How do you treat melanoma, its types with risk factors explained 2020
Melanoma is a form of skin cancer. Like other skin cancers (squamous cell and basal cell carcinoma), melanoma is easy to treat if the tumor is in its early stages. If not, the cancer cells can spread to the lymph nodes and other organs, after which melanoma is much more difficult to treat. Without treatment, melanoma can be fatal.
Every year, about 100,000 Americans are diagnosed with melanoma and more than 7,500 die from cancer. The overall rate of melanoma is increasing, although education about the risk of sunlight is recognized for the sudden decline in younger adults between the ages of 21 and 45.
Are you at risk for melanoma?
Melanoma is the least common of the various types of skin cancer. Left untreated, melanoma is also the most dangerous. Most skin cancer deaths are caused by melanoma. Although ultraviolet radiation and repeated sunburn are associated with melanoma, these are not the only risk factors: ethnicity, presence of moles, and family history may increase the chances of developing cancer.
Ethnicity, skin pigmentation and melanin levels
Caucasian men are twenty times more likely to develop melanoma than those of African descent. This is because people with darker skin contain more melanin in their skin. Melanin helps protect the skin from ultraviolet light (UVA and UVB). High melanin levels do not make a person immune to melanoma. No one is immune to skin cancer, but people with clean skin are at greater risk.
Melanocytes, melanin and skin pigmentation
The external layer of the skin is known as the epidermis. Cells called melanocytes are responsible for pigmentation of the skin. These cells are found at the base of the epidermis and produce melanin. It is a substance that helps protect the body from sun damage. The ultraviolet rays of sunlight stimulate melanin production, so sunlight results in tanned or darker skin.
Different melanin levels are responsible for changes in skin color. However, the number of melanocytes in the body does not change with ethnicity: everyone has the same number of such melanin-producing cells. If tumors develop in the melanocytes, melanoma may be the result.
Other physical properties increase a person’s risk of developing skin cancer.
In general, red or blonde hair, like blue eyes, increases the risk. People who are prone to freckles are also at greater risk than others. Often, these characteristics are perceived together: red-haired people usually have clean facial skin and are more likely to experience sunburn than others.
Moles and skin cancer
A high number of moles builds the danger of creating melanoma. A person with more than fifty moles is considered a higher risk. However, their shape and size may be more important than their number.
Moles are growths that occur when melanocytes contract. The clinical term for a mole is nevus (plural: nevi). Moles are most often harmless and completely normal. Everyone has moles: the average person usually has ten to forty moles.
Moles are usually small and symmetrical and can be flat or tall. They are available in a variety of colors, including black, brown, brown and pink. Some moles are only slightly darker than the pigmentation of the surrounding skin. If the moles increase in size, change color (including changing to red or white), bleed, or change shape, your doctor should evaluate these. Any change in the mole may indicate that the group of melanocytes has become cancerous.
Irregular-looking or dysplastic nevus are more likely to get cancer than a normal-looking mole. One in ten people has a dysplastic name. Irregularities may include dimensional or deformation, discoloration, or raised areas of previously flat moles. Dermatologists recommend monthly self-tests to detect changes in moles.
An unusual mole indicates an increased risk of melanoma, which should be checked by your doctor. Fifty percent of cases of melanoma are associated with dysplastic nevi, but in other cases they appear to have no association with abnormal moles.
Removing the mole seems to be one way to avoid melanoma, but studies suggest that removing the mole will not be beneficial for most people. Out of every 200,000 moles, only one is diagnosed as cancer in people under the age of forty.
Are you at risk for melanoma?
Ultraviolet light, sunburn and solarium
Sunlight or exposure to tanning lamps and tanning beds to ultraviolet light increases the risk of skin cancer. The two forms of ultraviolet light are UVA and UVB. Of the two, UVA infiltrates further into the body. UVB is associated with DNA mutations in skin cells.
Although there has been an association between melanoma and exposure to UVA and UVB rays, cancer can develop in parts of the body that are not exposed to the sun. Nevertheless, the disease has been linked to solariums, sun exposure, and a history of childhood sunburn. People with clean skin living in the tropics also have higher average incidence rates.
