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Melanoma

Melanoma is a dangerous malignant tumor that develops from melanocytes - the cells responsible for skin color and its changes during sun tanning.  Most often, this tumor develops on the skin, the most vulnerable areas being those frequently exposed to sunlight. However, melanoma can also appear in other organs containing melanocytes, such as eye retina or oral mucosa.  

Why is melanoma so dangerous?

Melanoma is a very aggressive tumor prone to rapid invasive growth deep into tissues and active metastatic spreading. Tumor cells spreading with the current of lymph or blood can affect both the nearest lymph nodes and distant organs - liver, lungs, bones, brain.

Melanoma removal and the best ways to do it

Removing melanoma is not only possible, but necessary - at present, surgery remains the main treatment option for melanoma. In this case, the tumor should be removed radically, that is, completely, otherwise the melanoma may keep growing from the remaining cells. For this reason, cryodestruction or laser removal arenot used to eliminate melanomas or melanoma-suspicious formations, as there is a great probability of leaving imperceptible tumor cells in the tissues and thus provoking their active spreading throughout the body.

It is also necessary to perform a histological study of the removed tissues (this, again, cannot be done with cryodestruction or laser ablation of the tumor). An expert will study the microscopic structure and properties of the removed tissues, as well as tumor thickness and depth of invasion in case of a malignant lesion. These findings will serve as the basis for determining the diagnosis, the disease stage and the tactics of further treatment. Immunohistochemical and genetic testing of melanoma tissue, in turn, will provide an opportunity to assess the susceptibility of tumor cells to different drug therapy options and to clarify the prognosis.

In general, the cause of melanoma is always the same, being the change in the cell's DNA that affects its further behavior. Malignant cells start growing and fissioning rapidly, their programmed death does not occur, and they are very weakly connected to each other and ready to go "freewheeling" through the body with blood or lymph flow.

As for melanoma, one of the proven causes of malignant cell transformation is exposure to ultraviolet radiation. Moreover, its source is not important, as it can be both natural sunlight and tanning lamps. It has been proven that visiting a solarium more than 20 times a year doubles the risk of developing skin cancer. Melanoma is also provoked by sunburns, especially if they occur repeatedly. Even more at risk are persons with pale skin, multiple moles and pigmented spots, or with a hereditary predisposition to malignant skin diseases.

How does melanoma manifest itself, and what should I focus on when I look at my skin? 

Melanoma has several prominent features:

  • it can resemble a normal mole
  • it is usually of an irregular asymmetric shape, and its edges are uneven and dissected;
  • its color is non-uniform or changes with time;
  • it has a large size (more than 6 mm), or its size changes;
  • there be peeling or sores on the surface.

If during a self-examination you found a formation that corresponds to any of the above signs, consult an oncologist, the earlier melanoma is suspected, the higher is the possibility of successful treatment.

Other possible causes for tumor development

Another, no less important mechanism for melanoma development is trauma of a mole or a pigmented spot. Benign skin lesions can be injured by clothing or in the course of contact sports, and if located on the scalp, when shaving or haircutting.

Inflammation is one of the theories for the causes of oncological conditions, and regular trauma will be  inevitably accompanied by inflammatory reactions. In this case, the cells of a benign lesion may begin to change due to the constant need for recovery, and initially these changes will be characterized by the term “dysplasia”. If the irritant effect preserves, their malignant transformation may by all means occur in the future.

What is the best way to deal with a traumatized mole?

First of all, it must be shown to an oncologist, and the expert will decide whether it is necessary to remove it. If melanoma is suspected, the tumor should be removed completely, with an indentation on healthy-looking skin, as some of its cells may be invisible to the eye. The obtained tissue shall be sent for histological examination, the only way to confirm or exclude the diagnosis of "melanoma" with the maximum accuracy.

You can apply for a consultation about existing moles and pigmented spots, as well as undergo a full examination for melanoma if necessary, by calling the phone: +7 (495) 151-14-47

Every person has moles and pigmented spots on the skin, and their size and number usually increase with age. Most of these formations do not pose a threat to human health, but malignant tumors may appear among them, the most dangerous of which being melanoma.

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What signs of skin melanoma can be seen with the naked eye?

