Abstract
The melanin fluorescence emitted by pigment cells of the human skin has been a central research topic for decades, because melanin, on the one hand, protects against (solar) radiation in the near-UV range, whereas on the other hand, melanocytes are the starting point for the malignant transformation into melanoma. Until recently, however, melanin fluorescence was not accessible in the context of conventional spectroscopy, because it is ultraweak and is overshadowed by the more intense so-called autofluorescence of endogenous fluorophores. The advent of a new method of laser spectroscopy has made this melanin fluorescence measurable in vivo. A stepwise two-photon absorption with 800 nm photons is used, which more selectively excites melanin (dermatofluoroscopy). Our review summarizes the experimental results on melanin fluorescence of the four types of cutaneous pigment cells from healthy and malignant tissues. Outstanding is the finding that different types of melanocytes (i.e., melanocytes of common nevi, versus dysplastic nevi or versus melanoma cells) show characteristically different fluorescence spectra. The possibilities of using this melanin fluorescence for melanoma diagnosis are shown. Moreover, the uniform fluorescence spectra emitted by different melanoma subtypes are essential. Conclusions are drawn about the molecular processes in the melanosomes that determine fluorescence. Finally, experimental suggestions for further investigations are given.
Highlights
Melanin may be viewed as a double-edged sword: on the one side, melanin acts as a parasol protecting epidermal stem cells from UV-induced DNA damage, and on the other side, the melanocytes that produce melanin carry the risk of transformation into melanoma, one of the most aggressive and deadliest forms of skin cancer
A strategy to escape from this dilemma is shown in Figure 1b: The melanin fluorescence is generated by means of a stepwise excitation by two photons of lower energy (800 nm)
The fluorescence spectrum of melanin in melanoma cells is given in Figure 2, lower right: It shows a uniformly increasing intensity over the entire measurement range of 430–650 nm. This spectral shape results (i) for all melanoma cells when measured on a melanoma, and (ii) for all melanomas of the examined subtypes so far: superficial spreading melanoma (SSM), acral lentiginous melanoma (ALM), nodular melanoma (NM), lentigo maligna melanoma (LMM), desmoplastic and hypomelanotic melanoma [20,24,25], and (iii) both for melanoma developing on a preexisting nevus and for de novo melanoma
Summary
Melanin may be viewed as a double-edged sword: on the one side, melanin acts as a parasol protecting epidermal stem cells from UV-induced DNA damage, and on the other side, the melanocytes that produce melanin carry the risk of transformation into melanoma, one of the most aggressive and deadliest forms of skin cancer. Melanin is characterized by a continuum of excited states; during the lifetime of such an excited intermediate state the fluorescent level can be reached by absorption of a second photon. Sci. 2021, 22, 5265 there is virtually no autofluorescence The latter applies “cum grano salis”: by the process of simultaneous two-photon excitation via a virtual intermediate state (Figure 1c), the endogenous fluorophores can be excited by the 800 nm photons to their fluorescent state.
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