Melanoma is a form of skin cancer that develops in melanocytes, the cells that produce skin pigment. While many skin cancers are slow-growing, certain melanomas behave more aggressively, posing a greater risk because they can grow quickly and spread. Understanding the characteristics that define this aggression helps explain why some melanomas require more intensive diagnosis and treatment.
Defining Aggressiveness in Melanoma
Aggressiveness in melanoma is defined by specific, measurable features identified under a microscope. One of the most significant predictors is its Breslow depth, which measures in millimeters how deeply the tumor has grown into the skin. A thicker tumor has a higher chance of spreading; for instance, melanomas less than 0.8 mm thick are low risk, while those greater than 4.0 mm have a high-risk profile.
Another characteristic is the presence of ulceration, which is a breakdown of the skin surface over the melanoma. Ulceration is associated with a higher risk of spread and is a component of cancer staging guidelines. Its presence can elevate a tumor to a higher-risk subcategory, which influences treatment recommendations.
A third feature is the mitotic rate, which measures how quickly cancer cells are dividing. Pathologists count the number of cells undergoing mitosis within a square millimeter of the tumor. A higher mitotic rate signifies a more aggressive cancer because it indicates rapid proliferation and is a powerful prognostic factor.
Types of Aggressive Melanoma
While any melanoma can become aggressive, certain subtypes are known for this tendency. Nodular melanoma is the most aggressive form of skin-based melanoma. Unlike melanomas that grow outward, nodular melanoma grows vertically into deeper skin layers from the start, meaning it often presents as a thicker, more advanced tumor at diagnosis.
Nodular melanomas appear as a raised bump or node that can be black or skin-toned, making them harder to identify. They account for 10% to 15% of melanoma cases and are commonly found on the trunk, head, or neck. Because they invade deeply and quickly, they are associated with a poorer prognosis.
A rarer subtype, acral lentiginous melanoma, is also aggressive, partly because it is often diagnosed late. This type appears on the palms, soles, or underneath nails and is the most common form of melanoma in people of African and Asian descent. Its location can cause it to be mistaken for a bruise or a dark streak, delaying detection until the cancer has progressed.
Advanced Diagnosis and Staging
If a skin lesion is suspicious for melanoma, the first step is a biopsy to have the tissue examined by a pathologist. An excisional biopsy, which removes the entire lesion with a small margin of normal skin, is preferred for accurate measurement of the tumor’s features. If the biopsy confirms an aggressive melanoma, further procedures are needed to determine if the cancer has spread.
For melanomas at least 0.8 mm thick or with other high-risk features, a sentinel lymph node biopsy (SLNB) is often performed. This procedure removes the first lymph node(s) to which cancer cells would most likely travel for examination by a pathologist. A positive SLNB result indicates the cancer has reached the lymphatic system, which influences the overall stage and treatment plan.
The findings from the biopsy and SLNB are combined within the TNM staging system to classify the cancer’s extent. “T” stands for the primary tumor and is based on its thickness and ulceration. “N” indicates if the cancer has spread to regional lymph nodes. “M” signifies metastasis, meaning the cancer has spread to distant organs.
Treatment for Advanced Melanoma
For advanced or spread melanomas, treatment has been transformed by systemic therapies. Immunotherapy is a primary approach that uses the body’s immune system to attack cancer cells. Checkpoint inhibitors, such as PD-1 inhibitors, block proteins on cancer cells that help them hide from the immune system. Drugs like nivolumab and pembrolizumab are checkpoint inhibitors used to treat advanced melanoma.
Targeted therapy is another treatment, but it is effective only for patients whose cancer cells have specific genetic mutations. About half of all skin melanomas have a mutation in the BRAF gene. Targeted drugs, like BRAF and MEK inhibitors, block signals from these mutated genes that cause cancer cells to grow. These therapies, such as dabrafenib combined with trametinib, can produce rapid responses.
For patients with BRAF-mutant melanoma, clinical trials show that starting with immunotherapy leads to better two-year survival rates compared to starting with targeted therapies. This suggests immunotherapy is often the preferred initial treatment. Surgery and radiation may still be used in advanced cases to remove specific metastatic tumors or relieve symptoms, but systemic treatments are the foundation of care.
Prognosis and Outlook
The prognosis for aggressive melanoma depends on the cancer’s stage at diagnosis. Factors like tumor thickness, ulceration, and spread to lymph nodes or distant organs determine outcomes. The 5-year survival rate for localized melanoma is over 99%, but this falls to 71% if it has spread to nearby lymph nodes and 32% if it has spread to distant organs.
These survival rates are statistical averages and cannot predict an individual’s outcome, as each case is different and response to treatment is a large factor. The landscape of melanoma treatment has also changed dramatically in recent years.
The development of immunotherapy and targeted therapies has significantly improved survival rates, even for patients with stage IV metastatic disease. These advanced therapies mean a substantial portion of patients are living much longer, offering a more hopeful outlook than was possible a decade ago.