Three Roots of Melanoma

Segura et al1 describe morphologic features of melanomas with a nodular component using in vivo reflectance-mode confocal microscopy (RCM) and correlate these RCM findings with histopathologic findings. The most striking observation made by the investigators is the remarkable difference in epidermal involvement between nodular melanoma (NM) and superficial spreading melanoma (SSM) with a nodular component. At RCM, SSMs frequently showed epidermal disarrangement and pagetoid infiltration, whereas NMs exhibited a preserved epidermal pattern and few pagetoid cells.1 This new observation provides fertile ground for revisiting the conventional concept of melanoma development. We propose an alternative hypothesis based on recent observations made in stem cell research and demonstrate how this hypothesis can better account for the observed clinical and epidemiologic differences between melanoma subtypes.