Melanoma is a malignant tumor that originates from melanocytes located at the dermoepidermal junction. It is most commonly found on the skin but can also appear in the eye (such as the conjunctiva and iris), the meninges, and the mucous membranes. Melanoma lesions are typically heavily pigmented, although amelanotic tumors (i.e., lacking dark coloration) also exist. It is considered the most aggressive form of skin cancer because it can metastasize and is potentially life-threatening.
Melanoma accounts for approximately 4–5% of all cancers. It primarily affects individuals of white ethnicity and is rare among Black and Asian populations. The incidence of the disease is significantly higher in Northern European countries, particularly in the Scandinavian region. In Greece, the rates are lower compared to other European countries, with approximately 12–13 new cases per 100,000 inhabitants annually. The average age at diagnosis is estimated at around 55 years, and both sexes appear to be affected equally.
Key risk factors for the development of melanoma include:
- Personal history of melanoma
- Family history of melanoma
- Inherited mutations in the CDKN2A and MC1R genes
- Xeroderma pigmentosum
- Atypical mole syndrome
- Immunosuppression
- Exposure to ultraviolet radiation – sunburns and a history of tanning bed use, especially at a young age
- Phenotypic characteristics (Fitzpatrick skin phototypes I and II)
- A high number of melanocytic nevi (more than 100)
- Presence of multiple dysplastic nevi
- Large congenital nevi (greater than 20 cm in adults).
The molecular classification refers to alterations in the following major signaling pathways:
- The RAS–RAF–MEK–ERK pathway
- The p16^INK4A–CDK4–RB pathway
- The ARF–p53 pathway
- And, to a lesser extent, the PTEN–PI3K pathway.
Anything that appears on our body from the list below should prompt a visit to the dermatologist for clinical and dermoscopic evaluation:
- A new mole appearing after the onset of puberty, especially in adults or the elderly, that shows changes in shape, color, or size
- An existing mole that changes in shape, color, or size
- Any mole with more than three colors or loss of symmetry
- A mole that bleeds or itches without prior trauma
- Any new persistent lesion—pigmented or vascular—without a clear diagnosis
- A new longitudinal pigmented streak on a nail, especially if it involves the nail matrix
- An enlarging subungual lesion
Melanoma is classified into the following most common clinical types:
- Superficial Spreading Melanoma (approximately 70% of cases): Initially characterized by horizontal (radial) growth, later progressing to vertical growth with the formation of a nodule. It typically begins as a heavily pigmented macule that spreads superficially, showing shades of brown and black with areas of red, gray, and white. As it invades deeper, a nodule may develop.
- Nodular Melanoma (10–15%): Characterized by the formation of a dark papule (a small, solid skin elevation ranging from a pinhead to 1 cm in diameter) that progresses into a nodule which may ulcerate.
- Acral Lentiginous Melanoma (less than 5%): Occurs on the soles, palms, and beneath the nails. As it thickens, the nail may stop growing normally. Clinically, it resembles lentigo maligna and superficial spreading melanoma.
- Lentigo Maligna Melanoma (5–8%): Seen mainly in older individuals in areas of chronic sun exposure (face, neck). It arises from a lentigo maligna lesion, part of which gradually thickens and may become nodular, indicating invasion through the basement membrane. It typically exhibits multiple colors within the lesion.
- Amelanotic Melanoma (about 0.5%): A rare and often nodular melanoma subtype that lacks pigmentation, making it more difficult to recognize.
- Desmoplastic Melanoma (less than 0.5%): Rare, observed in elderly individuals in chronically sun-exposed areas. It appears as a nodule or plaque and is a dermal tumor composed of spindle-shaped cells without melanin. It often extends into the subcutaneous fat and infiltrates nearby nerves.
A. General dermoscopic structure
Polymorphous pattern, characterized by:
- Asymmetry
- Four different colors
- Three types of dermoscopic structures: reticular, globular, and homogeneous
B. Specific dermoscopic findings
Melanoma-specific criteria include:
- Atypical pigment network
- Irregular dots and globules
- Irregular streaks, blue-white structures, irregular blotches
- Polymorphous vessels
- Areas of ulceration, regression structures, crusts
There are also specialized dermoscopic criteria for:
- Facial melanoma
- Acral (palmar and plantar) melanoma
- Subungual melanoma
- Amelanotic melanoma
- Pediatric melanoma
It can be divided into preadolescent and adolescent categories. The preadolescent type is further classified into:
- Congenital (present in utero or at birth)
- Neonatal (within the first year of life)
- Childhood melanoma (up to puberty)
Its annual incidence is estimated at 0.8 cases per million children. Recent studies show an increasing frequency, particularly in adolescent melanoma.
Due to the rarity of pediatric melanoma, clear clinical and dermoscopic criteria have not yet been established. Lesions are more commonly non-pigmented and nodular, often resembling pyogenic granulomas or non-pigmented Spitz nevi.
In clinical practice, melanoma is suspected in:
- Congenital pigmented nevi larger than 4 cm in diameter
- Spitz nevi appearing after the age of 12.
Dermatologists are confronted daily with a large number and variety of pigmented skin lesions. It is estimated that the ratio of melanomas to benign skin lesions is approximately 1 in 200,000. The dermatologist’s responsibility is to identify the malignant lesion among thousands of nevi—early and at a curable stage.
Thus, the dermatologist’s role is fundamental and includes:
- Early detection: through clinical examination, dermoscopic analysis, and annual preventive dermoscopic screening (total body scan)
- Initial excision: confirmation of diagnosis and disease staging
- Postoperative regular follow-up
The primary method of excision is surgical removal, most commonly through elliptical excision.
Surgical excision is the gold standard approach, performed with 2–3 mm of healthy peripheral margins and including subcutaneous tissue, when feasible depending on the lesion’s location.
Although this is a common myth, it is not scientifically accurate. Removing a mole that does not show any signs of malignancy does not cause skin cancer.
In cases where cancer developed after mole removal, it means that the mole was already malignant and had not been completely excised from the beginning. Unfortunately, this misconception has led many patients to delay seeking medical attention—often resulting in diagnosis at a more advanced stage of the disease.
If you notice any changes in an existing lesion or the appearance of a new one on your skin, you should consult your dermatologist immediately.
As a general rule, according to the Hellenic Society of Dermatology and Venereology, melanoma is characterized by a set of clinical features known as the ABCDE rule, which stands for:
- A – Asymmetry: one half of the lesion does not match the other
- B – Border: irregular, notched, or blurred edges
- C – Colour: uneven color or recent change in color; presence of multiple shades
- D – Diameter: greater than 6 mm
- E – Evolving: a lesion that is changing in size, shape, color, or behavior (such as bleeding or itching)
Any clinical change in a skin lesion that falls under one or more of these categories should be promptly evaluated by your dermatologist. Early diagnosis is your strongest ally in treatment!