Melanoma: Epidemiology And Diagnosis

John S. Walsh, M.D.
John S. Walsh, M.D. is with the Department of Dermatology at Mayo Clinic Jacksonville

Introduction

Melanoma is an increasingly common, potentially fatal form of skin cancer arising from the malignant transformation of melanocytes. Embryologically, melanocytes are derived from neural crest cells which migrate to the basal layer of the epidermis during development. Melanoma most commonly arises from melanocytes at this site. Far less frequently, melanoma may arise from altered melanocytes, or nevus cells, present within the dermis or from melanocytes present in other organs.

Incidence, Mortality And Survival Rates

The incidence of melanoma is increasing at a rate greater than any other form of cancer in the United States. Currently, melanoma is the seventh most common type of cancer and the most common malignancy in women ages 25-29.1 In 1935, the lifetime risk of developing melanoma in the United States was 1 in 1,500. In 1960, it was 1 in 600, and if current trends continue, the lifetime risk in the year 2000 will be 1 in 75.1 The reason for this dramatic rise in incidence is unclear, but lifestyle changes in which intense, intermittent, recreational sun exposure have become more common have been speculated to play a role. Melanoma mortality rates have also risen over the last several decades, albeit to a lesser extent. According to the Surveillance, Epidemiology, and End Results program (SEER), melanoma mortality rates have increased 32.7% from 1973 to 1995.2 Men and older individuals consistently have higher mortality rates than women and younger individuals, respectively. More recent data suggests that mortality rates may have begun to stabilize or even decline, particularly in younger populations.3 For the period 1990-1994, the state of Florida was second in the nation in the number of melanoma deaths at 2,284.3 Despite a rise in incidence and mortality rates during the past several decades, survival rates have increased. In 1940, the 5-year survival rate for melanoma was 40%. By 1975 the 5-year rate was 67%,4 and data from the SEER program indicates that this has increased to 88.2% for the period 1989 to 1994. Despite advances in chemotherapy and immunotherapy, increased survival is more likely due to heightened awareness among the lay and better screening by medical professionals, leading to earlier detection and curative surgical therapy.

Risk Factors

Numerous studies have identified risk factors for the development of melanoma. The major factors include excessive sun exposure, number of melanocytic nevi, cutaneous phenotype, and family and personal history of melanoma. Solar ultraviolet radiation appears to be the principle environmental factor responsible for melanoma in lightly pigmented individuals. This has been supported by studies which have demonstrated an inverse relationship between latitude and melanoma incidence.5 Moreover, immigrants to areas with higher levels of solar radiation have an increased rate of melanoma compared with similar individuals in their homeland.6,7 Melanomas can be induced by exposure to ultraviolet radiation in certain animals8,9 and recently, melanoma has been induced in human skin grafted onto mice with a single exposure to a chemical carcinogen followed by ultraviolet irradiation.10 Unlike the more common skin cancers that are associated with high cumulative doses of ultraviolet light, most melanomas appear to be associated with intense, intermittent exposure, particularly during childhood and adolescence.11,12,13,14

Epidemiologic studies have repeatedly shown an increased risk of melanoma with greater numbers of melanocytic nevi. Individuals with clinically atypical or "dysplastic" nevi have even a higher risk, particularly in the setting of a positive family history of melanoma. In one study, the risk of melanoma was double in individuals with 50 to 99 small nevi compared with those with less.15 In addition, the presence of a solitary dysplastic nevus doubled the risk of melanoma, while having 10 or more dysplastic nevi was associated with a 12-fold elevation in risk. Melanoma occurs more frequently in lightly pigmented individuals. Blue or green eyes, blond, fair, or red hair, tendency to freckle, and inability to tan are all documented risk factors. About 10% of all melanoma patients have a positive family history. Genetic linkage studies have identified a familial melanoma gene, CDKN2, on chromosome 9p21 which encodes the tumor suppressor protein p16.16 Mutations in this gene have been documented in up to 50 percent of familial melanoma patients that link to chromosome 9p. Of patients with nonfamilial melanoma, 1.5% to 8.2% will develop a secondary primary melanoma.

Clinical Presentation, Diagnosis, And Prognosis

In the United States, the ABCD checklist for detecting melanoma is often used. The criteria making up the ABCD checklist are all physical examination features. "A" refers to asymmetry, "B" to border irregularity, "C" to color variegation, and "D" to diameter greater than 6 mm. Lesions that have these features may potentially represent melanoma. It is important to realize that not all melanomas manifest these ABCD warning signs. Other physical examination findings, such as inflammation and crusting should be considered, and historical features such as a new, pruritic, bleeding, or changing nevus should also alert one to the possibility of melanoma.

