treatment for benign thyroid nodules, but it induces histological changes that can mimic malignancy. This study expands our previous series to characterize the histological and immunohistochemical changes occurring in these nodules after TA and to refine diagnostic criteria to prevent misdiagnosis of benign lesions as carcinoma. Twelve surgically excised thyroid nodules previously treated with laser thermal ablation were retrospectively analyzed. Histopathological examination focused on architecture, nuclear features, capsule characteristics, and degenerative changes. Immunohistochemistry was performed for galectin-3 (Gal-3), HBME-1, BRAF V600E, p53, and Ki-67. All nodules showed a fibrous capsule. Architecture was predominantly follicular (75%) or solid (25%). Sclerosis (83.3%) and subcapsular hemorrhage (91.7%) were common; necrosis and ischemia were rare. No true capsular or vascular invasion was observed. All cases were negative for Gal-3, and BRAF V600E. Eleven nodules were HBME-1-negative; one showed focal weak positivity; p53 was hyperexpressed in 3 cases. Ki-67 was consistently below 3%. TA induces characteristic degenerative and reactive changes that may simulate malignancy, including fibrosis, hemorrhage, and nuclear atypia. The consistent negativity of malignancy-associated immunohistochemical markers, together with low proliferative activity, confirms the benign nature of these alterations and supports the use of an integrated morphologic–immunohistochemical approach for accurate diagnosis. This expanded analysis reinforces that laser ablation induces reproducible histologic alterations in benign thyroid nodules that can simulate malignancy. Awareness of these changes, combined with a restricted immunohistochemical panel, allows confident recognition of treatment-related artifacts and prevents overdiagnosis of carcinoma.