melanoma

definition

Malignant melanoma is a highly malignant tumor that rapidly forms metastases in other organs. As the name suggests, it starts from the melanocytes of the skin. Almost 50% of all melanomas develop from pigmented birthmarks. However, they can also develop "spontaneously" on completely unremarkable skin.

Occurrence in the population (epidemiology)

Melanoma is the tumor with the world's highest increase in incidence.
In Germany, the so-called incidence rises by 8% every year. Incidence rates (melanoma / 100, 000 population / year) are lowest in sub-Saharan Africa at 0.1. In Australia, the incidence rate is highest at 60.
In Germany, the incidence is around 12 / 100, 000 inhabitants / year.
Due to improved early detection mortality was reduced to 20% of all cases. Most melanomas are discovered between the ages of 30 and 70 years.

Causes of a melanoma

Frequent sunburns favor melanomas.

There are several risk factors of melanoma formation. A malignant (malignant) melanoma can develop from a liver spot / birthmark (nevus cell nevus) that has existed for years.
Likewise, it can arise from completely unremarkable skin. For example, genetic factors play a role.
Increased risk of melanoma development is evident in FANN repair damage (see below), or familial accumulation of melanoma. Also, acquired factors, such as severe sunburns, can promote the development.

It is estimated that the following causes are distributed:

  • 30 to 70% of melanomas arise from long-standing liver spots
  • 30 to 70% of the melanomas develop on unremarkable skin
  • Ten to 20% of melanomas develop after years of melanotic precancerous lesions = precancerous lesions (eg Lentigo maligna).
    Under a precancerous condition one understands in this case a skin change, which can possibly degenerate to a tumor.
  • 10% of melanomas occur frequently in families:
    As part of familial melanoma, there are various nevi (birthmarks) that can be considered:
  • Clark nevus
  • Familial atypical nevus and melanoma (FAMM) syndrome

Staging of a melanoma

The malignant melanoma is classified into 5 stages according to the so-called TNM classification. This classification is based on the following three criteria:

  1. The tumor thickness (T). It is important to determine how deep the tumor has entered the skin. Below one millimeter, the risk of metastasis is very low, but over 4 mm there is a very high probability of metastasis of the malignant skin tumor. The reason for this is the connection of the tumor to the blood and lymph vessels, which sit in the deeper skin layers and over which the tumor can spread.
  2. The infestation of regional lymph nodes (N). These are the lymph nodes closest to the tumor. Because of their location to the tumor, they are the first station affected by metastasis and are therefore a good indicator of the stage of malignant melanoma. A distinction is made between metastases that are visible only under the microscope and metastases that have already led to a palpable or visible enlargement of the lymph nodes.
  3. The distant metastases (M). This refers to the spread of the tumor to other parts of the body. In malignant melanoma, there are no preferred organs that are infested with metastases, as is typical of other tumors. Occurrence in the liver, lungs, brain, bones and in the skin is possible. The peculiarity of the malignant melanoma is the metastasis in the heart. Since a malignant disease of the heart is very rare, this metastasis accounts for about 50% of all cardiac tumors.

In addition to these three main criteria, there are two secondary criteria that serve to break down the 5 stadiums:

  • The mitotic rates. This criterion describes the number of cell divisions of the tumor and thus its activity. This measure is particularly relevant for prognosis in tumors with a thickness of less than 1 mm.
  • Ulcerations. Thus, the property of the tumor is called to cause a deep skin damage that resembles a wound or an ulcer. The more pronounced this process is, the more advanced the tumor is.

According to these criteria, stage 0 corresponds to a tumor that only grows locally and has a low mitotic rate without metastasizing. In stage I the tumor thickness is <2mm and neither lymph nodes are affected nor are distant metastases present. Stage II is different in that the tumor is now> 2mm. From stage III, the lymph nodes are additionally affected, but there are no distant metastases. Only from the stage IV then distant metastases are present. Thus, the lower the stage, the better the prognosis.

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The prognosis in a melanoma

The prognosis of malignant melanoma depends on its stage, metastasis and many other factors.
These include:

  • the tumor thickness ( divided into Breslow )
  • the ulceration of the tumor and
  • the penetration depth ( after the Clark level )

In addition, the individual subtypes of melanoma have different chances of recovery. For example, lentigo-maligna melanoma (LMM) has a better prognosis than amelanotic melanoma (AMM). In addition, tumor location and gender are factors for the prognosis. Men generally have a worse prognosis than women. Overall, the Amelanotic Melanoma has a very poor prognosis, which is independent of sex and localization. In contrast, the darkness of the melanoma usually has no effect on the prognosis.

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In general, the chances of a cure are very good in an early diagnosis, especially if it is an "in situ melanoma". This has not yet passed through the basal membrane (boundary between the epidermis and the dermis), but is already potentially dangerous.
Therefore, it is important to regularly take a skin cancer screening.

