Cutaneous Malignant Melanoma
2006; Elsevier BV; Volume: 81; Issue: 4 Linguagem: Inglês
10.4065/81.4.500
ISSN1942-5546
AutoresDeborah L. Cummins, Jordan M. Cummins, Hardin Pantle, Michael A. Silverman, Aimee L Leonard, Arjun Chanmugam,
Tópico(s)Cutaneous lymphoproliferative disorders research
ResumoSkin cancer has become the most common neoplasm in the United States. With early diagnosis and appropriate management, most skin cancers have an overall 5-year survival rate of 95%. Cutaneous malignant melanoma (CMM), however, has a significantly higher morbidity and mortality, resulting in 65% of all skin cancer deaths. Although the long-term survival rate for patients with metastatic melanoma is only 5%, early detection of CMM carries an excellent prognosis, with surgical excision often being curative. Primary care physicians can play a critical role in reducing morbidity and mortality from CMM by recognizing patients at risk, encouraging the adoption of risk-reducing behaviors, and becoming adept at identifying suspicious lesions. Skin cancer has become the most common neoplasm in the United States. With early diagnosis and appropriate management, most skin cancers have an overall 5-year survival rate of 95%. Cutaneous malignant melanoma (CMM), however, has a significantly higher morbidity and mortality, resulting in 65% of all skin cancer deaths. Although the long-term survival rate for patients with metastatic melanoma is only 5%, early detection of CMM carries an excellent prognosis, with surgical excision often being curative. Primary care physicians can play a critical role in reducing morbidity and mortality from CMM by recognizing patients at risk, encouraging the adoption of risk-reducing behaviors, and becoming adept at identifying suspicious lesions. Outdoor activities have become an increasingly popular source of recreation in the United States. Unfortunately, the public has only recently recognized the dangers of prolonged skin exposure to sunlight, which include skin cancers. Skin cancer has become the most common neoplasm in the United States, with incidence reaching epidemic proportions. The American Cancer Society estimates that approximately 1 million new cases of basal cell or squamous cell carcinoma and approximately 54,200 new cases of malignant melanoma are diagnosed annually.1Skin cancer: preventing America's most common cancer. Centers for Disease Control and Prevention, Atlanta, Ga2003Available at: www.cdc.gov/cancer/nscpep/skin.htmGoogle Scholar An estimated 1 in 5 Americans will develop skin cancer in their lifetime.2Rigel DS Friedman RJ Kopf AW Lifetime risk for development of skin cancer in the U.S. population: current estimate is now 1 in 5 [editorial].J Am Ac ad Dermatol. 1996; 35: 1012-1013Abstract Full Text PDF PubMed Scopus (112) Google Scholar With early diagnosis and appropriate management, most skin cancers have an overall 5-year survival rate of 95%.3Gloster Jr, HM Brodland DG The epidemiology of skin cancer.Dermatol Surg. 1996; 22: 217-226Crossref PubMed Google Scholar However, one type of skin cancer, cutaneous malignant melanoma (CMM), has a significantly higher morbidity and mortality. Although it is the third most common skin cancer, accounting for only 3% of all skin cancers, CMM accounts for 65% of all skin cancer deaths.4Boring CC Squires TS Tong T Cancer statistics, 1991.Bol Asoc Med P R. 1991; 83: 225-242PubMed Google Scholar Melanoma is the fifth most common cancer in men and the sixth in women in the United States.1Skin cancer: preventing America's most common cancer. Centers for Disease Control and Prevention, Atlanta, Ga2003Available at: www.cdc.gov/cancer/nscpep/skin.htmGoogle Scholar From 1981 to 2002 the incidence of CMM has increased nearly 2.8-fold.5National Cancer Institute Cancer stat fact sheets: melanoma of the skin. National Institutes of Health, 2005Available at: http://seer.cancer.gov/statfacts/html/melan.htmlGoogle Scholar This increase is associated with an increased tendency to perform biopsies on pigmented lesions and has resulted in increased diagnosis of thin (<1 mm) CMM.6Jemal A Devesa SS Hartge P Tucker MA Recent trends in cutaneous melanoma incidence among whites in the United States.J Natl Cancer Inst. 2001; 93: 678-683Crossref PubMed Scopus (383) Google Scholar