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PRODUCED BY AND FOR MEMBERS OF THE DEPARTMENT OF SURGERY June 2014 | Archived Issues

Understanding How Melanoma Spreads From the Skin

By Richard Essner, MD
Director, Melanoma Surgery

Once an uncommon malignancy, cutaneous melanoma is increasing in frequency in the United States. It affects one in 80 Caucasians and is the fifth-most-common cancer. The rate of increase is exceeded only by lung cancer in women, making melanoma a significant health problem.

While most cases of melanoma can be cured by surgical excision of the primary tumor alone, about 20-30 percent of patients will develop metastases, and many of these patients will die from their disease.

The most common first site of metastases in melanoma is the adjacent, regional lymph nodes. Elective lymph node dissection (ELND) was described as a method of controlling melanoma metastases by removing the lymph nodes when they are clinically normal but may or may not contain microscopic disease. While ELND has never been proven to provide a survival advantage for all patients compared to those patients who undergo treatment of the primary tumor only, four randomized prospective trials of ELND have shown the importance of staging the regional lymph nodes and the survival benefit of removing lymph nodes when they contain microscopic disease.

As an alternative to ELND, selective lymph node dissection (SLND) was devised in the 1990s as a minimally invasive approach to the regional lymph nodes. SLND allows surgeons to remove the lymph node most likely to contain metastases, i.e., the sentinel node (SN), while leaving the remainder of the regional lymph nodes intact. Only when the SN contains metastases are the remaining lymph nodes removed.

While the SN provides accurate staging of the regional lymph nodes, there is no data to prove that removal of a tumor containing SN will improve patient survival, similar to ELND. Yet the SN may provide insights into the mechanisms of how melanoma spreads from the skin.

In our laboratory, we have evaluated the immune profile of SN and non-SN in the presence and absence of lymph node metastases. Our hypothesis is that the immune profile of the SN may predict the biology of the cutaneous melanoma.

We have found that when melanoma spreads from the skin to the SN, the SN appear to have an immune cytokine profile that suggests immune dysfunction demonstrating dendritic cells and T-cells that are incapable of mounting an immune response. The non-SNs or normal SNs do not have the same immune profile, suggesting the SN is distinct in its immune response, likely related to its direct connection to the melanoma primary site.

We have proposed using the SN as a target for immune therapy with a hope that we can reverse the immune compromise in the SN. Granulocyte-macrophage colony stimulating factor (GM-CSF) is one such agent that can active and cause maturation of dendritic cells, a potent first step in cancer antigen presentation.

By delivery GM-CSF directly to the SN, we hope that the immune dysfunction of the SN can be reversed. We anticipate these studies will provide useful information to the early process of immune activation or dysfunction in melanoma.