The reason for the good prognosis is that no metastasis has taken place in this case. The prognosis according to tumor stage is divided according to the 5-year survival rate. This indicates the proportion of patients who still lived 5 years after diagnosis.

  • In stage I, the chance of recovery is> 90%. The primary tumor is a maximum of 1.5mm thick and has a Clark level of <III.
  • In Stage II, the primary tumor is> 1.5mm thick and has a Clark level> IV. At this stage, the 5-year survival rate is 70%.
  • In stage III, the tumor has already metastasized to the nearest lymph nodes, or formed new skin metastases. Tumor thickness and Clark levels are irrelevant. The 5-year survival rate is 40%.
  • If the tumor has spread to more distant organs, stage IV and a probability of survival of 10% are present.
    The metastasis pathways are very different in a malignant melanoma and can thus occur in all organs. However, metastases are often found in the liver, skin, lungs, skeleton, heart or brain.

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Especially metastases in the liver or the brain affect the prognosis unfavorable. By contrast, lung metastases are often very slow-growing and therefore more treatable. In particular, the malignant tumors of the heart are very rare and can be found in 40-60% of cases as a metastasis of a malignant melanoma.

Basically, only premature, complete removal of the melanoma can lead to healing. Waiting, on the other hand, worsens the forecast significantly.

Note: For this reason, regular check-ups and early detection measures are very important.

Forms and symptoms of melanoma

In the case of melanoma, four classic growth forms and special forms are distinguished. All melanomas follow the ABCD rule in their irregularity. According to this rule, the contour (asymmetry), limitation, color (coloring), and size (diameter, > 5mm) are assessed. Symptoms may include itching and spontaneous bleeding.

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The four classic growth forms are described below.

  1. Superficial spreading malignant melanoma (SSM)

  2. Primary nodular malignant melanoma (NMM)

  3. Lentigo Malignant Melanoma (LMM)

  4. Acrolentiginous malignant melanoma (ALM)

Superficial spreading malignant melanoma (SSM)

SSM has a brownish-black color.

(superficial = superficial, malignant = malignant)

As described above, the melanomas in their initial phase follow horizontal growth (growth in width) within the epidermis (epidermis). This growth phase lasts about 5 to 7 years, so relatively long, which is why the early detection rate is steadily increasing.
More and more early forms, the so-called "melanoma in situ", are being discovered with relatively good prognosis. The "melanoma in situ" represents an increased growth of melanocytes within the epidermis.
This growth is associated with the emergence of atypical cells. The morphage (appearance) of superficial spreading malignant melanoma (SSM) is very different. It ranges from light brown to brownish-black and is initially a flat stove, which has nodules or nodules in the further course.
In the lighter areas of the tumor there is an immune reaction.

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The relative incidence of this condition is 65%, with areas of the skin that are often exposed to the sun (eg face) particularly affected.
The mean age of onset is about 50 years.

Primary nodular malignant melanoma

(nodular = nodular, malignant = malignant)

This form of melanoma seems to be more aggressive, because this is where the vertical growth phase begins immediately. The primary nodular malignant melanoma (NMM) consists of a fast - within months - growing node, which is usually dark brown - black, often also piebald patterned.
The melanoma cells form this node in the dermis (dermis). In the epidermis (epidermis) hardly any tumor parts are to be found.

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The relative frequency of this disease is 15%. Again, as with superficial spreading malignant melanoma (SSM), sun-exposed areas of the skin are particularly affected. The mean age of onset is close to that of the superficial spreading malignant melanoma (SSM) at 55 years of age.

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Lentigo Malignant Melanoma (LMM)

A lentigo maligna is an increase of atypical melanocytes within the epidermis (epidermis). These cells have a tendency to go into lentigo malignant melanoma (LMM).
Lentigo maligna can grow horizontally for years - even for decades - as precancerous lesions.
The transition to the vertical growth phase (deep growth) and thus to the lentigo maligna melanoma is characterized by the formation of small nodules. In this area, the tumor cells expand vertically in both directions.
The forecast is relatively good because of the long horizontal growth.

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The relative frequency of this disease is 10%, with the face and back of the hand particularly affected.
The mean age of onset is significantly higher at age 68 than in superficial spreading malignant melanoma (SSM) and primary nodular malignant melanoma (NMM).

Acrolentiginous malignant melanoma

(Akren = hands, feet, nose ears, malignant = malignant, lentigines = spots, similar to freckles, but larger and darker)

In this rather rare melanoma, first horizontal growth comes to the fore, later vertical growth with the formation of blackish nodes. This disease is similar in appearance and growth to lentigo maligna melanoma (LMM).
In dark-skinned peoples, acrolentiginous malignant melanoma (ALM) is the most common type of melanoma. Because their localization is not always easily accessible, the ALM are often diagnosed late and thus have a correspondingly unfavorable prognosis.

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The relative frequency of this disease is 5%. Affected are above all the akren = body ends (hand, foot, nose, ear ...) and the nail beds.
The mean age of onset is 63 years.

