Melanoma: Types, Symptoms, Causes, Risks, Diagnosis, Treatment, Outlook and Prevention

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melanoma in a mole macro

1Overview

Melanoma is increasing worldwide. It is especially prevalent in places where fair-skinned people receive excessive sun exposure. In the United States, the incidence of melanoma is 20-30 per 100,000 people and in Europe, it is 10-25 per 100,000. The most common phenotypic characteristic risk factor that leads to melanoma is fair skin, which tends to burn in the sun. Another risk factor is the inheritance of melanocortin-1 receptor, which is the most common genotype. Genetically determined as well, individuals with high numbers of common moles, those with large congenital moles, and those with large/atypical moles are at greater risk. Five to 10% of melanomas are seen in melanoma-prone families that carry susceptibility genes. The most prominent exogenous factor related to the development of melanoma is exposure to UV radiation and, in particular, intermittent exposure to the sun.

2Types

There are five types of melanoma, each with distinct histological features. The first type is superficial spreading melanoma, which is the most common type, comprising 55-60% of all cases. It is associated with patterns of irregular high sun exposure and is most often seen in young people. It usually starts as new brown or black spots that spread within the outer layers of the skin, the epidermis. It may also manifest as an existing spot, mole, or freckle that changes in shape, size, or color. This type of melanoma slowly grows and becomes more dangerous as it invades the dermis.

Nodular melanoma makes up about 10-15% of cases. The usual appearance of this type of melanoma is a round, raised lump on the skin. It is usually brown, black, or pink and is firm when touched. A crusty surface may develop that easily bleeds. Most commonly found in older people, nodular melanomas often occur on the head and neck on a severely sun-damaged skin. It is aggressive and fast-growing, spreading quickly through the dermis.

Lentigo maligna melanoma is most common in older people and makes up 10-15% of cases. It begins as a large freckle in sun-damaged skin, such as in the neck, head, face, and ears. It grows superficially and slowly over many years before it penetrates the dermis.

Acral lentiginous melanoma is an uncommon type, making up about 1-2% of cases. It is commonly found on hairless surfaces, such as the skin on palms, soles of feet, or under toenails and fingernails. It appears as a colorless Constipation. It grows slowly before it invades the dermis. 

3Symptoms

There is a classic “ABCD” mnemonic used to describe the characteristics of the signs and symptoms of melanoma. In summary, moles that are Asymmetric, which have irregular Borders, that have variable Color or changes in color within the lesion, and that are greater than 6mm in Diameter are said to be indicative of melanomas. In addition to these, bleeding, pruritus, and ulceration in moles are also early warning symptoms. However, it is important to remember that early melanomas may be less than 6mm in diameter and may be symmetric. 

4Causes

Although many risk factors for developing melanomas have been found, the exact mechanisms by which melanomas develop are unclear. For instance, while some moles may cause cancer, not all do. Epidemiological studies have been conducted to show the connection between these risk factors and melanoma. Exposure to ultraviolet (UV) radiation was consistently shown to be a major risk factor for melanoma development. For instance, one or more sunburns during childhood can increase the risk for melanoma for life. This suggests that intermittent exposure to UV radiation plays an important role in the tumorigenesis of melanomas. In addition, experiments have shown that UV radiation often leads to mutations in DNA. These mutations cause the formation of pyrimidine dimers or cytosine deamination which leads to the formation of thymidine. Aside from these, individuals who have a family history of melanoma are more sensitive to UV radiation compared to others. Thus, they are more likely to develop melanomas at an earlier age and their cancer is more likely to develop into multiple lesions.

5Risk Factors

There are numerous risk factors for developing melanomas, and the primary risk factor is exposure to UV radiation. Individuals who frequently tan themselves without using sunscreen on their bodies and faces are have an increased chance of acquiring the disease. In addition, geographical location also plays an important role. People who live in or near the equator, where sunlight directly hits the surface of the Earth, are exposed to more UV radiation than those who live nearer the poles. Thus, they are at an increased risk of developing melanomas.