Sunscreen is one of the best ways to protect against UV rays. Look for a sunscreen with an SPF (sun protection factor) of at least thirty. Thirty minutes before going outdoors, carefully pick up all open areas.
Sunlight and solarium
Melanoma is associated with the stimulation of melanin production by ultraviolet rays. Such rays are, of course, found in sunlight, but can also be found in the artificial lights used in solariums. Excessive exposure to sunlight or ultraviolet light, or tanning beds, puts you at greater risk of developing melanoma or other skin cancers.
Age, gender and family history
Fifty percent of all melanoma cases occur after the age of fifty. However, melanoma is also the most common cancer before the age of thirty, so age plays only a partial role in susceptibility.
Gender seems to play a greater role: men are at greater risk than women.
The lifetime incidence rate for men is increasing from 57. Men are more likely to develop tumors on the torso – the area between the shoulders and hips – or on the neck or head. The lower legs and arms are more common among women.
Although not generally affected by family history, ten percent of people with melanoma have at least one close relative in this form of skin cancer.
People with a suppressed immune system are more prone to melanoma than others. This has been demonstrated in studies on the incidence of long-term cancer in organ transplant patients. Transplant patients should use immunosuppressive drugs to prevent organ rejection.
Diagnosis and staging of melanoma and skin cancer
Melanoma is often asymptomatic: that is, it does not cause noticeable symptoms. Most diagnoses of skin cancer occur when patients notice an unusual birthmark or lesion and report it to their doctor. From time to time, you should check for new moles or moles that have grown or changed in color or shape. Monthly self-monitoring (or up to twice a month if there is a risk of developing skin cancer) allows you to track changes in moles or other skin lesions. If a mole appears suspicious, your doctor will likely order a biopsy.
ABCDE rule for melanoma
Self-monitoring for skin cancer is fairly easy to do. A full-length mirror, hand mirror, or family member can help inspect hard-to-see parts of the body. Observe the ABCDE rule for skin cancer: check for changes in asymmetry, border, color, diameter, or height.
Asymmetry: Does the mole have the same shape on one side as the other? If you split the mole in half, are the two sides the same? Odd-shaped moles should be reported to your doctor.
Boundary: The edges of the mole are usually smooth and clearly defined compared to the surrounding skin. “Combed” or “stained” edges can indicate a problem, as can a pigment that “bleeds” into the surrounding skin.
Color: Moles are usually solid in color. Multicolor growth or a change in color tone should be considered suspicious.
Diameter: A sudden increase in the size of the mole should be examined, especially if the increase is greater than six millimeters (around the pencil eraser).
Height: If a previously flat mole suddenly rises (lifts from the surrounding area), tell your doctor.
In addition to the ABCDE rule for skin cancer, report any moles that bleed, cause itching or pain, or become ulcerated (destroy epidermal tissue, causing pit-like pain). Keep in mind that the earlier melanoma is detected, the more likely it is to be cured.
Biopsies: Confirmation of diagnosis
No matter how suspicious the mole looks, only a biopsy can tell if the growth is cancerous. If the mole is small enough, the doctor will attempt to remove the entire growth using a procedure known as an excuse biopsy. If the growth is large, only the tissue sample should be removed. The biopsy specimen is then examined for microscopic signs of cancer.
Once melanoma has been diagnosed, it should be adjusted. The stage of skin cancer measures factors such as tumor thickness, lymph node involvement, and whether or not melanoma cells have affected other organs. Spread to other sites or organs is called metastasis.
The American Joint Committee on Cancer publishes cancer classification systems used by many medical organizations, including the American Cancer Society. The AJCC uses the TNM grading to classify melanoma by stages. The higher the stage, the more advanced the disease and the worse the prognosis. Melanoma’s stages are divided as follows:
Stage 0: The melanoma is present only in the epidermis – the top layer of the skin – and has not spread.
Stage IA (T1a, N0, M0): The melanoma is still localized and is less them 0.75 millimeters thick. The tumor has spread to the upper level of the dermis – the second layer of skin.
