Minimal or Absent Tumor Desmoplasia Predicts Lower Recurrence Risk in Papillary Thyroid Carcinoma

Background: Papillary thyroid carcinoma (PTC) has an excellent prognosis, yet recurrence remains a clinical concern. Patients at intermediate risk may benefit from additional prognostic markers. We aimed to evaluate whether tumor desmoplasia predicts recurrence in intermediate-risk PTC patients and to assess its prognostic clinical utility. Methods: We conducted a retrospective study with follow-up of at least 36 months at a high-volume tertiary endocrine center. We included 121 patients with intermediate-risk PTC who achieved an excellent or indeterminate response to initial therapy at 12 months. Tumor desmoplasia was assessed on hematoxylin-eosin-stained thyroid sections by two pathologists. Desmoplasia was graded on a semi-quantitative 4-point scale based on the proportion of tumor area occupied by fibrotic stromal tissue. Patients were followed for the occurrence of biochemical or structural recurrence, which was defined as the primary study endpoint. Results: Desmoplasia was significantly associated with recurrence (Odds Ratio = 2.99; 95%CI: 1.51-6.34; p<0.01). Receiver operating characteristic analysis identified grade 2 as the optimal cut-off for predicting recurrence. Notably, the negative predictive value reached 95% in patients with absent or mild desmoplasia. Kaplan-Meier analysis confirmed a significant difference in recurrence-free survival between patients with mild versus severe desmoplasia (Hazard Ratio = 3.00; 95%CI: 1.45-6.24; p = 0.003). Conclusions: Desmoplasia is an independent predictor of recurrence in intermediate-risk PTC. Patients with minimal or no desmoplasia have an extremely low risk of recurrence. These findings support the potential role of desmoplasia as a prognostic feature in risk stratification and personalized management of intermediate-risk PTC.