Melanoma is an aggressive malignancy of melanocytes. Melanoma may arise at sites of melanocytes including on the skin, on the mucous membranes, around the nail apparatus, and in the eye. Melanoma can metastasize to any organ of the body. The most frequent sites are skin / subcutaneous, lymph nodes, lungs, liver, and brain. This summary focuses on metastatic cutaneous melanoma.

The presence of nodal metastases connotes stage III disease per the American Joint Committee on Cancer (AJCC) staging system (eighth edition). Nodal disease may be occult and detectable on sentinel lymph node biopsy only, or it may be clinically detectable. Microsatellitosis (discrete nests of malignant melanocytes, 0.05 mm or more, at least 0.3 mm away from the main invasive portion of melanoma, as seen on histopathologic sections), satellitosis (clinical detectable metastases within 2 cm of the primary tumor), and in-transit metastases (intralymphatic spread of metastases more than 2 cm away from primary site) also connote stage III disease. Distant metastases, including distant skin, soft tissue, nonregional lymph node, visceral, and central nervous system (CNS) metastases, are categorized as stage IV disease.

Mutations in MAPK and downstream pathways have been found in melanoma, including in BRAF, NRAS, PTEN, KIT (mucosal melanoma), GNAQ (uveal melanoma), and CDKN2A. This has led to the development of new mutation-targeted therapies for metastatic melanoma. Historically, 5-year survival rates for advanced melanoma were less than 10%. The development of newer treatment strategies has afforded 5-year survival rates of up to 50% in some studies. In addition, complete remission has been seen in some patients.