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Clinical and histologic trends of melanoma
Clinical and histologic trends of melanoma Timothy M. Johnson, MD,a,b,c,d Olivia M. Dolan, MD,b Ted A. Hamilton, MS,b Melvin C. Lu, MD,b* Neil A. Swanson, MD,c‡ and Lori Lowe, MDb,e Ann Arbor, Michigan Background: Several changing clinical and histopathologic melanoma trends occurred from the 1950s to the 1980s. Objective: The purpose of this study was to evaluate melanoma trends during the past decade and to compare present trends to those documented during the past four decades. Methods: Sex, age at diagnosis, location, tumor thickness, stage, and histologic subtypes were evaluated from 1984 to 1995 and compared with trends during the past four decades. Results: Most changing trends from the past four decades have slowed or stabilized during the past decade. Conclusion: Complete reporting of all melanomas to central tumor registries is necessary to accurately analyze present and future melanoma trends. Ongoing and new prevention and control strategies beginning at birth may be necessary to continue the positive efforts to curtail the melanoma epidemic. (J Am Acad Dermatol 1998;38:681-6.)
During the past several decades the incidence of cutaneous melanoma in the United States increased at a more rapid rate than any other cancer.1 Annual increases of 3% to 8% have been reported in the United States and around the world.2-14 The melanoma incidence rate increased by 101.5% for the white Surveillance, Epidemiology and End Results (SEER) program population in the United States from 1973–1975 to 1990–1992. For all types of cancer in white persons, the percentage increase was 31.3% during this same time period. Melanoma now represents the fifth most common type of cancer in the United States, the most common type of cancer in women between 25 and 29 years of age, and second only to breast cancer in women 30 to 35 years of age. Melanoma occurs at a younger age than most cancers. In Michigan, melanoma is the most common cancer in white men and the third most common cancer in white women 25 to 44 years of From the Comprehensive Cancer Centera and the Departments of Dermatology,b Otolaryngology,c Surgery (Division of Plastic Surgery),d and Pathology,e University of Michigan Medical Center, Ann Arbor. Accepted for publication Dec. 22, 1997. Reprints are not available from the authors. *Dr. Lu is in private practice in Palm Harbor, Fla. ‡Dr. Swanson is in the Departments of Dermatology and Otolaryngology, Oregon Health Sciences Center, Portland, Ore. Copyright © 1998 by the American Academy of Dermatology, Inc. 0190-0622/98/$5.00 + 0 16/1/88406
age. Those who die of melanoma tend to do so at an earlier age than from most other cancers. As a result, melanoma represents one of the leading cancers in terms of average years of life lost per person.15 One in 84 Americans born in 1997 are projected to experience the development of melanoma during his or her lifetime.16,17 In 1996, approximately 40,000 new cases were reported, and 7300 melanoma-related deaths occurred (or one death every 72 minutes).18 From the 1950s to the 1980s, numerous changing trends in the clinical and histopathologic features of melanoma were documented. Most notably, investigators using large tumor registry data banks found significant increases in the proportion of melanomas located on the trunk, an increase in the superficial spreading histologic subtype, and a marked decrease in the median tumor thickness.1,4,5,13,19-28 Education efforts resulted in earlier detection and diagnosis of thinner lesions with an increase in overall survival rates of patients with melanoma during this same period.29 In fact, the overall 5-year survival rate for localized melanoma increased from 49% in 1954 to 80% to 85% today.16,30-33 Few attempts have been made to document changing trends in the various facets of melanoma during the 1980s to the 1990s and to compare the present features to those during the past four decades.9,34-38 We examined 1302 cases of 681
Journal of the American Academy of Dermatology May 1998
682 Johnson et al. Table I. Tumor location 1984–1989 Location
Trunk Head & neck Lower limb Upper limb Mucosal
1990–1995
Male(%) Female(%) Male (%) Female (%)
47.2 25.5 13.2 14.2 0
35.1 10.6 35.1 18.1 1.06
41.2 29.6 11.6 17.1 0.5
26.4 17.6 34.8 20.3 0.8
melanoma diagnosed between 1984 and 1995 to evaluate the present trends in the clinical and histologic features of melanoma. These present trends are collectively compared with those previously identified from the 1950s to the 1980s. METHODS The University of Michigan multidisciplinary melanoma clinic database was queried about patients with cutaneous melanoma from the 12-year time period of 1984 to 1995. This period was then divided into two 6-year periods 1984 to 1989 and 1990 to 1995 to compare the present trends to those documented in the past four decades and to investigate any changing trends during the last decade. A total of 1302 patients were identified, 201 patients from 1984 to 1989 and 1101 patients from 1990 to 1995. Although an imbalance in the number of patients in the two time periods exists, the characteristics of the patients in each group is correctly representative of the Michigan population in these two time periods based on a comparative concordance correlation between our populations and the populations reported to the Michigan Department of Community Health, Office of the State Registrar and Division of Health Statistics for each time period.39 A few community physicians referred most of their patients with melanoma to the new clinic in the first time period. In the second time period, a significantly larger number of community physicians referred most of their patients with melanoma to the melanoma clinic. Referral patterns remained relatively constant between the two time periods although the number of referring physicians increased about fivefold. The number of patients with advanced disease entered into investigational protocols was minimal in both time periods (n = 66), and the availability of sentinel lymph node mapping for intermediate thickness lesions in our clinic did not frequently occur until 1996. The two recent 6-year time periods were analyzed to compare past and present trends in the clinical and histopathologic features of melanoma with respect to sex, age at diagnosis, anatomic site, tumor thickness
