Melanoma
~Introduction
Melanoma is a malignant tumor that arises from melanocytes, the pigment-producing cells responsible for skin color. Although melanoma accounts for a smaller proportion of skin cancer cases compared to basal cell carcinoma and squamous cell carcinoma, it is the most aggressive and deadliest form of skin cancer due to its high potential for invasion and metastasis. Early detection is critical, as melanoma is highly curable in its initial stages but can become life-threatening once it spreads to lymph nodes or distant organs.
Melanoma primarily affects the skin but may also develop in mucosal surfaces and ocular tissues. The global incidence of melanoma has increased steadily over the past several decades, largely due to increased ultraviolet (UV) radiation exposure and lifestyle changes.
~Epidemiology
Melanoma occurs worldwide, with higher incidence in regions with greater sun exposure and predominantly fair-skinned populations.
More common in Caucasians
Higher incidence in men after age 50
More common in women under age 40
Rare in children but possible
Incidence continues to rise globally
Despite rising incidence, melanoma-related mortality has stabilized or declined in some countries due to improved early detection and advances in treatment.
~Melanocyte Biology and Pathogenesis
Melanocytes reside in the basal layer of the epidermis and produce melanin, which protects skin cells from UV-induced DNA damage. Melanoma develops when genetic mutations cause melanocytes to proliferate uncontrollably.
Key molecular events include:
DNA damage caused by UV radiation
Mutations in oncogenes such as BRAF, NRAS, and KIT
Inactivation of tumor suppressor genes like CDKN2A
Dysregulation of cell cycle control and apoptosis
Melanoma often progresses from benign melanocytic nevi through dysplastic nevi to invasive carcinoma.
~Risk Factors
1. Ultraviolet (UV) Exposure
Intermittent intense sun exposure and sunburns, especially during childhood, are the strongest risk factors for melanoma.
2. Fair Skin Phenotype
Light skin
Blonde or red hair
Blue or green eyes
Tendency to burn rather than tan
3. Multiple or Atypical Moles
Presence of >50 nevi
Dysplastic (atypical) nevi
4. Family History and Genetics
First-degree relative with melanoma
Genetic mutations (CDKN2A, BRAF)
5. Immunosuppression
Organ transplant recipients
HIV/AIDS patients
6. Artificial UV Sources
Tanning beds significantly increase melanoma risk
~Clinical Presentation
Melanoma typically presents as a changing pigmented skin lesion. The ABCDE rule is widely used for early recognition:
A – Asymmetry
B – Border irregularity
C – Color variation
D – Diameter >6 mm
E – Evolving lesion
Additional warning signs:
Itching or pain
Bleeding or ulceration
Rapid growth
New mole in adulthood
Melanoma can occur on sun-exposed or non–sun-exposed areas, including palms, soles, nail beds, and mucosal surfaces.
~Types of Melanoma
1. Superficial Spreading Melanoma
Most common subtype
Grows horizontally before invading deeper layers
2. Nodular Melanoma
Highly aggressive
Rapid vertical growth
Often dark blue or black nodules
3. Lentigo Maligna Melanoma
Occurs in chronically sun-exposed skin
Common in elderly patients
4. Acral Lentiginous Melanoma
Occurs on palms, soles, and under nails
More common in darker-skinned individuals
5. Amelanotic Melanoma
Lacks pigment
Often misdiagnosed, leading to delayed treatment
~Diagnosis
Clinical Examination
Full-body skin examination is essential, including nails, scalp, and mucosal surfaces.
Dermoscopy
Enhances visualization of pigment patterns and vascular structures.
Biopsy
Excisional biopsy with narrow margins is the gold standard.
Histopathological features include:
Atypical melanocytes
Pagetoid spread
High mitotic activity
Staging
Melanoma is staged using the AJCC TNM system, which incorporates:
Tumor thickness (Breslow depth)
Ulceration
Lymph node involvement
Distant metastasis
~Treatment
1. Surgical Excision
Primary treatment for localized melanoma
Margin width depends on tumor thickness
2. Sentinel Lymph Node Biopsy
Recommended for intermediate and high-risk melanomas
Helps assess regional spread
3. Immunotherapy
Revolutionized melanoma treatment:
PD-1 inhibitors (pembrolizumab, nivolumab)
CTLA-4 inhibitors (ipilimumab)
4. Targeted Therapy
Effective in tumors with BRAF mutations:
BRAF inhibitors (vemurafenib)
MEK inhibitors (trametinib)
5. Radiation Therapy
Limited role
Used for palliation or brain metastases
6. Chemotherapy
Now rarely used
Reserved for refractory disease
~Prognosis
Prognosis depends on stage at diagnosis:
Early-stage melanoma: 5-year survival >95%
Regional lymph node involvement: ~60–70%
Distant metastasis: <30%, though improving with modern therapy
Key prognostic factors:
Breslow thickness
Ulceration
Mitotic rate
Lymph node involvement
~Complications
Local recurrence
Lymphatic and hematogenous metastasis
Brain, lung, liver, and bone involvement
Treatment-related toxicities
Psychological distress
~Prevention
Sun Safety Measures
Broad-spectrum sunscreen (SPF ≥30)
Protective clothing
Avoid peak sun hours
Avoid tanning beds
Early Detection
Monthly self-skin examinations
Regular dermatological check-ups
Public Awareness
Education campaigns significantly reduce melanoma mortality through early diagnosis.
~Living With Melanoma
Survivors require long-term surveillance due to the risk of recurrence and secondary melanomas. Emotional support, lifestyle modifications, and adherence to follow-up schedules are essential for quality of life.
~Conclusion
Melanoma is a potentially lethal but largely preventable and curable cancer when detected early. Advances in molecular biology and immunotherapy have transformed the treatment landscape, offering renewed hope even for advanced-stage disease. Continued public awareness, preventive strategies, and research are essential to further reduce melanoma-related mortality worldwide.
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