Melanoma
A 1960s examination of nine Peruvian mummies revealed melanotic masses in the skin and diffuse metastases to the bones. These specimens were radiocarbon dated to be approximately 2400 years old, providing some of the earliest evidence of the disease in antiquity. John Hunter is reported to be the first to operate on metastatic melanoma in 1787. He described the excised tumor as a cancerous fungous excrescence without knowing precisely what it was. The preserved specimen later sat in the Hunterian Museum of the Royal College of Surgeons of England until microscopic examination in 1968 confirmed it as an example of metastatic melanoma. The French physician René Laennec was the first to describe melanoma as a distinct disease entity during a lecture for the Faculté de Médecine de Paris in 1804. His report was published as a bulletin in 1806. An English general practitioner from Stourbridge named William Norris presented the first English-language report of melanoma in 1820. In his later work in 1857 he remarked that there is a familial predisposition for development of melanoma. Norris also suggested a link between nevi and melanoma and observed that most of his patients had pale complexions.
The primary cause of melanoma is ultraviolet light exposure in those with low levels of the skin pigment melanin. UVB light emanating from the sun at wavelengths between 315 and 280 nm is absorbed directly by DNA in skin cells. This absorption results in cyclobutane pyrimidine dimers which are a type of direct DNA damage. UVA light presents at wavelengths longer than UVB between 400 and 315 nm but absorbs less efficiently about one hundredth to one thousandth of UVB. Occasional extreme sun exposure that results in sunburn on areas of the human body is causally related to melanoma. The International Agency for Research on Cancer finds that tanning beds are carcinogenic to humans. People who begin using tanning devices before the age of thirty years are 75% more likely to develop melanoma. Having more than 50 moles indicates an increased risk of melanoma. A weakened immune system makes cancer development easier due to the body's weakened ability to fight cancer cells. It is believed that 5-12% of melanoma is hereditary. Having a family history of melanoma increases one's risk with having a first-degree relative increasing one's risk of developing melanoma by 1.74 times.
Early signs of melanoma are changes to the shape or color of existing moles or the appearance of a new lump anywhere on the skin. At later stages the mole may itch ulcerate or bleed. Early signs of melanoma are summarized by the mnemonic ABCDEEFG which stands for Asymmetry Borders irregular with edges and corners Color variegated Diameter greater than about the size of a pencil eraser and Evolving over time. Visually inspecting the skin lesion in question is the first step in diagnosing a suspected melanoma. Moles that are irregular in color or shape are suspicious for melanoma. When used by trained specialists dermoscopy is more helpful to identify malignant lesions than use of the naked eye alone. Following a visual examination and a dermatoscopic exam a skin biopsy is done for lesions suspicious of being melanoma. A skin biopsy is required for definitive diagnosis of melanoma and staging the cancer. Elliptical excisional biopsies may remove the tumor followed by histological analysis and Breslow scoring. Incisional biopsies such as punch biopsies are usually contraindicated in suspected melanomas because of the possibility of sampling error or local implantation causing misestimation of tumour thickness.
Treatment typically is removal by surgery of the melanoma and the potentially affected adjacent tissue bordering the melanoma. Complete surgical excision with adequate surgical margins is standard often done by a wide local excision with 5 mm to 2 cm margins. Mohs surgery has been reported with cure rate as low as 77% and as high as 98.0% for melanoma-in-situ. Chemotherapy drugs such as dacarbazine have been commonly used for metastatic melanoma since the 1970s however their efficacy in terms of survival has never been proven in an RCT. In the early 2000s a relatively common strategy was to treat patients with a high risk of recurrence with up to a year of high-dose interferon treatment. A 2013 meta-analysis suggested that the addition of interferon alpha increased disease-free and overall survival for people with AJCC TNM stage II-III cutaneous melanoma. The five-year progression-free survival for immunotherapy with pembrolizumab is 21%. Nivolumab or pembrolizumab was associated with increased recurrence free survival at 12 months of treatment. Lifileucel Amtagvi is a tumor-derived autologous T-cell immunotherapy that was approved for medical use in the United States in February 2024.
Globally in 2012 melanoma occurred in 232,000 people and resulted in 55,000 deaths. Australia and New Zealand have the highest rates of melanoma in the world. In Australia melanoma incidence has increased by more than 30 per cent between 1991 and 2009. Australian melanoma age-standardized incidence rates were as of 2008 at least 12 times higher than the world average. It is estimated that in 2012 more than 12,000 Australians were diagnosed with melanoma given Australia's modest population this is better expressed as 59.6 new cases per 100,000 population per year. Melanoma incidence in Australia is a matter of significance for overall age-standardized cancer incidence in Australia is the highest in the world and this is attributable to melanoma alone. In the United States about 8-9,000 people die from melanoma a year and the death rate from melanoma is 1.40 deaths per 100,000 people. The incidence of melanoma in the United States increased from 8.8 cases per 100,000 people in 1975 to 27.7 cases per 100,000 people in 2021. In 2024 in the United States there were 100,640 cases of melanoma and 8290 deaths.
With treatment the five-year survival rates in the United States are 100% among those with localized disease 76% when the disease has spread to lymph nodes and 35% among those with distant spread. Stage IV melanoma in which it has metastasized is the most deadly skin malignancy: five-year survival in the United States was 34.6% for people diagnosed between 2015 and 2021. Metastases to the skin and lungs have a better prognosis while metastases to the brain bone and liver are associated with a worse prognosis. Survival rates have rapidly increased in the decade leading up to 2025. Factors that affect prognosis include tumor thickness in millimeters depth related to skin structures presence of ulceration and presence of lymphatic or perineural invasion. When melanomas have spread to the lymph nodes one of the most important factors is the number of nodes with malignancy. The extent of malignancy within a node is also important; micrometastases in which malignancy is only microscopic have a more favorable prognosis than macrometastases. About 200 genes are prognostic in melanoma with both unfavorable genes where high expression is correlated to poor survival and favorable genes where high expression is associated with longer survival times.
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Common questions
When was the earliest evidence of melanoma found in Peruvian mummies?
Radiocarbon dating placed nine Peruvian mummies with melanotic masses at approximately 2400 years old. This examination occurred during a study conducted in the 1960s.
Who first described melanoma as a distinct disease entity and when did this occur?
French physician René Laennec first described melanoma as a distinct disease entity during a lecture for the Faculté de Médecine de Paris on the 1st of January 1804. His report was subsequently published as a bulletin in 1806.
What is the primary cause of melanoma according to scientific research?
The primary cause of melanoma is ultraviolet light exposure in individuals with low levels of skin pigment melanin. UVB light between 315 and 280 nm wavelengths directly damages DNA by creating cyclobutane pyrimidine dimers.
How many people developed melanoma globally in 2012 and how many died from it?
Globally in 2012, melanoma occurred in 232,000 people and resulted in 55,000 deaths. Australia and New Zealand maintain the highest rates of melanoma worldwide.
When was lifileucel Amtagvi approved for medical use in the United States?
Lifileucel Amtagvi received approval for medical use in the United States on the 1st of February 2024. This tumor-derived autologous T-cell immunotherapy treats specific cases of melanoma.