It is not entirely clear why we have failed to see a decrease in mortality with earlier detection.7Welch HG Woloshin S Schwartz LM Skin biopsy rates and incidence of melanoma: population based ecological study.BMJ. 2005; 331: 481Crossref PubMed Scopus (258) Google Scholar One possible explanation is that there are certain subsets of the population, such as older men, who continue to present with thick lesions and therefore have a poor prognosis. According to one study, the median thickness of biopsy specimens of nodular melanomas did not change from 1988 to 1999 despite a 60% increase in the total number of melanomas diagnosed.8Demierre MF Chung C Miller DR Geller AC Early detection of thick melanomas in the United States: beware of the nodular subtype.Arch Dermatol. 2005; 141: 745-750Crossref PubMed Scopus (119) Google Scholar The incidence of melanoma in the United States is also increasing rapidly in children.9Strouse JJ Fears TR Tucker MA Wayne AS Pediatric melanoma: risk factor and survival analysis of the surveillance, epidemiology and end results database.J Clin Oncol. 2005; 23: 4735-4741Crossref PubMed Scopus (300) Google Scholar The annual incidence of melanoma in the United States from 1998 to 2002 was 17.2 per 100,000 population, a sharp increase from 5.7 per 100,000 population in 1973.5National Cancer Institute Cancer stat fact sheets: melanoma of the skin. National Institutes of Health, 2005Available at: http://seer.cancer.gov/statfacts/html/melan.htmlGoogle Scholar, 10Beddingfield III, FC The melanoma epidemic: res ipsa loquitur.Oncologist. 2003; 8: 459-465Crossref PubMed Scopus (119) Google Scholar The projected lifetime risk of developing CMM for Americans has approached 1 in 63.5National Cancer Institute Cancer stat fact sheets: melanoma of the skin. National Institutes of Health, 2005Available at: http://seer.cancer.gov/statfacts/html/melan.htmlGoogle Scholar The annual cost of treating newly diagnosed CMM is estimated to exceed $550 million.11Tsao H Rogers GS Sober AJ An estimate of the annual direct cost of treating cutaneous melanoma.J Am Acad Dermatol. 1998; 38: 669-680Abstract Full Text Full Text PDF PubMed Scopus (102) Google Scholar Several likely reasons exist for the substantial increase in the incidence of melanoma, but accumulating evidence suggests that exposure to sunlight and other sources of UV irradiation (UVR) is a critical factor. Recreational exposure to UVR (including temporal patterns), exposure to sunlamps and tanning beds, sunburn history, and sunscreen use have become subjects of intense scrutiny in recent literature, as efforts to identify significant and potentially correctable risk factors continue.12Gallagher RP Spinelli JJ Lee TK Tanning beds, sunlamps, and risk of cutaneous malignant melanoma.Cancer Epidemiol Biomarkers Prev. 2005; 14: 562-566Crossref PubMed Scopus (187) Google Scholar In addition, the depletion of the earth's ozone layer may be an exacerbating factor in the worldwide increase in the incidence of melanoma as more intense UV light is permitted to reach the earth's surface.13Henriksen T Dahlback A Larsen SH Moan J Ultraviolet-radiation and skin cancer: effect of an ozone layer depletion.Photochem Photobiol. 1990; 51: 579-582Crossref PubMed Scopus (87) Google Scholar The importance of prevention and early detection of CMM cannot be overemphasized. Early detection of melanoma is crucial to long-term survival, because a direct and steep correlation exists between tumor thickness and mortality.14Balch CM Soong SJ Atkins MB et al.An evidence-based staging system for cutaneous melanoma.CA Cancer J Clin. 2004; 54: 131-149Crossref PubMed Scopus (327) Google Scholar Although the long-term survival rate of patients with metastatic malignant melanoma is only 5%,15Brown TJ Nelson BR Malignant melanoma: a clinical review.Cutis. 