Molecular pathology in the diagnosis of cutaneous melanoma

Histopathological assessment of melanocytic proliferations remains the gold standard for their correct classification. The most recent 5th edition of the World Health Organization (WHO) classification of melanocytic tumours incorporates cumulative sun damage and, in particular, molecular genetic changes to achieve this task, and recognizes nine different genetic pathways leading to melanoma development. Melanoma is therefore not a single disease genetically, but rather represents nine different well-defined clinicopathological entities that differ in terms of biological behaviour and their response to various treatment modalities. In this article, genetic pathways in the development of cutaneous melanoma are reviewed, and practical recommendations for pathologists with regards to molecular testing are provided.