Clinics in Dermatology
Volume 27, Issue 6 , Pages 529-536 , November 2009

Childhood melanoma

  • Melinda Jen, MD

      Affiliations

    • Department of Dermatology, University of Connecticut Health Center, 263 Farmington Avenue, Farmington, CT 06030, USA
  • ,
  • Michael Murphy, MD

      Affiliations

    • Department of Dermatology, University of Connecticut Health Center, 263 Farmington Avenue, Farmington, CT 06030, USA
  • ,
  • Jane M. Grant-Kels, MD

      Affiliations

    • Department of Dermatology, MC 6230, The Carole and Ray Neag Comprehensive Cancer Institute, University of Connecticut Health Center, 263 Farmington Avenue, Farmington, CT 06030, USA
    • Corresponding Author InformationCorresponding author. Fax: +1 860 679 1267.

References 

  1. Rao B, Hayes F, Pratt C, et al. Malignant melanoma in children: its management and prognosis. J Pediatr Surg. 1990;25:198–203
  2. Karlsson P, Fredrikson M. Cutaneous malignant melanoma in children and adolescents in Sweden, 1993-2002: the increasing trend is broken. Int J Cancer. 2007;121:323–328
  3. Saenz N, Saenz-Badillos J, Busam K, et al. Childhood melanoma survival. Cancer. 1999;85:750–754
  4. American Cancer Society. Cancer facts & figures 2008. Available at: http://www.cancer.org/downloads/STT/2008CAFFfinalsecured.pdf
  5. Ries LAG, Krapcho M, Stinchcomb DG, et al. SEER Cancer Statistics Review, 1975-2005. Bethesda (Md): National Cancer Institute; 2008;
  6. Ceballos P, Ruiz-Maldonado R, Mihm MJ. Melanoma in children. N Engl J Med. 1995;332:656–662
  7. Prosdocimo T, Smith M, Polack E. The diagnosis and treatment of childhood melanoma. W V Med J. 2002;98:149–151
  8. Gibbs P, Moore A, Robinson W, et al. Pediatric melanoma: are recent advances in the management of adult melanoma relevant to the pediatric population. J Pediatr Hematol Oncol. 2000;22:428–432
  9. Strouse J, Fears T, Tucker M, et al. Pediatric melanoma: risk factor and survival analysis of the surveillance, epidemiology and end results database. J Clin Oncol. 2005;23:4735–4741
  10. Hoang M, Eichenfield L. The rising incidence of melanoma in children and adolescents. Dermatol Nurs 2000;12:188-9, 92-3.
  11. Karlsson P, Boeryd B, Sander B, et al. Increasing incidence of cutaneous malignant melanoma in children and adolescents 12-19 years of age in Sweden 1973-92. Acta Derm Venereol. 1998;78:289–292
  12. McWhirter W, Dobson C, Ring I. Childhood cancer incidence in Australia, 1982-1991. Int J Cancer. 1996;65:34–38
  13. Whiteman D, Valery P, McWhirter W, et al. Incidence of cutaneous childhood melanoma in Queensland, Australia. Int J Cancer. 1995;63:765–768
  14. Berg P, Lindelöf B. Differences in malignant melanoma between children and adolescents. A 35-year epidemiological study. Arch Dermatol. 1997;133:295–297
  15. Ruiz-Maldonado R, Orozco-Covarrubias M. Malignant melanoma in children. A review. Arch Dermatol. 1997;133:363–371
  16. Hamre M, Chuba P, Bakhshi S, et al. Cutaneous melanoma in childhood and adolescence. Pediatr Hematol Oncol. 2002;19:309–317
  17. de Vries E, Steliarova-Foucher E, Spatz A, et al. Skin cancer incidence and survival in European children and adolescents (1978-1997). Report from the Automated Childhood Cancer Information System project. Eur J Cancer. 2006;42:2170–2182
