Melanoma: what it is, causes, common symptoms and cures

What is it

It is a malignant tumor of the skin that can affect any part of the body, caused by the uncontrolled proliferation of melanocytes.

Melanocytes are the cells that (together with keratinocytes) make up the superficial layer of the skin, the epidermis, and that produce melanin, the skin pigment through which the body defends itself from damage caused by ultraviolet radiation.

It can also develop on the mucous membranes (such as, for example, those of the eyes, nose and mouth) and, in particular, on the conjunctiva; But, in some (rare) cases, it can also occur in extracutaneous sites such as the eye (ocular melanoma), the meninges or the inner part of the ears. Very rare in children, it mainly affects the age group 30-60 years.

Once considered a rare disease, in recent years it has become more frequent: in fact, researchers have noticed that its incidence on the world population, in the last 10 years, has practically doubled; probably also due to the thinning of the atmospheric ozone layer that shields ultraviolet rays.

And the same happened in Italy, where, according to some estimates, in the last ten years new diagnoses have gone from 7,000 to almost 14,000, and are affected above all by the under 50s and women. The localization of cutaneous melanoma is more frequent in the upper and lower parts of the body for women, while in men it is more present on the trunk and head.

Depending on the skin layers it invades, the development of melanoma is divided into several stages, of increasing severity. At first, in fact, melanoma affects only the epidermis, then progressively invades the superficial dermis first and then the deep one, to finally reach the subcutaneous tissues.

According to the staging system in use, melanoma is also classified into four stages of severity, depending on the extent, location and possible presence of ulceration. We speak of stage I and II for localized primary melanoma, stage III when the lymph nodes of the region where the lesion is located are also affected, and stage IV for metastatic melanoma, with involvement of other organs.

Cutaneous melanoma is one of the malignant tumors of the skin, but it is not the only one. In reality it represents only 5% of the total skin cancers, much more frequent but also much more easily treatable. Melanoma is the most aggressive form of skin cancer, and is associated with high mortality rates unless diagnosed at a very early stage.

Histopathological classification

Cutaneous melanomas can result from congenital nevi (i.e. from moles present from birth) or they can appear during the course of life. In this case they are called acquired melanomas.

Depending on the type of spread, melanomas are divided into four types, each of which underlies a different genetic mutation. The identification of this type is essential for the elaboration of the prognosis of melanoma and therefore for the prediction of its evolution.

Superficial diffusion melanoma

It concerns 76 cases out of 100. It is typically asymptomatic and occurs most commonly on the legs, in women, and on the trunk, in men. Usually the lesions consist of a plaque with raised areas. The basic coloring is brown; On the lesion there may be red, white, black and blue patches or small nodules between blue and black. The margins can be notched, and the stain can vary in size and color.

Nodular melanoma

It accounts for 15 to 30% of all melanomas and can occur anywhere on the body, such as a dark or gray-black spot. It generally does not give symptoms but extends rapidly, developing an invasive component, which is why medical advice is required in most cases.

Malignant lentigo melanoma

Representing only 5% of melanoma cases, this form is one of the least frequent and mainly affects older people. It usually appears on the face or in areas very exposed to sunlight. It is an irregular brown patch in turn covered with darker brown spots scattered on the surface. It results from an evolution of lentigo maligna, which occurs when malignant melanocytes invade the dermis. In lentigo maligna, on the other hand, both normal and malignant melanocytes remain confined to the epidermis.

Acral-freckled melanoma

It affects one in ten cases and is the most common form in dark-skinned individuals. It occurs on the skin of the palms of the hands and under the soles of the feet and nails.

Causes

At the origin of melanoma there is a malignant degeneration of melanocytes, i.e. the cells that produce melanin, an indispensable substance to defend the skin from solar radiation.

Several factors, both genetic and environmental, contribute to its onset, and in particular excessive exposure to the sun, whose ultraviolet rays can damage cellular DNA, triggering tumor transformation and favoring the development of the disease.

Risk factors

People who have many moles, many freckles and fair skin are most at risk of developing melanoma. Other risk factors for melanoma include:

• familiarity;
• previous severe sunburn, with the appearance of vesicles;
• treatments with psoralen plus ultraviolet A (PUVA);
• therapy with immunosuppressive drugs;
• freckles;
• fair complexion, eyes and hair;
• many atypical or pigmented nevi, in particular in numbers greater than ten;
• another skin cancer.