measured in millimeters, stage, and histologic subtype. The histologic subtypes used for analysis included lentigo maligna melanoma, superficial spreading melanoma (SSM), nodular melanoma, acral lentiginous melanoma, amelanotic melanoma, in situ, and other unclassified or not otherwise specified. The American Joint Commission on Cancer (AJCC) staging system was used. AJCC stages I and II represent local disease of 1.5 mm or less and more than 1.5 mm, respectively. Stage III represents regional nodal disease and in-transit metastasis. Stage IV represents distant disease.40
Statistical analysis Tests for association of the proportional distributions of categoric variables such as sex, histologic subtype, and tumor location with respect to time period were made with Pearson’s chi-square test. Comparisons of continuous variables such as Breslow depth and age between time periods were made with Student two-sample t test. All p values are two-tailed. The data were analyzed with SAS Statistical Software (SAS Institute Inc., Cary, N.C.). RESULTS
In the 1984 to 1989 time period, 53% of the patients were men and 47% were women (male/female ratio, 1.1:1). From 1990 to 1995, 56.5% of the patients were men and 43.5% were women (male/female ratio, 1.3:1). This difference is insignificant (p = 0.35). Examination of the age distribution at the time of diagnosis revealed a broad range with most patients (77%) between the ages of 30 and 70 years. The mean age in the time period 1984 to 1989 for men was 50.6 years and for women was 46.3 years. The mean age for the time period 1990 to 1995 for men was 55.0 years and for women was 50.5 years. For both time periods, men were significantly older than women (1984 to 1989, p = 0.04; 1990 to 1995, p = 0.0001). The two time periods were compared for each sex. For men, the mean age increased from 50.6 to 55.0 years (p = 0.008). For women, the mean age increased from 46.3 to 50.5 years (p = 0.03). Analysis of tumor location (Table I) showed that the greatest proportion of lesions in men occurred on the trunk (47.2% in 1984 to 1989 and 41.2% in 1990 to 1995) followed by the head and neck region (25.5% in 1984 to 1989 and 29.6% in 1990 to 1995). In women the greatest percentage of melanomas were found on the trunk (35.1% in 1984 to 1989 and 26.4% in 1990 to 1995) and
Journal of the American Academy of Dermatology Volume 38, Number 5, Part 1
lower extremity (35.1% in 1984 to 1989 and 34.8% in 1990 to 1995). No statistical change was found between location of melanoma and time period for either sex (male, p = 0.58; female, p = 0.2). An analysis of the overall mean tumor thickness measured in millimeters for all cases between the two time periods showed no significant difference, with a mean tumor thickness of 1.27 mm for 1984 to 1989 and 1.52 mm for 1990 to 1995 (p = 0.08). Analysis of tumor thickness by categories of thin (< 1 mm), intermediate (1 to 4 mm), and thick (> 4 mm) revealed no significant differences in tumor thickness by categories between the two time periods for either men (p = 0.18) or women (p = 0.68). For women, the mean thickness was 1.31 mm in 1984 to 1989 and 1.42 mm in 1990 to 1995 (p = 0.64). However, for men, an increase in tumor thickness occurred, that is, from 1.23 mm for 1984 to 1989 to 1.60 mm for 1990 to 1995 (p = 0.04). An analysis of the overall stage distribution between the two time periods found no difference in the mean stage of 1.39 for 1984 to 1989 and 1.33 for 1990 to 1995 (p = 0.41). The percentage of in situ melanomas diagnosed in 1984 to 1989 was 9% compared with 12% for 1990 to 1995 (p = 0.24). The percentage of patients with stages 0, I, and II was 86% in 1984 to 1989 and 91% in 1990 to 1995. For stages III and IV, the percentage was 14% in 1984 to 1989 and 9% in 1990 to 1995. This demonstrates a significant decrease in patients with advanced stage III and IV in the latter time period (p = 0.04). Evaluation of melanoma histologic subtype revealed a marked predominance of SSM in both men (59.4% in 1984 to 1989 and 59.3% in 1990 to 1995) and women (52.1% in 1984 to 1989 and 63.2% in 1990 to 1995) over both time periods, with a significant increase in SSM in women between the time periods (p = 0.04). In situ lesions increased in men from 7.5% to 13% from the earlier to the later time period, but statistical significance was not present (p = 0.11). DISCUSSION
Numerous studies from the 1950s to the 1980s documented several changing trends in the clinical and histopathologic features of melanoma.1,5,12,13,19-27,41 Our results comparing the more recent time periods of 1984 to 1989 and