1999; 63 (281-284.): 275-278PubMed Google Scholar early disease carries an excellent prognosis, with surgical excision often being curative. Therefore, there has been considerable interest in improving public awareness of the risk factors (Table 1) and clinical manifestations of skin malignancy. Primary caregivers can play a critical role in disease management by recognizing patients at risk, encouragingthe adoption of risk-reducing behaviors, and becoming adept at identifying lesions suggestive of melanoma.Table 1Risk Factors for Cutaneous Malignant Melanoma History of melanoma or nonmelanoma skin cancerFamily history of cutaneous malignant melanomaAtypical nevi or numerous neviHistory of severe (blistering) sunburns or intense intermittent sun exposuresLight skin, blond hairGiant melanocytic nevus Open table in a new tab Melanoma is a malignant tumor derived from epidermal melanocytes and can occur in any tissue that contains these cells, including noncutaneous sites such as the oral mucosa, nasopharynx, paranasal sinuses, tracheobronchial tree, vulva, vagina, anus, urinary tract, central nervous system, and eye.16Chang AE Karnell LH Menck HR American College of Surgeons Commission on Cancer, American Cancer Society The National Cancer Data Base report on cutaneous and noncutaneous melanoma: a summary of 84,836 cases from the past decade.Cancer. 1998; 83: 1664-1678Crossref PubMed Scopus (1237) Google Scholar Fortunately, however, most melanomas arise on the skin surface and are therefore amenable to early detection. Although clinical presentations may vary, the ABCD criteria highlight key characteristics suggestive of CMM in any atypical skin lesion: asymmetry, border (and surface) irregularity, color variegation (especially black, red, blue, or white hues), and diameter greater than 6 mm (the size of a pencil eraser).17Lang Jr, PG Malignant melanoma.Med Clin North Am. 1998; 82: 1325-1358Abstract Full Text Full Text PDF PubMed Scopus (33) Google Scholar Many lesions suggestive of melanoma will have some but not have all of these characteristics. For example, melanomas may be less than 6 mm in diameter, and thus it is important that even small skin lesions with atypical appearance be considered for biopsy.18Helsing P Loeb M Small diameter melanoma: a follow-up of the Norwegian Melanoma Project.Br J Dermatol. 2004; 151: 1081-1083Crossref PubMed Scopus (32) Google Scholar The ABCD criteria have been expanded to ABCDE by many dermatologists to include the evolution of skin lesions.19Rigel DS Friedman RJ Kopf AW Polsky D ABCDE—an evolving concept in the early detection of melanoma.Arch Dermatol. 2005; 141: 1032-1034Crossref PubMed Scopus (136) Google Scholar Indeed, any change in a preexisting nevus, such as growth, pigmentary changes, pain, bleeding, or ulceration, is an indication for biopsy. In addition, the development of any new lesion is a reason for concern. Roughly one third of CMMs arise from preexisting nevi (including both acquired and congenital types), whereas the remainder appear to arise de novo.20Gruber SB Barnhill RL Stenn KS Roush GC Nevomelanocytic proliferations in association with cutaneous malignant melanoma: a multivariate analysis.J Am Acad Dermatol. 1989; 21: 773-780Abstract Full Text PDF PubMed Scopus (92) Google Scholar The presence of numerous melanocytic nevi, whether normal or atypical in appearance, confers risk of the development of cutaneous melanoma (Figure 1). The total number of moles on all body surfaces has been determined to be a critical risk factor for melanoma, conferring a relative risk of 7.6 for individuals with more than 100 moles compared with those with 10 or fewer moles.21Garbe C Buttner P Weiss J et al.Risk factors for developing cutaneous melanoma and criteria for identifying persons at risk: multicenter case-control study of the Central Malignant Melanoma Registry of the German Dermatological Society.J Invest Dermatol. 1994; 102: 695-699Abstract Full Text PDF PubMed Google Scholar However, it appears that the probability of malignant degeneration is proportional to the total surface area of melanocytic nevi rather than sheer number. This concept is exemplified by the rare giant congenital nevus, or bathing trunk nevus, which has a significantly increased risk of malignant degeneration.22Watt AJ Kotsis SV Chung KC Risk of melanoma arising in large congenital melanocytic nevi: a systematic review.Plast Reconstr Surg. 2004; 113: 1968-1974Crossref PubMed Scopus (152) Google Scholar Fortunately, most congenital nevi are small (<1.5 cm) and singular and pose substantially less threat.23Fitzpatrick TB Dermatology in General Medicine. 4th ed. McGraw-Hill, New York, NY1993Google Scholar Some risk factors for CMM are clearly inherited. A family history of CMM can be documented in 6% to 12% of new cases.23Fitzpatrick TB Dermatology in General Medicine. 