Melanoma 101: Introduction to a Deadly Skin Cancer

  • Medical Author: Jeffrey John Meffert, MD
  • Medical Editor: Melissa Conrad Stöppler, MD
    Melissa Conrad Stöppler, MD

    Melissa Conrad Stöppler, MD

    Melissa Conrad Stöppler, MD, is a U.S. board-certified Anatomic Pathologist with subspecialty training in the fields of Experimental and Molecular Pathology. Dr. Stöppler's educational background includes a BA with Highest Distinction from the University of Virginia and an MD from the University of North Carolina. She completed residency training in Anatomic Pathology at Georgetown University followed by subspecialty fellowship training in molecular diagnostics and experimental pathology.

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What is metastatic melanoma?

Metastatic melanoma is melanoma that has spread beyond the skin to other organs. There are several types of metastatic melanoma. There may be spread through the lymphatic system to local lymph nodes. This may show up as swollen lymph glands (usually painless) or as a string of skin tumors along a lymphatic chain. Melanoma may also spread through the bloodstream (hematogenous spread), where it may appear in one or more distant sites, such as the lungs, liver, brain, remote skin locations, or any other body location.

What are the signs of symptoms of metastatic melanoma?

Signs and symptoms depend upon the site of metastasis and the amount of tumor there. Metastases to the brain may first appear as headaches, unusual numbness in the arms and legs, or seizures. Spread to the liver may be first identified by abnormal blood tests of liver function long before the patient has jaundice, a swollen liver, or any other signs of liver failure. Spread to the kidneys may cause pain and blood in the urine. Spread to the lungs may cause shortness of breath, other trouble breathing, chest pain, and continued cough. Spread to bones may cause bone pain or broken bones called pathologic fractures. A very high tumor burden may lead to fatigue, weight loss, weakness and, in rare cases, the release of so much melanin into the circulation that the patient may develop brown or black urine and have their skin turn a diffuse slate-gray color. The appearance of multiple blue-gray nodules (hard bumps) in the skin of a melanoma patient may indicate widespread melanoma metastases to remote skin sites.

What are the treatments for metastatic melanoma?

Historically, metastatic and recurrent melanoma have been less responsive to radiation therapy and traditional forms of chemotherapy than other forms of cancer. Immunotherapy in which the body‘s own immune system is used to fight the tumor has been a focus of research for decades. A variety of newer medications target different points in the pathways of melanoma cell growth and spread. While the most appropriate use of these medications is still being defined, the best treatment for melanoma remains complete surgical excision while it is still small, thin, and has not yet had a chance to spread.

Initial therapies to stimulate the immune system to help contain metastatic melanoma included infusions of interferon-alpha and interleukin-2 (both parts of the immune response to cancer and infection), and some patients have responded to these therapies. There has, however, been an explosion recently in the approval of a number of targeted therapies that act on specific stages in the cell cycle, especially those of abnormal cells, and affect those growth processes of the tumor cells. Drugs that inhibit the kinase enzymes such as MEK, which is necessary for cell reproduction, include cobimetinib (Cotellic) and trametinib (Mekinist). Others target the signals for cell growth from abnormal BRAF genes and the enzymes they drive. Such medications in this family include dabrafenib (Tafinlar), vemurafenib (Zelboraf), and nivolumab (Opdivo). Pembrolizumab (Keytruda) blocks the tumor‘s ability to use alternate enzyme pathways for a better immune response. Ipilimumab (Yervoy) works directly on the T-lymphocyte pathway of the immune system. Many of these medications are now being used in combination to get better therapeutic effects than they would by themselves. All of these medications have significant side effects, including some that are life-threatening, and are indicated only for stage 3 tumors to try to prevent recurrence and spread and stage 4 metastatic tumors that are no longer amenable to surgery.

What are the survival rates for metastatic melanoma?

Survival rates for melanoma, especially for metastatic melanoma, vary widely according to many factors, including the patient's age, overall health, location of the tumor, particular findings on the examination of the biopsy, and of course the depth and stage of the tumor. Survival statistics are generally based on five-year survival rates rather than raw cure rates. Much of the success reported for the targeted therapies focuses on disease-free time because in many cases the actual five-year survival is not affected. It is hoped that combination therapy discussed above will change that.

  • For stage 1 (thin melanoma, local only), five-year survival is near 100%.
  • For stage 2 (thicker melanoma, local only), five-year survival is 80%-90%.
  • For stage 3 (local and nodal metastasis), five-year survival is around 50%.
  • For stage 4 (distant metastasis), five-year survival is 10%-25% depending upon sex and other demographic factors.
Medically Reviewed by a Doctor on 6/30/2016

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