  18. Lange J, Palis B, Chang D, et al. Melanoma in children and teenagers: an analysis of patients from the National Cancer Data Base. J Clin Oncol. 2007;25:1363–1368
  19. Boddie AJ, Smith JJ, McBride C. Malignant melanoma in children and young adults: effect of diagnostic criteria on staging and end results. South Med J. 1978;71:1074–1078
  20. Fishman C, Mihm MJ, Sober A. Diagnosis and management of nevi and cutaneous melanoma in infants and children. Clin Dermatol. 2002;20:44–50
  21. Richardson S, Tannous Z, Mihm MJ. Congenital and infantile melanoma: review of the literature and report of an uncommon variant, pigment-synthesizing melanoma. J Am Acad Dermatol. 2002;47:77–90
  22. Alexander A, Samlowski W, Grossman D, et al. Metastatic melanoma in pregnancy: risk of transplacental metastases in the infant. J Clin Oncol. 2003;21:2179–2186
  23. Conti E, Cercato M, Gatta G, et al. Childhood melanoma in Europe since 1978: a population-based survival study. Eur J Cancer. 2001;37:780–784
  24. Kaplan E. The risk of malignancy in large congenital nevi. Plast Reconstr Surg. 1974;53:421–428
  25. Marghoob A. Congenital melanocytic nevi. Evaluation and management. Dermatol Clin 2002;20:607-16, viii.
  26. Ferrari A, Bono A, Baldi M, et al. Does melanoma behave differently in younger children than in adults? A retrospective study of 33 cases of childhood melanoma from a single institution. Pediatrics. 2005;115:649–654
  27. Jafarian F, Powell J, Kokta V, et al. Malignant melanoma in childhood and adolescence: report of 13 cases. J Am Acad Dermatol. 2005;53:816–822
  28. Elwood J, Jopson J. Melanoma and sun exposure: an overview of published studies. Int J Cancer. 1997;73:198–203
  29. Roth M, Grant-Kels J, Kuhn M, et al. Melanoma in children. J Am Acad Dermatol. 1990;22:265–274
  30. Downard C, Rapkin L, Gow K. Melanoma in children and adolescents. Surg Oncol. 2007;16:215–220
  31. Pappo A. Melanoma in children and adolescents. Eur J Cancer. 2003;39:2651–2661
  32. Tromberg J, Bauer B, Benvenuto-Andrade C, et al. Congenital melanocytic nevi needing treatment. Dermatol Ther. 2005;18:136–150
  33. Tannous Z, Mihm MJ, Sober A, et al. Congenital melanocytic nevi: clinical and histopathologic features, risk of melanoma, and clinical management. J Am Acad Dermatol. 2005;52:197–203
  34. Krengel S, Hauschild A, Schäfer T. Melanoma risk in congenital melanocytic naevi: a systematic review. Br J Dermatol. 2006;155:1–8
  35. Schaffer J, Bolognia J. The clinical spectrum of pigmented lesions. Clin Plast Surg 2000;27:391-408, viii.
  36. Kadonaga J, Frieden I. Neurocutaneous melanosis: definition and review of the literature. J Am Acad Dermatol. 1991;24:747–755
  37. Schmid-Wendtner M, Berking C, Baumert J, et al. Cutaneous melanoma in childhood and adolescence: an analysis of 36 patients. J Am Acad Dermatol. 2002;46:874–879
  38. Novakovic B, Clark WJ, Fears T, et al. Melanocytic nevi, dysplastic nevi, and malignant melanoma in children from melanoma-prone families. J Am Acad Dermatol. 1995;33:631–636
  39. Greene M. Dysplastic nevus syndrome. Hosp Pract (Off Ed) 1984;19:91-103, 7-8.
  40. Salopek T. The dilemma of the dysplastic nevus. Dermatol Clin 2002;20:617-28, viii.
  41. Whiteman D, Milligan A, Welch J, et al. Germline CDKN2A mutations in childhood melanoma. J Natl Cancer Inst. 1997;89:1460
