Jean Jacques Grob, Caroline Gaudy‐Marqueste, Kelly B. Cha, Timothy M. Johnson, Alison B. Durham, Reinhard Dummer, Simone M. Goldinger


Molecular studies, as well as epidemiological observation, support the concept of distinct molecular pathways to melanoma, suggesting that there are different melanoma subtypes with different biological aggressiveness, kinetics and prognosis. The incidence of melanoma is still rising worldwide, despite sun‐protection campaigns. Although sun exposure is considered as the main risk factor, genetics may play the significant role, not only in familial forms but also in apparently sporadic cases that may result from a chance combination of many low susceptibility genes. Mortality, at best, has plateaued despite earlier detection in the high‐risk population under dermatological surveillance. Indeed, most aggressive melanomas may develop in this population, suggesting that education to self‐detection should target the whole community. Melanoma detection remains a clinical challenge based on cognitive, comparative and dynamic recognition.
Pigmented lesions suspicious for melanoma on the basis of history or physical examination warrant appropriate biopsy and histopathological diagnosis. Most melanoma is clinically localized to the primary site and requires definitive treatment with wide local excision with an appropriate margin. As the most frequent site of first metastasis is the regional nodal basin, consideration should also be given to sentinel lymph node biopsy in the correct clinical context.
The treatment of advanced melanoma is in a very dynamic state of change. After years of standstill, melanoma has evolved into a paradigm for precision medicine based on substantial progress in molecular biology and tumour immunology. Both immunotherapy using anti‐checkpoint antibodies such as anti‐CTLA‐4 or anti‐PD‐1 antibodies and targeted therapy including BRAF inhibitors and mitogen extracellular kinase inhibitors are able to improve the prognosis of melanoma patients. Treatment decisions in melanoma patients are based on the basic prognostic parameters such as tumour thickness, involvement of the regional lymph nodes, extent of internal organ involvement with special attention to brain metastases, growth dynamics and, in addition, on the molecular assessment of the tumour concerning mutations (in particular BRAF and NRAS mutations) that facilitate the use of selective small kinase inhibitors. In order to support this rapid development, patients with advanced disease should be referred to tertiary skin cancer centres that can offer clinical trial participation.
Keywords melanoma, epidemiology, detection, sun exposure, genetics, early detection, prevention, diagnosis, prognosis, naevus
Keywords melanoma, biopsy, wide local excision, margin, sentinel lymph node biopsy
Keywords immunotherapy, kinase inhibition, clinical trial, anti‐CTLA‐4 antibody, anti‐PD‐1 antibody, anti‐PD‐L1 antibody, BRAF inhibitor, mitogen extracellular kinase inhibitor, MEK inhibitor, c‐Kit inhibitor, chemotherapy


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