eMedicine Specialties > Oncology > Carcinomas of the Skin

Malignant Melanoma

Author: Wendy Brick, MD, Consulting Staff, Department of Internal Medicine, Division of Hematology and Oncology, Mecklenburg Medical Group
Coauthor(s): Russell Burgess, MD, Department of Internal Medicine, Division of Hematology/Oncology, East Carolina Internal Medicine
Contributor Information and Disclosures

Updated: Jun 28, 2006

Introduction

Background

Malignant melanoma is a neoplasm of melanocytes or of the cells that develop from melanocytes. Once considered an uncommon disease, the annual incidence of melanoma has increased dramatically over the last few decades.

Pathophysiology

Melanomas originate from melanocytes, which arise from the neural crest and migrate to the epidermis, uvea, meninges, and ectodermal mucosa. The melanocytes, which reside in the skin and produce a protective melanin, are contained within the basal layer of the epidermis, at the junction of the dermis and epidermis.

Melanomas may develop in or near a previously existing precursor lesion or in healthy-appearing skin. A malignant melanoma developing in healthy skin is said to arise de novo, without evidence of a precursor lesion. Many of these melanomas are induced by solar irradiation. The greatest risk of sun exposure–induced melanoma is associated with acute, intense, and intermittent blistering sunburns. This risk is different than that of squamous and basal cell skin cancers, which are associated with prolonged, long-term sun exposure.

Melanoma also may occur in unexposed areas of the skin, including the palms, soles, and perineum. Certain lesions are considered to be precursor lesions of melanoma, including the common acquired nevus, dysplastic nevus, congenital nevus, and cellular blue nevus.

Melanomas have 2 growth phases, radial and vertical. During the radial growth phase, malignant cells grow in a radial fashion in the epidermis. With time, most melanomas progress to the vertical growth phase, when the malignant cells invade the dermis and develop the ability to metastasize.

Many genes are implicated in the development of melanoma, including CDKN2A (p16), CDK4, RB1, CDKN2A (p19), PTEN/MMAC1, and ras. CDKN2A (p16) appears to be especially important in both sporadic and hereditary melanomas. This tumor suppressor gene is located on band 9p21, and its mutation plays a role in various cancers.

Five different forms or histologic types of melanoma exist, as follows:

Superficial spreading melanomas

Approximately 70% of cutaneous malignant melanomas are the superficial spreading melanoma (SSM) type and often arise from a pigmented dysplastic nevus. SSMs typically develop after a long-standing stable nevus changes; typical changes include ulceration, enlargement, or color changes. A SSM may be found on any body surface, especially the head, neck, and trunk of males and the lower extremities of females.

Nodular melanomas

Nodular melanomas (NMs) represent approximately 10-15% of melanomas and also are found commonly on all body surfaces, especially the trunk of males. These lesions are the most symmetrical and uniform of the melanomas and are dark brown or black in color. The radial growth phase may not be evident in NMs; however, if this phase is evident, it is short-lived because the tumor advances rapidly to the vertical growth phase, thus making the NM a high-risk lesion. Amelanotic melanomas represent approximately 5% of all NMs.

Lentigo maligna melanomas

Lentigo maligna melanomas (LMMs) also account for 10-15% of melanomas. They typically are found on sun-exposed areas (eg, hand, neck). LMMs may have areas of hypopigmentation and often are quite large. LMMs arise from a lentigo maligna precursor lesion. For more information, see Lentigo Maligna Melanoma.

Acral lentiginous melanomas

Acral lentiginous melanomas (ALMs) are the only melanomas that have an equal frequency among blacks and whites. They occur on the palms, soles, and subungual areas. Subungual melanomas often are mistaken for subungual hematomas (splinter hemorrhages). Like the NM, ALM is extremely aggressive, with rapid progression from the radial to vertical growth phase.

Mucosal lentiginous melanomas

Mucosal lentiginous melanomas (MLMs) develop from the mucosal epithelium that lines the respiratory, gastrointestinal, and genitourinary systems. These lesions account for approximately 3% of the melanomas diagnosed annually and may occur on any mucosal surface, including the conjunctiva, oral cavity, esophagus, vagina, female urethra, penis, and anus. Noncutaneous melanomas commonly are diagnosed in patients of advanced age. When compared to cutaneous melanomas, MLMs appear to have a more aggressive course, although this may be because they commonly are diagnosed at a later stage of disease than the more readily apparent cutaneous melanomas.

Frequency

United States

Although melanoma accounts for only approximately 5% of skin cancers, it is responsible for 3 times as many deaths each year as nonmelanoma skin cancers. The incidence of melanoma increases by 5-7% yearly, an annual increase second only to lung cancer in women. While the lifetime risk of developing melanoma in 1935 was only 1 per 1500, the lifetime risk in 2000 was estimated at 1 per 75.

