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The information on this page was reviewed and approved by
Maurie Markman, MD, President, Medicine & Science at CTCA.

This page was updated on July 19, 2021.

Amelanotic melanoma

If you’re familiar with skin cancer, you’ve probably heard of its most serious form, melanoma. Though melanoma is the least common type of skin cancer, it’s also the most likely to spread to surrounding areas—and it’s the cause of most skin cancer deaths.

Melanoma has many characteristics that make it easier to recognize. The beginning letters of the alphabet, or the ABCDEs of melanoma, serve as helpful guidelines in recognizing the warning signs.

  • A means asymmetrical.
  • B represents the uneven borders that most melanomas possess.
  • C is for color—melanomas may be black, brown or tan, with spots of pink, red, white or blue.
  • D signifies diameter, with melanomas measuring about 1/4 inch across.
  • E stands for evolving (any changes to a lesion on your skin), including size, shape or color and symptoms (such as bleeding, itching or oozing/crusting).

It’s important to pay attention to any new or unusual growths on your skin, as well as any changing moles or lesions. While it’s helpful to use the ABCDEs to identify potential melanomas, there are exceptions to every rule.

Amelanotic melanomas, for example, don’t produce the pigment melanin that gives most melanomas their dark appearance. As a result, they don’t look like other melanomas. Instead, they may appear skin-colored, pink or even reddish, with gray or brownish edges.

Amelanotic melanomas may be easily confused with basal or squamous cell carcinomas, or misidentified as harmless scars or moles, which is dangerous, because they often spread faster than the more easy-to-recognize melanomas.

What causes amelanotic melanoma?

Amelanotic melanomas are rare. According to 2014 research published in JAMA Dermatology, amelanotic melanomas make up about 2 percent to 20 percent of all melanomas. Though their appearance makes them harder to detect, the causes of amelanotic melanomas are the same as their more recognizable counterparts. Most often, genetic changes to the cells in moles cause them to turn into cancerous cells, or melanoma.

All of your cells contain DNA, a chemical that controls how your genes work. When DNA mutations cause your genes to function abnormally, cells may grow uncontrolled, becoming cancerous. The most common cause of these cellular changes is exposure to ultraviolet (UV) rays from the sun or a tanning bed, though it may take years after UV exposure for these mutations to occur.

Rare, inherited genetic mutations may also play a role in causing melanoma. Inherited melanomas are caused by changes to tumor suppressor genes, impairing their ability to control cellular growth and ultimately contributing to cancer. People with a condition called xeroderma pigmentosum (XP) have an inherited mutation in the genes that repair damaged cellular DNA after UV exposure. These genes don’t work properly in those with XP, making them more susceptible to melanoma.

Amelanotic melanoma risk factors

Though these risk factors don’t mean someone will develop melanoma, they are linked with increased risk of all forms of the cancer, including amelanotic melanoma.

Exposure to UV rays: Damage to DNA in your skin cells, from exposure to UV rays (both UVA and UVB), is the No. 1 risk factor for all types of melanoma. Both natural sunlight and artificial tanning lamps increase the risk of developing this type of skin cancer. Getting many sunburns during childhood also has been associated with the development of melanoma on the chest, back and legs.

Moles: If you have a lot of moles or have atypical moles, you’re at greater risk of developing melanoma. Additionally, patients with the inherited condition dysplastic nevus syndrome are at a high risk of developing melanoma during their lifetime.

Fair skin: People who have light-colored, freckled skin and blond or red hair with blue or green eyes are at a greater risk of developing melanoma. This is especially true if your skin tends to burn as opposed to tanning when exposed to UV rays.

Race: Melanoma is 20 times more likely for white people than it is for black people, according to the American Society of Clinical Oncology (ASCO).

Family and personal history: If your close relatives have a history of melanoma, you’re at increased risk. If you’ve previously had melanoma or another type of skin cancer, the chance of developing it again is also greater.

Weakened immune system: People who take immunosuppressive drugs or have weakened immune systems from illnesses such as human immunodeficiency virus (HIV) are at greater risk of melanoma.

Age and gender: Melanoma risk increases with age, though it’s one of the more frequently diagnosed cancers in people younger than 30. Men are at greater risk of developing melanoma after age 50, while women are at greater risk before age 50.

Xeroderma pigmentosum (XP): If you have this inherited condition, the ability to fix DNA damage on a cellular level is impaired, thereby increasing the risk of melanoma.

Amelanotic melanoma symptoms

The five-year survival rate for melanoma is 99 percent when it’s detected in its early stages, according to the Skin Cancer Foundation. That’s why it’s so important to look for changes to your skin every month by performing a full-body skin scan. If you spot any of the following, consult your doctor:

  • A growth that has changed in size and looks unusual (remember that with amelanotic melanoma, there may be no coloration)
  • A mole or spot on your skin that grows, becomes thicker, changes in texture or color (anything larger than a pencil eraser is of particular concern). A mole, spot or sore that becomes painful or begins to bleed, ooze or crust over should also be examined by a doctor.
  • An open sore that takes more than three weeks to heal should be checked out immediately.

