Dermatological Center for Skin Health

How melanoma is formed

Melanocytes are cells found in the bottom layer of the epidermis. These cells produce melanin, the substance responsible for skin pigmentation. That’s why melanomas often present as dark brown or black spots on the skin. Melanomas may also look like moles or can arise from existing moles. It is important for you to conduct regular self-examinations of your skin in order to detect any potential skin cancer early, when it’s more easily treated.

Most melanomas are caused by overexposure to the sun beginning in childhood. However, inherited gene mutations can lead to a much higher risk of developing melanoma. Some melanomas occur in sites with minimal sun exposure.

Early detection and diagnosis

Advances in early detection and diagnosis of melanoma is leading to earlier treatment and an increase in overall survival rates. If you’ve been identified as being at a higher risk for a melanoma diagnosis because you have light skin and greater sensitivity to the sun, have multiple atypical nevi or moles, large congenital moles, a family history of melanoma, or a history of blistering sunburns, we can help.  

Melanoma is predominantly a disease of Caucasians, and is slightly more common in men than women. Primary lesions occur most commonly on the trunk in males, while melanomas in females occur most commonly on the lower extremities.

Where melanoma begins

Cutaneous melanomas usually begin in cells known as the epidermal melanocyte. Features that should increase suspicion of melanoma include:

• Lesion asymmetry or border irregularity on moles

• Bleeding or crusting

• Recent changes in moles

• Variation of color on existing moles (though some are non-pigmented)

• Diameter over 6 millimeters

• Development of an elevated area (when a flat lesion becomes raised)

About melanomas

Melanomas may be discovered when they are still in situ — meaning they are still “in the site” where their cell of origin, the melanocyte normally resides, staying in only the top layer of the skin — the epidermis.  Melanomas which have breached beneath the top layer are invasive.  Invasive melanomas are more serious, as they have penetrated deeper into the skin and may have spread to other areas of the body.

The stage of disease describes how advanced disease has become.  Melanoma stages I and II are localized, and more stages III and IV have spread (metastasized) to other parts of the body. There are also subdivisions within stages.

If the disease has advanced to Stage IV, the melanoma cells have traveled through the body via the bloodstream or lymph vessels and have settled into another distant area of the body, likely far from the original tumor site. These cells may have reached distant lymph nodes or invaded the internal organs. This can be in addition to or instead of in-transit metastases or local spread to the regional lymph nodes. When it spreads locally, the melanoma can travel to skin or subcutaneous tissue more than 2 cm from the primary tumor, but not beyond the regional lymph nodes. 

What are the risk factors for developing a melanoma?

Anything that increases your chance of getting melanoma is considered a risk factor. Sun damage, especially a history of blistering sunburns, is a risk factor for melanoma. Ultraviolet light is a known risk factor for skin cancer. There is no evidence that UV exposure from any type of tanning bed is less harmful than UV exposure from the sun.

Other risk factors for melanoma include:

• Fair complexion: People with blond or red hair, light skin, blue eyes and a tendency to sunburn are at increased risk

• Previous melanoma

• A large amount of benign (non-cancerous) moles

• Family history of melanoma

• Atypical mole and melanoma syndrome (AMS)

  • If you have AMS, you and your family members should be screened regularly

Not everyone with risk factors gets melanoma. Ask yourself these questions:

What is a person's risk if melanoma runs in the family?

If a person has a first-degree relative with melanoma, his or her risk of developing melanoma is two to three times greater than the average risk. The risk is higher if several family members that live in different locations have been diagnosed with melanoma.

Which inherited genetic mutations raise the risk of melanoma?

There are several genes thought to be associated with an increased risk of melanoma. However, research to better understand how these genes affect the risk of melanoma is ongoing.

• Familial malignant melanoma. There are at least three different genes have been linked to hereditary melanoma. Families with mutations in these genes may have multiple dysplastic nevi (flat moles that are irregular in shape or color). Although dysplastic nevi are likely to be related to altered genes, the specific genes involved have not been identified. The association of familial melanoma and multiple dysplastic nevi is also sometimes called familial atypical multiple mole melanoma (FAMMM) or atypical nevus syndrome. Families with inherited melanoma may also have an increased risk of developing pancreatic cancer and possibly other cancers.

• Melanoma-astrocytoma syndrome. People with this rare condition have an increased risk of melanoma and astrocytoma (a type of brain tumor). The specific gene for this condition is thought to be located on chromosome 9. Families with both melanoma and astrocytoma have been shown to have changes in a gene called CDKN2A gene, which affects tumor growth.

Are there other genetic conditions associated with an increased risk of melanoma?

Other genetic conditions that are associated with an increased risk of melanoma include:

• Xeroderma pigmentosum. Xeroderma pigmentosum (XP) is a group of rare conditions that makes a person's cells unable to repair DNA damage caused by ultraviolet (UV) light exposure, such as sunshine. Signs of XP are caused by the increased sensitivity to UV light, and include dry skin, abnormal pigmentation, severe freckling, and blistering after minimal sun exposure. People with this condition have a high risk of skin cancer, including melanoma (more than a thousand times more likely than the general population), and noncancerous skin abnormalities. People with XP also have an increased risk of other types of cancers including leukemia, brain tumors, stomach cancer, lung cancer, breast cancer, uterine cancer, and testicular cancer.

• Retinoblastoma. Retinoblastoma is a childhood eye tumor. Children with hereditary retinoblastoma have an increased risk of developing other cancers as they grow older, especially melanoma (50 times more likely than the general population). They also have a higher risk for osteosarcoma (a type of bone cancer).

Early and accurate diagnosis is important in melanoma care. This helps us to know if the cancer has spread so we can choose the most effective treatment.