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.
Schematic model shows the origin of lentigo maligna, nodular melanoma, and superficial spreading melanoma from melanoma stem cells of the hair follicle, the dermis, and the epidermal basal layer, respectively. Melanoma stem cells (yellow concentric ring) produce progenitor cells (green stars) that drive proliferation and progression of melanoma cells (brown circles). A-C, Lentigo maligna deriving from stem cells of the outer sheet of the facial hair follicle. D-F, Superficial spreading melanoma deriving from stem cells in the epidermal basal layer. G-I, Nodular melanoma deriving from dermal stem cells.
Lentigo maligna. A, Clinical appearance. B, Dermoscopic examination revealed asymmetric pigmented hair follicles as the earliest sign of tumor growth (arrow) (original magnification ×10). C, At histopathologic analysis, melanocytes are arranged in nests and single units at the dermoepidermal junction. The papillary dermis exhibits solar elastosis, scattered melanophages, and a sparse lymphoid infiltrate (hematoxylin-eosin, original magnification ×40). D, Note the prominent perifollicular arrangement of melanocytes at higher magnification (hematoxylin-eosin, original magnification ×200).
Superficial spreading melanoma. A, Clinical appearance. B, Dermoscopic examination exhibited a clearly discernible flat area around the nodular part. The flat area shows a pigment network that corresponds histopathologically to melanocytes along the rete ridges of the basal layer (original magnification ×10). C, At histopathologic analysis, secondary nodular superficial spreading melanoma exhibits a broad melanoma in situ component with atypical melanocytes in nest and single cell formations within all epidermal layers, surrounding a central nodular melanoma component (hematoxylin-eosin, original magnification ×40). D, Note the atypical melanocytes in higher layers of epidermis (pagetoid spread) above a nodular melanoma component (hematoxylin-eosin, original magnification ×100).
Nodular melanoma. A, Clinical appearance. B, Dermoscopic view. In contrast to the melanoma shown in Figure 3, no lateral flat part or pigment network structures are seen (original magnification ×10). C, At histopathologic analysis, nodular melanoma consists of sheets of atypical melanocytes in the papillary and reticular dermis with asymmetric distribution of melanophages (hematoxylin-eosin, original magnification ×20). D, Note the lack of intraepidermal melanocytes (hematoxylin-eosin, original magnification ×200).
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