The increasing incidence of skin cancer and the importance of early diagnosis is a challenge, which requires the development of reliable, cost-effective, noninvasive, diagnostic techniques. Several such methods based on optical imaging techniques are available and currently being investigated. A novel method in this field is multiphoton laser scanning microscopy (MPLSM). This technique is based on the nonlinear process of 2-photon excitation of endogenous fluorophores, which can be used to acquire horizontal optical sectioning of intact biological tissue samples. When studying human skin, MPLSM provides high-resolution fluorescence imaging, allowing visualization of cellular and subcellular structures of the epidermis and upper dermis. This review covers the application of MPLSM as a diagnostic tool for superficial skin cancers, such as basal cell carcinomas, squamous cell carcinoma in situ, and melanomas. MPLSM has also been applied in other research areas related to skin, which will be mentioned briefly. The morphologic features observed in MPLSM images of skin tumors are comparable to traditional histopathology. Safety issues, limitations, and further improvements are discussed. Although further investigations are required to make MPLSM a mainstream clinical diagnostic tool, MPLSM has the potential of becoming a noninvasive, bedside, histopathologic technique for the diagnosis of superficial skin cancers.
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