Short answers, pulled from the story.
John Hunter removed the first recorded case of metastatic melanoma in 1787. The excised mass was preserved in the Hunterian Museum of the Royal College of Surgeons of England and confirmed as melanoma through microscopic examination in 1968.
Ultraviolet light is the primary architect of melanoma and damages the DNA of skin cells by creating cyclobutane pyrimidine dimers. UVB light with wavelengths between 280 and 315 nanometers is absorbed directly by DNA while UVA light contributes to the formation of thymine dimers and reactive oxygen species.
Specific mutations in the BRAF gene occurring in the 600th codon are found in 50% of cases and render the protein constitutively active. Other mutations in the NRAS, HRAS, and KRAS genes appear in 30% of cases while loss-of-function mutations in tumor suppressor genes like TP53 and CDKN2A further destabilize the cell.
The Breslow depth of the lesion and the Clark level of invasion are critical metrics used to stage the disease with thicker tumors and deeper invasion correlating with a worse prognosis. When the tumor thickness exceeds 1 millimeter and involves the deeper parts of the dermis the cancer can travel through blood or lymph vessels to distant organs.
The five-year survival rate for localized melanoma in the United States is 100% but this drops to 76% when the disease has spread to lymph nodes and to 35% among those with distant spread. Metastatic melanosa diagnosed between 2015 and 2021 carries a five-year survival rate of 34.6%.
Amelanotic melanomas have very little to no pigmentation and are more difficult to detect than pigmented lesions. Thirty to 40% of acral melanomas are amelanotic and these tumors often present in areas that do not usually get sun exposure such as the soles of the feet and palms of the hands.