Melanoma


The melanoma is a type of skin cancer that occurs when cells called melanocytes become malignant. The most dangerous form of skin cancer. In advanced stage, it can be a serious illness; extending to the internal organs through metastasis.

Possible signs and symptoms of melanoma

The most important signal for melanoma is a new mole on the skin or an existing one that has changed in size, shape or color. Another important sign is a mole that looks different from the others on your skin (known as the sign of the ugly duckling). Therefore, if you have any of these signs, see your doctor for a skin patch.

Stay alert and notify your doctor if you notice moles that have any of the following characteristics:

Asymmetry: half of the mole or birthmark does not correspond to the other half.
Edge: the edges are irregular, uneven, jagged or poorly defined.
Color: the color is not uniform and may include shades of brown or black, or sometimes with pink, red, blue or white spots.
Diameter: The mole is more than 6 millimeters wide (about ¼ inch or about the size of a pencil eraser), although melanomas can sometimes be smaller than this.
Evolution: the size, shape or color of the mole are changing.

Melanoma
Melanoma

Some melanomas do not follow the rules described above. It is important to inform your doctor about any changes in your skin or new lunar, or growths that you see as something different from the rest of your moles.

Congenital Melanocytic Nevus
Congenital Melanocytic Nevus

Other warning signs are:    

  • A sore that does not heal.
  • Propagation of the pigment from the edge of a stain to the surrounding skin.
  • Redness or a new inflammation beyond the edge.
  • Change in sensation (itching, sensitivity or pain).
  • Change in the surface of a mole (scaling, exudation, bleeding, or the appearance of a lump or nodule).

5 general criteria in the diagnosis of melanoma.

Causes, risk factors and prevention

A risk factor is anything that affects the likelihood that you have a disease, such as cancer.

  • Exposure to ultraviolet light (UV)

Exposure to ultraviolet (UV) rays is a major risk factor for most melanomas. Sunlight is the main source of ultraviolet radiation. Sunlamps and tanning beds are also sources of ultraviolet radiation.

Although UV rays represent only a small portion of the sun’s rays, they are the main cause of sun damage to the skin. UV rays damage the DNA of skin cells. Skin cancers begin when this damage affects the DNA of the genes that control the growth of skin cells.

The nature of exposure to ultraviolet light could play a role in the development of melanoma. For example, melanoma on the trunk (chest and back) and legs has been linked to frequent sunburns (especially in childhood). This could also have something to do with the fact that these areas are not constantly exposed to UV light. Some experts believe that melanomas that originate in these areas are different from those in the face, neck and arms, where exposure to the sun is more constant. Likewise, any of these melanomas is different to those that originate in the palms of the hands, the soles of the feet, under the nails or on internal surfaces, such as the mouth and vagina, where there has been little or no sun exposure.

  • Moles

A mole (also known as nevus or nevus) is a benign (non-cancerous) pigmented tumor. In general, moles are not present in babies at birth, but begin to appear in childhood and when people become young adults. Most moles will never cause any problems, although a person who has many moles is more prone to melanoma.

Atypical moles (dysplastic nevi): these moles look slightly like normal moles, but they also have some characteristics of melanoma. These are usually larger than other moles, and have an abnormal shape or color. For descriptions of the appearance of moles and melanomas, read the section “Signs and symptoms of melanoma skin cancer.” Moles can appear on the skin exposed to sunlight, as well as on skin that is usually covered, such as on the buttocks or scalp.

The moles that are present at birth are called congenital melanocytic nevi. The risk of a melanoma developing in congenital melanocytic nevi during the course of life is estimated at around 0 to 10%, depending on the size of the nevus. People with very large congenital nevi have a higher risk.

Congenital nevi are sometimes surgically removed so they do not have the chance to become cancer. The recommendation of the doctor to remove or not a congenital nevus depends on several factors including size, location and color of the nevus. Many doctors recommend that congenital nevi that are not removed should be examined regularly by a dermatologist and the patient should be taught how to perform monthly self-exams of the skin.

  • Very white skin, freckles and light hair.

The risk of melanoma is much higher in white people than in black people. White people with blond or red hair who have blue or green eyes, or very white skin, who burn or fill freckles with ease, are at increased risk.

  • Family history of melanoma.

Your risk of melanoma is greater if one or more of your first-degree relatives (mother, father, brother, son / daughter) have had melanoma. Approximately 10% of all people with melanoma have a family history of this disease.

The increased risk may be because they shared a lifestyle of frequent sun exposure in the family, a family of very white skin, certain genetic changes (mutations) that are more frequent in a family, or a combination of factors.

Most experts do not recommend that people with a family history of melanoma undergo genetic testing to identify mutations, as it is not yet clear how useful this could be. Rather, experts recommend that these people do the following:

  1. Skin exams by a dermatologist periodically.
  2. Thorough examination of your skin once a month.
  3. Be particularly careful about sun protection and avoid artificial ultraviolet rays (such as rays that come from tanning booths).
  • Weakened immune system

A person’s immune system helps fight cancers of the skin and other organs. People whose immune systems have weakened (due to certain diseases or medical treatments) are more likely to have many types of skin cancers, including melanoma.

