Cutaneous melanoma is readily curable-85% of diagnosed patients will enjoy survival following surgical excision. Unfortunately, this prognosis cannot be offered to those with metastatic disease. Overall, the median survival is six to nine months, but in the subset of patients with bone metastases, the survival is only four months. Bone metastasis is usually a late occurrence is the course of the disease.
Etiology and Pathogenesis:
Melanoma can be broadly divided into two categories: sporadic (90 %) and familial (10 %). As is true with most neoplasms the cause is multifactorial. A host of environmental and genetic factors combine in synergy to produce unregulated cell proliferation. In the case of sporadic melanoma, exposure to ultraviolet B (290 to 320 nm) and ultraviolet A (320 to 400 nm) is the most significant environmental factor. The most influential genetic component of this disease is a deletion or mutation in the p16INK4 gene. Normally, this protein regulates cell proliferation by inhibiting the assembly of cyclin D/CDK 4/6 complex. This genetic error occurs in 25 to 40 percent of sporadic melanomas. Other risk factors include, in decreasing order: past history of melanoma; family history of melanoma or dysplastic nevus; presence of large congenital nevi; presence of ten or greater dysplastic nevi; presence of 100 or greater common acquired nevi; fair skin; red hair; and high intermittent sun exposure.
Malignant melanoma is the final lesion in a series of premalignant lesions that follow a predictable pattern of progression. First, a normal melanocyte escapes keratinocyte control and becomes a nevus cell. Next, the cell separates from the basement membrane and demonstrates cytologic atypia, thus becoming a dysplastic nevus cell. Subsequently, the cell exhibits a radial growth phase, followed by a vertical growth phase. The Breslow Depth (0.76 mm) is the most reliable predictor of the behavior of the primary lesion, so that the likelihood of metastatic transformation increases with the depth of vertical growth. The ability to spread to distant sites is a function of the b3 subunit of the vitronectin receptor.
Lancaster is credited with discovering a relationship between melanoma incidence and latitude. As the distance to the equator decreases, the incidence and rate of melanoma mortality in whites increases. Interestingly, there are 30 cases per 100,000 people in Australia. Australia exhibits the highest melanoma incidence in the world because of its equatorial climate, fair-skinned population, and ozone depletion. In the United States, the incidence has increased from 1 per 100,000 in 1935 to 15 per 100,000 in 1996. In 1973, the mortality was 1.6 per 100,000 individuals; in 1996, the mortality rate was 2.3 per 100,000 individuals. At present, melanoma ranks as the sixth most common cancer in American men, and the seventh most common cancer among American women. The risk for developing melanoma among white Americans is 1 in 85.
Cutaneous melanoma is distinguished by its asymmetry, diffuse borders, variegated color, diameter greater than 5 mm, and evolving morphology. Ten percent of lesions ulcerate and bleed. In a study of 84,000 with melanoma, 2.2% of all melanoma presented without signs of a primary lesion (Chang, Cancer 1998; 83: 1664). These patients are usually younger than other melanoma patients, and they tend to be male. The prognosis is similar to that of patients with known primary cutaneous melanoma. The most common sites for metastasis are skin, lungs, liver, brain, and bone.
Brain metastases are present in 8% to 46% of melanoma patients.
Lymph node core biopsy with subsequent immunohistochemical analysis provides a definitive diagnosis. Ninety percent of melanomas are positive for S-100 antigen. HMB-45 (Melanoma Associated Marker) is more specific for melanoma than S-100, but it is less sensitive. Melanoma cells do not exhibit cytokeratin, leukocyte common antigen, or desmin.
At present, there is no cure for disseminated melanoma (Stage IV: M1). Because brain metastases cause symptoms via compression of neural parenchyma, all therapy is geared toward reducing intracranial pressure. This can be achieved via corticosteroids, gamma knife irradiation or conventional surgery (in the case of a solitary brain lesion), and/or whole brain radiotherapy (in the case of multiple lesions). The pain associated with bone metastases is successfully treated by radiotherapy.