Johnson et al. 683 1990 to 1995 demonstrate that several of the earlier changing trends may have slowed or stabilized during the past decade. Sex Melanoma was more common in women than men in the 1960s; the male to female ratio was approximately 0.83:1. The proportion of men with melanoma increased in the 1970s when the male to female ratio was 1.11:1.22,25,42,43 In our series, the male to female ratio stabilized during the past decade. Age An increase in the mean age at diagnosis for patients with melanoma occurred from the 1950s to the 1980s, and women tended to be seen at an earlier age than men. The mean age at diagnosis has increased during the last several decades from the mid 40s to the mid 50s in ours and other series.5,9,22 Our results indicate that a continuing significant shift has occurred during the last decade with an increase in the mean age at diagnosis of both men and women with melanoma. The increasing mean age at diagnosis may reflect the increasing age of the United States population at large. Our results also indicate that women continue to be diagnosed with melanoma at an earlier age than men by approximately 5 years. Our population is reflective of the overall Michigan population of reported cases of melanoma. The overall mean age in our population in the second time period was 54 years compared with 56.5 years for all reported Michigan melanoma cases.39 During this same time the median age of diagnosis for all cancer types in Michigan was 68 years.39 Location Melanoma occurs predominantly on the trunk in men and trunk and lower extremity in women. Several reports during the past several decades have documented a significant increase in melanoma on the trunk in men and women and lower extremities in women.20,22,27,34,35,44 This was attributed, in part, to behavioral, cultural, and lifestyle changes with respect to sun exposure, dress habits, and tropical vacationing that occurred after the 1940s. Others have theorized that the trunk and lower extremities are exposed to more intermittent acute episodes of ultraviolet radiation and are thus at greater risk for sunburns
684 Johnson et al. and the development of melanoma.45-48 Our results indicate a stable site distribution during the last decade; the trunk is still the most common site in men, and the trunk and lower extremity remains the most common site in women. Histologic subtype The incidence of superficial spreading melanoma increased significantly although the incidence of nodular melanoma decreased from the 1950s to the 1980s.22,42 Our results demonstrated that the SSM remained the most common histologic subtype during the last decade. There was a small shift in SSM in our female patients (52% to 63%; p = 0.04) during the last decade. Reports of a dramatic sixfold increase in the ageadjusted rate for melanoma in situ from 0.4 to 2.3 per 100,000 occurred from 1973 to 1987.27 In our series, the percentage of in situ lesions remained relatively stable in women and almost doubled in men. However, in men, this increase was not statistically significant (p = 0.11). Referral bias is possible because melanoma in situ may easily be managed in the office and never reported to a central tumor registry. Tumor thickness Numerous studies have revealed that tumor thickness changed markedly from the 1950s to the 1980s.5,12,13,22-24,28,41 During this period tumor thickness decreased from a predominance of more than 3 mm to an average of approximately 1 mm after 1980.22 The decrease in tumor thickness was attributed to increased public and physician education, awareness, and subsequent earlier detection.16 In 1994, 85.5% of all reported cases in the state of Michigan were diagnosed at a local stage: 11.3% in situ and 74.2% stages I and II. In our series from 1990 to 1995, 91% of cases were localized: 12% in situ and 79% stages I and II. From 1985 to 1994, our population parallels the percentages of total melanoma cases by stage at diagnosis reported to the Michigan Department of Community Health, Office of the State Registrar, and Division of Health Statistics.39 Although our population accurately reflects the reported cases, bias may exist because many thin lesions treated in the private practice office are not reported to the central registry. However, although a small increase in the proportion of cases staged as local-
Journal of the American Academy of Dermatology May 1998
ized occurred from 1984 to 1995 (86% to 91%), the overall mean tumor thickness slightly increased from 1.27 mm in 1984 to 1989 to 1.52 mm in 1990 to 1995 (p = 0.08). Furthermore, mean tumor thickness increased in men from 1.23 mm in the earlier period to 1.60 mm in the later period. The percentage of lesions ≥ 1 mm was 41% for the earlier time period compared with 47% for the latter period. The mean stage between the two periods also remained similar. Even with the possibility of referral bias, the national relatively stable overall survival of 80% to 85% during the past decade compared with 49% in 1954 supports the possibility that the trend of earlier detection may be slowing.16,30-33 Our tumor thickness results are similar to those reported in Connecticut. In the Connecticut study, 418 cases of melanoma from the time periods 1974 to 1976 and 1985 to 1987 were compared for changes in tumor thickness. The mean overall tumor thickness decreased from 2.03 mm in the first time period to 1.64 mm in the latter period. In men the mean thickness decreased from 2.08 to 1.87 mm and in women from 2.02 to 1.49 mm.49 The stage of disease and tumor thickness during the past decade in our series and the State of Michigan Central Melanoma Registry indicate an increase in the proportion of patients diagnosed with local disease probably because of the successful melanoma education programs. The current trend of stabilization in overall tumor thickness during the past decade suggests a slowing in the heightened awareness that occurred between the 1950s to the 1980s. Prevention programs, riskdirected interventions, and early school-based education programs are all important in stopping the melanoma epidemic. School-based programs that begin at an early age should be reviewed and carefully monitored for long-term behavioral changes and outcomes to determine effectiveness. Further research will be necessary to determine whether skin cancer prevention education can be effectively developed within the context of a broader health education program. Sun protection measures should be initiated with newborns and maintained throughout life.50-56 REFERENCES 1. Miller BA, Ries LAG, Hankey BF, et al. editors. SEER cancer statistics review: 1973 to 1990. Bethesda (MD): National Cancer Institure; 1993.