4th ed. McGraw-Hill, New York, NY1993Google Scholar Physicians should also be aware of the familial dysplastic nevus syndrome (or B-K mole syndrome), a disorder characterized by the development of numerous atypical nevi. Members of affected families share a 50% cumulative lifetime risk of developing a cutaneous melanoma.24Greene MH Clark Jr, WH Tucker MA Kraemer KH Elder DE Fraser MC High risk of malignant melanoma in melanoma-prone families with dysplastic nevi.Ann Intern Med. 1985; 102: 458-465Crossref PubMed Scopus (356) Google Scholar Regardless of family history, certain phenotypic characteristics are known to be predisposing factors for CMM. Light hair, skin, and eyes, especially when associated with Central or Northern European ancestry, are examples. These qualities, which are often associated with the inability to tan and the tendency to freckle or develop moles, underscore the importance of UVR in the development of cutaneous neoplasm.25Holly EA Aston DA Cress RD Ahn DK Kristiansen JJ Cutaneous melanoma in women, I: exposure to sunlight, ability to tan, and other risk factors related to ultraviolet light.Am J Epidemiol. 1995; 141: 923-933PubMed Google Scholar, 26Holly EA Aston DA Cress RD Ahn DK Kristiansen JJ Cutaneous melanoma in women, II: phenotypic characteristics and other host-related factors.Am J Epidemiol. 1995; 141: 934-942PubMed Google Scholar, 27Beitner H Norell SE Ringborg U Wennersten G Mattson B Malignant melanoma: aetiological importance of individual pigmentation and sun exposure.Br J Dermatol. 1990; 122: 43-51Crossref PubMed Scopus (134) Google Scholar UV light appears to play a role in the etiology of malignant melanoma by harming the skin through DNA damage. Nowhere is this more clearly demonstrated than in patients with xeroderma pigmentosa, in whom the normal DNArepair machinery is faulty. Exposure to sunlight in these individuals leads to a high incidence of CMM and other cutaneous neoplasms.28Kraemer KH Lee MM Andrews AD Lambert WC The role of sunlight and DNA repair in melanoma and nonmelanoma skin cancer: the xeroderma pigmentosum paradigm.Arch Dermatol. 1994; 130: 1018-1021Crossref PubMed Scopus (482) Google Scholar Furthermore, epidemiological evidence strongly supports the linkage between UVR exposure and development of cutaneous melanoma. Frequent sunburns, particularly in childhood25Holly EA Aston DA Cress RD Ahn DK Kristiansen JJ Cutaneous melanoma in women, I: exposure to sunlight, ability to tan, and other risk factors related to ultraviolet light.Am J Epidemiol. 1995; 141: 923-933PubMed Google Scholar, 29Lew RA Sober AJ Cook N Marvell R Fitzpatrick TB Sun exposure habits in patients with cutaneous melanoma: a case control study.J Dermatol Surg Oncol. 1983; 9: 981-986PubMed Google Scholar, 30Osterlind A Tucker MA Stone BJ Jensen OM The Danish case-control study of cutaneous malignant melanoma, II: importance of UV-light exposure.Int J Cancer. 1988; 42: 319-324Crossref PubMed Scopus (329) Google Scholar but also after the age of 19 years,31Westerdahl J Olsson H Ingvar C At what age do sunburn episodes play a crucial role for the development of malignant melanoma [published correction appears in Eur J Cancer. 1995;31A:287].Eur J Cancer. 1994; 30A: 1647-1654Abstract Full Text PDF PubMed Scopus (80) Google Scholar have been demonstrated to increase the risk of CMM.32Whiteman D Green A Melanoma and sunburn.Cancer Causes Control. 1994; 5: 564-572Crossref PubMed Scopus (98) Google Scholar, 33Elwood JM Jopson J Melanoma and sun exposure: an overview of published studies.Int J Cancer. 1997; 73: 198-203Crossref PubMed Scopus (620) Google Scholar Moreover, it is becoming clear that certain patterns of sun exposure are associated with different risks. For example, patients with long-term exposure to sunlight, such as farmers, show increased incidence of nonmelanoma skin cancer, such as basal cell and squamous cell carcinomas.3Gloster Jr, HM Brodland DG The epidemiology of skin cancer.Dermatol Surg. 1996; 22: 217-226Crossref PubMed Google Scholar Meanwhile, for reasons yet to be elucidated, malignant melanoma risk is associated with intense intermittent episodes of sun exposure, especially those resulting in sunburns, such as resort sunbathing and exposure during hot, midday hours.3Gloster Jr, HM Brodland DG The epidemiology of skin cancer.Dermatol Surg. 1996; 22: 217-226Crossref PubMed Google Scholar, 29Lew RA Sober AJ Cook N Marvell R Fitzpatrick TB Sun exposure habits in patients with cutaneous melanoma: a case control study.J Dermatol Surg Oncol. 