Abstract
Melanoma is the most lethal form of skin cancer in the United States. Current American Joint Committee on Cancer (AJCC) staging uses Breslow depth and ulceration as the two primary tumor factors that predict metastatic risk in cutaneous melanoma. Early disease stages are generally associated with high survival rates. However, in some cases, patients with thin melanomas develop advanced disease, suggesting other factors may contribute to the metastatic potential of an individual patient’s melanoma. This review focuses on the role of the lymphatic system in the metastasis of cutaneous melanoma, from recent discoveries in mechanisms of lymphangiogenesis to elements of the lymphatic system that ultimately may aid clinicians in determining which patients are at highest risk. Ultimately, this review highlights the need to integrate pathological, morphological, and molecular characteristics of lymphatics into a “biomarker” for metastatic potential.
Highlights
Melanoma is responsible for the majority of skin cancer related deaths in the United States
The lymphatic system makes a critical contribution in melanoma metastasis
Recent studies have suggested that factors like VEGFC and the lymphatic endothelium itself play an important role in altering the immune system to support melanoma metastasis [22, 25]
Summary
Melanoma is responsible for the majority of skin cancer related deaths in the United States. While the initial Shields et al study had a relatively small sample size of 21 melanomas, several subsequent studies have reported that increased lymphatic density leads to a poor prognostic outcome [4, 7, 11, 12] Both Emmett et al and Spiric et al attempted to use the Shields index to predict whether a melanoma was likely to metastasize (Table 1). Several studies that found no association between lymphatic invasion and metastasis had large sample sizes, further contributing to this controversy (Table 2) These studies suggest that lymphatic vessel density (LVD) and the Shields index are valuable predictive tools. Even the more cumbersome method of calculating lymphatic vessel density has the potential to provide important prognostic information for melanoma patients
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