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Melanoma of Skin

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Skin Care
Health & Wellness
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Contributed byKrish Tangella MD, MBAJan 22, 2022

What are the other Names for this Condition? (Also known as/Synonyms)

  • Cutaneous Melanoma
  • Malignant Melanoma of Skin

What is Melanoma of Skin? (Definition/Background Information)

  • A melanoma is a type of cancer that develops from cells, called melanocytes. Melanocytes are cells that produce melanin; the pigment that gives skin its color
  • Normal skin is composed of three layers:
    • Epidermis - the outermost protective layer
    • Dermis - the middle layer containing blood vessels, sweat glands, hair follicles, and nerves
    • Subcutis - composed of fat and a protein called collagen

The epidermis and dermis are separated by a layer, called the basement membrane.

  • Although a less common form of skin cancer, Melanoma of Skin is far more dangerous and capable of spreading to other parts of the body
  • Melanomas that are confined to the epidermis and have not yet penetrated through the basement membrane are called melanoma in situ. Melanomas that have spread to areas besides the skin are called metastatic melanomas
  • Melanomas are usually brown or black in color, but sometimes they may be pink, tan, or white. Although, these can occur anywhere on the body, the common sites of occurrence include:
    • Chest and back in men
    • Legs in women
    • Neck and face

There are four basic types of melanoma:

  • Superficial Spreading Melanoma: This usually occurs in a previously benign mole and accounts for almost 70% of all diagnosed melanomas. It may initially start like a freckle that appears to be spreading, getting darker or lighter and is capable of a rapid progression
  • Lentigo Maligna Melanoma: Usually occurs over the face of middle-aged or older individuals and maybe mistaken for sun spots. This type accounts for 10% of all diagnosed melanomas
  • Acral Lentiginous Melanoma: These may occur anywhere on the body, including the palms and soles and also underneath the nails (subungual melanoma), starting-off as a streak or bruise. It accounts for 5% of all diagnosed melanomas. Melanomas, in general, are more common in light-skinned individuals than dark-skinned individuals. However, of the melanomas that occur in dark-skinned individuals, Acral Lentiginous Melanoma is the most common type
  • Nodular Melanoma: The most aggressive type of melanoma, it is commonly seen in males and older adults. 15% of all diagnosed melanomas are of this type

Cutaneous Melanoma (or Melanoma of Skin) is diagnosed with the help of a biopsy. Once a definitive diagnosis has been made, it is surgically removed (excised). Depending on how far the disease has progressed, additional modes of therapy may be needed. The outcomes are good when the diagnosis is made early; the prognosis gets poorer and poorer, as the disease advances.

Who gets Melanoma of Skin? (Age and Sex Distribution)

  • Melanoma of Skin can occur in young, as well as old individuals, and is one of the most common cancers in people younger than 30 years
  • In the United States, it has been observed that women are at increased risk before the age of 40 years, while men are at a higher risk after the age of 40 years
  • Cutaneous Melanoma also occurs more frequently in Caucasians, as compared to other races

What are the Risk Factors for Melanoma of Skin? (Predisposing Factors)

The following factors increase the risk of Malignant Melanoma of Skin:

  • Exposure to ultra violet (UV) rays is a major risk factor. UV rays are present in sunlight, and also in tanning lamps and beds
  • Nevus (medical term for mole) is a non-cancerous pigmented tumor. While most nevi never become cancerous (or malignant), a small number of atypical/dysplastic nevi (moles with abnormal shape/borders/color) may turn cancerous. When such dysplastic nevi run in families, the condition is called dysplastic nevus syndrome. Individuals with this condition have a 10% increased risk of developing melanoma. Despite the above and irrespective of the condition, whether the nevi are present since birth, or are normal, or atypical; more the number of moles, more is the risk
  • Fair-skinned individuals are at a higher risk; more so those with freckles or those who develop sun burns, easily
  • Previous history of melanoma or a history of melanoma in parents/siblings
  • An inherited condition called xeroderma pigmentosum, where the ability of the cells to repair sun-induced damage to genetic material is impaired
  • Weakened immune system, as a result of infections (like HIV), drugs (chemotherapy or immunosuppressants), and due to the presence of cancers (like lymphoma)

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one's chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Melanoma of Skin? (Etiology)

The exact reason behind why some moles turn cancerous and others do not is still not exactly known. However, the potential causes for Melanoma of Skin include:

  • Uncontrolled activity of oncogenes (rogue genes that promote cell growth and division) or depressed action of tumor suppressor genes (genes that normally keep a check on cell growth and division) is thought to play a role in the development of melanomas
  • About 50% of all melanomas have a mutation (change) involving the BRAF oncogene
  • UV-radiation induces damage to DNA (genetic material that determines all of our traits and functions), which in turn may turn-on oncogenes or turn-off tumor suppressor genes
  • In families with inherited melanomas, gene mutations that increase the risk of cancer are passed on from one generation to the next

What are the Signs and Symptoms of Melanoma of Skin?

