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Dr. Mariappan Natarajan*


Skin cancers are on the rise globally. Cutaneous melanomas are associated with bad prognosis and are difficult to treat after metastasis has occurred. Melanomas represent a serious public health problem; early diagnosis is crucial for effective therapy and to reduce the clinical and financial burden of the disease. Histopathologic diagnosis pose a significant challenge and alternate diagnostic tools facilitate prompt recognition and confirmation of malignant lesions. Cutaneous melanomas develop as result of a number of genetic mutations and UV radiation is the common mutagenic risk factor. Apoptosis is required to avoid malignant transformation of healthy cells. Natural and artificial UV radiations cause mutations, that inactivate apoptosis. Melanoma and its younger sister, Merkel cell carcinoma are the most lethal and deadliest of cancers. Genetic testing has improved detection of molecular alterations, and reveal vital information for diagnosis and prediction of prognosis. Rapid detection of genetic alterations help choosing appropriate treatment protocols and to develop targeted therapies for melanoma. Conventional invasive diagnostic techniques are associated with anxiety and poor patient compliance. Non-invasive skin cancer diagnostic methods include photography, Dermoscopy, sonography, terahertz spectroscopy, Raman spectroscopy, confocal microscopy, fluorescence spectroscopy, optical coherence tomography, multispectral imaging technique, thermography, electrical bio-impedance, tape stripping and computer-aided analysis. Study of molecular pathology of melanoma marks a paradigm shift in the diagnosis and management of melanomas. Detection of molecular markers aids in precise diagnosis where histological assessments pose a challenge. Identification of common mutations (BRAF or NRAS) help narrow down diagnosis, predict prognosis, and guide treatment. Knowledge regarding relationship between vitamin D and melanogenesis may bring in new clinical therapies for melanoma. The markers should become reflexive when melanoma is suspected and after diagnosis they must contribute to improve patient outcomes. This review aims at refreshing and to update our knowledge regarding the genetic and molecular basis of melanomas. Non-invasive diagnostic modalities and basis for therapeutic aspects related to cutaneous melanomas are also discussed.

Keywords: skin cancer; UV irradiation; molecular pathology; immunotherapy; molecular testing; genetic mutations; early detection; imaging; surveillance; survivorship; Immune checkpoint inhibitor; PD-1 inhibitor; Pseudo progression; Hyper progression; hyperspectral;

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