  42. Soufir N, Ollivaud L, Bertrand G, et al. A French CDK4-positive melanoma family with a co-inherited EDNRB mutation. J Dermatol Sci. 2007;46:61–64
  43. Eliason M, Larson A, Florell S, et al. Population-based prevalence of CDKN2A mutations in Utah melanoma families. J Invest Dermatol. 2006;126:660–666
  44. Gensini F, Sestini R, Piazzini M, et al. The p.G23S CDKN2A founder mutation in high-risk melanoma families from Central Italy. Melanoma Res. 2007;17:387–392
  45. Goldstein A, Chan M, Harland M, et al. Features associated with germline CDKN2A mutations: a GenoMEL study of melanoma-prone families from three continents. J Med Genet. 2007;44:99–106
  46. Helsing P, Nymoen DA, Ariansen S, et al. Population-based prevalence of CDKN2A and CDK4 mutations in patients with multiple primary melanomas. Genes Chromosomes Cancer. 2008;47:175–184
  47. Lang J, Boxer M, MacKie R. CDKN2A mutations in Scottish families with cutaneous melanoma: results from 32 newly identified families. Br J Dermatol. 2005;153:1121–1125
  48. Ung-Juurlink C. American Academy of Dermatology 1999 Awards for Young Investigators in Dermatology. The prevalence of CDKN2A in patients with atypical nevi and malignant melanoma. J Am Acad Dermatol. 1999;41:461–462
  49. Newton Bishop J, Gruis N. Genetics: what advice for patients who present with a family history of melanoma?. Semin Oncol. 2007;34:452–459
  50. Tsao H, Niendorf K. Genetic testing in hereditary melanoma. J Am Acad Dermatol. 2004;51:803–808
  51. Della Torre G, Pasini B, Frigerio S, et al. CDKN2A and CDK4 mutation analysis in Italian melanoma-prone families: functional characterization of a novel CDKN2A germ line mutation. Br J Cancer. 2001;85:836–844
  52. Pjanova D, Engele L, Randerson-Moor J, et al. CDKN2A and CDK4 variants in Latvian melanoma patients: analysis of a clinic-based population. Melanoma Res. 2007;17:185–191
  53. Zuo L, Weger J, Yang Q, et al. Germline mutations in the p16INK4a binding domain of CDK4 in familial melanoma. Nat Genet. 1996;12:97–99
  54. Molven A, Grimstvedt M, Steine S, et al. A large Norwegian family with inherited malignant melanoma, multiple atypical nevi, and CDK4 mutation. Genes Chromosomes Cancer. 2005;44:10–18
  55. Goldstein A, Chidambaram A, Halpern A, et al. Rarity of CDK4 germline mutations in familial melanoma. Melanoma Res. 2002;12:51–55
  56. Snels D, Hille E, Gruis N, et al. Risk of cutaneous malignant melanoma in patients with nonfamilial atypical nevi from a pigmented lesions clinic. J Am Acad Dermatol. 1999;40:686–693
  57. Garbe C, Büttner 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;102:695–699
  58. Holly E, Kelly J, Shpall S, et al. Number of melanocytic nevi as a major risk factor for malignant melanoma. J Am Acad Dermatol. 1987;17:459–468
  59. Bataille V, Bishop J, Sasieni P, et al. Risk of cutaneous melanoma in relation to the numbers, types and sites of naevi: a case-control study. Br J Cancer. 1996;73:1605–1611
  60. MacKie R, Freudenberger T, Aitchison T. Personal risk-factor chart for cutaneous melanoma. Lancet. 1989;2:487–490
  61. Grob J, Gouvernet J, Aymar D, et al. Count of benign melanocytic nevi as a major indicator of risk for nonfamilial nodular and superficial spreading melanoma. Cancer. 1990;66:387–395