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2. Osterlind A. Epidemiology on malignant melanoma in Europe. Acta Oncol 1992;31:903-8. 3. Thorn M, Adami H, Bergstrom R, Ringborg U, Krusemo UB. Trends in survival from malignant melanoma: remarkable improvement in 23 years. J Natl Cancer Inst 1989;81:611-7. 4. Magnus K. Incidence of malignant melanoma in the skin in Norway 1955 to 1970. Variations in time and space and solar radiation. Cancer 1973;32:1275-86. 5. Garbe C, Wiebelt H, Orfanos CE. Change of epidemiological characteristics of malignant melanoma during the years 1962 to 1972 and 1983 to 1986 in the Federal Republic of Germany. Dermatologica 1989;178:131-5. 6. Osterlind A, Engholm G, Jensen OM. Trends in cutaneous malignant melanoma in Denmark 1943 to 1982 by anatomic site. APMIS 1988;96:953-63. 7. Green A, MacLennan R, Youl P, Martin N. Site distribution of cutaneous melanoma in Queensland. Int J Cancer 1993;53:232-6. 8. Elwood JM. Epidemiology and control of melanoma in white populations and in Japan. J Invest Dermatol 1989;92:214S-21S. 9. Urist MM, Karnell LH. The National Cancer Database: report on melanoma. Cancer 1994;74:782-8. 10. Roush GC, Schumura MJ, Holford TR. Patterns of invasive melanoma in the Connecticut tumor registry. Is the long-term increase real? Cancer 1988;61:2586-95. 11. Roush GC, Schumura MJ, Holford TR. Risk for cutaneous melanoma in recent Connecticut birth cohorts. Am J Pub Health 1985;75:679-82. 12. English DR, Heenan PJ, Holman C, et al. Melanoma in western Australia 1975-76 to 1980-81: trends in demographic and pathological characteristics. Int J Cancer 1986;37:209-15. 13. Balch 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;52:1748-53. 14. Anaise D, Steinitz R, Hur HB. Solar radiation: a possible etiological factor in malignant melanoma in Israel: a retrospective study. Cancer 1978;42:299-304. 15. Kosary CL, Ries LAG, Miller BA, et al. SEER cancer statistics review, 1973-1992: tables and graphs. NIH Pub No. 96-2789 ed. Bethesda (MD): National Cancer Institute; 1995. 16. Friedman RJ, Rigel DS, Silverman MK, Kopf AW, Vossaert KA. Malignant melanoma in the 1990’s: the continued importance of early detection and self-examination of the skin. CA Cancer J Clin 1991;41:201-26. 17. Sober AJ. Cutaneous melanoma: opportunity for cure. CA Cancer J Clin 1991;41:197-9. 18. Parker SL, Tong T, Bolden S, Wingo PA. Cancer statistics, 1996. CA Cancer J Clin 1997;47:5-27. 19. Sober A, Lew RA, Koh HK, Barnhill RL. Epidemiology of cutaneous melanoma. An update. Dermatol Clin 1991;9:617-29. 20. Magnus K. Habits of sun exposure and risk of malignant melanoma: an analysis of incidence rates in Norway 1955-1977 by cohort, sex, age, and primary tumor site. Cancer 1981;48:2329-35. 21. MacKie R, Hunter JAA, Aitchison TC, et al. Cutaneous malignant melanoma, Scotland, 1979-89. The Scottish Melanoma Group. Lancet 1992;339:971-5. 22. Balch CM, Shaw HM, Soong SJ, Milton GW. Changing trends in clinical and pathologic features of melanoma. In: Balch CM, Milton GW, Sahw HM, Soong SJ, editors.
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23. 24. 25. 26.
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Cutaneous melanoma. 1st ed. Philadelphia: JB Lippincott; 1985. p. 314-9. Kopf AW, Kripke ML, Stern RS. Sun and malignant melanoma. J Am Acad Dermatol 1984;11:674-84. Bagley FH, Cady B, Lee A, Legg MA. Changes in clinical presentation and management of malignant melanoma. Cancer 1981;47:2126-34. McGregor SE, Birdsell JM, Grace MA, et al. Cutaneous malignant melanoma in Alberta: 1967-1976. Cancer 1983;52:755-61. Gallagher RP, Becky BA, McLean DJ, et al. Trends in basal cell carcinoma, squamous cell carcinoma, and melanoma of the skin from 1973 through 1987. J Am Acad Dermatol 1990;23:413-21. Elder DE. Skin cancer: melanoma and other specific nonmelanoma skin cancers. Cancer 1995;75:245-56. Shafir R, Hiss J, Tsur H, Bubis JJ. The thin malignant melanoma: changing patterns of epidemiology and treatment. Cancer 1982;50:817-9. Koh KH. Cutaneous melanoma. N Engl J Med 1991;325:171-82. Halpern AC, Schuchter LM. Prognostic models in melanoma. Sem Oncol 1997;24:S4-2-7. Kawakami Y, Eliyahu S, Sakaguchi K, et al. Identification of the immunodominant peptides of the MART-1 human melanoma antigen recognized by the majority of HLA-A2-restricted tumor infiltrating lymphocytes. J Exp Med 1994;180:347-52. Balch CM, Soong SJ, Milton GW, et al. A comparison of prognostic factors and surgical results in 1786 patients with localized (stage I) melanoma treated in Alabama, USA, and New South Wales, Australia. Ann Surg 1982;196:677-84. Clark WH Jr, Elder DE, Guerry P IV, et al. Model predicting survival in stage I melanoma based on tumor progression. J Natl Cancer Inst 1989;81:1893-904. Percy C. SEER program (1973-1992) incidence of melanoma. J Registry Management 1996;23:21-3. Engar EM, Eisner ME. Focus study on cutaneous melanoma. J Registry Management 1996;23:28-34. Lambert WE, Davidson A. Changing trends in skin cancer in New Mexico: The need for school-based intervention. J Registry Management 1996;23:38-43. Cress RD, Davidson-Sawyer K. Cutaneous melanoma among hispanic and non-hispanic white men and women in California, 1988-1993. J Registry Management 1996;23:24-7. Rebelo PAP, Rebelo MS. Cutaneous malignant melanoma in Brazil. J Registry Management 1996; 23:35-7. DeGuire PJ, Spivak GH. Cutaneous malignant melanoma: special report. In: Anonymous Michigan Department of Community Health Cancer Incidence & Mortality 1994. Lansing: Michigan Department of Community Health; 1994. p. 1-19. Anonymous. Malignant melanoma of the skin (excluding eyelid). In: Beahrs OH, Henson DE, Hutter RVP, Kennedy BJ, editors. American Joint Committee on Cancer Manual for Staging of Cancer. 4th ed. Philadelphia: JB Lippincott; 1992. p. 143-8. Garbe C, Orfanos CE. Epidemiology of malignant melanoma in central Europe: risk factors and prognostic predictors. Results of central malignant melanoma registry of the German Dermatologic Society. Pigment Cell Res 1992;2:285S-94S. Little JH, Holt J, Davis N. Changing epidemiology of
