Malignant melanoma

Skin cancer ---> Melanoma skin cancer

Melanoma arises from malignant proliferation of melanocytes.
Epidemiology
The incidence of and mortality from melanoma are increasing. Its incidence is approximately 10 per 100 000 per year. The highest incidence occurs in white-skinned individuals in Australia and New Zealand. Melanoma is more common in women than in men.
Pathology
Ultraviolet exposure is a major etiological factor, particularly short, intense exposure resulting in sunburn during childhood. Phenotypic factors associated with melanoma include fair skin, red or blonde hair, blue eyes, inability to tan, freckles, lentigines, large numbers of benign melanocytic nevi and the presence of dysplastic nevi.
Important risk factors for malignant melanoma
Presence of precursor lesions (dysplastic melanocytic nevi)
Family history of melanoma in parents or siblings
Skin phototypes I and II with an inability to tan
Excess sun exposure, especially during childhood
Clinical features
Malignant melanoma has two patterns of growth, radial and vertical. Radial growth is horizontal within the epidermis and superficial dermal layers, as in the lentigo maligna, acral/mucosal lentiginous and superficial spreading types. During this stage of growth the tumor does not have the capacity to metastasize. Vertical growth occurs with time, and the melanoma grows downwards into the deeper dermal layers as an expansile mass, lacking cellular maturation. This correlates with the emergence of a clone of cells with metastatic potential. The nature and extent of this vertical growth phase determine the biological behavior of malignant melanoma. The different types of malignant melanoma are categorized on morphology and histological findings.
Superficial spreading
Superficial spreading is the most common variant of melanoma (70%), presenting as a macule or papule, usually greater than 0.5 cm in diameter. There is variable pigmentation (from pale brown to blue-black), an irregular edge, and surface oozing or crusting. In males it most frequently presents on the back, while in females the leg is the most common site. In the radial growth phase it is characterized by atypical melanocytes, singly and in clusters, widely scattered throughout the layers of the epidermis. Left untreated it may progress to the vertical growth phase over months to years.
Nodular melanoma
Nodular melanoma is the second most common variant (14%) and, by definition, presents in the vertical growth phase. It classically presents as a rapidly enlarging, frequently ulcerated, blue-black nodule.
Lentigo maligna
Lentigo maligna presents as an irregularly pigmented macule, slowly enlarging over many years, commonly on the cheek or temple of an elderly person. It is characterized by basally located atypical melanocytes. Development of a more rapidly growing, deeply pigmented papule or nodule indicates dermal invasion by malignant melanocytes (lentigo maligna melanoma).
Acral lentiginous melanoma
Acral lentiginous melanoma is an uncommon subtype, although it is the predominant variant in the Afro-Caribbean population. The sole of the foot is most often affected and lesions may also arise on the digits. Subungual or periungual melanoma, a variant of acral lentiginous melanoma, occurs either as a linear pigmented streak in the nail or an isolated nail dystrophy, accompanied by the pigmentation of the proximal nail fold (Hutchinson's sign).
Amelanotic melanoma
Amelanotic melanoma is a non-pigmented variant of melanoma.
Malignant melanoma on mucous membranes
Malignant melanoma on mucous membranes is very rare and may affect the vulva, urethra and anus. It has a poor prognosis, due in part to its often advanced stage at presentation.
Investigations
Skin biopsy
An excision skin biopsy must be performed to confirm the diagnosis. This will give important histological data and provide valuable staging information.
Management
The management of malignant melanoma varies according to the stage at presentation, and ranges from surgical excision to radiotherapy and chemotherapy.
Prognosis
Melanoma has a mortality rate of 25% and therefore early diagnosis and treatment is essential. Prognostic factors include thickness, level of invasion, gender and site of tumor.
Histological data from melanoma
Clarke's level
I melanoma cells confined to epidermis
II melanoma cells invade papillary dermis
III melanoma cells completely occupy papillary dermis
IV melanoma cells invade mid-reticular dermis
V melanoma cells invade subcutaneous fat

Tumor thickness in mm from granular layer of the epidermis to maximum depth (Breslow thickness)
Presence of radial or vertical growth
Tumor infiltrating lymphocytes
Mitoses per mm2
Presence or absence of tumor regression (mitosis, inflammatory infiltrate, pigmentary incontinence, fibrosis and dermal scarring, and vascular proliferation)
Microsatellites
Evidence of perineural infiltrate
Evidence of vascular and lymphatic invasion
Whether excision is complete

TNM staging system for melanoma
Stage (T) Primary tumor Lymph node (N) Distant metastases (M)
0 In situ tumors No nodes No Distant metastases (M)
IA -1mm, IIB 2.01-4 mm with ulceration No nodes No Distant metastases (M)
>4 mm, no ulceration No nodes No Distant metastases (M)
IIC >4 mm with ulceration No nodes No Distant metastases (M)
IIIA Any Breslow thickness, no ulceration Micrometastases in nodes No Distant metastases (M)
IIIB Any Breslow thickness with ulceration Micrometastases in nodes No Distant metastases (M)
Any Breslow thickness, no ulceration Up to 3 palpable nodes No Distant metastases (M)
Any Breslow thickness ± ulceration No nodes but in-transit metastases or satellites None
IIIC Any Breslow thickness with ulceration Up to 3 palpable nodes No Distant metastases (M)
Any Breslow thickness ± ulceration 4 or more palpable nodes or matted nodes or in-transit metastases with nodes No Distant metastases (M)
IV M1: skin, subcutaneous or distant lymph nodes
M2: lung
M3: all other sites or any site with raised lactate dehydrogenase