People who have had melanoma are also at greater risk of developing a new one, as well as those who have a lesion, which appeared in adulthood, with an area greater than 6 millimeters or whose size has increased rapidly.

Finally, sunbeds and tanning lamps, as a source of UV rays, can cause the same damage and should therefore be used with extreme caution and avoided by children and adolescents.

Most common symptoms

Often, the first sign is represented by the modification of the size, shape, color or sensitivity to touch of a pre-existing mole. Melanoma can also occur on apparently healthy skin.

The melanomatous mole has some characteristics, summarized in what is known as the ABCDE rule.

Complications

Melanoma is an aggressive tumor that metastasizes easily. The most frequent metastases are to extra-regional lymph nodes, lung, liver, brain, bones.

Melanomas that are more than a millimeter thick have a higher risk of progression and metastasizing to the lymph nodes and blood vessels.

Some studies have highlighted a possible relationship, in women, between the presence of a high number of nevi and the increased risk of developing a breast neoplasm belonging to the estrogen-positive type, probably due to the role of female hormones on melanocyte activity. However, this is not a cause-and-effect relationship.

Treatment

The therapy depends on the stage in which the disease is found, it being understood that the surgical removal of the mole is the treatment of choice.

If the melanoma is at an early stage, it may be sufficient to remove only the nevus with a small part of surrounding tissue, with a healing rate of more than 90 percent.

If the thickness of the tumor is greater, the sentinel lymph node (the closest) is also removed to see if it already contains cancer cells. In the more advanced stages, surgical therapy is accompanied by chemotherapy and / or immunotherapy (to stimulate the immune system) and / or radiotherapy, and, usually, the choice between the combination of several treatments and the single one is made according to the needs of the patient.

In addition to these, then, targeted therapies are also used, which involve the use of drugs designed to act on specific DNA mutations (such as that of the BRAF gene) and so-called loco-regional therapies, which consist in the administration of high doses drugs on individual parts of the body.

Early diagnosis is the most important factor: in fact, the outcome of the disease can be very different depending on the extent of melanoma, and progressively worsens with increasing thickness of the lesion. The anamnesis is always done through a biopsy, or through the taking of a tissue sample then analyzed in the laboratory under a microscope. Normally, however, this phase is preceded by a complete examination, which is essential for the evaluation of the person’s medical history, and by a visual examination of the skin, conducted using a dermatoscope, an instrument that allows enlargement and illumination.

Sometimes other tests may also be ordered, such as chest X-rays, CT scans, pet scans and MRIs, in order to understand if and to what extent the disease has spread.

As with other cancers, we cannot speak of a single tumor, but of many different molecular types of melanoma, characterized, at the cellular level, by different genetic mutations that regulate its growth and respond differently to therapies.

Advances in research are highlighting characteristics of the disease on the basis of which it will be possible to develop personalized therapies in the future.

Prevention

The sun is one of the main causes of skin cancer: not only melanomas, but for example also squamous cell carcinoma and basal cell carcinoma, more frequent in people who have spent a lot of their lives working outdoors.

As far as melanoma is concerned, the basis of prevention is careful and controlled sun exposure. It is therefore necessary to:

• avoid prolonged exposure during the hottest hours, when the sun’s rays are particularly strong;
• If you still have to stay outdoors it is good to wear a long-sleeved shirt or shirt and hats with visor;
• use high protection sunscreens appropriate to your skin type, to be applied often in order to ensure continuous coverage;
• Check the nevi periodically, either by consulting a dermatologist or by independently observing your own skin. For people with many nevi a mapping is performed that allows to control their evolution over time;
• take care of nutrition, taking foods rich in vitamins, especially A, C, E, D.

In the case of children, then, it is necessary to be very careful because their skin is very sensitive to sunburn.

When to consult your doctor

Since the prognosis and the possibility of recovery depend in an essential way on the timeliness with which the tumor is identified, it is good to consult the doctor in the face of any changes you notice in the moles you have, as well as any new suspicious nevus (such as a nevus that shows to grow rapidly).

Other alarm bells for which the dermatologist’s opinion is necessary are a nevus that bleeds, that generates itching or that is surrounded by a lump or a reddened area.