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malignant melanoma in Queensland. Med J Aust 1980;1:66-9. Houghton A, Flannery J, Viola MV. Malignant melanoma in Connecticut and Denmark. Int J Cancer 1980;25:95-104. Crombie IK. Distribution of malignant melanoma on the body surface. Br J Cancer 1981;43:842-9. Elwood JM, Gallagher RP, Hill GB, Pearson JC. Cutaneous melanoma in relation to intermittent and constant sun exposure: the Western Canadian Melanoma Study. Int J Cancer 1985;35:427-33. Osterlind 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;42:319-24. Armstrong B. Epidemiology of malignant melanoma: intermittent or total accumulated exposure to the sun. J Dermatol Surg Oncol 1988;14:835-49. Holman CDJ, Armstrong BK, Heenan PJ. Relationship of cutaneous malignant melanoma to individual sun-light exposure habits. J Natl Cancer Inst 1986;76:403-14. Berwick MF, Fine JA, Sagebiel R, et al. Changes in incidence of melanoma by Breslow depth in Connecticut between 1974-76 and 1985-87. Melanoma Res 1997;7:S68.
50. Maducdoc LR, Wagner RF, Wagner KD. Parent’s use of sunscreen on beach-going children. Arch Dermatol 1992;128:628-9. 51. Banks BA, Silverman RA, Schwartz RH, Tunnessen WW. Attitudes of teenagers toward sun exposure and sunscreen use. The burnt child dreads the fire. Pediatrics 1992;89:40-2. 52. Bolognia JL, Berwick M, Fine JA, Simpson P, Jasmin M. Sun protection in newborns: a comparison of educational methods. Am J Dis Child 1991;145:1125-9. 53. Hurwitz S. The sun and sunscreen protection: recommendations for children. J Dermatol Surg Oncol 1988;14:657-60. 54. MacKie RM, Hole D. Audit of public education campaign to encourage earlier detection of malignant melanoma. BMJ 1992;304:1012-5. 55. Fork HE, Wagner RF, Wagner KD. The Texas peer education sun awareness project for children: primary prevention of malignant melanoma and nonmelanocytic skin cancers. Cutis 1992;50:363-4. 56. Hughes BR, Altman DG, Newton JA. Melanoma and skin cancer: evaluation of a health education programme for secondary schools. Br J Dermatol 1993;128:412-7.
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During the past several decades the incidence of cutaneous melanoma in the United States increased at a more rapid rate than any other cancer.1 Annual increases of 3% to 8% have been reported in the United States and around the world.2-14 The melanoma incidence rate increased by 101.5% for the white Surveillance, Epidemiology and End Results (SEER) program population in the United States from 1973–1975 to 1990–1992. For all types of cancer in white persons, the percentage increase was 31.3% during this same time period. Melanoma now represents the fifth most common type of cancer in the United States, the most common type of cancer in women between 25 and 29 years of age, and second only to breast cancer in women 30 to 35 years of age. Melanoma occurs at a younger age than most cancers. In Michigan, melanoma is the most common cancer in white men and the third most common cancer in white women 25 to 44 years of From the Comprehensive Cancer Centera and the Departments of Dermatology,b Otolaryngology,c Surgery (Division of Plastic Surgery),d and Pathology,e University of Michigan Medical Center, Ann Arbor. Accepted for publication Dec. 22, 1997. Reprints are not available from the authors. *Dr. Lu is in private practice in Palm Harbor, Fla. ‡Dr. Swanson is in the Departments of Dermatology and Otolaryngology, Oregon Health Sciences Center, Portland, Ore. Copyright © 1998 by the American Academy of Dermatology, Inc. 0190-0622/98/$5.00 + 0 16/1/88406
age. Those who die of melanoma tend to do so at an earlier age than from most other cancers. As a result, melanoma represents one of the leading cancers in terms of average years of life lost per person.15 One in 84 Americans born in 1997 are projected to experience the development of melanoma during his or her lifetime.16,17 In 1996, approximately 40,000 new cases were reported, and 7300 melanoma-related deaths occurred (or one death every 72 minutes).18 From the 1950s to the 1980s, numerous changing trends in the clinical and histopathologic features of melanoma were documented. Most notably, investigators using large tumor registry data banks found significant increases in the proportion of melanomas located on the trunk, an increase in the superficial spreading histologic subtype, and a marked decrease in the median tumor thickness.1,4,5,13,19-28 Education efforts resulted in earlier detection and diagnosis of thinner lesions with an increase in overall survival rates of patients with melanoma during this same period.29 In fact, the overall 5-year survival rate for localized melanoma increased from 49% in 1954 to 80% to 85% today.16,30-33 Few attempts have been made to document changing trends in the various facets of melanoma during the 1980s to the 1990s and to compare the present features to those during the past four decades.9,34-38 We examined 1302 cases of 681
Journal of the American Academy of Dermatology May 1998
