The natural course of cutaneous melanoma.

The natural course of cutaneous melanoma (CM) is determined by its metastatic spread and depends on tumor thickness, ulceration, gender, localization, and the histologic subtype of the primary tumor. CM metastasis develops via three main metastatic pathways and occurs as satellite or in-transit metastasis, as regional lymph node metastasis or as distant metastasis at the time of primary recurrence. About 50% of all CM patients with tumor progression firstly develop regional lymph node metastases. In the other 50% the first metastases are satellite or in-transit metastases (about 20%), or immediately distant metastases (about 30%). Development of distant metastasis appears to be an early event in metastatic spread and may in the majority of cases originate from the primary tumor, only few cases may develop secondarily to locoregional metastasis. Reporting of organ involvement in distant metastasis greatly differs between the results of imaging techniques and autopsy results in respect to the metastatic patterns detected, pointing out that there is a need of improved imaging systems. Proliferation, neovascularization, lymphangiogenesis, invasion, circulation, and embolism are important steps in the pathogenesis of CM metastasis, with tumor vascularity as an important independent significant prognostic factor. The expression of chemokine receptors in cancer cells associated with the expression of the respective chemokine receptor ligands in the target sites of the metastasis is an interesting observation which may stimulate the development of new therapeutic strategies.