  • Mole asymmetry, irregular form.
  • Uneven, “geographic” or “blurred” formation edges.
  • Non-uniform color - a mosaic combination of dark and light areas, a gradual change in color from one formation edge to another.
  • Size - large moles (more than 6 mm in diameter) cause more suspicion.
  • "Restlessness" of the formation - itching, pain, inflammation, sores or peeling.

Presence of even one of these symptoms is a serious reason to consult a doctor for melanoma screening, while the appearance or disappearance of these signs over time, including an abrupt mole diminution or lightening, should cause the greatest concern.

Melanoma detection at the initial stages often can be done only by an experienced expert.

Can melanoma develop imperceptibly?

It should be remembered that some of the possible melanoma localizations are inaccessible during self-examination - for example, the scalp or the central part of the back, and some cannot be examined without special tools, such as the nasal mucosa and eye retina.

Most often, melanoma in the initial stages looks like a small uneven dark spot on the skin, however, in approximately 5% of cases, the pigment-free form occurs. It may be pink, mauve, red or not differing in color from the surrounding skin, while looking like a scar or rugosity.

Melanoma cells are very weakly connected to each other, and detaching from the main tumor they can move around the body with lymph or blood current, affecting other organs and resulting in appearance of growing metastases in them. Enlarged lymph nodes, the presence of nodular formations in the liver, lungs, bones or brain can also be signs of melanoma. Often, only at this stage the patient's condition begins to significantly disturb the general state of health, with appearance of symptoms such as headaches, cough, bone pains.

If you find yourself having any of the melanoma symptoms, do not delay your visit to the doctor, since only an expert will help you make a plan for the necessary examinations, and in case of diagnosis confirmation, will suggest a treatment option. To arrange a consultation, call the phone: +7 (495) 151-14-47

Melanoma prevention methods are well known by now - physicians recommend avoiding exposure to direct sunlight, applying sunscreeners, and not abusing the tanning bed.  Unfortunately, compliance with these rules can only significantly reduce the risk of developing melanoma, while the 100% warranty of its non-appearance is impossible. At the same time, melanoma responds well to treatment in the initial stages, and early diagnosis plays a key role here.

What activities are carried out for the timely diagnosis of melanoma?

A big step towards detecting melanoma in the early stages is the annual Melanoma Detection Day, when you can have a free screening for malignant skin lesions. The Melanoma Detection Day takes place both in Moscow and in other cities across Russia - for example, in 2016, over 1,000 physicians from more than 90 cities took part in this program. The Melanoma Detection Day is traditionally held in May, before the beach season, and in addition to screening, it also offers educational possibilities.

Even for a physician is not always easy to distinguish melanoma from benign formations. In our center, consultations and treatment are carried out by experienced qualified experts using advanced high-tech equipment, which ensures optimum accuracy and promptness of diagnostics.

What should cause alarm when examining moles and pigmented spots?

You should not disregard the moles that change in size or color, especially if they began to itch, peel, or have a small sore on their surface. Besides, in about 5% of cases, melanoma does not differ in color from the surrounding skin, and may look like a scar or an insect bite mark.  In order to detect such non-pigmented melanomas, and also to distinguish skin cancer from a benign pigmented nevus, a special device called dermatoscope is used. It ensures accurate diagnostics of skin melanoma without injuring the tumor itself, which is the key to successful further treatment.

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Examinations for suspected melanoma

Almost always, a biopsy (removal or resection of the suspicious formation) is required for the final diagnosis. In some cases, removal of the sentinel lymph node, the most likely organ for melanoma metastasis lesion, is also indicated. The removed tissue will be sent for histological examination, where the expert will study under the microscope a specially prepared and stained sample, assessing cell changes and the presence of tumor cells in the margins of the material. Also, if necessary, additional examinations will be performed using reagents that will accurately determine the type of tumor. If the diagnosis is confirmed, the test for a BRAF mutation is extremely important, which can also be carried out on the material obtained during the operation. The presence or absence of a BRAF mutation will play an important role for the choice of a melanoma treatment drug.

Given the high propensity of melanomas to metastasize, even with a small tumor size, if melanoma is suspected, it is necessary to undergo a series of additional examinations. In order to assess the size of the main tumor and the presence of metastases, ultrasound examinations, computed and magnetic resonance imaging, scintigraphy and a number of other methods are used.

