Melanoma: Clinic, diagnosis and treatment

• Melanoma is a type of skin cancer that develops from melanocytes, the cells responsible for producing melanin, the pigment that gives skin its color. It is considered the most serious type of skin cancer because of its ability to spread rapidly to other parts of the body and to metastasize.
• Melanoma usually appears as a nevus (or 'mole'), which is a spot or lesion on the skin that can change in size, shape or color over time.
• The main risk factors for melanoma include excessive exposure to UV radiation (from the sun or artificial sources), family and personal history of melanoma, light phototype (fair skin, blond or red hair, blue or green eyes), atypical moles, a high number of moles and a history of frequent or severe sunburn.
• Treatment for melanoma depends on many factors, including the size, location, and extent of the tumor, as well as the patient's general health. Treatment options may include surgical removal of the tumor, radiotherapy, chemotherapy, immunotherapy and targeted therapy.

• Melanoma is characterized by abnormal growth and proliferation of melanocytes.
• This tumor growth is often due to genetic and epigenetic mutations that alter the regulatory mechanisms of cell growth and programmed cell death.
• The most common genetic alterations in melanoma are mutations in the CDKN2A, NRAS, BRAF and PTEN genes, which regulate cell growth and proliferation.
• Mutations in the BRAF gene are the most common, with a prevalence of approximately 50% of cutaneous melanomas.
• Tumor cells may also secrete growth factors and cytokines that promote their own growth and the formation of new blood vessels, which supply essential nutrients to the tumor. This can promote the progression of the tumor and its ability to spread to other parts of the body.
• Exposure to UV radiation is the main modifiable risk factor for melanoma. UV radiation can damage cells’ DNA and lead to genetic mutations that promote the growth and proliferation of melanocytes. Excessive exposure to UV radiation can also suppress the immune response and promote melanoma progression.
• A family history of melanoma is also an important risk factor. People who have a first-degree relative with melanoma have a higher risk of developing the disease.
• Light skin is another important risk factor. People with fair skin have less melanin to protect their skin from UV radiation, making them more susceptible to sun damage. People with many atypical moles or who have suffered severe or frequent sunburns are also at greater risk of developing melanoma.
• Certain skin conditions, such as congenital giant nevus, can increase the risk of developing melanoma.

General characteristics

• Appears after puberty, over the age of 15.
• 80% of melanomas appear on healthy skin and 20% develop on a pre-existing "mole": change in color, shape and size.
• Usually found on the legs in women, on the back in men.

Most common patterns³

Superficial spreading melanoma (S.S.M.)

• It is the most common melanoma (70-80%). It corresponds to the multiplication of cancer cells horizontally in the epidermis.
• This phase lasts several years.

Without excision at this horizontal stage, the growth of the cancer cells becomes vertical:

• On the surface: appearance of nodules at the level of the lesion.
• Deep down: damage to the dermis and hypodermis.

Nodular melanoma (N.M.)

• It accounts for about 20% of cases.
• Its development is rapid with the appearance of a domed nodule, more or less pigmented, often brown black, corresponding to a vertical growth of cancer cells from the start.
• Some of these melanomas are achromic, giving a fleshy bud appearance which delays diagnosis.

Dubreuilh's melanoma (L.L.M. = Lentigo Malignant Melanoma)

• It corresponds to 5 to 10% of melanomas.
• It affects elderly people in the face.
• It develops over a very long period of time, from 5 to 20 years.
• A pigmented, black or polychrome patch is found, with progressive extension.
• Late in the course of the disease, the appearance of a nodule, often greyish, signals the transition to the vertical phase.

Acral Lentiginous melanoma (A.L.M.) or melanoma of the extremities

• It occurs on the palms of the hands, soles of the feet and under the nails.
• It occurs in phototypes with dark skin (V and VI).

Specific forms 

Melanoma on pre-existing nevus

Nail melanoma

• Appearance of a longitudinal pigmented band, a few millimeters long, on a nail.
• Secondarily, the pigmentation extends to the skin at the base of the nail (Hutchinson's sign).

Mucosal melanoma

Poor prognosis

Melanoma in children

Although very rare, it poses the problem of early removal of extensive congenital pigmentary nevi.

Melanoma revealed by cutaneous, lymph node or visceral metastases

In these cases, the initial melanoma was either removed without histological examination (which is inadmissible) or regressed spontaneously in its entirety.

• Early diagnosis of melanoma is crucial for effective treatment and increased survival. Many actors can be involved in the early diagnosis of melanoma: GP or specialist, nurse, chiropodist, physiotherapist. Because of their position in the care pathway, GPs play a major role in screening people at risk and liaising with dermatologists¹.
• The clinical examination is the first step in the diagnosis of melanoma. It consists of a thorough evaluation of the skin, looking for signs of melanoma such as suspicious pigmented lesions.

• In addition to this ABCDE method, there is the Ugly Duckling method, which consists of screening for a malignant mole or spot by comparing it to others in the same area.
• In the presence of a suspicious lesion, the GP can assess of the risk level, and can then refer the patient to a dermatologist to screen for the presence of a melanoma. Only a biopsy (performed by a dermatologist) will allow the diagnosis of cutaneous melanoma to be reached by histopathology.

Factors to assess the level of risk¹

• History of skin cancers (personal or family).
• History of sunburn with second-degree burns in childhood or adolescence.
• Numerous (≥ 40) or large (+ 5 mm) and irregular nevi.
• Exposure to artificial UV light.
• State of immunodepression, constitutional or acquired (immunosuppressive treatment, HIV).
• Occupational exposure to risk factors: UV, arsenic, polycyclic aromatic hydrocarbons (PAHs), ionizing radiation: people working outdoors, metal welding, iron and steel industry, medical and industrial radiology, or use of arsenical pesticides.

In the case of a patient with one or more risk factors and no suspicious lesions, the GP should encourage the patient to self-examine regularly (every 3 months) using the ABCDE method. It is important to clearly inform the patient about what should alert them:

• A melanocytic lesion that is different from his other moles already present on the body (Ugly Duckling method).
• A wound that does not heal.
• A mole that is getting bigger.