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Melanoma

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Melanoma is a serious type of cancer that develops from melanocytes. These are the specialized cells responsible for producing melanin, the pigment that colors our skin. While it is most commonly recognized as a skin cancer, it can also occur in other locations. It may rarely appear in the mouth, the intestines, or the eye, which is known as uveal melanoma. In extremely rare instances, it can occur in the lungs. This is called primary pulmonary melanoma and accounts for only 0.01% of primary lung tumors.

Diagram showing where melanoma is most likely to develop CRUK 383
Diagram showing where melanoma is most likely to develop CRUK 383

The disease progresses through distinct biological stages. It begins with a radial growth phase. During this early stage, the tumor is less than 1 mm thick and stays within the basal epidermis. Because the cells have not reached deep blood vessels, the risk of spreading is very low. The next stage is the invasive radial growth phase. Here, individual cells acquire the potential to invade surrounding tissue. Finally, the cancer enters the vertical growth phase (VGP). In this stage, the tumor grows deeper into the dermis and becomes capable of traveling through the blood or lymph vessels to other parts of the body.

Diagram showing the T stages of melanoma CRUK 373
Diagram showing the T stages of melanoma CRUK 373

Ultraviolet (UV) radiation is the primary cause of melanoma. This radiation comes from the sun or from indoor tanning devices. UV light causes damage to the DNA within skin cells. Specifically, UVB light, which has wavelengths between 280 and 315 nm, is absorbed directly by DNA. This can create cyclobutane pyrimidine dimers, where adjacent pyrimidine bases join together. UVA light has longer wavelengths between 315 and 400 nm. While it is absorbed by DNA, it does so at much lower efficiencies than UVB. Using tanning beds before age 30 increases the risk of melanoma by 75%.

Melanoma vs normal mole ABCD rule NCI Visuals Online
Melanoma vs normal mole ABCD rule NCI Visuals Online

Genetics play a significant role in determining a person's risk. It is believed that 5% to 12% of melanoma cases are hereditary. Having a first-degree relative with the disease increases an individual's risk by 1.74 times. Some people carry specific genetic mutations that increase susceptibility. For example, the MC1R gene, which is linked to red hair, can increase risk by two to 3.6 times. Other mutations, such as those in the CDKN2A gene, are associated with dysplastic nevus syndrome (FAMMM). People with this syndrome have a 30% lifetime risk of developing melanoma.

Histopathology of superficial spreading melanoma
Histopathology of superficial spreading melanoma

Doctors use specific clinical signs to help identify potential melanoma. For many types, they use the "ABCDEEFG" mnemonic. This includes looking for asymmetry, irregular borders, variegated colors, and a diameter greater than 6 mm. It also tracks how the lesion evolves over time. However, nodular melanoma follows different rules. It may simply appear as a new, firm lump that is elevated above the skin surface. If the cancer reaches a metastatic stage, it may cause nonspecific symptoms like fatigue, nausea, or loss of appetite. Brain metastases are particularly common in these advanced cases.

Photography of nodular melanoma
Photography of nodular melanoma

Statistics show that melanoma is a significant global health concern. In 2015, 3.1 million people had active disease, leading to 59,800 deaths. While the number of cases is rising, mortality rates are decreasing due to new treatments. Worldwide, there were 331,722 cases in 2022, and this is expected to reach 510,000 by 2040. About 80% of all global cases occur in adults aged 50 or older. Australia and New Zealand report the highest rates in the world. In the United States, melanoma is 1.6 times more common in men than in women.

Worldwide Melanoma of Skin Cancer Incidence - 2008 Globocan
Worldwide Melanoma of Skin Cancer Incidence - 2008 Globocan

Treatment depends heavily on how far the cancer has spread. If the melanoma is localized, surgery to remove the tumor and adjacent tissue is common. Most people are cured if metastasis has not occurred. If the cancer spreads to the lymph nodes, the five-year survival rate in the United States is 76%. If the disease has spread to distant organs, the survival rate is 35%. For these advanced cases, doctors may use immunotherapy, biologic therapy, radiation, or chemotherapy. The success of treatment often depends on the tumor's thickness and how fast the cells are dividing.

5YearSurvival2008to14
5YearSurvival2008to14

Understanding the connection between environment and biology is vital. For instance, people working in airplanes may face higher risks due to increased UV exposure. Socioeconomic conditions also influence rates, with higher incidence seen in professional workers compared to unskilled workers. Additionally, the degree of skin pigmentation matters, as less melanin provides less protection from radiation. By combining genetic knowledge with UV protection, such as using sunscreen, the impact of this disease can be managed.

Diagram showing the most common places for melanoma to spread to CRUK 312
Diagram showing the most common places for melanoma to spread to CRUK 312
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🖼️ Images & Media (20)
File:Diagram showing where melanoma is most likely to develop CRUK 383.svg
Diagram showing where melanoma is most...
File:Metastatic Melanoma Cells Nci-vol-9872-300.jpg
Metastatic Melanoma Cells Nci-vol-9872-300.jpg
File:Melanoma vs normal mole ABCD rule NCI Visuals Online.jpg
Melanoma vs normal mole ABCD rule NCI...
File:Pie chart of incidence and malignancy of pigmented skin lesions.png
Pie chart of incidence and malignancy of...
File:Superficial spreading melanoma in situ on dermoscopy.jpg
Superficial spreading melanoma in situ on...
File:Histopathology of superficial spreading melanoma.jpg
Histopathology of superficial spreading...
File:Photography of nodular melanoma.jpg
Photography of nodular melanoma.jpg
File:Histopathology of nodular melanoma.jpg
Histopathology of nodular melanoma.jpg
File:Photograph of lentigo maligna melanoma.jpg
Photograph of lentigo maligna melanoma.jpg
File:Histopathology of lentigo maligna melanoma.jpg
Histopathology of lentigo maligna melanoma.jpg
File:Photography of a large acral lentiginous melanoma.jpg
Photography of a large acral lentiginous...
File:Histopathology of invasive acral lentiginous melanoma.jpg
Histopathology of invasive acral...

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