The major subtypes of melanoma include superficial spreading, nodular, lentigo maligna melanoma, and acral lentiginous melanoma. Superficial spreading melanoma represents 70% of all melanomas (Figure 1). It can occur anywhere on the skin, but most frequently involves the trunk in men and lower extremities in women. The median age at diagnosis is 44. They generally arise from preexisting nevi and demonstrate asymmetry, pigment variegation, and irregular borders. Nodular melanomas are the second most common form of melanoma. As their name implies, they are usually nodular or polypoid. They can be black, brown, or lack pigment entirely (Figures 2 and 3). They may be evenly pigmented and have regular borders and be easily mistaken for a basal cell carcinoma, seborrheic keratosis, or a benign nevus. Lentigo maligna melanoma occurs on sun-exposed skin, especially the face of elderly patients (Figure 4). Unlike superficial spreading and nodular melanomas, this subtype is associated with high cumulative doses of ultraviolet light. They tend to grow slowly and often are confined to the epidermis (lentigo maligna) for years before dermal invasion occurs (lentigo maligna melanoma). They are frequently asymmetric, have pigment variegation and irregular borders. Acral lentiginous melanomas are uncommon in Caucasians but form a high proportion of malignant melanomas in non-whites (Figure 5). They usually involve the palms, soles, or subungual region. Many lesions present as a pigmented band of the nail bed. Pigmentation of the proximal nail fold is strongly suggestive of subungual melanoma (Hutchinson's sign).

walshfig.jpg (11031 bytes)Figure 1. Superficial spreading melanoma on the leg of a 33-year old woman. walshfi2.jpg (5762 bytes)
Figure 2. Pigmented
nodular melanoma. 		walshfi3.jpg (5903 bytes)

 

 

Figure 3. Flesh colored (amelanotic) nodular melanoma mimicking a basal cell carcinoma on the nose of a 77-year old woman.
walshfi0.jpg (7960 bytes)

 

 

 

Figure 4. (Right) Acral lentiginous melanoma. Note pigmentation of the proximal nail fold.

walshfi1.jpg (11099 bytes)

 

 

 

Figure 5. (Left) Lentigo maligna (melanoma in-situ) occurring on actinically damaged skin of the cheek.

Lesions that are suspicious for melanoma should be removed by excisional biopsy. Shave biopsies are contraindicated in any case in which the diagnosis of melanoma is possible. An accurate determination of the tumor depth and level of invasion is important for tumor staging. Lesions are usually removed by a standard elliptical excision with a 1 mm margin. Punch biopsy can be used if the lesion can be easily surrounded. All excisions should go down to subcutaneous fat. Occasionally, suspicious lesions are too large for complete excision. In those cases, an incisional biopsy of the thickest area of the lesion is acceptable, but should still reach the level of subcutaneous fat.

The prognosis of melanoma is related to tumor thickness. Depth for depth, all melanomas have the same metastatic potential, regardless of subtype. Melanoma is curable if detected early and appropriately surgically excised. Melanoma that is confined to the epidermis (in-situ) is greater than 99% curable, and patients with thin lesions (< 0.75 mm) have a 5-year survival rate of greater than 98%. This is in contrast to patients with thicker lesions (> 4 mm) who have 5-year survival rate of less than 50%. There have been studies, however, suggesting distant late metastases even in patients with initial thin tumors.17,18

Although there have been considerable advances and breakthroughs in the treatment of melanoma, our therapy for metastatic disease is limited. Until the time comes when melanoma is curable at all stages, our efforts should be centered around risk reduction by limiting ultraviolet light exposure and early detection when surgical therapy is most effective.

REFERENCES

  1. Rigel DS, Friedman RJ, Kopf AW. The incidence of malignant melanoma in the United States: Issues as we approach the 21st century. J Am Acad Dermatol. 1996;34:839-47.
  2. Cosary CL, et al. SEER Cancer Statistics Review, 1973-1992: National Cancer Institute, NRH Pub No. 96-2789, Bethesda, Maryland, 1995.
  3. Hall HI, Miller DR, Rogers JD, Bewerse B. Update on the incidence and mortality from melanoma in the United States. J Am Acad Dermatol. 1999;40:35-42.
  4. Cutler SJ, Meyers MH, Green SE. Trends in survival rates in patients with cancer. N Engl J Med. 1975;293:122-4.
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  6. Holman CD et al. Epidemiology of pre-invasive and invasive malignant melanoma in Western Australia. Int J Cancer. 1980;25:317-23.
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  8. Kusewitt DF, Applegate LA, Ley RD. Ultraviolet radiation-induced skin tumors in a South American opossum (Monodelphis domestical). Vet Pathol. 1991;28:55-56.
  9. Setlow RB, Woodhead AD, Grist E. Animal model for ultraviolet radiation-induced melanoma: platyfish-swordtail hybrid. Proc Natl Acad Sci USA. 1989;86:8922-6.
  10. Atillasoy ES, et al. UVB induces atypical melanocytic lesions and melanoma in human skin. Am J of Path. 1998;152(5):1179-86.
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  12. Holman CDJ, Armstrong BK, Heenan PJ. Relationship of cutaneous malignant melanoma to individual sunlight-exposure habits. J Natl Cancer Inst. 1986;76:403-14.
  13. Nelemans PJ et al. Effect of intermittent exposure to sunlight on melanoma risk among indoor workers and sun-sensitive individuals. Environ Health Perspect. 1993;101:252-5.
  14. Holley EA, Cress RD, Aston DA, Ahn DK, Kristiansen JJ. Cutaneous melanoma in women. Exposure to sunlight, ability to tan and other risk factors related to ultraviolet light. Am J Epidemiol. 1995;141:923-33.
  15. Tucker MA, et al. Clinically recognized dysplastic nevi: a central risk factor for cutaneous melanoma. JAMA. 1997;277:1439-44.
  16. Monzon J, et al. CDKN2A mutations in multiple primary melanomas. N Engl J Med. 1998;338:879-87.
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October, 1999/ Jacksonville Medicine

 

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