For the timely melanoma diagnosis, it is recommended to consult with an oncologist or a dermatologist at least once a year. Sign up for a scheduled examination by phone: +7 (495) 151-14-47

Melanoma is often called skin cancer, but in essence this is not correct. “True” skin cancers are squamous and basal cell carcinomas. They are much more common than melanoma. However, it is melanoma that everyone has heard of. The malignant tumor of pigment cells has earned its notoriety because of its very aggressive behavior. It metastasizes early and often leads to death of patients.

Where to look for malignant melanoma?

The tumor arises from melanocytes, the cells that produce brown pigment melanin. It determines the color of human skin and is the source of suntan.

Most often melanomas occur on the skin. Much less often they are found in other locations: on the mucosa of the mouth, genital organs, in eyes. "Malignant moles" tend to appear where the skin is most often exposed to sunlight, such as the face or neck. In men, the typical place of their localization is the back and chest, in women, the legs.

Why does melanoma occur?

Currently it is believed that the main reason is skin exposure to ultraviolet rays, the source of which is solar radiation. Whenever a person gets sunburns, the risks increase, and this is especially dangerous in childhood. UV rays damage the DNA of skin cells, including the genes that control cell proliferation.

Other risk factors include:

  • Multiple moles on the body.
  • Atypical moles: they look not quite regular, can be very large and asymmetrical.
  • Congenital pigmented nevuses (moles and birthmarks that the child has from birth).
  • Pale skin, blue eyes, blond or red hair.
  • Age. Most often, melanoma is found in older people. However, it is one of the most common malignant tumors in the age under 30 years
  • Reduced immunity. People having HIV/AIDS or taking immunosuppressive drugs after organ transplantation have an increased risk of developing malignant tumors, including melanoma.
  • Risks are increased if melanoma is diagnosed in one’s close relatives.
  • Xeroderma pigmentosum, a hereditary disease in which the skin is especially sensitive to sunlight.
  • The risk of melanoma for any person during life is 0.1-2.6%, depending on skin color.

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How to detect melanoma in time?

A malignant tumor can be detected on one’s own by regular visual examination of the skin. In order to inspect the back and other hard-to-reach places, one can use a mirror, or ask another person for help. It is necessary to pay attention to the five signs indicating that the mole might be malignant:

  • Asymmetry: one half of the mole is very different from the other.
  • Irregular contours: jagged, “pitted”, indistinct.
  • Non-uniform color: different shades from light brown to black, sometimes with blue, white, pink or red spots.
  • Diameter: most often melanomas have a size exceeding 6 mm.
  • Changes: the mole gradually changes its shape, color, size.

Melanoma does not always look like a dark spot or a mole. Sometimes tumor cells do not produce melanin, and the tumor is colored pink or white.

Screening helps in timely diagnosis of melanoma. Sometimes physicians recommend regular dermatoscopy, an examination of the skin with a special tool under magnification. Modern devices like FotoFinder help to create a “map of moles” by entering data into the computer and monitoring the skin status over time.

The biopsy helps to finally confirm the diagnosis.

Melanoma treatment

The main method of melanoma treatment at stages 0, I and II is surgery. A wide excision is performed, when the tumor is removed with capturing of healthy tissue around and under it. The amount of healthy tissue that should be removed is determined by the neoplasm size and localization. For example, if the melanoma is located on the face, the cosmetic effect is important, therefore less tissue is usually removed here.

At stages 0 and IA (when the tumor invades the skin by less than 0.8 mm and there is no ulceration), a wide excision is the only treatment method, and the patient should be monitored afterwards.

At stages IB and II, a sentinel biopsy is performed during the operation. A radiopharmaceutical or a fluorescent colorant is injected into the tumor. It penetrates the lymphatic vessels and spreads through them to lymph nodes. Then the lymph nodes are determined which were the first to be infiltrated by the contrast agent. Such lymph nodes are called sentinel or signal. They are removed, and a biopsy is performed. If tumor cells are found in them, removal of regional lymph nodes is necessary. The physician may prescribe an adjuvant therapy in high doses for a year.

At stage III, the primary tumor and lymph nodes are removed. After surgery, different adjuvant therapy options are prescribed:

  • Immunodrugs
  • Targeted drugs
  • Radiotherapy of the pool of affected lymph nodes for patients from high-risk groups.
  • Biochemotherapy: a combination of immunodrugs with chemotherapeutic agents.

