Melanoma tumour progression (based on the Clark model)
 - Benign melanocytic nevi: controlled proliferation of normal melanocytes to produce a benign nevus.
 - Atypical/dysplastic nevi: abnormal growth of melanocytes in a pre-existing nevus or new location resulting in a pre-malignant lesion with random cytologic atypia. These appear as flat macules, > 5mm in size, with irregular borders and variable pigmentation.
 - Radial growth: melanocytes acquire ability to proliferate horizontally in the epidermis and histologically show continuous atypia (melanoma in situ).  E-cadherin helps confine the cells intraepidermally but a few cells may invade the papillary dermis. 
 - Vertical growth: numerous biochemical events including the loss of E-cadherin and expression of N-cadherin allow malignant cells to invade basement membrane and proliferate vertically in the dermis as an expanding nodule with metastatic potential. 
 - Metastasis: malignant melanocytes spread to other areas of body, usually first to lymph nodes then to skin, subcutaneous soft tissue, lungs and the brain.


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