  62. Naldi L, Lorenzo Imberti G, Parazzini F, et al. Pigmentary traits, modalities of sun reaction, history of sunburns, and melanocytic nevi as risk factors for cutaneous malignant melanoma in the Italian population: results of a collaborative case-control study. Cancer. 2000;88:2703–2710
  63. Roush G, Nordlund J, Forget B, et al. Independence of dysplastic nevi from total nevi in determining risk for nonfamilial melanoma. Prev Med. 1988;17:273–279
  64. Grulich A, Bataille V, Swerdlow A, et al. Naevi and pigmentary characteristics as risk factors for melanoma in a high-risk population: a case-control study in New South Wales, Australia. Int J Cancer. 1996;67:485–491
  65. Tucker M, Halpern A, Holly E, et al. Clinically recognized dysplastic nevi. A central risk factor for cutaneous melanoma. JAMA. 1997;277:1439–1444
  66. Penn I. Development of cancer in transplantation patients. Adv Surg. 1978;12:155–191
  67. Tucker M, Misfeldt D, Coleman C, et al. Cutaneous malignant melanoma after Hodgkin's disease. Ann Intern Med. 1985;102:37–41
  68. Baird E, McHenry P, MacKie R. Effect of maintenance chemotherapy in childhood on numbers of melanocytic naevi. BMJ. 1992;305:799–801
  69. Melnik M, Urdaneta L, Al-Jurf A, et al. Malignant melanoma in childhood and adolescence. Am Surg. 1986;52:142–147
  70. Wechsler J, Bastuji-Garin S, Spatz A, et al. Reliability of the histopathologic diagnosis of malignant melanoma in childhood. Arch Dermatol. 2002;138:625–628
  71. Roaten J, Partrick D, Bensard D, et al. Survival in sentinel lymph node-positive pediatric melanoma. J Pediatr Surg. 2005;40:988–992[discussion 92]
  72. Gamblin T, Edington H, Kirkwood J, et al. Sentinel lymph node biopsy for atypical melanocytic lesions with spitzoid features. Ann Surg Oncol. 2006;13:1664–1670
  73. Lohmann C, Coit D, Brady M, et al. Sentinel lymph node biopsy in patients with diagnostically controversial spitzoid melanocytic tumors. Am J Surg Pathol. 2002;26:47–55
  74. Su L, Fullen D, Sondak V, et al. Sentinel lymph node biopsy for patients with problematic spitzoid melanocytic lesions: a report on 18 patients. Cancer. 2003;97:499–507
  75. Balch C. Cutaneous melanoma: prognosis and treatment results worldwide. Semin Surg Oncol. 1992;8:400–414
  76. LeBoit P. “Safe” Spitz and its alternatives. Pediatr Dermatol. 2002;19:163–165
  77. Mones J, Ackerman A. “Atypical” Spitz's nevus, “malignant” Spitz's nevus, and “metastasizing” Spitz's nevus: a critique in historical perspective of three concepts flawed fatally. Am J Dermatopathol. 2004;26:310–333
  78. Barnhill R, Flotte T, Fleischli M, et al. Cutaneous melanoma and atypical Spitz tumors in childhood. Cancer. 1995;76:1833–1845
  79. Gurbuz Y, Apaydin R, Muezzinoğlu B, et al. A current dilemma in histopathology: atypical spitz tumor or Spitzoid melanoma?. Pediatr Dermatol. 2002;19:99–102
  80. Bauer J, Bastian B. Distinguishing melanocytic nevi from melanoma by DNA copy number changes: comparative genomic hybridization as a research and diagnostic tool. Dermatol Ther. 2006;19:40–49
  81. Sander B, Karlsson P, Rosdahl I, et al. Cutaneous malignant melanoma in Swedish children and teenagers 1973-1992: a clinico-pathological study of 130 cases. Int J Cancer. 1999;80:646–651
  82. Balch C, Buzaid A, Soong S, et al. Final version of the American Joint Committee on Cancer staging system for cutaneous melanoma. J Clin Oncol. 2001;19:3635–3648