682 Johnson et al. Table I. Tumor location 1984–1989 Location
Trunk Head & neck Lower limb Upper limb Mucosal
1990–1995
Male(%) Female(%) Male (%) Female (%)
47.2 25.5 13.2 14.2 0
35.1 10.6 35.1 18.1 1.06
41.2 29.6 11.6 17.1 0.5
26.4 17.6 34.8 20.3 0.8
melanoma diagnosed between 1984 and 1995 to evaluate the present trends in the clinical and histologic features of melanoma. These present trends are collectively compared with those previously identified from the 1950s to the 1980s. METHODS The University of Michigan multidisciplinary melanoma clinic database was queried about patients with cutaneous melanoma from the 12-year time period of 1984 to 1995. This period was then divided into two 6-year periods 1984 to 1989 and 1990 to 1995 to compare the present trends to those documented in the past four decades and to investigate any changing trends during the last decade. A total of 1302 patients were identified, 201 patients from 1984 to 1989 and 1101 patients from 1990 to 1995. Although an imbalance in the number of patients in the two time periods exists, the characteristics of the patients in each group is correctly representative of the Michigan population in these two time periods based on a comparative concordance correlation between our populations and the populations reported to the Michigan Department of Community Health, Office of the State Registrar and Division of Health Statistics for each time period.39 A few community physicians referred most of their patients with melanoma to the new clinic in the first time period. In the second time period, a significantly larger number of community physicians referred most of their patients with melanoma to the melanoma clinic. Referral patterns remained relatively constant between the two time periods although the number of referring physicians increased about fivefold. The number of patients with advanced disease entered into investigational protocols was minimal in both time periods (n = 66), and the availability of sentinel lymph node mapping for intermediate thickness lesions in our clinic did not frequently occur until 1996. The two recent 6-year time periods were analyzed to compare past and present trends in the clinical and histopathologic features of melanoma with respect to sex, age at diagnosis, anatomic site, tumor thickness
measured in millimeters, stage, and histologic subtype. The histologic subtypes used for analysis included lentigo maligna melanoma, superficial spreading melanoma (SSM), nodular melanoma, acral lentiginous melanoma, amelanotic melanoma, in situ, and other unclassified or not otherwise specified. The American Joint Commission on Cancer (AJCC) staging system was used. AJCC stages I and II represent local disease of 1.5 mm or less and more than 1.5 mm, respectively. Stage III represents regional nodal disease and in-transit metastasis. Stage IV represents distant disease.40
Statistical analysis Tests for association of the proportional distributions of categoric variables such as sex, histologic subtype, and tumor location with respect to time period were made with Pearson’s chi-square test. Comparisons of continuous variables such as Breslow depth and age between time periods were made with Student two-sample t test. All p values are two-tailed. The data were analyzed with SAS Statistical Software (SAS Institute Inc., Cary, N.C.). RESULTS
In the 1984 to 1989 time period, 53% of the patients were men and 47% were women (male/female ratio, 1.1:1). From 1990 to 1995, 56.5% of the patients were men and 43.5% were women (male/female ratio, 1.3:1). This difference is insignificant (p = 0.35). Examination of the age distribution at the time of diagnosis revealed a broad range with most patients (77%) between the ages of 30 and 70 years. The mean age in the time period 1984 to 1989 for men was 50.6 years and for women was 46.3 years. The mean age for the time period 1990 to 1995 for men was 55.0 years and for women was 50.5 years. For both time periods, men were significantly older than women (1984 to 1989, p = 0.04; 1990 to 1995, p = 0.0001). The two time periods were compared for each sex. For men, the mean age increased from 50.6 to 55.0 years (p = 0.008). For women, the mean age increased from 46.3 to 50.5 years (p = 0.03). Analysis of tumor location (Table I) showed that the greatest proportion of lesions in men occurred on the trunk (47.2% in 1984 to 1989 and 41.2% in 1990 to 1995) followed by the head and neck region (25.5% in 1984 to 1989 and 29.6% in 1990 to 1995). In women the greatest percentage of melanomas were found on the trunk (35.1% in 1984 to 1989 and 26.4% in 1990 to 1995) and
Journal of the American Academy of Dermatology Volume 38, Number 5, Part 1
lower extremity (35.1% in 1984 to 1989 and 34.8% in 1990 to 1995). No statistical change was found between location of melanoma and time period for either sex (male, p = 0.58; female, p = 0.2). An analysis of the overall mean tumor thickness measured in millimeters for all cases between the two time periods showed no significant difference, with a mean tumor thickness of 1.27 mm for 1984 to 1989 and 1.52 mm for 1990 to 1995 (p = 0.08). Analysis of tumor thickness by categories of thin (< 1 mm), intermediate (1 to 4 mm), and thick (> 4 mm) revealed no significant differences in tumor thickness by categories between the two time periods for either men (p = 0.18) or women (p = 0.68). For women, the mean thickness was 1.31 mm in 1984 to 1989 and 1.42 mm in 1990 to 1995 (p = 0.64). However, for men, an increase in tumor thickness occurred, that is, from 1.23 mm for 1984 