Stage IB (T1b-2a, N0, M0): The tumor is between 0.75 mm and 1.5 millimeters thick, and has penetrated further into the dermis.
Stage IIA (T2b-3a, N0, M0): The tumor is now between 1.5 to 4 millimeters in-depth, and has reached the lower dermis.
Stage IIB (T3b-4a, N0, M0): At a thickness of more than four millimeters, cancer has penetrated deeper than the dermis. The melanoma is, however, still localized.
Stage III (T4, any N, M0): Lymph nodes have been infiltrated with melanoma cells. This may occur at any thickness.
Stage IV (any T, any N, any M1): Cancer has spread to other organs or other areas of the skin.
Metastasis may occur at any thickness level, and with or without lymph node involvement. This stage offers the worst prognosis.
The Clark method is a slightly different method for treating melanoma. Instead of measuring the total thickness of the tumors, the Clark stage only measures how deeply the tumor has penetrated the skin. In general, the AJCC transition system is preferred. If your doctor used the Clark methods, their levels are approximately equivalent to your AJCC scores:
Other prognostic factors
In addition to TNM factors, the presence of tumor ulcers is also important in the prognosis. Tests may reveal high levels of lactate dehydrogenase (LDH) in the blood. LDH levels indicate possible tissue damage. Like ulcers, high LDH levels are a negative prognostic factor.
Types of melanoma and prognosis of skin cancer
While all melanoma develops from a single cell type, melanocyte, melanoma, is further divided into four subtypes, each with its own prognosis and metastatic rate. The four subtypes are classified based on their radial and vertical growth patterns. Radial growth indicates how aggressively skin cancer has spread to the skin. Vertical growth indicates how far cancer spreads to the skin.
Superficial melanoma (SSM)
Superficial melanoma is the most common type, accounting for more than two-thirds of all cases diagnosed. Skin cancer first spreads radially and slowly. As SSM increases vertically (a process lasting one to five years), the chance of metastasis increases.
Superficial melanoma can affect any part of the body and affects people between the ages of forty and fifty on average. The disease can occur at any age and is the most common form diagnosed after puberty. Growth changes shape as the disease progresses and usually manifests as dark growth, whether flat or only slightly elevated. Superficial melanoma can appear in a variety of colors.
Because it tends to grow slowly, SSM has a good prognosis.
Nodular melanoma (NM)
Nodular melanoma is the second most common subtype after SSM, accounting for fifteen to twenty percent of cases. It has very little radial growth, but its vertical growth rate is aggressive. As a result, NM has a high rate of early metastases. It can appear in any part of the body, although areas exposed to sunlight are the most common places.
Unlike other subtypes, nodular melanoma does not usually begin with the mother; instead, the tumor appears on normal skin. The tumor itself is small (usually less than one or two centimeters). It is often black or reddish-brown in color and may be mistaken for blood film. The surface is raised and round, the edges are usually smooth. Nodular melanoma is usually diagnosed between the ages of forty and fifty and is often advanced at the time of diagnosis.
Due to its rapid growth rate and frequent metastasis, the prognosis of NM is very poor.
Acral Lentigenic Melanoma (ALM)
Acral lentigenic melanoma is the most common subtype in dark-skinned people: sixty percent of melanomas diagnosed in darker-skinned people are ALM. The rate is much lower in people with light skin, accounting for two to eight percent of cases.
Acral lentigenic melanoma has a radial growth pattern and is most commonly found on the palms, soles, and under the nails. It is also found in the mucous membranes. Tumors can be quite large, often more than three inches in diameter.
An ALM injury looks like a brown or black “spot,” a blood bubble, or a bruise that doesn’t heal. The disease slowly spreads radially to the skin and then begins to grow vertically. The average age at diagnosis is sixty. Like NM, acral lentiginous melanoma is often well advanced at diagnosis.
The prognosis of ALM is between SMM and NM. When ALM occurs on the mucosa, the prognosis is unfavorable.
Lentigo Maligna Melanoma (LMM)
Lentigo maligna melanoma is the least common of the various types of melanoma, accounting for only four to ten% of cases. It most commonly occurs in areas exposed to the sun. The tumor spreads radially, rarely grows into the skin, and is usually flat. The edges of the mole are often irregular and can grow up to three to six inches.