While 20 percent to 30 percent of melanomas develop in existing moles, according to the Skin Cancer Foundation, the majority develop on skin that is normal in appearance. Since amelanotic melanoma is harder to identify, pay attention to any changes to your skin, especially those with little-to-no pigmentation. Use the ABCDEs to spot abnormalities on your own, but be sure to see a dermatologist for regular skin checks, too.

How is amelanotic melanoma diagnosed?

 

To diagnose all forms of melanoma, a biopsy must be taken in order to determine whether cancerous cells are present. The area of concern may be treated first with a local anesthetic, and the unusual mole or growth is carefully removed to be evaluated by a dermatopathologist, a specialist in diagnosing skin cancer. The specialist completes a pathology report that includes the following details:

Thickness. The pathology report will include details on the thickness of the melanoma, which may be thin (smaller than 1 mm), intermediate (1 to 4 mm) or thick (more than 4 mm). Thin melanomas have the lowest risk of metastasizing (spreading).

Ulceration. Also included is whether there is ulceration, or loss of surface skin, on the melanoma. The presence of ulceration is linked with increased risk of metastasis and a greater chance that the cancer will occur again.

Mitotic rate. The rate at which cells are dividing is also noted, as it’s helpful in determining the odds of recovering from the melanoma.

Tumor-infiltrating lymphocytes. Whether these immune cells are found in the biopsy will also be determined.

Melanoma is diagnosed as one of these four types:

  • Superficial spreading melanoma is the most common melanoma, and it often evolves from an existing mole. This form makes up about 70 percent of all melanomas and may be amelanotic, according to the ASCO.
  • Lentigo maligna melanoma is more common in older patients and most often found on areas of the body that have experienced frequent sun exposure (face, ears, arms).
  • Nodular melanoma accounts for about 15 percent of all melanomas, according to the ASCO, and usually forms rapidly on the skin. It may appear as a raised bump that’s black, red or pink.
  • Acral lentiginous melanoma may be found on the palms of your hands, under your nail beds, or on the soles of your feet. These melanomas may be amelanotic.

Finally, the stage of melanoma is established. Melanoma stages are categorized by the following:

  • Stage 0. The melanoma is limited to the outer layer of skin, also known as melanoma in situ.
  • Stage 1. Reserved for cancers under 1 mm in thickness, these melanomas may or may not be ulcerated, and have grown beyond the surface layer of skin.
  • Stage 2: These melanomas are greater than 1 mm, with or without ulceration. While they haven’t yet spread, they are at high risk of doing so.
  • Stage 3: These advanced melanomas have spread to the lymph nodes or to a nearby surrounding area.
  • Stage 4: These melanomas have spread to distant areas of the body, including organs such as the lungs, liver and brain, or the lymph nodes, bone and digestive tract.

Staging likely requires further imaging tests. Usually, such testing is done only when melanomas are greater than 1 mm in thickness or are higher-risk types, such as amelanotic melanomas. These tests may also help you find out whether cancer has spread to other areas.

Treatments for amelanotic melanoma

Treatment for all melanomas depends on the staging and is tailored to your symptoms. Your doctor works with you in a process called shared decision-making to determine the best course of treatment depending on your situation and goals.

One, or a combination, of the following treatments may be recommended:

Surgery is the most common treatment for melanoma and typically removes the cancerous tumor as well as a small amount of healthy surrounding tissue, called a margin. Wide excision involves removal of the primary melanoma and may include a skin graft. Lymph node dissection to remove the affected lymph nodes may be done if cancer is found during SLNB testing.

Radiation therapy, which uses high-dose energy rays to kill cancer cells, may be used as treatment to prevent your melanoma from recurring, to manage symptoms if it’s spread to your bones, and when the cancer has spread to a large area of lymph nodes or skin that cannot be treated surgically.

Immunotherapy augments the body’s immune system, boosting your ability to fight the cancer. Treatments include: PD-1 and PD-L1 inhibitors, CTLA-4 inhibitors, Interleukin-2, Interferon and virus therapy.

Targeted therapy targets the genes, proteins or tissue environment that is causing your cancer to flourish. It helps prevent the growth of cancer cells by blocking the pathways necessary for melanomas to grow. Targeted therapy includes: BRAF inhibitors, MEK inhibitors, KIT inhibitors and tumor-agnostic treatment.

Chemotherapy is used to kill cancer cells, but chemotherapy drugs are a less likely option than other treatments.

Isolated limb infusion therapy involves delivering chemotherapy drugs only to the affected limb, to shrink the tumors located there. This is typically used in the case of multiple melanotic tumors.

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