Your Patient With Melanoma: Staging, Prognosis, and Treatment
Your Patient With Melanoma: Staging, Prognosis, and Treatment
ABSTRACT: Melanoma, a cancer of melanocytes, pigment-producing cells in the skin, is the most serious form of skin cancer. Its incidence is increasing rapidly and reaching epidemic proportions. When detected early, it is considered curable, but when detected at later stages it is arguably one of the most lethal malignancies and is the cause of more years of lost life than any other cancer except leukemia. Because most cutaneous melanomas are visible, however, melanoma in general is a cancer highly amenable to early detection. Surgery is standard treatment for localized melanoma. There is no standard therapy fo advanced-stage melanoma. Metastatic melanoma disseminates widely and it frequently involves sites that are not commonly affected in other cancers, such as the gastrointestinal tract and skin. The median survival time for patients with metastatic melanoma is less than 1 year. Despite these grim statistics, long-term survival occurs occasionally. This article will review diagnosis, staging, and treatment for malignant melanoma and will discuss the nursing role in the care of patients with melanoma.
Melanoma affects persons of all ages, causing more years of lost life than any other cancer except leukemia. The American Cancer Society estimates that about 68,720 new melanomas will be diagnosed in the US in 2009, with more than 8,650 deaths, and an estimated lifetime risk of 1 in 50 for whites, 1 in 200 for Hispanics, and 1 in 1,000 for blacks. Melanoma is currently the second leading cancer diagnosis among women under 40 years of age, and the third leading cancer diagnosis among men in this age group. Five-year survival has increased from 80% in the period from 1975–1976 to 92% between 1995 and 2001. The improvement in survival, however, is limited to younger patients.
Among those over the age of 54 years, both the incidence of melanoma and the mortality rate are increasing, with the highest mortality occurring in older white males. Globally, melanoma incidence varies widely, with annual age-adjusted incidence rates of < 1 per 100,000 persons in Japan and India, to 37.8 and 29.4 per 100,000 among Australian males and females, respectively. African Americans have the lowest risk of melanoma, though they tend to present with metastatic disease more frequently.
Certain populations have been identified as being at higher risk than the average person for development of melanoma (see Table 1). They include persons with lighter complexions, an inability to tan, blonde or red hair and blue eyes, and those with multiple nevi, particularly atypical nevi. Immunosuppression, sun sensitivity, and exposure to ultraviolet radiation are additional risk factors. Patients with multiple nevi have a relative risk of 5–12 of developing melanoma, and those with multiple atypical nevi have a relative risk of 7–27. Patients at the greatest risk for developing melanoma include those with a strong family history of melanoma and multiple clinically atypical moles. Interestingly, though some moles are precursors to melanoma, dysplastic nevi are considered to be cutaneous markers that identify persons at an increased risk for developing melanoma compared with the general population. Another higher-risk population includes patients with a personal history of melanoma, with the greatest risk period being 2 years after diagnosis.
The greatest environmental risk factor for development of melanoma is sun exposure; however, genetics also has an impact on melanoma risk. In the past decade, progress has been made towardidentifying genes that contribute to inherited susceptibilityto melanoma. Among themultiple genes thatconfera higher predisposition to melanoma is cyclin-dependent kinase inhibitor A (CDKN2A), also known as p16. This gene is located on chromosome 9 andregulates the cell cycle.
Germ line mutations in this gene have been identified in about 20% of melanoma-prone families that have been studied to date. It is estimated that people with a CDKN2A alteration havea greater than 50% chance of developing melanoma during their lifetime as well as an increased risk of developing more than one primary melanoma, andthey are typically diagnosed at younger ages.Furthermore, persons with CDKN2Amutations have demonstrated a 13–22 fold increase in development of pancreatic cancer, and an increased risk of developing breast cancer. Though only a small proportion of people with melanoma or a family history of melanoma have hereditary alterations in CDKN2A, understanding these increased risks is paramount to management of this population.
While assays for germ line CDKN2A mutationsare commercially available, the Melanoma Genetics Consortium argues that clinical CDKN2A genetic testing is premature, owing to uncertainties regarding penetrance and the efficacy of melanoma prevention and risk-reduction strategies.Providers caring for patients with melanoma who may have undergone genetic testing must recognize that negative CDKN2A test results in families without known mutations would not disprove hereditary melanoma, as certain mutations may be undetectable with current molecular methodologies or because mutations might be present in other melanoma suppressor genes. Providers must also anticipatethat somepatientsmaynot wish to know their status, sincepositive results may increase anxiety.On the other hand, negative results may contribute to a false sense of security.Genetic counseling should be considered to address these concerns.
What Does Melanoma Look Like?
Pigmented lesions can be difficult to evaluate even for very experienced clinicians, particularly in patients with multiple nevi. When evaluating atypical nevi, it is essential to be mindful of the goal of screening: to properly identify melanoma in its earliest stages, when it is considered curable. It is standard practice to remove any pigmented or nonpigmented lesion that is suggestive of melanoma and to perform histologic examination.[13,14] This is necessary to ensure that the lesion is not a melanoma, or if it is, that the proper recommendations for further treatment are determined. The implications for missing a melanoma are far too great to forego biopsy of moderately or highly suspicious lesions. Identifying such lesions accurately is a challenge, however.
It is important to be cognizant that the majority of melanomas arise de novo rather than from pre-existing nevi. Only about one-third of melanomas follow the ABCDE rule of melanoma recognition (see Figure 1), and many lesions determined to be melanoma are clinically innocuous. Argenziano et al. emphasize that while the majority of melanomas exhibit a sufficient array of clinical features to justify biopsy, melanoma may occasionally mimic a variety of benign lesions, such as common melanocytic nevi or seborrheic keratosis.
Furthermore, very early melanomas and nodular melanoma can sometimes be symmetric, well-demarcated, homogenously pigmented, and less than 5 mm in size. Amelanotic melanoma can mimic other skin lesions, particularly more benign lesions, therefore it must be considered in the differential diagnosis of nonpigmented lesions. Though melanomas frequently display irregularities in shape, color, and border, these features are neither invariant nor specific.
Clinicians use several general approaches to recognize melanoma. These include overall pattern recognition (gestalt; eg, instant recognition of an image) as well as analytical recognition criteria such as the ABCDEs of melanoma. Differential recognition, also known as the “ugly duckling,” is based on the concept that nevi in the same individual tend to resemble one another and that melanoma often deviates from the individual’s nevus pattern.