  83. NCCN . NCCN clinical practice guidelines in oncology: melanoma (V.2.2008). Washington, DC: National Comprehensive Cancer Network; 2008;
  84. Topar G, Zelger B. Assessment of value of the sentinel lymph node biopsy in melanoma in children and adolescents and applicability of subcutaneous infusion anesthesia. J Pediatr Surg. 2007;42:1716–1720
  85. Bütter A, Hui T, Chapdelaine J, et al. Melanoma in children and the use of sentinel lymph node biopsy. J Pediatr Surg. 2005;40:797–800
  86. Baas P, Hoekstra H, Schraffordt Koops H, et al. Hyperthermic isolated regional perfusion in the treatment of extremity melanoma in children and adolescents. Cancer. 1989;63:199–203
  87. Boddie AJ, Cangir A. Adjuvant and neoadjuvant chemotherapy with dacarbazine in high-risk childhood melanoma. Cancer. 1987;60:1720–1723
  88. Hayes F, Green A. Malignant melanoma in childhood: clinical course and response to chemotherapy. J Clin Oncol. 1984;2:1229–1234
  89. Huynh P, Grant-Kels J, Grin C. Childhood melanoma: update and treatment. Int J Dermatol. 2005;44:715–723
  90. Bernstein I, Wright P. Immunology and immunotherapy of childhood neoplasia. Pediatr Clin North Am. 1976;23:93–109
  91. Morton D, Eilber F, Malmgren R, et al. Immunological factors which influence response to immunotherapy in malignant melanoma. Surgery. 1970;68:158–163[discussion 63-4]
  92. Arons M, Hurwitz S. Congenital nevocellular nevus: a review of the treatment controversy and a report of 46 cases. Plast Reconstr Surg. 1983;72:355–365
  93. Eilber F, Morton D, Holmes E, et al. Adjuvant immunotherapy with BCG in treatment of regional-lymph-node metastases from malignant melanoma. N Engl J Med. 1976;294:237–240
  94. Kölmel K, Grange J, Krone B, et al. Prior immunisation of patients with malignant melanoma with vaccinia or BCG is associated with better survival. An European Organization for Research and Treatment of Cancer cohort study on 542 patients. Eur J Cancer. 2005;41:118–125
  95. Moritz M, Wallack M. Survival after malignant melanoma in a black child. A case report and review of the literature. Am J Clin Oncol. 1984;7:545–549
  96. Agarwala S, Neuberg D, Park Y, et al. Mature results of a phase III randomized trial of bacillus Calmette-Guerin (BCG) versus observation and BCG plus dacarbazine versus BCG in the adjuvant therapy of American Joint Committee on Cancer Stage I-III melanoma (E1673): a trial of the Eastern Oncology Group. Cancer. 2004;100:1692–1698
  97. Kefford R. Adjuvant therapy of cutaneous melanoma: the interferon debate. Ann Oncol. 2003;14:358–365
  98. Kirkwood J, Strawderman M, Ernstoff M, et al. Interferon alfa-2b adjuvant therapy of high-risk resected cutaneous melanoma: the Eastern Cooperative Oncology Group Trial EST 1684. J Clin Oncol. 1996;14:7–17
  99. Chiarion-Sileni V, Del Bianco P, Romanini A, et al. Tolerability of intensified intravenous interferon alfa-2b versus the ECOG 1684 schedule as adjuvant therapy for stage III melanoma: a randomized phase III Italian Melanoma Inter-group trial (IMI - Mel.A.) [ISRCTN75125874]. BMC Cancer. 2006;6:44
  100. Navid F, Furman W, Fleming M, et al. The feasibility of adjuvant interferon alpha-2b in children with high-risk melanoma. Cancer. 2005;103:780–787
  101. Rosenberg S, Yang J, White D, et al. Durability of complete responses in patients with metastatic cancer treated with high-dose interleukin-2: identification of the antigens mediating response. Ann Surg. 1998;228:307–319
