Second Opinion on Melanoma

Melanoma is a malignant tumor that develops from melanocytes, the cells responsible for producing melanin. It most commonly arises in the skin, although melanomas can also occur in other tissues containing melanocytes. The prognosis largely depends on the depth of tumor invasion and whether the disease has spread beyond the primary lesion. When melanoma is detected at an early stage and completely removed, the chances of cure are generally very high.

Advanced melanoma is considerably more difficult to treat, but its therapeutic landscape has changed dramatically in recent years. Immune checkpoint inhibitors and molecularly targeted drugs have substantially improved outcomes at advanced stages. For this reason, patients with high-risk, recurrent or metastatic melanoma may benefit from an expert second opinion. A specialist review can assess the molecular profile of the tumor, evaluate the current treatment strategy and identify appropriate clinical trials or innovative treatment options.

Diagnosis

The diagnostic process usually begins with a clinical skin examination and dermoscopy of a suspicious lesion. A definitive diagnosis requires histological examination of tumor tissue. The pathology report provides important information such as tumor thickness and ulceration, which influence staging and treatment decisions.

Depending on the characteristics of the primary tumor, a sentinel lymph node biopsy may be recommended to determine whether melanoma cells have reached the regional lymphatic system. If lymph node involvement is suspected or confirmed, additional staging may include ultrasound, CT or MRI.

For advanced melanoma, molecular testing can also be clinically important. For example, identification of a BRAF mutation may make the patient eligible for targeted therapy.

Stages of melanoma

Melanoma is staged using the TNM system, which evaluates the characteristics of the primary tumor (T), regional lymph node involvement (N) and distant metastases (M). In simplified terms:

For stage III and IV disease, treatment decisions are particularly complex and should be made by a multidisciplinary tumor board.

Modern treatment: from surgery to cell therapy

Surgery remains the cornerstone of treatment for localized melanoma. The tumor is removed with an appropriate safety margin, with the extent of surgery determined primarily by the characteristics of the primary lesion. Patients with a significant risk of recurrence may receive additional adjuvant treatment after surgery.

One of the most important advances in melanoma treatment has been immune checkpoint blockade. Drugs targeting PD-1 and CTLA-4 can restore the activity of T cells and help the immune system recognize and attack tumor cells. Examples include immune checkpoint inhibitors nivolumab, pembrolizumab and ipilimumab, which may be used alone or in combination depending on the clinical situation.

Another major treatment category is targeted therapy for tumors carrying specific molecular alterations. In patients with a BRAF V600 mutation, for example, combinations of BRAF and MEK inhibitors may be used. Modern melanoma treatment therefore increasingly relies not only on disease stage but also on the biological characteristics of the tumor.

An important area of innovation is cell and gene therapy (CGT). One of the most promising cellular approaches for melanoma is TIL therapy (tumor-infiltrating lymphocyte therapy). T cells are isolated from the patient's own tumor tissue, selected for their ability to recognize tumor cells and expanded to a large number in the laboratory. After preparative treatment, these cells are infused back into the patient with the aim of generating a stronger and more targeted anti-tumor immune response. The concept behind this approach is to use the patient’s own immune cells while preserving their natural anti-tumor specificity.

TIL therapy is particularly relevant to advanced melanoma, including cases in which the disease has become resistant to conventional systemic treatment. Unlike standard drug therapy, TIL therapy uses a personalized cellular product derived from the patient's own tumor, preserving naturally occurring tumor-reactive lymphocytes.

TIL and other advanced cellular therapies should nevertheless be considered specialized approaches whose availability, indications and regulatory status depend on the patient's individual clinical situation and the treatment setting. For patients with advanced or treatment-resistant melanoma, a comprehensive assessment may include standard immunotherapy, targeted therapy, surgery, clinical trials and, where appropriate, innovative cellular therapies. A multidisciplinary expert evaluation can help determine which strategy offers the most suitable option for the individual patient.