The 2018 World Health Organization Classification of Cutaneous, Mucosal, and Uveal Melanoma Detailed Analysis of 9 Distinct Subtypes Defined by Their Evolutionary Pathway

Context.-There have been major advances in the understanding of melanoma since the last revision of the World Health Organization (WHO) classification in 2006. Objective.-To discuss development of the 9 distinct types of melanoma and distinguishing them by their epidemiology, clinical and histologic morphology, and genomic characteristics. Each melanoma subtype is placed at the end of an evolutionary pathway that is rooted in its respective precursor, wherever appropriate and feasible, based on currently known data. Each precursor has a variable risk of progression culminating in its fully evolved, invasive melanoma. Data Sources.-This review is based on the "Melanocytic Tumours'' section of the 4th edition of the WHO Classification of Skin Tumours, published in 2018. Conclusions.-Melanomas were divided into those etiologically related to sun exposure and those that are not, as determined by their mutational signatures, anatomic site, and epidemiology. Melanomas on the sun-exposed skin were further divided by the histopathologic degree of cumulative solar damage (CSD) of the surrounding skin, into low and high CSD, on the basis of degree of associated solar elastosis. Low-CSD melanomas include superficial spreading melanomas and high-CSD melanomas incorporate lentigo maligna and desmoplastic melanomas. The "nonsolar'' category includes acral melanomas, some melanomas in congenital nevi, melanomas in blue nevi, Spitz melanomas, mucosal melanomas, and uveal melanomas. The general term melanocytoma is proposed to encompass "intermediate'' tumors that have an increased (though still low) probability of disease progression to melanoma.