Lentigo maligna melanoma usually occurs after the age of seventy and is the least aggressive form of melanoma. The disease is rarely metastatic. Although LMM generally has an excellent prognosis, neglected or untreated lesions can eventually result in an unfavorable prognosis.
Cancer melanocytes can also affect the eye, a condition known as ophthalmic melanoma. The cancer can spread to the eye from other locations, but the eye canoma can also be a primary tumor that originates in the eyelid or pigment layers of the eye. The symptoms are not necessarily obvious, although people may experience painful red eyes, swollen eyes, discoloration of the eyes, and vision problems in the affected area.
Ophthalmoma is treated with laser surgery, chemotherapy and radiation therapy. Without treatment, vision can be permanently affected and cancer can spread to the brain. If metastasis is possible, the eye should be removed to prevent cancer from spreading to other organs.
Skin cancer surgery: Mohs surgery, node necropsy and biopsy
95% of all melanoma cases are treated surgically. Surgery for skin cancer can be as simple as removing a suspicious molecule for a biopsy, or as complex as removing local lymph nodes. If the cancer has not shown metastasis, skin cancer surgery can completely cure the disease.
Easy excision and biopsy
A biopsy is the main sure approach to analyze melanoma. During the biopsy, the tissue sample is cut from the body and examined for evidence of cancer microscopically. Small tumors can be completely removed by biopsy, a procedure called simple excision. Simple excision removes the tumor and the layer of normal surrounding tissue. A scar remains to remove the tumor. If the tumor is large, it is not completely emptied during the biopsy: instead, only the tissue sample is taken.
Rejection of the tumor
On the off chance that the biopsy results demonstrate malignancy, re-extraction expels extra tissue from the tumor territory. The strategy endeavors to evacuate all hints of the tumor. Once the tumor has been completely removed for biopsy, the second layer of healthy tissue is removed if cancer cells have invaded the lower layers.
The area surrounding healthy tissue removed is determined by how deep the melanoma has penetrated the skin. Usually, a millimeter deep tumor requires the removal of an inch of surrounding tissue. For tumors, one millimeter thicker, two centimeters should be removed. To close the resulting wound, the surgeon can use a skin graft – a piece of skin taken from a healthy area of the body.
Mohs surgery is a special form of discharge. The procedure is often used in areas of the body where normal emptying is difficult or distorting, such as the eyelids, ears and nose. Surgeons performing Mohs surgery require special training in the procedure.
Melanoma is removed from the layer. Each layer is examined microscopically for signs of cancer. The operation continues until a layer shows a malignancy. This allows the surgeon to remove as many cancers as possible while preserving the surrounding skin tissue.
Melanoma of the toe or toe may require amputation of that number. Amputation was also once used to treat melanoma in the arms and legs, but advances in medicine offer less dramatic alternatives to such extreme measures.
Skin Laser surgery
With laser skin surgery, tumors can be removed with minimal scarring. Thin melanoma growth can be removed with a carbon dioxide laser. For deeper tumors, laser skin surgery called photodynamic therapy can be used.
The photodynamic treatment utilizes unique synthetic compounds that respond to laser light. The chemicals are injected into the tumors and then exposed to laser light. This triggers a chemical reaction that kills the tumor cells.
Sentinel lymph node biopsy
If melanoma spreads, it first attacks the nearby lymph nodes. A sentinel lymph node biopsy (SLNB) can be performed to determine if proliferation has begun. For melanoma every millimeter thicker, SLNB is recommended.
Either dye or slightly radioactive material is injected into the tumors. This material then flows through the lymphatics and into the lymph nodes. The node closest to the tumor is indicated by a signaling node, and this will be the first to absorb the dye or radioactive material. The marker nodule is then removed for biopsy. If no cancer is found at the sentinel node, it is generally assumed that the disease has not spread further in the body.
Autopsy of the lymph nodes
Because cancer is sometimes found in local lymph nodes, therapeutic lymph node dissection or TLND may be required. In TLND, suspicious or abnormal lymph nodes are removed from the cancerous area.
