Melanoma
Melanoma is the most aggressive form of skin cancer and carries the highest death rate. It arises when melanocytes, the pigment-producing cells in the basal layer of the epidermis, undergo malignant genetic change. Although melanoma makes up only about 1% of all skin cancers, it accounts for most skin cancer deaths worldwide because it invades local tissue aggressively and can spread early to regional lymph nodes, lungs, liver, bone and brain.
At Haute-Derma, our melanoma care follows international evidence-based guidelines (NCCN/BAD): full-body digital mole mapping (total body photography), high-resolution dermoscopy, proper excisional biopsy for histology, curative surgery with clear (R0) margins, sentinel lymph node biopsy (SLNB), and coordinated access to modern immunotherapy and targeted therapy.
Clinical and Pathological Features
Causes and Genetic Mutations
- UV radiation: Ultraviolet exposure, especially severe sunburns in childhood and adolescence, causes irreversible DNA damage in melanocytes.
- Oncogenic signaling pathways:
- BRAF mutations: Found in about 50% of cutaneous melanomas (mostly BRAF V600E or V600K), switching the MAPK/ERK pathway permanently on and driving unchecked cell growth.
- NRAS mutations: About 15–20% of cases.
- KIT mutations: More common in special subtypes such as mucosal melanoma and acral lentiginous melanoma.
Main Clinical Subtypes
- Superficial spreading melanoma (SSM): The most common type (~70%). It grows sideways within the epidermis (radial growth phase) before invading the dermis.
- Nodular melanoma (NM): The most aggressive type (~15%). It skips the radial phase and grows straight downward (vertical growth phase), forming a raised, dome-shaped purple-black or non-pigmented (amelanotic) bump.
- Lentigo maligna melanoma (LMM): Develops on chronically sun-damaged skin in older adults (face, neck).
- Acral lentiginous melanoma (ALM): The characteristic type in Asian people. It appears on the palms, soles, between the toes or under a nail (with a positive Hutchinson sign) and is not related to UV exposure.
Histopathology and Breslow Thickness
- Microscopic appearance: Atypical melanocytes with large nuclei, prominent nucleoli and abnormal mitoses, arranged chaotically, climbing into the upper epidermis (pagetoid spread) and breaking through the basement membrane into the dermis.
- Breslow thickness: The distance in millimeters from the granular layer of the epidermis (or the base of an ulcer) to the deepest tumor cell in the dermis or subcutis. It is the single most important independent prognostic factor and determines stage and surgical management.
- Clark level: Grades depth of invasion by anatomic skin layer (levels I to V).
Differential Diagnosis and Immunohistochemistry (IHC)
| Condition | Distinguishing Histology and Immunohistochemistry (IHC) |
|---|---|
| Melanoma | Atypical cells, loss of maturation, mitoses (+), pagetoid spread (+). S100 (+); SOX10 (+); Melan-A (+); HMB-45 (+) in deep dermis; Ki-67 (> 10–30%). |
| Atypical (dysplastic) nevus | Junctional proliferation, no widespread pagetoid spread, maturation preserved. Diffuse p16 (+); Ki-67 (< 2%); HMB-45 (−) in deep dermis. |
| Pigmented cutaneous squamous cell carcinoma (cSCC) | Atypical keratinocyte proliferation with intercellular bridges. p63/p40 (+); CK5/6 (+); S100 (−); SOX10 (−). |
| Merkel cell carcinoma (MCC) | Small round blue cell tumor. Dot-like CK20 (+); synaptophysin (+); S100 (−); SOX10 (−). |
Our Approach to Melanoma Care
At Haute-Derma, melanoma management follows a strict protocol built on the highest standards of medical safety:
- No laser or electrocautery on suspicious lesions: Destroying the lesion would lose the tissue needed for pathology and could stimulate tumor spread.
- Standard excisional biopsy: We always remove the whole lesion with a 1–3 mm margin so Breslow thickness can be measured accurately before planning definitive surgery.
- Sentinel lymph node assessment (SLNB) based on Breslow thickness: SLNB is recommended for melanomas 0.8 mm or thicker (or under 0.8 mm with ulceration or a mitotic rate above 1/mm²).
- Multidisciplinary team (MDT) care: Wide local excision, gene mutation testing (BRAF, NRAS, KIT) and adjuvant immunotherapy or targeted therapy where indicated.
How We Diagnose Melanoma at Haute-Derma
To confirm melanoma at the earliest possible stage (in situ / T1a), Haute-Derma uses a four-step process:
- ABCDE rule and the "ugly duckling" sign: We look for a pigmented lesion that stands out and looks clearly different from all of the patient's other moles.
- High-resolution dermoscopy: Detects the telltale features of melanoma: an atypical pigment network, a blue-white veil, radial streaks or pseudopods, asymmetrically distributed dots and abnormal vessel patterns.
- Complete excisional biopsy: The entire lesion is removed down to the subcutaneous fat and sent for pathology to report Breslow thickness, ulceration and mitotic rate.
- Genetic profiling and full staging: Gene sequencing for BRAF V600 mutations and whole-body PET/CT for stage IIB and above to look for distant spread.
How Melanoma Is Treated at Haute-Derma
Treatment is planned according to the stage of disease and Breslow thickness:
- Wide local excision (WLE):
- Performed once the excisional biopsy results are available. Surgical margins are set strictly by Breslow thickness:
- Melanoma in situ: 0.5–1.0 cm margin.
- Breslow ≤ 1.0 mm: 1.0 cm margin.
- Breslow 1.01–2.0 mm: 1.0–2.0 cm margin.
- Breslow > 2.0 mm: 2.0 cm margin.
- Performed once the excisional biopsy results are available. Surgical margins are set strictly by Breslow thickness:
- Lymph node management and reconstruction:
- Sentinel lymph node biopsy (SLNB) is done at the same time as WLE. If the SLNB is positive, the patient is evaluated for regional lymph node dissection along with systemic therapy.
- Skin flaps or cosmetic skin grafts are used to close the defect after wide excision.
- Advanced adjuvant and systemic therapy:
- Targeted therapy: A BRAF inhibitor (dabrafenib, vemurafenib) combined with a MEK inhibitor (trametinib, cobimetinib) for patients with a BRAF V600 mutation.
- Immune checkpoint inhibitors: Anti-PD-1 antibodies (pembrolizumab, nivolumab), alone or with the anti-CTLA-4 antibody ipilimumab, substantially improve survival in advanced or metastatic melanoma.