International

Queensland, Australia, has the highest incidence of melanoma in the world, approximately 57 cases per 100,000 people per year. Israel also has one of the highest incidences, at approximately 40 cases per 100,000 people annually.

Mortality/Morbidity

If detected early, melanoma can be cured with surgical excision.

• Stage IA: Lesions less than or equal to 1 mm thick with no evidence of ulceration or metastases (T1aN0M0) are associated with a 5-year survival rate of 95%.
• Stage IB: Lesions less than or equal to 1 mm thick with ulceration noted but without lymph node involvement (T1bN0M0) or lesions 1.01-2 mm thick without ulceration or lymph node involvement (T2aN0M0) are associated with a 5-year survival rate of approximately 91%.
• Stage IIA: Melanomas greater than 1 mm but less than 2.01 mm in thickness with no evidence of metastases but with evidence of ulceration (T2bN0M0) or lesions 2.01-4.0 mm without ulceration or lymph node involvement (T3aN0M0) are associated with an overall 5-year survival rate of 77-79%.
• Stage IIB: Melanomas 2.01-4 mm thick with ulceration but no lymph node involvement (T3bN0M0) or lesions greater than 4 mm without ulceration or lymph node involvement (T4aN0M0) are associated with a 5-year survival rate of 63-67%.
• Stage IIC: Lesions greater than 4 mm with ulceration but no lymph node involvement (T4bN0M0) are associated with a 5-year survival rate of 45%.
• Stage IIIA: Patients with any depth lesion, no ulceration and 1 positive (micrometastatic) lymph node (T1-4a,N1a,M0) have a 5-year survival rate of 70%. T1-4a,N2a,M0 lesions (any depth lesion, no ulceration but 2-3 nodes positive for micrometastasis) are associated with a 5-year survival rate of 63%.
• Stage IIIB: Patients with any depth lesion, positive ulceration and 1 lymph node positive for micrometastasis (T1-4b,N1a,M0) or 2-3 nodes positive for micrometastasis (T1-4b,N2a,M0) have a 5-year survival rate of 50-53%. Patients with any depth lesion, no ulceration and 1 lymph node positive for macrometastasis (T1-4a,N1b,M0) or 2-3 nodes positive for macrometastasis (T1-4a,N2b,M0) have a 5-year survival rate of 46-59%.
• Stage IIIC: Patients with any depth lesion, positive ulceration and 1 lymph node positive for macrometastasis (T1-4b,N1b,M0) or 2-3 nodes positive for macrometastasis (T1-4b,N2b,M0) or 4 or more metastatic lymph nodes, matted lymph nodes, or in transit met(s)/satellite(s) have a 5-year survival rate of 24-29%.
• Stage IV: Melanoma metastatic to skin, subcutaneous tissue, or lymph nodes with normal LDH (M1a) is associated with a 5-year survival rate of 19%. M1b disease (metastatic disease to lungs with normal LDH) has a 5-year survival rate of 7%. M1c disease (metastatic disease to all other visceral organs and normal LDH or any distant disease with elevated LDH) is associated with a 5-year survival rate of 10%.

Race

Melanoma is more common in whites than in blacks and Asians. The rate of melanoma in blacks is estimated to be one twentieth that of whites. White people with dark skin also have a much lower risk of developing melanoma than those with light skin. The typical patient with melanoma has fair skin and a tendency to sunburn rather than tan. White people with blond or red hair and excessive freckling appear to be most prone to melanomas. In Hawaii and the southwestern United States, whites have the highest incidence, approximately 20-30 cases per 100,000 people per year.

Sex

Melanoma is slightly more common in men than women (1.2:1). Melanoma is the sixth most common malignancy in women and the seventh most common malignancy in men. Women tend to have thinner, nonulcerated lesions than men.

Age

Melanoma may occur at any age, although children younger than 10 years rarely develop a de novo melanoma.

• The average age at diagnosis is 57 years, and up to 75% of patients are younger than 70 years.
• Melanoma is the most common malignancy in women aged 25-29 years and accounts for more than 7000 deaths annually.