For example, people who receive an organ transplant are usually given medications that weaken their immune system, to help prevent them from rejecting the new organ. This increases your risk of melanoma.

People infected with HIV, the virus that causes AIDS, often have weakened immune systems and are also at higher risk of melanoma.

Can melanoma skin cancer be prevented?


Not all melanomas can be prevented, but there are steps you can take that could reduce your risk of melanoma and other skin cancers.

Limit your exposure to ultraviolet (UV) rays.

Avoid tanning beds and sun lamps

Many people believe that UV rays from tanning beds are not harmful, but this is not true. Tanning lamps emit UV rays that can cause long-term skin damage and contribute to skin cancer. The use of tanning beds has been associated with an increased risk of melanoma, especially if these beds were first used before the person turned 30 years of age. Most dermatologists (skin doctors) and health organizations do not recommend the use of tanning beds or sunlamps.

Pay attention to abnormal moles

Examining your skin regularly can help identify any mole or other new or abnormal growth. Ask your doctor to examine it before it is likely to develop into skin cancer.

If you find a new, unusual mole, or notice a change in a mole, this should be examined by a skin doctor.

Melanoma treatment.

After the diagnosis, tests are done to determine if cancer have spread within the skin or to other organs.

  • Physical examination and background.
  • Mapping of lymph nodes and sentinel lymph node biopsy.
  • CT scan.
  • Exploration with PET (scan with positron emission tomography).
  • Magnetic resonance imaging (MRI) with gadolinium.
  • Biochemical studies of blood.

The results of these tests, together with the results of the tumor biopsy to determine what stage the melanoma is.
The following stages are used for melanoma:

Stage 0 (melanoma in situ):

In stage 0, abnormal melanocytes are found in the epidermis. These can become cancerous and spread to nearby normal tissue.

Usually, these melanomas are treated with surgery to remove the melanoma and a margin of about 1/5 of an inch. If it is discovered that the edges of the sample that was extracted contain cancer cells, a excision of the area may be repeated. Some doctors may consider using imiquimod cream (Zyclara) or radiation therapy.

For melanomas in sensitive areas of the face, some doctors might use Mohs surgery.  Other option is an imiquimod cream if the surgery could cause disfigurement. Although not all doctors agree with the use of this cream.

 

Stage I:

The cancer was formed. The stage I is divided into stages IA and IB.

  • IA: in this stage, the tumor does not measure more than one millimeter thick, without ulceration.
  • IB: in stage IB, the tumor does not measure more than a millimeter thick, and it has ulceration; or It measures more than one but not more than two millimeters thick, without ulceration.

it is treated by wide excision (surgery to remove the melanoma as well as a margin of normal skin that is around). The amount of normal skin removed depends on the thickness and location of the melanoma, although it is not necessary to remove more than 2 cm (4/5 of an inch) of normal skin from all sides of the melanoma. The healing of wider margins is more difficult and has not been found to help people live longer.

Some doctors may recommend sentinel lymph node biopsy, especially if the melanoma is stage IB or has other characteristics that make propagation to lymph nodes more likely. You and your doctor should discuss this option.

If cancer cells are discovered in the sentinel lymph node biopsy, a lymph node dissection (removal of all the lymph nodes near the cancer) is often recommended, but it is not clear whether it can improve survival. Some doctors may also recommend adjuvant (additional) treatment with interferon after surgery of the lymph nodes.

Stage II: 

Stage II is divided into stages IIA, IIB and IIC.

  • IIA: It measures more than one but not more than two millimeters thick, with ulceration; or It measures more than two but not more than four millimeters thick, without ulceration.
  • IIB: It sizes is more than two but not more than four millimeters thick, with ulceration; or It measures more than four millimeters thick, without ulceration.
  • IIC: The tumor is more than four millimeters thick, with ulceration.

Wide excision (surgery to remove melanoma and a surrounding normal skin margin) is the standard treatment for stage II melanoma. The amount of normal skin removed depends on the thickness and location of the melanoma, but it should not be more than 2 cm (4/5 of an inch) of skin surrounding all sides of the melanoma.

Because melanoma may have spread to lymph nodes near melanoma, many doctors also recommend a sentinel lymph node biopsy. You and your doctor should discuss this option. If this procedure is performed and the sentinel node contains cancer cells, then a lymph node dissection will be done (all lymph nodes are surgically removed in that area) probably at a later date.

For some patients (such as those with lymph nodes who have cancer), doctors may recommend interferon therapy after surgery (adjuvant therapy). In addition, other medications or perhaps vaccines may be recommended as part of a clinical trial to try to reduce the likelihood that the melanoma will return.

Stage III:

The tumor can have any thickness with or without ulceration. One or more of the following situations occur:    

  • The cancer has spread to one or more lymph nodes.
  • The lymph nodes become inflamed
  • The cancer is in a lymphatic vessel between the primary tumor and nearby lymph nodes. The cancer is more than two centimeters away from the primary tumor.
  • Very small tumors appear on or below the skin no more than two centimeters from the primary tumor.

