Tumor type-specific and skin region-selective metastasis of human cancers: another example of the “seed and soil” hypothesis

Metastasis of human cancer is an organ-selective process that is determined by anatomical and biological factors as well as by specific microenvironmental properties. Dissemination of visceral malignancies to the skin is rather rare and usually occurs in a later stage of the disease. Using statistical approaches, both positive (renal and lung cancers) and negative (pancreatic and liver cancers) organ preferences can be identified in a variety of cancers. While certain cancer types are characterized by random distribution for skin metastasis (liver cancer), a number of cancers demonstrate a colonization preference to the region of origin: lung cancer to the supradiaphragmatic (mostly chest) and colorectal cancers to the infradiaphragmatic (abdominal) skin regions. In certain cases, however, skin metastasis develops more frequently at specific distant locations, as evidenced by the dissemination of renal cancer at the head and neck region. These findings are clinically relevant and useful especially in patients where skin metastasis is the first indication of a malignancy. Nevertheless, it is a strong argument for the predominant role of microenvironmental factors in cancer dissemination. On the other hand, skin metastases of visceral cancers provide a unique model to analyze the pathomechanisms determining organ selectivity, including the organ-specific vascularization, the dermatome-specific innervation, or immunological and developmental factors.