Background:  Sentinel lymph node (SLN) metastasis is a major determinant for staging, prognostication and clinical management of patients with cutaneous melanoma. However, the role of lymphatic vs. vascular invasion (VI) for SLN spread remains unclear.

Methods:  We compared the frequency of lymphatic invasion (LI) vs. VI in melanoma sections from 94 patients with a mean three‐year clinical follow up using immunostains for the lymphatic endothelial markers D2‐40 (podoplanin) and LYVE‐1 and the panvascular marker CD31.

Results:  LI occurred more frequently than VI (16 vs. 3%, respectively, p = 0.001) and correlated with higher American Joint Committee on Cancer stage at diagnosis (p = 0.0004). In a univariate analysis, LI was strongly associated with SLN metastasis (p = 0.008), independent of tumor thickness. In a multivariate analysis, LI was not a significant risk factor for SLN metastasis. The presence of intratumoral lymphatics (ITLs) was associated with distant metastasis, whereas VI was rare and did not correlate with SLN or distant metastasis. A combination of LI and ITL had higher positive and negative predictive values for the risk of developing SLN metastasis compared with routine histology and VI.

Conclusion:  Detection of LI in the primary tumor may aid in identifying melanoma patients with the propensity to develop SLN metastasis.