1983; 9: 981-986PubMed Google Scholar, 30Osterlind A Tucker MA Stone BJ Jensen OM The Danish case-control study of cutaneous malignant melanoma, II: importance of UV-light exposure.Int J Cancer. 1988; 42: 319-324Crossref PubMed Scopus (329) Google Scholar, 33Elwood JM Jopson J Melanoma and sun exposure: an overview of published studies.Int J Cancer. 1997; 73: 198-203Crossref PubMed Scopus (620) Google Scholar, 34Autier P Dore JF Lejeune F EORTC Malignant Melanoma Cooperative Group et al.Recreational exposure to sunlight and lack of information as risk factors for cutaneous malignant melanoma: results of an European Organization for Research and Treatment of Cancer (EORTC) case-control study in Belgium, France and Germany.Melanoma Res. 1994; 4: 79-85Crossref PubMed Scopus (63) Google Scholar As a result, the increasingly popular use of sunlamps and tanning beds has come under scrutiny. Several states, including New York, Minnesota, Illinois, and Georgia, have introduced bills in 2005 proposing limitations on parlor tanning for those younger than 18 years. Although some studies have found no link between sunlamp and tanning bed use and CMM,25Holly EA Aston DA Cress RD Ahn DK Kristiansen JJ Cutaneous melanoma in women, I: exposure to sunlight, ability to tan, and other risk factors related to ultraviolet light.Am J Epidemiol. 1995; 141: 923-933PubMed Google Scholar, 30Osterlind A Tucker MA Stone BJ Jensen OM The Danish case-control study of cutaneous malignant melanoma, II: importance of UV-light exposure.Int J Cancer. 1988; 42: 319-324Crossref PubMed Scopus (329) Google Scholar other studies have demonstrated an association, especially when exposure has resulted in sunburn.35Autier P Dore JF Lejeune F EORTC Melanoma Cooperative Group et al.Cutaneous malignant melanoma and exposure to sunlamps or sunbeds: an EORTC multicenter case-control study in Belgium, France and Germany.Int J Cancer. 1994; 58: 809-813Crossref PubMed Scopus (138) Google Scholar, 36Walter SD Marrett LD From L Hertzman C Shannon HS Roy P The association of cutaneous malignant melanoma with the use of sunbeds and sunlamps.Am J Epidemiol. 1990; 131: 232-243Crossref PubMed Scopus (179) Google Scholar The type of UVR responsible for the induction of cutaneous neoplasms was originally believed to be primarily, if not exclusively, UV-B, which has long been known to induce both benign and malignant skin lesions in experimental animals through direct damage to genetic material. In recent years, however, it has become increasingly clear that exposure to UV-A, which was previously considered safer, may contribute to the development of CMM as well.37Drobetsky EA Turcotte J Chateauneuf A A role for ultraviolet A in solar mutagenesis.Proc Natl Acad Sci U S A. 1995; 92: 2350-2354Crossref PubMed Scopus (229) Google Scholar Indeed, UV-A can cause sunburn in humans and has been shown to induce epidermal tumors38Kligman LH Akin FJ Kligman AM The contributions of UVA and UVB to connective tissue damage in hairless mice.J Invest Dermatol. 1985; 84: 272-276Crossref PubMed Scopus (249) Google Scholar and CMM in animal models.39Setlow RB Grist E Thompson K Woodhead AD Wavelengths effective in induction of malignant melanoma.Proc Natl Acad Sci U S A. 1993; 90: 6666-6670Crossref PubMed Scopus (598) Google Scholar In 1992, UV-A was reclassified as a 2A carcinogenic agent by the International Agency for Research on Cancer,40IARC monographs on the evaluation of carcinogenic risks to humans: solar and ultraviolet radiation.IARC Monogr Eval Carcinog Risks Hum. 1992; 55: 1-316PubMed Google Scholar which may have important implications for people using tanning equipment. Tanning beds, which formerly emitted UV-B radiation, were modified in the early 1980s to emit primarily UV-A in an effort to reduce the risk of sunburns and benign and malignant skin lesions. Whether or not exposure to artificial tanning equipment will continue to confer risk of CMM is controversial. Although one study found no association between CMM and use of sunbeds after 1980, the authors point out that this may reflect the long latent period between UVR exposure and development of symptomatic disease.35Autier P Dore JF Lejeune F EORTC Melanoma Cooperative Group et al.Cutaneous malignant melanoma and exposure to sunlamps or sunbeds: an EORTC multicenter case-control study in Belgium, France and Germany.Int J Cancer. 