  102. Phan G, Attia P, Steinberg S, et al. Factors associated with response to high-dose interleukin-2 in patients with metastatic melanoma. J Clin Oncol. 2001;19:3477–3482
  103. Bauer M, Reaman G, Hank J, et al. A phase II trial of human recombinant interleukin-2 administered as a 4-day continuous infusion for children with refractory neuroblastoma, non-Hodgkin's lymphoma, sarcoma, renal cell carcinoma, and malignant melanoma. A Childrens Cancer Group study. Cancer. 1995;75:2959–2965
  104. Osenga K, Hank J, Albertini M, et al. A phase I clinical trial of the hu14.18-IL2 (EMD 273063) as a treatment for children with refractory or recurrent neuroblastoma and melanoma: a study of the Children's Oncology Group. Clin Cancer Res. 2006;12:1750–1759
  105. Ribeiro R, Rill D, Roberson P, et al. Continuous infusion of interleukin-2 in children with refractory malignancies. Cancer. 1993;72:623–628
  106. Roper M, Smith M, Sondel P, et al. A phase I study of interleukin-2 in children with cancer. Am J Pediatr Hematol Oncol. 1992;14:305–311
  107. Soni S, Lee D, DiVito JJ, et al. Treatment of pediatric ocular melanoma with high-dose interleukin-2 and thalidomide. J Pediatr Hematol Oncol. 2002;24:488–491
  108. Hamm C, Verma S, Petrella T, et al. Biochemotherapy for the treatment of metastatic malignant melanoma: a systematic review. Cancer Treat Rev. 2008;34:145–156
  109. Mitchell M, Abrams J, Thompson J, et al. Randomized trial of an allogeneic melanoma lysate vaccine with low-dose interferon Alfa-2b compared with high-dose interferon Alfa-2b for Resected stage III cutaneous melanoma. J Clin Oncol. 2007;25:2078–2085
  110. Ives N, Stowe R, Lorigan P, et al. Chemotherapy compared with biochemotherapy for the treatment of metastatic melanoma: a meta-analysis of 18 trials involving 2,621 patients. J Clin Oncol. 2007;25:5426–5434
  111. Sasse A, Sasse E, Clark L, et al. Chemoimmunotherapy versus chemotherapy for metastatic malignant melanoma. Cochrane Database Syst Rev. 2007;CD005413
  112. Recchia F, Candeloro G, Necozione S, et al. Multicenter phase II study of chemoimmunotherapy in the treatment of metastatic melanoma. Anticancer Drugs. 2008;19:201–207
  113. Spieth K, Kaufmann R, Dummer R, et al. Temozolomide plus pegylated interferon alfa-2b as first-line treatment for stage IV melanoma: a multicenter phase II trial of the Dermatologic Cooperative Oncology Group (DeCOG). Ann Oncol. 2008;19:801–806
  114. Terando A, Faries M, Morton D. Vaccine therapy for melanoma: current status and future directions. Vaccine. 2007;25(Suppl 2):B4–B16
  115. Mitchell M, Jakowatz J, Harel W, et al. Increased effectiveness of interferon alfa-2b following active specific immunotherapy for melanoma. J Clin Oncol. 1994;12:402–411
  116. Vaishampayan U, Abrams J, Darrah D, et al. Active immunotherapy of metastatic melanoma with allogeneic melanoma lysates and interferon alpha. Clin Cancer Res. 2002;8:3696–3701
  117. Livestro D, Kaine E, Michaelson J, et al. Melanoma in the young: differences and similarities with adult melanoma: a case-matched controlled analysis. Cancer. 2007;110:614–624

PII: S0738-081X(08)00188-0

doi: 10.1016/j.clindermatol.2008.09.011

Clinics in Dermatology
Volume 27, Issue 6 , Pages 529-536 , November 2009