Melanoma is a serious form of skin cancer that originates from pigment-producing cells called melanocytes. While often detected early, its ability to spread, known as metastasis, poses a significant concern. Understanding how and where melanoma cells travel is crucial for comprehending the disease’s progression.
Understanding Metastasis
Metastasis refers to the process where cancer cells detach from their original tumor and travel to other parts of the body to establish new tumors. These new growths, known as metastatic or secondary tumors, are distinct from the primary tumor. This spread is a defining characteristic of advanced cancers, including melanoma, and signifies a more aggressive stage of the disease.
The Journey of Melanoma Cells
Melanoma cells spread from the primary tumor through a series of sequential steps.
Local Invasion
Initially, melanoma cells detach from the primary tumor and infiltrate surrounding healthy tissues. This involves breaking down the extracellular matrix, the network of molecules that provides structural support to cells.
Intravasation
Following local invasion, these cells can enter the circulatory system through intravasation. Melanoma cells penetrate the walls of tiny blood vessels or lymphatic vessels, gaining access to these transport networks. The lymphatic system is a common initial pathway for melanoma spread.
Circulation
Once inside blood or lymphatic vessels, melanoma cells circulate throughout the body. During this transit, circulating tumor cells face challenges, including attacks from the immune system and physical stresses of blood flow. Despite these obstacles, some cells survive.
Extravasation
Upon reaching a distant site, surviving melanoma cells undergo extravasation, exiting the blood or lymphatic vessels. This process, the reverse of intravasation, involves cells adhering to the vessel lining and migrating into the new tissue.
Colonization
Finally, these extravasated cells must establish a new tumor in the distant organ, a process known as colonization. For these new tumors to grow, they often require angiogenesis, the formation of new blood vessels that provide necessary nutrients and oxygen.
Common Sites of Melanoma Spread
Melanoma tends to spread to specific organs and tissues once it metastasizes. The most common initial sites are the regional lymph nodes, small, bean-shaped organs that filter lymph fluid. After affecting lymph nodes, melanoma commonly spreads to distant skin and soft tissues.
Beyond these regional areas, common visceral sites include the lungs, liver, brain, and bones. The lungs are frequently affected, with some studies indicating that between 70% and 87% of individuals with metastatic melanoma experience lung involvement. The liver is also a common visceral organ for melanoma metastasis, and brain metastases are particularly notable, often resulting in severe neurological symptoms.
Factors Influencing Metastasis
Several factors influence the likelihood and pattern of melanoma metastasis. Primary tumor characteristics play a role, with tumor thickness (Breslow depth) being a significant indicator of higher spread risk. Ulceration, a break in the skin over the tumor, also suggests a greater risk. A higher mitotic rate, indicating faster cell division, is another prognostic factor.
Genetic mutations within melanoma cells significantly impact their metastatic potential. For example, mutations in the BRAF gene are found in many melanomas and can drive progression. Other genetic alterations, such as those in the CDKN2A gene or TERT promoter mutations, also contribute to the metastatic process. Inherited genetic variations can also influence how melanoma progresses and spreads. The host’s immune system also plays a part in controlling metastatic spread. Melanoma cells can evade the immune system, allowing them to survive and colonize new sites. This interplay between tumor characteristics, genetic makeup, and the body’s defenses determines the course of metastatic melanoma.