Sometimes secondary tumors are located close to the primary one, and/or cancer cells are found in the lymphatic vessels, but not in the lymph nodes. In such cases, treatment tactics may be different. If the tumor is unresectable (cannot be completely removed surgically), the therapy is prescribed as for stage 4 melanoma with metastases. In other cases, it is possible to completely remove the tumor tissue and achieve a negative resection margin. There are also other treatment options:

  • Radiation therapy.
  • Isolated hyperthermic perfusion (LIMB) is a procedure during which a heated chemotherapy agent is injected into the artery of the arm or leg. The drug gets only into a certain part of the body and does not penetrate into the general bloodstream, and due to the higher temperature, it destroys cancer cells more effectively. Sometimes this procedure helps to avoid limb amputation.

For stage IV melanoma, palliative surgery is performed. It does not eliminate the melanoma, but helps reduce the size of the tumor, alleviate pain and other symptoms, and prolong the patient’s life.

For palliative purposes, immunodrugs, targeted and chemotherapy drugs are prescribed.

Immunotherapy for melanoma

Normally, the immune system uses certain molecular mechanisms to keep itself from attacking healthy tissues, which helps prevent severe autoimmune conditions. Malignant tumors are able to make use of the same molecular mechanisms. Special molecules called control points inhibit the activity of immune cells. Special drugs, control point inhibitors, help re-activate the immune system and make it attack melanoma cells. They were developed relatively recently. Three control point inhibitors are used to fight melanoma:

  • PD-1 blockers affect the protein that resides on the surface of T-cells and inhibits their ability to attack a tumor.
  • CTLA-4 blocker. CTLA-4 is another protein on the surface of T cells that inhibits their activity.

It has been proven that control point inhibitors help prolong the life of melanoma patients, but there is no evidence that such treatment can lead to remission.

Other drugs for melanoma immunotherapy:

  • Cytokines, substances that stimulate the immune system. They help reduce melanoma size in 10–20% of patients. Sometimes these drugs are prescribed in combination with chemotherapy. In order for the drug to work effectively, it must be administered in large doses. Not all patients can sustain such treatment due to serious collateral effects.
  • Oncolytic viruses infect and destroy malignant cells, as well as help strengthen antitumor immune responses.
  • BCG vaccine stimulates antitumor immunity. Like the oncolytic virus, it must be injected directly into the tumor. BCG vaccine is usually used for stage III melanoma.
  • Immunomodulatory agent is used in the form of a cream. It is applied to the tumor-affected skin area 2–5 times a week for three months. Sometimes it is used for stage III melanoma, but not all physicians and researchers believe this method of treatment is worth practicing.

Targeted melanoma therapy

A normal cell becomes a tumor one when certain mutations occur in its genes and proteins are produced that promote its uncontrolled reproduction. Some molecules «guilty» of tumor development and progression can be blocked. The action of targeted drugs is based on this fact.

Targeted therapy of melanomas with the BRAF gene mutation

The BRAF gene mutation is present in about half of melanomas. It results in production of the protein having the same name, which activates proliferation of tumor cells. In these patients, two groups of targeted drugs are used:

  • BRAF inhibitors: These drugs are used for stage IV melanoma with metastases, they help prolong the patient’s life. Targeted drugs can be prescribed as adjuvant therapy after stage III melanoma surgery. BRAF inhibitors are taken in the form of tablets or capsules 1–2 times a day.
  • MEK inhibitors affect the protein that operates together with the BRAF protein. Together with BRAF inhibitors, they provide a more pronounced effect, and there is evidence that combined therapy entails a lower risk of serious collateral effects. MEK inhibitors are taken in the form of tablets 1–2 times a day.

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Targeted therapy of melanomas with the C-KIT gene mutation

In a small amount of melanomas, a C-KIT gene mutation is detected. These are usually melanomas located on the palms and soles, mucous membranes, on body areas chronically exposed to sunlight (neck, face). C-KIT inhibitors are prescribed for patients with such tumors.

Melanoma chemotherapy

Chemotherapy drugs are infrequently used for melanoma, as they are often not very effective, the tumor quickly develops resistance to them and begins to progress again during treatment.

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How effective is the treatment against melanoma? What is the survival prognosis?

Currently, the following five-year survival rates for melanoma have been achieved:

  • Stage I: 92–97%
  • Stage II: 53–81%
  • Stage III: 40–78%
  • Stage IV: 15–20%

Various clinical studies are performed currently, and scientists are looking for new effective methods to fight melanoma.