to 1989 to 1.60 mm for 1990 to 1995 (p = 0.04). An analysis of the overall stage distribution between the two time periods found no difference in the mean stage of 1.39 for 1984 to 1989 and 1.33 for 1990 to 1995 (p = 0.41). The percentage of in situ melanomas diagnosed in 1984 to 1989 was 9% compared with 12% for 1990 to 1995 (p = 0.24). The percentage of patients with stages 0, I, and II was 86% in 1984 to 1989 and 91% in 1990 to 1995. For stages III and IV, the percentage was 14% in 1984 to 1989 and 9% in 1990 to 1995. This demonstrates a significant decrease in patients with advanced stage III and IV in the latter time period (p = 0.04). Evaluation of melanoma histologic subtype revealed a marked predominance of SSM in both men (59.4% in 1984 to 1989 and 59.3% in 1990 to 1995) and women (52.1% in 1984 to 1989 and 63.2% in 1990 to 1995) over both time periods, with a significant increase in SSM in women between the time periods (p = 0.04). In situ lesions increased in men from 7.5% to 13% from the earlier to the later time period, but statistical significance was not present (p = 0.11). DISCUSSION
Numerous studies from the 1950s to the 1980s documented several changing trends in the clinical and histopathologic features of melanoma.1,5,12,13,19-27,41 Our results comparing the more recent time periods of 1984 to 1989 and
Johnson et al. 683 1990 to 1995 demonstrate that several of the earlier changing trends may have slowed or stabilized during the past decade. Sex Melanoma was more common in women than men in the 1960s; the male to female ratio was approximately 0.83:1. The proportion of men with melanoma increased in the 1970s when the male to female ratio was 1.11:1.22,25,42,43 In our series, the male to female ratio stabilized during the past decade. Age An increase in the mean age at diagnosis for patients with melanoma occurred from the 1950s to the 1980s, and women tended to be seen at an earlier age than men. The mean age at diagnosis has increased during the last several decades from the mid 40s to the mid 50s in ours and other series.5,9,22 Our results indicate that a continuing significant shift has occurred during the last decade with an increase in the mean age at diagnosis of both men and women with melanoma. The increasing mean age at diagnosis may reflect the increasing age of the United States population at large. Our results also indicate that women continue to be diagnosed with melanoma at an earlier age than men by approximately 5 years. Our population is reflective of the overall Michigan population of reported cases of melanoma. The overall mean age in our population in the second time period was 54 years compared with 56.5 years for all reported Michigan melanoma cases.39 During this same time the median age of diagnosis for all cancer types in Michigan was 68 years.39 Location Melanoma occurs predominantly on the trunk in men and trunk and lower extremity in women. Several reports during the past several decades have documented a significant increase in melanoma on the trunk in men and women and lower extremities in women.20,22,27,34,35,44 This was attributed, in part, to behavioral, cultural, and lifestyle changes with respect to sun exposure, dress habits, and tropical vacationing that occurred after the 1940s. Others have theorized that the trunk and lower extremities are exposed to more intermittent acute episodes of ultraviolet radiation and are thus at greater risk for sunburns
684 Johnson et al. and the development of melanoma.45-48 Our results indicate a stable site distribution during the last decade; the trunk is still the most common site in men, and the trunk and lower extremity remains the most common site in women. Histologic subtype The incidence of superficial spreading melanoma increased significantly although the incidence of nodular melanoma decreased from the 1950s to the 1980s.22,42 Our results demonstrated that the SSM remained the most common histologic subtype during the last decade. There was a small shift in SSM in our female patients (52% to 63%; p = 0.04) during the last decade. Reports of a dramatic sixfold increase in the ageadjusted rate for melanoma in situ from 0.4 to 2.3 per 100,000 occurred from 1973 to 1987.27 In our series, the percentage of in situ lesions remained relatively stable in women and almost doubled in men. However, in men, this increase was not statistically significant (p = 0.11). Referral bias is possible because melanoma in situ may easily be managed in the office and never reported to a central tumor registry. Tumor thickness Numerous studies have revealed that tumor thickness changed markedly from the 1950s to the 1980s.5,12,13,22-24,28,41 During this period tumor thickness decreased from a predominance of more than 3 mm to an average of approximately 1 mm after 1980.22 The decrease in tumor thickness was attributed to increased public and physician education, awareness, and subsequent earlier detection.16 In 1994, 85.5% of all reported cases in the state of Michigan were diagnosed at a local stage: 11.3% in situ and 74.2% stages I and II. In our series from 1990 to 1995, 91% of cases were localized: 12% in situ and 79% stages I and II. From 1985 to 1994, our population parallels the percentages of total melanoma cases by stage at diagnosis reported to the Michigan Department of Community Health, Office of the State Registrar, and Division of Health Statistics.39 Although our population accurately reflects the reported cases, bias may exist because many thin lesions treated in the private practice office are not reported to the central registry. However, although a small increase in the proportion of cases staged as local-