Age is another factor, with melanomas being more common in the elderly population. This is presumably due to the time that it takes for mutations in melanocyte-relevant genes to accumulate, subsequently driving carcinogenesis. The natural decline in cellular immunity is also a risk factor.

Indoor tanning beds are increasingly being used in the United States. However, the UV radiation emitted by lamps in tanning beds are more powerful than natural sunlight. It is estimated that 30 minutes in a tanning bed is equivalent to 300 minutes unprotected underneath natural sunlight.

Although persons of any race can have melanomas, fair-skinned individuals are at much greater risk. The amount of black melanin in the skin determines skin tone. Eumelanin, or black melanin, block UV radiation and is found in low levels in fair-skinned persons.

Nevis, or moles, are another risk factor for melanomas. The more moles that a person has, the more likely the person will develop melanomas. However, it should be noted that the risk of a mole becoming malignant is very low. Studies have shown that individuals that have a hundred moles are seven times more likely to have melanomas.

6Diagnosis

A dermatologist is responsible for diagnosing melanomas. There are three preliminary analyses that need to be conducted before other procedures are done. First, the dermatologist visually analyzes the melanomas, although there are melanomas that may mimic seborrheic keratoses in some instances. Then, the physician compares the nevus with other moles that the patient has. The third step consists of a chronological analysis of the nevus; that is, evidence that it evolved over time should be presented.

Dermoscopy is then conducted to clarify the diagnosis. In addition to dermoscopy, other non-invasive methods are also used. These include reflective confocal microscopy.

Histopathologic diagnosis is used to confirm the suspicion of melanoma. The skin lesion is removed and examined for cellular changes.

7Treatment

The primary mode of treatment for melanomas is surgical excision. In this case, an excision biopsy is preferred because the malignancy can be removed and at the same time, the borders of the malignancy can be evaluated for residual tumor growth.

Another treatment option is lymph node removal in case the melanoma has spread to the lymph nodes. Adjuvant therapies may also be prescribed, such as radiotherapy, targeted therapy, and immunotherapy. Radiotherapy is used to kill cancer cells. Targeted therapy is the use of drugs to kills genes that allow cancer cells to grow. Immunotherapy is the use of drugs to strengthen the body’s immune system.

The types of drugs approved for targeted therapy include dabrafenib and trametinib. These drugs block the effects of the BRAF mutation. They also reduce the growth of the melanoma.

Immunotherapy drugs include ipilimumab, nivolumab, and pembrolizumab. These are approved for the treatment of melanoma. They are also known as checkpoint inhibitors because they inhibit proteins that suppress the responses of the immune system.

8Outlook

The prognosis for cancer patients with melanomas differs depending on the staging and the type of melanoma present. If the tumor is diagnosed early on, the prognosis is very good and survival rates are close to 100%. There are several factors that affect prognostication.

Breslow’s depth or the thickness of the tumor affects prognosis, as well as the skin structure depth (Clark level). The type of melanoma, the presence of ulceration, the involvement of lymph nodes, lesion location, satellite lesions, and regional or distant metastasis are all factors that affect prognosis.

There are also stages applied when prognosticating melanomas. Stage 0 has a 99.9% survival rate. Stage I has an 89-95% survival rate, while stage II has a 45-79% survival rate. Stage III has a survival rate of 24-70% and stage IV has a 7-19% survival rate.

The prognosis of melanomas depends on the comorbidities that a person has. Other co-morbidities may be present that will intensify the person’s condition and hasten deterioration.

9Prevention

Excessive exposure to sunlight is the single most important preventive factor against melanomas. Other preventive measures include performing regular self-examinations, recognizing the “ABCD” signs, and consulting a doctor if moles change in shape, size, or color. The religious use of sunscreens on the body and face is also preventive, as is avoiding tanning beds. Sun exposure between 10 AM and 4 PM should be limited, so patients should be advised to stay indoors during this time. Wearing protective clothing is another preventive measure. Annual skin exams are also recommended so that physicians can alert patients if any nevi are evolving over time and developing into malignant nevi.