Cutaneous Melanoma (Melanoma of Skin) can develop from an existing mole or appear as a new spot. The signs and symptoms may include:

  • A pigmented area that is Asymmetrical in shape, whose Borders are irregular or ragged
  • A pigmented area that is not Colored uniformly, unlike a benign mole, which has an even distribution of shades
  • Any suspicious looking spot, whose Diameter is more than ¼ inches (6 millimeters)
  • Any suspicious looking spot that is Evolving, or changing in shape/color

These signs are often collectively referred to as the ‘ABCDE characteristics’ of melanoma, by physicians. (Source: The Skin Cancer Foundation, New York)

  • A suspicious looking spot or a ‘potential melanoma’ often differs in appearance from other benign moles on the body. This variability is sometimes called the ugly duckling sign by physicians (Source: The Skin Cancer Foundation, New York)
  • A suspicious pigmented area/spot showing a spread of color to the surrounding skin and with any swelling, redness or itching (due to inflammation). Such areas may also be scaly, or exhibit some oozing of fluid or bleeding

How is Melanoma of Skin Diagnosed?

A thorough history and a complete physical exam by a physician are crucial for the diagnosis of Melanoma of Skin. This is followed by some tests which include:

  • Biopsy of skin: A sample of the skin from any suspected area found on physical examination is taken and examined under a microscope for signs of cancer by a pathologist. The types of biopsy performed include:
    • Excisional biopsy: After numbing the area with a local anesthetic, the entire mole is removed with a small border of surrounding skin. Where possible, this is the generally preferred method
    • Punch biopsy: After numbing the area with a local anesthetic, a circular blade is pressed into the skin around the suspicious area and a round piece of skin removed. This type of biopsy is carried out when the lesion (the suspicious area) is large in size
    • Incisional biopsy: After numbing the area with a local anesthetic, a portion of the tumor is removed using a surgical knife
    • Sentinel lymph node biopsy: Performed to determine if the melanoma has spread to nearby lymph nodes. A dye is injected into the area from where the melanoma is removed. The first lymph node that takes up the dye is biopsied and examined for cancer cells under a microscope
  • Sometimes, biopsy of other large lymph nodes in the area near the melanoma may be performed using fine needle aspiration cytology (FNAC) technique. In this, a sample of cells is removed from the mass, using a syringe with a hollow needle and then examined under a microscope
  • If the melanoma is suspected to have metastasized (spread) to internal organs, imaging tests such as X-ray, CT or MRI scan of the affected areas may be carried out
  • In rare cases, biopsies of areas other than skin may have to be done, when the primary source/origin of the tumor cannot be determined

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Melanoma of Skin?

Early stage melanomas include melanoma in situ (confined to just the upper skin layer called epidermis) or locally invasive melanomas that have spread to the deeper layers of the skin. The more advanced stages metastasize beyond the skin, to lymph nodes and other organs. Organs that are commonly involved in metastasis include:

  • Lung
  • Liver
  • Brain
  • Bone
  • Gastrointestinal tract

How is Melanoma of Skin Treated?

The choice of treatment for Melanoma of Skin depends on how far the cancer has progressed. This is estimated through staging of the tumor. Some of the factors taken into consideration during staging include:

  • The thickness of the melanoma (also called Breslow’s measurement): Tumors can be thin, intermediate, or thick, depending on how deep into the skin they have penetrated. The thinner the tumor, the better the chances of a cure
  • Presence of any ulceration (open sores) over the tumor.
  • Spread of melanoma to lymph nodes or other internal organs

The melanoma is sorted into one of four stages depending on how far it has progressed, with I and II being early stages, III and IV being later stages, where melanoma has spread to sites beyond the skin. While early stage melanomas can be treated by surgery alone, the later stages of the disease often require a combination of treatment measures.

Treatment options for melanoma include:

Surgery:

  • Simple excision of the tumor along with some normal, non-cancerous skin at the edges (called margin). The width of the margin is based on the thickness of the tumor; as the thickness of the melanoma increases, the margin required increases as well
  • Mohs micrographic surgery:
    • Being used of late by some surgeons as an alternative technique to standard excision of melanoma
    • A thin layer of skin is removed and checked for cancer. This process is the carried out continuously, until a cancer-free slice of skin is obtained
    • This procedure is rarely used as a surgical treatment option for melanoma
  • Lymph node dissection, in cases where the melanoma has spread to involve the nodes: Lymph nodes help in drainage of tissue fluid (lymph). Removal of these nodes may therefore lead to a build-up of lymph causing swelling (lymphedema)

Chemotherapy:

  • Drugs are used to kill the tumor cells, which may be given as oral pills, or injected into veins
  • Side effects of chemotherapy may include nausea, vomiting, hair loss, loss of appetite, diarrhea, and fatigue, increased risk of infection, mouth sores, or easy bruising, depending on the drug used
  • In cases, where the melanoma is advanced, but remains confined to an arm or leg; chemotherapy is only circulated through the affected the limb, by a process called isolated limb perfusion

Immunotherapy:

  • This therapy stimulates the immune system and involves the use of substances produced naturally by the body or such similar synthetics, made in a laboratory
  • Drugs used include, synthetic immune proteins and proteins that boost the immune system, called cytokines- interferon alpha or interleukin-2
  • Side effects of cytokines may include chills, fatigue, fever, headaches and muscle aches; while synthetic immune proteins may cause the immune system to start attacking other parts of the body

Targeted therapy:

  • Involves the use of drugs tailored to target the differences in a melanoma cell, as compared to a normal cell
  • Half of all melanomas involve a mutation in the BRAF gene. This is targeted by a drug vemurafenib
  • Side effects may include nausea, joint pain, fatigue, rash, itching, hair loss, sensitivity to the sun, and rarely heart rhythm problems, liver problems, severe allergic reactions, and severe skin or eye problems

Radiation therapy:

  • This uses high energy beams to kill cancer cells
  • Generally, this method is not used to treat the original melanoma, but often to relieve symptoms, when the melanoma has spread to other organs; or following lymph node dissection, where many nodes were found to be cancerous
  • The most common side effect is fatigue, but this gets resolved, once the treatment is complete

How can Melanoma of Skin be Prevented?

A few steps to prevent of Melanoma of Skin include:

  • Avoid direct exposure to UV rays and remain in the shade, as and when possible
  • When heading out into the sun:
    • Slip on a shirt
    • Slop on some sunscreen. Sunscreens with SPF values higher than 30, and those offering broad spectrum protections (against UV-A and UV-B rays), are recommended. Apply an ounce to all exposed areas, 30 minutes before heading outdoors. Reapply every two hours, and also after excessive sweating
    • Slap on a hat
    • Wrap on sunglasses

This is encapsulated as the “Slip! Slop! Slap! Wrap” method for skin cancer prevention. (Source: The American Cancer Society, Atlanta)

  • Avoid tanning beds and sun lamps
  • Perform self-examination of your skin, from head to toe, once a month
  • Get a professional skin exam from a healthcare provider, once a year
  • All patients with melanoma should undergo skin examinations regularly even after treatment, at least once a year throughout their lives

What is the Prognosis of Melanoma of Skin? (Outcomes/Resolutions)

  • Individuals with early-stage Melanoma of Skin, have better outcomes compared to those with more advanced melanoma, where the cancer has spread to lymph nodes or other organs
  • Almost 98% of those diagnosed and treated very early, live up to 5 years after detection. This drops to 62%, if the disease has spread to involve the lymph nodes, and 15% with metastasis to the organs
  • The prognosis depends upon a set of several factors, which include:
    • Stage of tumor: With lower-stage tumors, when the melanoma is confined to site of origin, the prognosis is usually excellent with appropriate therapy. In higher-stage cancers, such as those with metastasis, the prognosis is poor
    • Overall health of the individual: Individuals with overall excellent health have better prognosis compared with those with poor health
    • Age of the individual: Older individuals generally have poorer prognosis than younger individuals
    • The size of the melanoma: Individuals with small-sized melanomas fare better than those with large-sized ones
    • Individuals with bulky disease have a poorer prognosis
    • Involvement of vital organs may complicate the condition
    • The surgical resectability of Melanoma of Skin (meaning, if the melanoma can be removed completely)
    • Whether the cancer is occurring for the first time, or is recurrent. Recurring cancers have worse prognosis compared to those that do not recur
    • Response to treatment: Melanomas that respond well to treatment have better prognosis compared to melanomas that do not respond to treatment
    • Progression of the condition makes the outcome worse (progressive Cutaneous Melanoma)
  • An early diagnosis and prompt treatment of the condition generally yields better outcomes than a late diagnosis and delayed treatment

Additional and Relevant Useful Information for Melanoma of Skin:

  • Melanoma is the most common form of cancer in young adults, aged 25-29 years. 1 in 50 Americans, have a lifetime risk of developing melanoma
  • New types of melanoma treatment are currently under study. These include vaccines and newer targeted therapies that work on altered genes, or proteins in melanoma cells
  • The ‘Slip-Slop-Slap campaign’ was initially launched in Australia, by Cancer Council Victoria in the 1980s, to promote awareness about skin cancer and methods for its prevention. This was then adopted in New Zealand as the ‘Slip-Slop-Slap-Wrap campaign’ (Source: The Wikipedia)
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