1994; 58: 809-813Crossref PubMed Scopus (138) Google Scholar Another study demonstrated a relatively high risk of developing CMM in patients younger than 30 years who had a history of more than 10 sunbed exposures per year, which presumably involved tanning equipment designed after 1980.41Westerdahl J Olsson H Masback A et al.Use of sunbeds or sunlamps and malignant melanoma in southern Sweden.Am J Epidemiol. 1994; 140: 691-699PubMed Google Scholar The authors of both studies advocate a prudent approach to tanning equipment until the relative risks are better defined. The use of sunscreen products has long been advocated as an important strategy for reducing the risk of developing skin cancer. Since the introduction of para-aminobenzoic acid-based sunscreens in the 1920s, topical UV-absorbing products have been widely used for the prevention of sunburn and almost universally accepted as protection against the development of sun-associated neoplasms. Some evidence exists to support this. Sunscreen products certainly prevent sunburn,42Cripps DJ Hegedus S Protection factor of sunscreens to monochromatic radiation.Arch Dermatol. 1974; 109: 202-204Crossref PubMed Scopus (21) Google Scholar, 43Pathak MA Sunscreens: topical and systemic approaches for protection of human skin against harmful effects of solar radiation.J Am Acad Dermatol. 1982; 7: 285-312Abstract Full Text PDF PubMed Scopus (135) Google Scholar and regular use can retard the development of age-associated skin changes.38Kligman LH Akin FJ Kligman AM The contributions of UVA and UVB to connective tissue damage in hairless mice.J Invest Dermatol. 1985; 84: 272-276Crossref PubMed Scopus (249) Google Scholar, 44Kligman LH Akin FJ Kligman AM Prevention of ultraviolet damage to the dermis of hairless mice by sunscreens.J Invest Dermatol. 1982; 78: 181-189Crossref PubMed Scopus (187) Google Scholar, 45Thompson SC Jolley D Marks R Reduction of solar keratoses by regular sunscreen use.N Engl J Med. 1993; 329: 1147-1151Crossref PubMed Scopus (664) Google Scholar, 46Harrison JA Walker SL Plastow SR Batt MD Hawk JL Young AR Sunscreens with low sun protection factor inhibit ultraviolet B and A photoaging in the skin of the hairless albino mouse.Photodermatol Photoimmunol Photomed. 1991; 8: 12-20PubMed Google Scholar, 47Synder DS May M Ability of PABA to protect mammalian skin from ultraviolet light-induced skin tumors and actinic damage.J Invest Dermatol. 1975; 65: 543-546Crossref PubMed Scopus (74) Google Scholar Moreover, in several animal and in vitro models, sunscreens have been shown to protect against UV-induced tumor initiation and promotion.47Synder DS May M Ability of PABA to protect mammalian skin from ultraviolet light-induced skin tumors and actinic damage.J Invest Dermatol. 1975; 65: 543-546Crossref PubMed Scopus (74) Google Scholar, 48Kligman LH Akin FJ Kligman AM Sunscreens prevent ultraviolet photocarcinogenesis.J Am Acad Dermatol. 1980; 3: 30-35Abstract Full Text PDF PubMed Scopus (165) Google Scholar, 49Naylor MF Boyd A Smith DW Cameron GS Hubbard D Neldner KH High sun protection factor sunscreens in the suppression of actinic neoplasia.Arch Dermatol. 1995; 131: 170-175Crossref PubMed Scopus (349) Google Scholar Interestingly, however, scientific and epidemiological evidence that regular use of sunscreens can prevent the development of CMM is lacking.50Wolf P Donawho CK Kripke ML Effect of sunscreens on UV radiation-induced enhancement of melanoma growth in mice.J Natl Cancer Inst. 1994; 86: 99-105Crossref PubMed Scopus (112) Google Scholar Although CMM has been associated with sunburns, no consistent evidence exists that prevention of sunburn in the context of ongoing sun exposure confers protection against the development of CMM. Indeed, several countries, including the United States and Australia, in which sunscreen use was adopted readily and early, have shown paradoxical increases in the incidence of CMM despite sunscreen use.51MacLennan R Green AC McLeod GR Martin NG Increasing incidence of cutaneous melanoma in Queensland, Australia.J Natl Cancer Inst. 1992; 84: 1427-1432Crossref PubMed Scopus (231) Google Scholar, 52Balch CM Soong SJ Milton GW et al.Changing trends in cutaneous melanoma over a quarter century in Alabama, USA, and New South Wales, Australia.Cancer. 