Pentraxin-3 in thyroid nodules: a systemic marker of pathology and a local mediator of inflammation and carcinoma

Background Thyroid nodules are extremely common, yet the exact physio-pathological mechanisms underlying their benign or malignant development remain poorly understood. Pentraxin-3 (PTX3) is an innate immune inflammatory mediator involved in inflammation, tissue remodeling, and oncogenesis, processes often coexistent in thyroid pathology. This study evaluated plasma and tissue PTX3 in patients undergoing thyroidectomy for benign or malignant nodules.Methods A total of 52 patients were enrolled. Plasma PTX3 levels were assessed by ELISA before surgery and again 45 days afterward. PTX3 expression, along with the abundance of two immune cell populations (e.g. macrophages and mast cells) was evaluated by immunohistochemistry using a tissue microarray.Results Preoperative plasma PTX3 levels were significantly elevated (4.58 ng/mL, p<0.05) compared with the normal reference range and declined significantly after surgery (3.58 ng/mL, p<0.05). No significant differences in plasma PTX3 were observed between benign and malignant conditions. In tissue analysis, PTX3 expression was significantly elevated in malignant tissues relative to healthy thyroid counterparts, in which it was entirely absent; however, its overall expression levels remained low to moderate across most malignant samples. CD68 and tryptase showed variable patterns, with a higher abundance of macrophages and mast cells in carcinomas and a significant association between mast cell presence and thyroid cancer (p = 0.0025).Conclusions Our findings suggest that increased PTX3 levels may indicate an active inflammatory response or tissue stress linked to thyroid nodular disease. Nevertheless, its specificity for distinguishing benign from malignant lesions has yet to be determined. Its strong local expression in thyroiditis and consistently low expression in most carcinomas further support the concept that the long pentraxin PTX3 plays an important role in innate immune activation and inflammation-driven thyroid tissue remodeling. Additional studies are needed to better define its potential prognostic value in thyroid carcinoma.