Clinical

History

• Family history: Carefully obtain the family history of melanoma or skin cancer. Also, a family history of irregular, prominent moles is important. Approximately 10-20% of all patients with melanoma have a family history of melanoma. These patients typically develop melanoma at an earlier age and tend to have multiple dysplastic nevi. These patients also more likely have multiple primaries.
• Patient history: Previous history of melanoma must be elicited from patients, because these patients are at an increased risk of developing a second melanoma. Patients have reported as many as 8 or more primary melanomas. Multiple primaries especially are prevalent in patients with multiple dysplastic nevi. The term familial atypical mole or melanoma (FAMM) syndrome is used to describe this hereditary tendency to develop multiple dysplastic nevi and melanomas.
• Sun exposure: Question the patient extensively about previous sun exposure, including severe sunburns in childhood. The capacity to tan also is important because individuals who tan easily are less likely to develop a melanoma than those who burn easily.
• Moles: Question the patient about any changes noted in moles. Any history of change in size, color, or symmetry, as well as knowledge of bleeding or ulceration of the lesion must be obtained. Also elicit history or family history of multiple nevus syndrome.

Physical

• Total body examination
  • A total body skin examination is crucial when evaluating a patient with an atypical nevus or a melanoma. The skin examination should be performed both on initial evaluation of the patient and at all subsequent visits.
  • Crucial to a good skin examination is a well-lit examining room and a completely disrobed patient.
  • Serial photography and new techniques, such as epiluminescence microscopy and computerized image analysis, are useful adjuncts. Epiluminescence microscopy uses a magnifying lens to examine a lesion that has had oil applied. Computerized image analysis stores images of the lesions and makes them available for comparison over time.
• Skin examination: During a skin examination, assess the total number of nevi present on the patient's skin. Attempt to differentiate between typical and atypical lesions. See Images 1-3 for examples of melanomas. The ABCDs for differentiating early melanomas from benign nevi include the following:
  • A - Asymmetry (melanoma lesion more likely to be asymmetric)
  • B - Border irregularity (melanoma more likely to have irregular borders)
  • C - Color (melanoma more likely to be very dark black or blue and have variation in color than a benign mole, which more often is uniform in color and light tan or brown)
  • D - Diameter (mole <6 mm in diameter usually benign)
• Lymph node examination: If a patient is diagnosed with a melanoma, examine all lymph node groups. Melanoma may disseminate both through the lymphatics, leading to involvement of regional lymph nodes, and hematogenously, leading to involvement of any node basin in the body.

Causes

• Exposure to ultraviolet radiation (UVR) is a critical factor in the development of most melanomas.
  • Both ultraviolet A (UVA), wavelength 320-400 nm, and ultraviolet B (UVB), 290-320 nm, potentially are carcinogenic and actually may work in concert to induce a melanoma.
  • UVR appears to be an effective inducer of melanoma through many mechanisms, including suppression of the immune system of the skin, induction of melanocyte cell division, free radical production, and damage of melanocyte DNA.
  • Interestingly, melanoma does not have a direct relationship with the amount of sun exposure because it is more common in white-collar workers than in those who work outdoors.
  • The greatest risk for melanoma is associated with acute, intermittent, blistering sunburns, especially on areas that occasionally receive sun exposure. LMM is an exception to this rule, because it frequently appears on the head and neck of older individuals who have a history of long-term sun exposure.
• Importantly, other factors exist that may predispose an individual to melanoma; chemicals and viruses are 2 etiologic agents that also have been implicated in the development of melanoma.
• Greatly elevated risk factors for cutaneous melanoma
  • Changing mole
  • Dysplastic nevi in familial melanoma
  • Greater than 50 nevi, 2 mm or greater in diameter
• Moderately elevated risk factors for cutaneous melanoma
  • One family member with melanoma
  • Previous history of melanoma
  • Sporadic dysplastic nevi
  • Congenital nevus
• Slightly elevated risk factors for cutaneous melanoma
  • Immunosuppression
  • Sun sensitivity
  • History of acute, severe, blistering sunburns
  • Freckling

• Search for CME/CE on This Topic »

• Malignant Melanoma (Dermatology)
• Oral Malignant Melanoma (Dermatology)
• Melanoma, Conjunctival (Ophthalmology)
• Melanoma, Ciliary Body (Ophthalmology)

• Cancer and Tumors Center
• Skin Cancer Overview
• Skin Cancer Causes
• Skin Cancer Symptoms
• Skin Cancer Treatment
• Skin Biopsy Introduction
• Skin Biopsy Preparation
• Procedures Center
• Mole Removal Preparation
• Mole Removal Introduction

• Interferon Alfa for Malignant Melanoma: Is It Worth the Toxicities?
• Modified Herpes Virus Shows Promise Against Metastatic Melanoma
• ASCO 2009: Investigational Targeted Therapy for Metastatic Melanoma Shrinks Tumors, Causes Stir at Meeting

• Malignant Melanoma in African-Americans
• Avoiding Delayed Diagnosis of Malignant Melanoma
• Vitiligo: A Good Prognostic Factor in Melanoma?

• Melanoma Resource Center