1983; 52: 1748-1753Crossref PubMed Scopus (67) Google Scholar Several studies have even suggested that the use of sunscreen itself is paradoxically associated with an increased risk of melanoma.53Autier P Dore JF Schifflers E EORTC Melanoma Cooperative Group et al.Melanoma and use of sunscreens: an EORTC case-control study in Germany, Belgium and France.Int J Cancer. 1995; 61: 749-755Crossref PubMed Scopus (185) Google Scholar, 54Westerdahl J Olsson H Masback A Ingvar C Jonsson N Is the use of sunscreens a risk factor for malignant melanoma?.Melanoma Res. 1995; 5: 59-65Crossref PubMed Scopus (134) Google Scholar, 55Wolf P Quehenberger F Mullegger R Stranz B Kerl H Phenotypic markers, sunlight-related factors and sunscreen use in patients with cutaneous melanoma: an Austrian case-control study.Melanoma Res. 1998; 8: 370-378Crossref PubMed Scopus (64) Google Scholar These findings have raised concerns that rather than conferring protection against UV-induced CMM, sunscreen use may promote the development of CMM by delaying sunburn and encouraging prolonged sun exposure.54Westerdahl J Olsson H Masback A Ingvar C Jonsson N Is the use of sunscreens a risk factor for malignant melanoma?.Melanoma Res. 1995; 5: 59-65Crossref PubMed Scopus (134) Google Scholar, 56Garland CF Garland FC Gorham ED Rising trends in melanoma: an hypothesis concerning sunscreen effectiveness.Ann Epidemiol. 1993; 3: 103-110Abstract Full Text PDF PubMed Scopus (107) Google Scholar In a double-blind, randomized trial, 2 groups of vacationers assigned either sun protection factor (SPF) 30 or SPF 10 sunscreen were compared. Although the study was limited by a small sample size and an inability to ethically include a control group, a provocative finding was a greater mean daily and cumulative sun exposure in the group wearing SPF 30 sunscreen.57Autier P Dore JF Negrier S et al.Sunscreen use and duration of sun exposure: a double-blind, randomized trial.J Natl Cancer Inst. 1999; 91: 1304-1309Crossref PubMed Scopus (226) Google Scholar Furthermore, Stokes and Diffey58Stokes R Diffey B How well are sunscreen users protected?.Photodermatol Photoimmunol Photomed. 1997; 13: 186-188Crossref PubMed Scopus (116) Google Scholar demonstrated that sunscreen users routinely apply less than the recommended amount of 2 mg/cm2, achieving a mean of only 20% to 50% of the sun protection expected from the product's SPF. Coupled with increased exposure time, this observation may partially explain the findings of increased CMM in sunscreen users. Several other possible explanations for these findings exist. First, most of these studies did not control for skin phenotype. A confounding variable may be fair-skinned individuals who, as a result of their increased propensity to sunburn, are more likely to wear sunscreen regularly. These individuals are at a higher risk of developing cutaneous neoplasm because of their skin type. Furthermore, until 1989, most chemical sunscreens absorbed UV-B exclusively. The more recently recognized role of UV-A in UV photocarcinogenesis has led to the development of UV-A-absorbing products, which may enhance the protective effects of sunscreens. However, most products still block only a fraction of the UV-A spectrum59Kaidbey K Gange RW Comparison of methods for assessing photoprotection against ultraviolet A in vivo.J Am Acad Dermatol. 1987; 16: 346-353Abstract Full Text PDF PubMed Scopus (69) Google Scholar and may not block the deeply penetrating UV-A photons as effectively. A study by Wolf et al50Wolf P Donawho CK Kripke ML Effect of sunscreens on UV radiation-induced enhancement of melanoma growth in mice.J Natl Cancer Inst. 1994; 86: 99-105Crossref PubMed Scopus (112) Google Scholar showed that a combination UV-A/UV-B-absorbing sunscreen did not prevent the formation of CMM outgrowths in
Referência(s)