The treatment of a melanoma

The first and most important measure of a malignant melanoma is its complete removal, while maintaining a sufficient safety margin so that no residual, initially invisible tissue remains and leads to further growth of the melanoma. Surgical removal is avoided only in elderly people in a very advanced stage of malignant melanoma without any chance of recovery. For very large melanomas, a skin graft may be necessary, either as a donation or donated by others. In addition, the so-called sentinel lymph node, ie the lymph node, which is located first in the lymphatic drainage area of ​​the melanoma, is removed. For this purpose, it is labeled with the radioactive substance technetium 99 and removed by a small skin incision. Subsequently, this is also examined to exclude metastasis. Should a metastasis be detected in this sentinel lymph node, the other lymph node stations will be removed and examined. If a lymph node is already enlarged, the entire lymph node region is removed directly without first examining the sentinel lymph node.
Further therapy depends on the stage of the disease and is determined both by the tissue examination of the surgically removed melanoma and by the study of distant metastases.

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There are several attempts to treat malignant melanoma in addition to surgical removal:

  • Chemotherapy: Chemotherapy is used on existing distant metastases. There is the alternative to perform the therapy with only one drug or you can apply a scheme of two or three different drugs. The combination therapy is only in question if the physical condition allows this increased load. Combination therapy is beneficial for 25-55% of those treated. With the administration of only one drug, it is only 14-33% that benefit from the therapy, but also significantly fewer side effects are to be expected. A cure can not be achieved with chemotherapy.
  • Interferon therapy: Interferons are proteins that occur naturally in the body and are additionally given to the body in this therapy. They activate the natural killer cells in the body that can actively destroy cancer cells. In addition to surgery, interferon therapy is currently an effective and approved method for the treatment of melanoma.
  • Radiotherapy: Radiotherapy is used for inoperable tumors and inoperable lymph node metastases. Visible tumor remnants after surgical removal are also irradiated. In 70% of cases, the tumor can be kept under control, but radiotherapy is not able to cure the disease.
  • Vaccines: For the treatment with a vaccine, cancer cells are taken from the patient, which are modified in the laboratory and then re-administered in a modified form. The body should destroy these modified cells and thereby recognize the other cancer cells in the body better and also destroy it. So far, this therapy has not led to any success.
  • Antibody therapy: A new method attempts to produce targeted antibodies in the laboratory against surface proteins of the tumor cells. These antibodies bind to the tumor cell and cause their degradation via the immune system. For the malignant melanoma, an efficacy of the antibody ipilimumab was found. The therapy only affects every sixth patient and has many side effects. Therefore, this option for the treatment of melanoma has so far been recommended only to a limited extent.
  • Mistletoe therapy: Mistletoe is a plant that is able to affect the immune system. This effect should be exploited for the treatment of tumors, however, the mistletoe therapy is suspected to favor tumor growth and should therefore not be used.
  • Hyperthermic limb perfusion: In this method, chemotherapeutic agents are delivered in high doses into the bloodstream of one limb, which is tied off during treatment by the rest of the body. In addition, this body part is overheated to destroy cells due to the high temperature. The advantage is that by separating the extremity from the body, one can choose a significantly higher dosage of chemotherapy that would normally not be tolerated by the body. Since the removal of the body cycle as a complication, an amputation of the body part in question may be necessary, this method is used only very rarely and only in certain tumor types. For lymph node metastases, this treatment option is not recommended.
  • Immune stimulation: The goal of immune stimulation is the attack of the body against foreign cells, especially against cancer cells. The previously tested agents levamisole and BCG are not able to target the body specifically on the destruction of tumor cells. Therefore, the therapy is ineffective and is not recommended.

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The drugs of choice therefore remain the surgical removal of the melanoma and / or therapy with interferons.

Summary

Melanomas are very malignant tumors that emanate from melanocytes and very often metastasize.

Malignant melanoma is one of the most dangerous cancers.

Melanomas are therefore malignant, rapidly metastasizing tumors emanating from melanocytes. Melanocytes are cells of the skin that have stored the pigment melanin. Melanin causes, among other things, the tanning of the skin.
This tumor spreads very quickly and early through the lymphatic system (lymph) and the blood. This fact makes him so dangerous. Other skin tumors, such as the basalioma, scatter very rarely, which makes them relatively harmless in comparison.

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Depending on the type of melanoma, the biological behavior of the tumors also differs. Some are more common than others.
The course, however, is the same for ellen melanomas. They develop from a single cell clone that has the predisposition to degenerate, from which the primary tumor arises.
It first grows within the epidermis, the so-called melanoma in situ, and later, when it breaks through the basal membrane of the skin, as an invasive melanoma. This growth is called vertical growth. The more superficial the melanoma has grown into the skin, the greater the chance of recovery.

People with sun-sensitive skin are more at risk than others. Red-blond hair and a correspondingly light skin tone bring about a five-fold higher risk than black hair with a darker skin tone.

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