Optional lymph node dissection removes all lymph nodes surrounding the tumor. ELND is more invasive than TLND and may have additional side effects. Studies have not shown that ELND improves long-term survival rates, so treatment remains controversial.
Both therapeutic and optional lymph node dissection can result in lymphedema or fluid accumulation. Lymph nodes under the arms and in the lumbar region help fluid leak out of the body. If this ability is compromised, fluid retention may occur in certain areas of the body.
Adjuvant treatment for melanoma: Radiation therapy and interferon
Most melanoma skin cancers are treated with surgery. Adjuvant treatment is a drug or therapy that is provided after surgical removal of a tumor. Adjuvant treatment is used to prevent the recurrence of melanoma and to kill cancer cells that may have avoided surgical removal.
Interferon alfa-2b is a modulator of the immune system: it stimulates the immune system and makes it more effective against cancer. Interferons are naturally occurring proteins that bind to cells and produce specific immune responses. Proteins suppress the ability of cells to replicate, slowing the growth of cancer.
Interferon also enhances phagocytic immune cells – also white blood cells such as macrophages that surround and absorb foreign bodies. In addition, interferon increases the anti-cancer properties of lymphocytes, another form of white blood cells.
Interferon is the only adjuvant treatment that has been shown in clinical trials to increase melanoma survival and prevent cancer recurrence. The FDA has approved interferon for use in patients at high risk of recurrent melanoma.
Interferon treatment lasts for one year and carries a high risk of side effects. Almost all people who take interferon experience flu-like symptoms. Twenty to thirty percent experience chronic fatigue, sometimes so debilitating that you will be forced to stop taking the drug. Another two to ten percent develop psychological difficulties, most commonly depression and anxiety.
However, side effects can be treated. Influenza-like symptoms can be treated by altering drug levels of interferon. Antidepressants may be needed for associated psychological difficulties. Chronic fatigue is perhaps the most problematic side effect. Methylphenidate is used in clinical trials to treat fatigue.
Radiation therapy, lymph nodes and metastases
Radiation therapy is not usually used as an adjuvant treatment for melanoma, although it is occasionally used when metastases have been detected in the lymph nodes. Nevertheless, its ability to prevent the recurrence of melanoma and the spread of cancer in the lymph nodes remains unproven.
Clinical trials are investigating the use of radiation therapy to treat metastases.
Studies are ongoing to evaluate the safety and efficacy of stereotactic radiosurgery. Stereotactic radiological surgery uses a narrow-focus beam to kill tumors. The method can be used to treat melanoma that has been transmitted to the brain.
Palliative care in patients with melanoma
Palliative care does not cure melanoma. Instead, treatments reduce symptoms and reduce disease progression. Palliative care is most commonly used for advanced or metastatic skin cancer, although treatment to reduce symptoms can be used at any stage of the disease.
Once melanoma shows metastasis, surgery is no longer able to cure skin cancer. However, surgical removal of the original tumor can help slow the disease and relieve advanced symptoms such as bleeding, pain, and tumor ulcers.
Although radiation therapy is rarely used for the direct treatment of melanoma, it is often used in palliative care. When melanoma shows metastasis to other parts of the body, radiation therapy can be used to reduce symptoms and relieve pain. Melanoma tends to cause breakthroughs in the lymph nodes, brain and bones, although cancer can spread anywhere on the body.
External radiation therapy delivers a highly focused beam of skin to the tumors, destroying the cancer cells. Another method, internal radiation therapy, works by placing small radioactive materials called radioactive isotopes as close to the tumors as possible. The proximity of radioisotopes to cancer cells allows them to deliver higher doses of radiation for extended periods of time while reducing the exposure of healthy tissues to radiation exposure.
Chemotherapy and isolated limb perfusion
Chemotherapy uses powerful drugs to kill fast-growing cells. Drugs are systemic, meaning they affect the whole body, not just cancer cells. As a result, fast-growing cells are damaged during chemotherapy and can lead to side effects such as hair loss, fatigue, and nausea.
