Skin Cancer--Melanoma

Updated 3/2017-- photos and all links (except to my own posts) removed as many no longer active.

Melanoma is a malignancy of pigment-producing cells (melanocytes) located predominantly in the skin, but also found in the eyes, ears, GI tract, leptomeninges, and oral and genital mucous membranes. Melanoma accounts for only 4% of all skin cancers; however, is responsible for more than 77% of skin cancer deaths worldwide. Early detection of thin cutaneous melanoma is the best means of reducing mortality. In the United States, one person each hour dies from metastatic melanoma.

The development of melanoma appears to be related to multiple risk factors, including fair complexion, excessive childhood sun exposure and blistering childhood sunburns, an increased number of common and dysplastic moles, a family history of melanoma, the presence of a changing mole or evolving lesion on the skin, and, importantly, older age. Melanoma occurs most commonly on the trunk in white males and the lower legs and back in white females. In African American, Hispanic, and Asian person, the most common site is the plantar foot (sole), followed by subungual, palmar, or mucosal sites.  

A new or changing mole or blemish is the most common warning sign for melanoma. ABCDE criteria (Friedman, 1985, Abassi 2004) for a changing mole is very useful. They have the greatest diagnostic accuracy when used in combination. More recent use of the "ugly duckling" warning sign, wherein skin examination is focused on recognition of a pigmented or clinically amelanotic lesion that simply looks different from the rest, may assist with detection of lesions that lack the classic ABCDE criteria (Grob, 1998; Gachon, 2005).

Asymmetry: Half the lesion does not match the other half.
Border irregularity: The edges are ragged, notched, or blurred.
Color variegation: Pigmentation is not uniform and may display shades of tan, brown, or black. White, reddish, or blue discoloration is of particular concern.
Diameter: A diameter greater than 6 mm (the size of a pencil eraser) is characteristic, although some may have smaller diameters. Any growth in a nevus warrants an evaluation.
Evolving: Changes in the lesion over time are characteristic. This factor is critical for nodular or amelanotic (no color or pigment) melanoma, which may not exhibit the classic criteria above.

Four major subtypes of primary cutaneous melanoma have been identified:
Superficial spreading melanoma is most common on the trunk in men and women, and on the legs in women. It is most commonly seen in individuals aged 30-50 years. It manifests as a flat or slightly elevated brown lesion with variegate pigmentation (ie black, blud, pink, or white discoloration). It is generally greater than 6 mm in diameter, irregular, and with asymmetric borders.

Nodular melanoma occurs in 15-30% of patients. It is most commonly seen on the legs and trunk. Rapid growth may occur over weeks to months. This subtype is responsible for the most thick melanomas. It manifests as a dark brown-to-black papule or dome-shaped nodule, which may ulcerate and bleed with minor trauma. It may also be amelanotic. It tends to lack the typical ABCDE melanoma warning signs and may elude early detection.

Lentigo maligna melanoma is typically located on the head, neck, and arms (chronically sun-damaged skin) of fair-skinned older individuals (average age 65 yrs). It grows slowly over 5-20 years. The in-situ precursor lesion is usually large (1-3 cm or more in diameter), present for a minimum of 10-15 years, and demonstrates macular pigmentation ranging from dark brown to black, although hypopigmented (white) areas are common within lentigo maligna. Dermal invasion (progression to lentigo maligna melanoma) is characterized by the development of raised blue-black nodules within the in-situ lesion.

Acral lentiginous melanoma is the least common subtype (2-8% of melanoma cases in white persons). It accounts for 29-72% of melanoma cases in dark-skinned individuals (African American, Asian, and Hispanic persons) and because of delays in diagnosis, may be associated with a worse prognosis. Acral lentiginous melanoma occurs on the palms, on the soles, and beneath the nail plate (subungual variant). Subungual melanoma may manifest as diffuse nail discoloration or a longitudinal pigmented band within the nail plate. It must be differentiated from a benign junctional melanocytic nevus of the nail bed which has a similar appearance. Pigment spread to the proximal or lateral nail folds is termed the Hutchinson sign and is a hallmark for acral lentiginous melanoma.

Rare melanoma variants (less than 5%) include desmoplastic/neurotropic melanoma, mucosal (lentiginous) melanoma, malignant blue nevus, melanoma arising in a giant congenital nevus, and melanoma of soft parts (clear cell sarcoma).

Amelanotic melanoma (less than 5% of melanomas) is non-pigmented. It appears, clinically, pink or flesh-colored, often mimicking basal cell or squamous cell carcinoma or a ruptured hair follicle. It occurs most commonly in the setting of the nodular melanoma subtype or melanoma metastasis to the skin.

Primary risk factor for or clinical warning signs of melanoma include:
Changing mole (most important clinical warning sign)
Clinical atypical/dysplastic nevi (particulary more than 5-10)
Large number of common nevi (more than 100)
Large (giant) congenital nevi (more than 20 cm in diameter in an adult)
Personal history of melanoma or First-degree relative with melanoma
Sun sensitivity/history of excessive sun exposure
Prior nonmelanoma skin cancer (BCC or SCC)
Male
Age older than 50 years
Presence of xeroderma pigmentosum or familial atypical mole melanoma syndrome (Both of these genodermatoses confer a 500-1000 fold greater relative risk of developing melanoma)
A fair-skin phenotype (blue/green eyes, blond or red hair, light complexion, sun sensitivity) and the occurrence of blistering sunburn(s) in childhood and adolescence are universal risk factors for melanoma.

Surgery is the primary mode of therapy for localized cutaneous melanoma. The narrowest efficacious margins for cutaneous melanoma have yet to be determined. Surgical margins of 5 mm are currently recommended for melanoma-in-situ, and margins of 1 cm are recommended for melanomas up to 1 mm in depth (low-risk primaries). In some settings, tissue sparing may be critical and Mohs margin-controlled excision may be appropriate. Prophylactic lymph node dissection for primary cutaneous melanoma of intermediate thickness initially was believed to confer a survival advantage on patients with tumors of 1-4 mm in depth. Lymphatic mapping and sentinel node biopsy have effectively solved the dilemma of whether to perform regional lymphadenectomy (in the absence of clinically palpable nodes) in patients with thicker melanomas (>1 mm in depth).

Surgical oncologist will usually do the surgical excision, lymph node excision, etc. Medical oncologist are needed to discuss adjuvant therapy with IFN alfa, experimental melanoma vaccines, or other clinical trials. They may also discuss (and initiate) treatment of metastatic melanoma (stage IV) with chemotherapy, high-dose IL-2, biochemotherapy, or clinical trials, as indicated. Radiation oncologist may be needed for adjuvant treatment of resected regional nodal metastasis with extracapsular extension or for palliative treatment fo distant metastatic disease (particularly bone metastasis or brain involvement).