Excerpt from Lentigo Maligna Melanoma

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Background

The overall incidence of cutaneous melanoma (skin cancer) is increasing faster than that of any other neoplasm. In 2006 and 2007, approximately 60,000-62,000 new cases of invasive skin melanoma and more than 48,000 in situ melanomas were diagnosed.^{1, 2}

Lentigo maligna (LM) is a subtype of melanoma in-situ. Lentigo maligna melanoma (LMM) is one of the 4 main subtypes of invasive melanoma and represents 5-15% of cases. The other types are superficial spreading (70%), nodular (10-15%), and acral lentiginous melanoma (5%).³

Lentigo maligna melanoma is most often found in the head and neck. Approximately 10-30% of all cutaneous melanoma arise in this region.

Sir John Hutchinson first described lentigo maligna in 1890; the disease continues to be called Hutchinson melanotic freckle on occasion. The Hutchinson melanotic freckle was originally thought to be infectious because of its slow yet progressive growth. The lesion has subsequently been characterized as malignant lentigo of elderly people, junctional nevus, and melanoma in situ. Most authors currently refer to it as lentigo maligna when it is confined to the epidermis and lentigo maligna melanoma when it violates the dermis.

See also Malignant Melanoma.

Pathophysiology

Many authors consider lentigo maligna to be a preinvasive lesion induced by long-term cumulative ultraviolet injury. Conceptually, the term melanoma is used when atypical melanocytes invade the rich vascular and lymphatic networks of the dermis, thereby establishing metastatic potential.

Most malignant melanomas arise as superficial tumors confined to the epidermis, which is often known as horizontal growth. At some point, a stepwise accumulation of genetic abnormalities leads to proliferation and progression to the vertical growth phase, which leads to dermal and deeper involvement and subsequently nodal metastases.

See related CME at Predictors of Rapid Growth Identified for Melanomas.

Frequency

United States

For all types of melanoma, in the United States, the American Cancer Society projects that 62,480 (34,950 male and 27,530 female) new cases will be diagnosed in 2008. They predict that 8,420 (5,400 male and 3,020 female) deaths will occur in 2008 attributable to melanoma.^{4, 5}

The incidence of lentigo maligna is greatest in Hawaii, intermediate in the central and southern states, and lowest in the northern states.

International

The incidence of melanoma is highest in Australia, where lentigo maligna can be found at an annual rate of 1.3 cases per 100,000 population.⁶

Mortality/Morbidity

Melanoma is second only to adult leukemia in years of potential life lost in young adults. The disease is responsible for death in a disproportionately high number of young and middle-aged adults.

Lentigo maligna melanoma has mortality rate similar to that of other melanoma types if depth of the tumor is taken into account.

About 10% of melanomas are familial. A first-degree relative has an 8-12 times increased risk of melanoma. The major gene resides on chromosome arm 9p and encodes a tumor suppressor gene called CDKN2A or MTS1.⁷ The second gene that has been noted in melanoma prone families is CDK4, and germline mutations have been identified in this group.

Patients with neck and scalp melanoma have shorter survival compared to melanoma at other sites (extremities, face, trunk). In an analysis of the Surveillance, Epidemiology, and End Results (SEER) program data patients with scalp and neck have a 1.84 risk of dying compared to other sites such as extremity melanoma (HR 1.84; confidence interval, 1.62-2.10). The 5- and 10-year Kaplan Meier survival probabilities for scalp and neck melanoma were 83.1% and 76.2%, respectively, compared to melanoma of other sites 92.1% and 88.7%, respectively.

Race

Melanoma is the most frequent cancer in white women aged 25-29 years and the second most frequent (after breast cancer) in white women aged 24-30 years with fair skin.

Sex

A slight female preponderance is seen among patients with lentigo maligna.

Age

Patients with lentigo maligna tend to be older than those with superficial spreading malignant melanoma or nodular melanoma.

• Generally, patients with lentigo maligna are older than 40 years, with a mean age of 65 years.
• The peak incidence occurs in the seventh to eighth decades of life.
• Lentigo maligna and lentigo maligna melanoma are associated with higher occupational exposure and lower recreational sun exposure.

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