SkinCancerNet Article
Melanoma: How It Returns, Where It Spreads

Melanoma is known as "the most lethal form of skin cancer" because it accounts for 77% of all deaths from skin cancer. Melanoma can spread rapidly - and with the exception of some rare forms of skin cancer — it is the skin cancer most likely to spread to lymph nodes and internal organs. Melanoma also may recur (return after treatment).

For these reasons, everyone treated for melanoma should continue a lifetime of regular:

• Examinations by a dermatologist

• Self-examinations of their skin

About Recurrence
Should melanoma return, it will recur in one of these ways:

1. Local recurrence. Melanoma that develops in or near the site where the primary melanoma was completely removed is called "local recurrence." Recurrence is often an indication that the tumor has metastasized. Patients who have locally recurrent melanoma after the primary tumor has been removed have a low rate of survival. Local recurrence can occur months to years after surgical removal of the primary tumor.

2. Second primary. A "second primary" is defined as a new melanoma that develops at another site on the patient’s body either simultaneously or after complete removal of the primary tumor. All patients who have had melanoma are at risk of developing a second primary. This risk increases if you have atypical moles (dysplastic nevi) or a family history of melanoma.
   
   It is vital that anyone who has had melanoma continue self-examinations and see a dermatologist for regular full-body skin examinations as often as prescribed. Early detection increases the likelihood that the second primary will be detected when it is in an early and curable stage.

3. Recurrence at a distant site. Recurrence at a distant site is known as "metastatic melanoma," which means the cancer has spread.

About Metastasis
Metastasis is a risk for anyone who has been treated for melanoma. However, when the primary melanoma (original tumor) is thin (less than 1 millimeter in thickness), surgical removal offers a complete cure in 95% of patients because the melanoma tends to be confined to the top layers of skin and is not likely to spread. This does not mean that you can be lax about self-examinations and checkups. Since 5% of thin melanomas are not completely cured, it is extremely important to perform regular self-examinations of your skin and lymph nodes and keep all appointments for checkups.

When your physician suspects that the melanoma may have spread, diagnostic testing will be conducted to determine if the cancer has spread and to where. Tests used to determine if melanoma has spread include blood tests, x-rays, and other imaging studies. Your dermatologist or oncologist will determine which diagnostic tests are needed.

When melanoma cells spread from the primary tumor, they first pass through the lymph channel nearest the melanoma. Once melanoma has spread to the regional lymph nodes (nodes nearest the tumor), there is a risk that the melanoma will spread to distant sites (other lymph nodes and organs). Once melanoma has spread to distant sites, it is in stage IV. Treatment in stage IV may include selective surgical excision, chemotherapy, immunotherapy, and radiation therapy. However, the prognosis is poor, and organ failure often causes death. It is important to know that some people do survive stage IV melanoma.

In stage IV, melanoma can metastasize to organs in nearly every part of the body. However, cancer cells do not randomly shoot off in all directions. Each type of cancer (breast, pancreatic, etc.) has a strong likelihood of spreading to certain sites more often than others. The following table shows what organs melanoma is most likely to travel to once it spreads.

Table 1: Where Melanoma Most Likely to Spread

Source: Meyers ML, Balch CM. “Diagnosis and Treatment of Metastatic Melanoma.” Cutaneous Melanoma. Balch CM, Houghton AN, Sober AJ, Soong S-J (Eds): St. Louis: Quality Medical Publishing, Inc. 1998:329.

Why Melanoma Spreads to Specific Organs
While scientists know where melanoma is most likely to spread, it is not clear why different cancers are more likely to metastasize to specific sites. Scientists have three hypotheses:

• Cancerous cells indiscriminately colonize at any distant site, but multiply only in those sites that have appropriate cellular growth factors

• Cancerous cells become "glued" to specific sites

• Cancerous cells are selectively attracted to specific sites by organ-specific molecules — a process called "chemoattraction"

A study published in March 2001 analyzed breast cancer and melanoma because both cancers tend to spread to the lymph nodes, lungs, liver, and bone. Researchers found that organ-specific chemoattractive molecules called "chemokines" are released from various organs and tend to attract circulating cancer cells to metastasize to a specific site. Melanoma’s tendency of spreading to the skin correlated with the presence of a skin-specific chemokine and a high level of corresponding chemokine receptors in melanoma cells. The researchers found that the melanoma cells had many more chemokine receptors than the cells not affected by cancer.

Why Follow-up Examinations So Important
It is important for patients to know that melanoma can spread "silently," meaning that the patient does not experience symptoms. This makes follow-up examinations vital. Be sure to perform regular self-examinations of your skin and lymph nodes as instructed and keep all dermatologic appointments for follow-up examinations.

Reference:
Muller A, Homey B, Soto H et al. “Involvement of chemokine receptors in breast cancer metastasis.” Nature 2001; 410:50-56.

All content solely developed by the American Academy of Dermatology