If the melanoma is limited to a single limb, an experimental procedure called hyperthermic isolated limb perfusion is possible. A tower is applied to the limb to temporarily stop blood flow. The chemotherapeutic drug is then delivered to the limb. Theoretically, this allows the maximum effect of chemotherapy on cancer cells while minimizing exposure of the rest of the body to the drug. Isolated limb perfusion is under clinical investigation and is currently only available in clinical trials.
Clinical trials: Dacarbazine and MDX-010
Dacarbazine is a drug that can slow or stop the growth of cancer cells, making it a possible treatment for melanoma in metastomosis. The efficacy of dacarbazine in combination with other drugs is being investigated in clinical trials.
An antibody called MDX-010 is currently being studied for its effect in the treatment of melanoma that is metastatic in combination with dacarbazine. MDX-010 targets a molecule called CTLA-4, which is found on T cells. CTLA-4 suppresses the immune system. MDX-010 targets and blocks CTLA-4 stimulates the immune system and strengthens the body’s natural defenses.
Upcoming skin cancer and melanoma treatments
Clinical trials are exploring exciting new treatments for skin cancer and melanoma. Gene therapy research in melanoma is a particularly important and stimulating branch of ongoing clinical trials.
Gene therapy research attempts to introduce genetic material into cancer melanocytes to make them more “visible” to the immune system. Alternatively, genetic material can be added to a tumor that makes skin cancer cells more sensitive to the effects of chemotherapy or other drugs.
Search for a melanoma vaccine
Most people are familiar with vaccines. Vaccines against measles, meningitis and chickenpox protect people from diseases. Melanoma vaccination would not be preventive. Instead, the treatment is used to prevent the disease from happening again after surgery, or to help the immune system recognize a pre-existing but unnoticed tumor.
The human immune system is not good enough to tell the difference between cancerous and healthy tissues. For the cancer vaccine to work, the treatment must make it easier for the immune system to separate the two types of tissue.
Four major cancer vaccines are currently being studied in clinical trials. The researchers hope that these studies will result in an FDA-approved melanoma vaccine in the near future.
Antigen Vaccination: An antigen vaccine obtains proteins from melanoma cells or healthy melanocytes. These proteins or antigens can elicit immune responses. Antigens are combined with substances that also trigger the immune system.
Once reintroduced into the body, the modified antigens are targeted and destroyed by the immune system. Theoretically, this teaches the immune system to target the same antigens in cancerous tissues.
Proteins tested for antigen vaccines include tyrosinase, gp100, MART-1 peptides, and tyrosinase-related protein-2 (TRP-2).
Dendritic Cell Vaccine: Dendritic cells are white blood cells (WBCs) that play an important role in the immune system. Melanoma antigens are collected from the tumor and tested for the patient’s own dendritic cells in Petri dishes. As soon as dendritic cells “learn” to detect antigens as a threat, they re-enter the bloodstream. Here, WBCs activate immune T cells, which proliferate and kill cancer cells that contain antigens.
DNA inoculation: DNA strands from melanoma cells are reproduced in the laboratory and serve as antigens for antigen-presenting cells (APCs). Antigen-infected APCs are then reintroduced into the body, where the DNA antigens present them to the immune system. In this way, the immune system recognizes the DNA as “bad” and can then attack melanoma cells that contain the same “bad” DNA.
Whole-cell vaccines: Whole-cell vaccines were the first type of cancer vaccine evaluated in clinical trials, and more vaccines could receive FDA approval over the next few years. Dead tumor cells are also removed from another person’s patient and provide a number of different antigens that can be used to train the immune system.
Clinical studies have shown that some people live longer when treated with modified whole cells. Material from the patient’s own tumor gives the best response, but such “individualized” treatment is quite expensive.
Current gene therapy research: Allovectin-7
Allovectin-7 is an experimental drug that stimulates the immune system in a way that is slightly different from the vaccines discussed above. Allovectin-7 is injected directly into the tumor, where melanoma tumors express a gene known as HLA-B7. Because HLA-B7 does not usually occur in humans, research suggests that due to its presence, tumor cells can trigger the immune system, virtually resulting in its own destruction.
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