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Melanoma


What is it ?

Melanoma, most commonly known as skin cancer, is a type of cancer that attacks melanocytes, skin cells that are found in the skin, mucous membranes, conjunctival membranes, and nervous system tissues. For simplicity, we will refer to cutaneous (skin-specific) melanoma as melanoma. There were 130,000 new cases of melanoma globally in 2020. Exposure to ultraviolet radiation, the main risk factor for cutaneous melanoma, particularly for lighter skin types, is most prevalent in these geographic latitudes. The other risk factors are mainly genetic.

Patient Testimonial

 

Thierry, who has melanoma, explains how he discovered his cancer and describes his journey.

Clinical presentation

Cutaneous melanoma usually appears as a pigmented lesion, either a new growth or a pre-existing birthmark or mole (nevus) that gradually changes.

The warning signs for Melanoma follow the ABCDE rule: Asymmetry: Most skin cancers are asymmetrical.

Border: Melanoma borders are usually uneven with ragged edges. Normal moles are typically smooth and even.

Color: Multiple colors could be the sign of a melanoma. Diameter: Larger lesions (bigger that the size of a pencil eraser) should be noted and examined. Evolving: Changes in size, shape or color is a warning sign, as is itching or bleeding.

Note that these criteria remain reductive and it should be remembered that any modified, newly appearing, persistent, or hemorrhagic skin lesion requires medical attention Melanoma can also present as a nonspecific pink papule, especially with so-called achromic melanomas. The dermatologist will perform a clinical examination of the skin and the lesion itself. A dermatoscopic examination (a tool with magnifying lens and polarized light) is an integral part of the clinical examination. Based on a certain number of validated criteria, the exam may result in surgical excision of the entire lesion. A pathological examination of the removed tissue then enables a more certain diagnosis. A tissue biopsy is not recommended because of the limited histological analysis of the lesion, although it is an option in certain cases (e.g., large lesions.)

Screen for suspicious lesions

Self-monitoring is a key element of effective skin cancer prevention. Should a new skin lesion appear, or an existing skin lesion change in any way, consult a doctor.

Analysis of genotyping

Analysis of genotyping and BRAF mutation is an essential step in determining the appropriate therapeutic strategy. in any therapeutic strategy.

Targeted therapies and immunotherapy

Targeted therapies (BRAF inhibitor + MEK inhibitor) and immunotherapies (mainly immune checkpoint inhibitors) have revolutionized melanoma management. Classic chemotherapy is no longer amongst the first set of recommended treatments.

Treatment evolution

Metastatic melanoma is no longer seen as a short-term fatal disease, but as a potentially chronic disease that can be kept in remission. There is still progress to be made, particularly in managing early and more advanced stages of the disease. For this reason, one should consider inclusion in clinical research trials.

Different subtypes and tumor growth

There are different histological subtypes of melanoma: Superficial spreading melanoma,
(SSM; the most common form and found on skin intermittently exposed to the sun),
nodular melanoma, Acral lentiginous melanoma, and Dubreuilh melanoma
(found on skin chronically exposed to the sun).

These different histological subtypes do not present the same evolutionary characteristics nor do they have the same mutational molecular profile.
For example, while nearly 50% of SSM melanomas exhibit a BRAF activating mutation on the MAPK kinase pathway, the same is found in less than 15% of Dubreuilh or Acral lentiginous melanoma melanomas.

 

The primary diagnostic factors to consider are:

Tumor thickness 
(Histological sections are measured in mm and assigned a value according to the Breslow index)

Whether or not
the primary tumor is ulcerated

The status of the sentinel node aimed at detecting the presence or absence of micrometastasis (small groups of spreading cancer cells) in the lymph node drainage area. 
The sentinel node biopsy is done on a case-by-case basis, depending on the Breslow index and/or the ulcerative nature of the primary tumor. 
depending on the Breslow index and/or the ulcerative nature of the primary tumor.

If a sentinel node biopsy is recommended or the tumor has a Breslow index greater than or equal to 1, a complete imaging workup including a cerebral and Thoraco-Abdominal scan should be performed.

A brain MRI and PET scan may also be recommended.  

Mutational analysis (exploration for BRAF mutations in particular) is not systematically performed for all melanomas and will be recommended on a case-by-case basis.

Treatments

The different therapeutic strategies are determined based on stage of the disease.
(The specific criteria are according to the AJCC 8th edition classification.)

For stage I-II melanoma

the treatment is surgical with surgical revision for safety margins: 1 cm if Breslow melanoma thickness measures 1 mm. 

2 cm for melanoma thickness > 1 mm.
The sentinel lymph node biopsy not considered to be a treatment; it is a prognostic tool to assess possible risk of recurrence determine the necessity of additional medical treatment.

For stage III or stage IV melanoma

(after surgical management), additional treatment will be proposed

according to BRAF mutation status. Targeted therapies (a combination of BRAF inhibitor + MEK inhibitor) and anti-PD1 antibody immunotherapies are recommended for melanoma tumors with a high risk of recurrence.

In these instances, treatment usually lasts one year

For stage IV melanoma

Treatment is based on BRAF mutation status. The different possibilities of first-line metastatic treatment including targeted therapies, immunotherapy as a monotherapy or in combination (antiCTLA4 + anti PD1 antibodies), or radiation therapy. Inclusion in a clinical research trial will be recommended by a multidisciplinary team depending on:

  • BRAF mutation status
  • the patient’s comorbidities
  • the presence or absence of brain tumors
  • speed of tumor progression, size of the tumor mass, the presence or absence of other potentially threatening symptoms

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