Lymphatic invasion in cutaneous melanoma is associated with sentinel lymph node metastasis

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.

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.

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.

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