Journal of the American Academy of Dermatology May 1998
ized occurred from 1984 to 1995 (86% to 91%), the overall mean tumor thickness slightly increased from 1.27 mm in 1984 to 1989 to 1.52 mm in 1990 to 1995 (p = 0.08). Furthermore, mean tumor thickness increased in men from 1.23 mm in the earlier period to 1.60 mm in the later period. The percentage of lesions ≥ 1 mm was 41% for the earlier time period compared with 47% for the latter period. The mean stage between the two periods also remained similar. Even with the possibility of referral bias, the national relatively stable overall survival of 80% to 85% during the past decade compared with 49% in 1954 supports the possibility that the trend of earlier detection may be slowing.16,30-33 Our tumor thickness results are similar to those reported in Connecticut. In the Connecticut study, 418 cases of melanoma from the time periods 1974 to 1976 and 1985 to 1987 were compared for changes in tumor thickness. The mean overall tumor thickness decreased from 2.03 mm in the first time period to 1.64 mm in the latter period. In men the mean thickness decreased from 2.08 to 1.87 mm and in women from 2.02 to 1.49 mm.49 The stage of disease and tumor thickness during the past decade in our series and the State of Michigan Central Melanoma Registry indicate an increase in the proportion of patients diagnosed with local disease probably because of the successful melanoma education programs. The current trend of stabilization in overall tumor thickness during the past decade suggests a slowing in the heightened awareness that occurred between the 1950s to the 1980s. Prevention programs, riskdirected interventions, and early school-based education programs are all important in stopping the melanoma epidemic. School-based programs that begin at an early age should be reviewed and carefully monitored for long-term behavioral changes and outcomes to determine effectiveness. Further research will be necessary to determine whether skin cancer prevention education can be effectively developed within the context of a broader health education program. Sun protection measures should be initiated with newborns and maintained throughout life.50-56 REFERENCES 1. Miller BA, Ries LAG, Hankey BF, et al. editors. SEER cancer statistics review: 1973 to 1990. Bethesda (MD): National Cancer Institure; 1993.
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2. Osterlind A. Epidemiology on malignant melanoma in Europe. Acta Oncol 1992;31:903-8. 3. Thorn M, Adami H, Bergstrom R, Ringborg U, Krusemo UB. Trends in survival from malignant melanoma: remarkable improvement in 23 years. J Natl Cancer Inst 1989;81:611-7. 4. Magnus K. Incidence of malignant melanoma in the skin in Norway 1955 to 1970. Variations in time and space and solar radiation. Cancer 1973;32:1275-86. 5. Garbe C, Wiebelt H, Orfanos CE. Change of epidemiological characteristics of malignant melanoma during the years 1962 to 1972 and 1983 to 1986 in the Federal Republic of Germany. Dermatologica 1989;178:131-5. 6. Osterlind A, Engholm G, Jensen OM. Trends in cutaneous malignant melanoma in Denmark 1943 to 1982 by anatomic site. APMIS 1988;96:953-63. 7. Green A, MacLennan R, Youl P, Martin N. Site distribution of cutaneous melanoma in Queensland. Int J Cancer 1993;53:232-6. 8. Elwood JM. Epidemiology and control of melanoma in white populations and in Japan. J Invest Dermatol 1989;92:214S-21S. 9. Urist MM, Karnell LH. The National Cancer Database: report on melanoma. Cancer 1994;74:782-8. 10. Roush GC, Schumura MJ, Holford TR. Patterns of invasive melanoma in the Connecticut tumor registry. Is the long-term increase real? Cancer 1988;61:2586-95. 11. Roush GC, Schumura MJ, Holford TR. Risk for cutaneous melanoma in recent Connecticut birth cohorts. Am J Pub Health 1985;75:679-82. 12. English DR, Heenan PJ, Holman C, et al. Melanoma in western Australia 1975-76 to 1980-81: trends in demographic and pathological characteristics. Int J Cancer 1986;37:209-15. 13. Balch 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;52:1748-53. 14. Anaise D, Steinitz R, Hur HB. Solar radiation: a possible etiological factor in malignant melanoma in Israel: a retrospective study. Cancer 1978;42:299-304. 15. Kosary CL, Ries LAG, Miller BA, et al. SEER cancer statistics review, 1973-1992: tables and graphs. NIH Pub No. 96-2789 ed. Bethesda (MD): National Cancer Institute; 1995. 16. Friedman RJ, Rigel DS, Silverman MK, Kopf AW, Vossaert KA. Malignant melanoma in the 1990’s: the continued importance of early detection and self-examination of the skin. CA Cancer J Clin 1991;41:201-26. 17. Sober AJ. Cutaneous melanoma: opportunity for cure. CA Cancer J Clin 1991;41:197-9. 18. Parker SL, Tong T, Bolden S, Wingo PA. Cancer statistics, 1996. CA Cancer J Clin 1997;47:5-27. 19. Sober A, Lew RA, Koh HK, Barnhill RL. Epidemiology of cutaneous melanoma. An update. Dermatol Clin 1991;9:617-29. 20. Magnus K. Habits of sun exposure and risk of malignant melanoma: an analysis of incidence rates in Norway 1955-1977 by cohort, sex, age, and primary tumor site. Cancer 1981;48:2329-35. 21. MacKie R, Hunter JAA, Aitchison TC, et al. Cutaneous malignant melanoma, Scotland, 1979-89. The Scottish Melanoma Group. Lancet 1992;339:971-5. 22. Balch CM, Shaw HM, Soong SJ, Milton GW. Changing trends in clinical and pathologic features of melanoma. In: Balch CM, Milton GW, Sahw HM, Soong SJ, editors.
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