Depending on cytologic atypia, melanocytic lesions range from dysplastic<unk>  to melanoma. The progression to melanoma usually involves the serine-threonine kinases of the MAPK/ERK pathway (mitogen-activated protein kinase) following mutation of either the N-RAS or BRAF oncogene. It is thought that the progression to melanoma requires multiple genetic mutations, where activation of the oncogene alone does not lead to the development of melanoma, and additional mutations (multiple hits), such as loss-of-function mutation of P53 tumor suppressor gene (or less commonly P16/CDKN2A or PTEN in familial cases) is required for the development of melanoma. The development of melanoma may arise de novo or from pre-existing nevi. In both cases, mutations result in dysplasia and cytologic atypia that predispose to the malignant potential of the cells. As more genes are mutated and the tumor grows, changes include the overexpression of N-cadherin, αVβ3 integrin, MMP2, MSH, cAMP, and survivin, and the loss of E-cadherin and TRMP1 proteins.
Dysplastic nevus pathophysiology
Melanoma pathophysiology
Hemangioma pathophysiology
Vitiligo pathophysiology
Uveal melanoma pathophysiology
Lymphangioma pathophysiology
Dysplastic nevus epidemiology and demographics
Lipoma pathophysiology