The Prognostic Role of Lymphatic Vessel Density in Papillary Thyroid Carcinoma: A Systematic Review and Meta‐analysis

Background/Aim: Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer accounting for 75-85% of cases. Despite its favorable prognosis, 30-50% of patients develop regional lymph node metastases. Lymphatic vessel density (LVD) is a potential predictor of tumor progression, metastasis, and patient survival in PTC. This systematic review and meta-analysis evaluate the prognostic significance of LVD in PTC, focusing on intratumoral and peritumoral LVD and their association with nodal metastasis. Materials and Methods: A systematic review and meta-analysis were conducted following PRISMA guidelines and the Cochrane Handbook. Eligible studies included patients with PTC who underwent tumor resection and had LVD assessed via immunohistochemistry (D2-40, LYVE-1). Literature search was performed in MEDLINE, Cochrane Library, and PubMed. Two independent reviewers screened studies and extracted data, including survival outcomes and LVD measurements. Hazard ratios (HRs) and mean differences were calculated using fixed-effects or random-effects models, with heterogeneity assessed via I2 statistics. Results: A total of 21 studies were identified, with nine meeting eligibility criteria. Meta-analysis demonstrated a significant association between high overall LVD and increased nodal metastasis (summary mean difference: 2.64; 95%CI=1.45, 3.82; p<0.001, I2=30.6%). No statistically significant association was observed for intratumoral (summary HR=1.33; 95%CI=0.88-2.02; p=0.176, I2=74.3%) or peritumoral LVD (summary HR=1.58; 95%CI=0.51-4.89; p=0.429, I2=74.7%). Heterogeneity across studies suggested potential variability in LVD measurement techniques and patient populations. Conclusion: This meta-analysis highlights the prognostic role of overall LVD in predicting nodal metastasis in PTC. However, intratumoral and peritumoral LVD did not show a significant correlation, indicating the need for further research. Standardization of LVD assessment and integration with molecular markers could enhance risk stratification and personalized treatment approaches in PTC management.