These cancers have already reached the lymph nodes when melanoma was diagnosed. Surgical treatment for stage III melanoma usually requires extensive excision of the primary tumor as in earlier stages, along with lymph node dissection.

After surgery, adjuvant treatment with immunotherapy (such as Yervoy or interferon) or targeted therapy (for cancers with changes in the BRAF gene) may help decrease the risk of return of the melanoma. In addition, other medications or perhaps vaccines may be recommended as part of a clinical trial to try to reduce the likelihood that the melanoma will return. Another option is to give radiation therapy to areas where the lymph nodes were removed, especially if many lymph nodes contain cancer.

If melanomas are found in the lymphatic vessels near or below the skin (known as tumors in transit), all of them should be removed, if possible. Other options include administering Bacillus Calmette-Guerin (BCG), interferon, or interleukin-2 (IL-2) injections directly into the melanoma, radiation therapy; or apply imiquimod cream. For melanomas in an arm or leg, another option might be isolated limb perfusion (infusing the extremity with a heated solution of the chemotherapy drug). Other possible treatments may include targeted therapy, immunotherapy, chemotherapy, or a combination of immunotherapy and chemotherapy (biochemotherapy).

Some patients may benefit from more recent treatments that are being tested in clinical trials. Many patients with stage III melanoma may not be cured with current treatments, so they should consider participation in clinical trials.

Stage IV:

In stage IV, the cancer has spread to other parts of the body, such as the lung, liver, brain, bone, soft tissue, or gastrointestinal (GI) tube. The cancer may have spread to sites on the skin far away from where it started.

Cancer spreads in the body in three ways:

  • Tissue.
  • Lymphatic system.
  • Blood:

 

  1. Tissue. Cancer spreads from where it started and extends to nearby areas.
  2. Lymphatic system. Cancer spreads from where it started to enter the lymphatic system. The cancer travels through the lymphatic vessels to other parts of the body.
  3. Blood. Cancer spreads from where it started and enters the blood. The cancer travels through the blood vessels to other parts of the body.

Stage IV melanomas are very difficult to cure, because they have spread to distant lymph nodes or other areas of the body. Skin tumors or enlarged lymph nodes that produce symptoms can often be removed by surgery or treated with radiation therapy. Metastases in internal organs can sometimes be removed, depending on how many are present, where they are located and the likelihood of causing symptoms. Metastases that cause symptoms, but can not be removed, can be treated with radiation, immunotherapy, targeted therapy, or chemotherapy.

In recent years, the treatment of melanomas that have spread widely has changed as newer forms of immunotherapy.

Ipilimumab (Yervoy), a newer immunotherapy drug, has been shown to help some people with advanced melanoma live longer. Occasionally, it can cause serious side effects so patients receiving it need to be closely monitored. Other new immunotherapy drugs, including pembrolizumab (Keytruda) or nivolumab (Opdivo), may also be options. These medications appear to be more likely to reduce tumors than Ipilimumab, and are less likely to cause serious side effects. Other types of immunotherapy may also be useful, but are currently only available in clinical studies.

In about half of all melanomas, cancer cells have changes in the BRAF gene. If this genetic change is discovered, treatment with more recent targeted therapy drugs, such as vemurafenib (Zelboraf), dabrafenib (Tafinlar), trametinib (Mekinist) and cobimetinib (Cotellic) may be useful. These medications can be treated before or after new immunotherapy medications, but they are not used at the same time. Like Ipilimumab, these medications can help prolong the lives of some people, although they have not shown that they cure these melanomas.

A small portion of melanomas shows changes in the C-KIT gene. Targeted drugs, such as imatinib (Gleevec) and nilotinib (Tasigna), may be useful in the treatment of these melanomas, although, again, these drugs are not known to cure these melanomas.

Immunotherapy with interferon or interleukin-2 can help a small number of people with stage IV melanoma live longer. The higher doses of these medications seem to be more effective, but they can also cause more serious side effects. Therefore, it may be necessary to administer them in the hospital.

Chemotherapy can help some people with stage IV melanoma, although other treatments are usually tried first. Dacarbazine (DTIC) and temozolomide (Temodar) are the chemotherapy drugs that are used most often, either alone or in combination with other medications. Even though chemotherapy reduces the size of these cancers, the effect often only lasts an average of several months before the cancer starts growing again. On rare occasions, these medications are effective for longer periods of time.

Some doctors may recommend biochemotherapy, a combination of chemotherapy and interleukin-2, interferon, or both. For example, some doctors use interferon with temozolomide. The combination of both drugs causes a greater reduction in tumor size, which can make patients feel better. However, the combination has not been shown to help patients live longer. Another combination of medication uses low doses of interferon, interleukin-2, and temozolomide. Each one seems to benefit some patients. It is important to carefully consider the possible benefits and side effects of each treatment that is recommended before starting it.

Because stage IV melanoma is difficult to treat with current therapies, patients may want to consider participation in a clinical trial. Many studies are currently underway to investigate new targeted drugs, immunotherapies, chemotherapy drugs, and combinations of different types of treatments.

Although the overall prognosis of people with stage IV melanoma is usually not favorable. A small number of people respond very well to treatment and survive for many years after diagnosis.

 

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