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Melanoma in Children and Teenagers

  • Ines B. Brecht
  • Ira J. Dunkel
  • Claus GarbeEmail author
Living reference work entry

Abstract

Melanoma occurs in all age groups. While under the age of 10 years melanoma is exceedingly rare, increasing numbers are seen within puberty and young adulthood. Under the age of 10 years, melanoma qualifies as an orphan disease, and the annual incidence is <2 per million; no clinical studies exist, evidence-based guidelines for diagnosis and treatment as well as information on biological behavior are scarce. Before puberty, melanoma often presents with atypical amelanotic or raised lesions and does not follow the ABCDE rule. Diagnosis is often challenging as no consensus criteria for “melanocytic tumors of uncertain malignant potential” (MELTUMP), atypical Spitz tumors, and true melanoma do exist. On the other hand, survival and risk factors are similar to those found in adults. While surgical and medical management still follows adult guidelines, there has been a better understanding of specific characteristics of pediatric melanoma, recently. First pediatric clinical studies have been conducted.

References

  1. Balch CM1, Buzaid AC, Soong SJ, Atkins MB, Cascinelli N, Coit DG, Fleming ID, Gershenwald JE, Houghton A Jr, Kirkwood JM, McMasters KM, Mihm MF, Morton DL, Reintgen DS, Ross MI, Sober A, Thompson JA, Thompson JF (2001). Final version of the American Joint Committee on Cancer staging system for cutaneous melanoma. J Clin Oncol 19(16):3635–48PubMedCrossRefGoogle Scholar
  2. Balch CM, Soong SJ, Gershenwald JE, Thompson JF, Coit DG, Atkins MB, Ding S, Cochran AJ, Eggermont AM, Flaherty KT, Gimotty PA, Johnson TM, Kirkwood JM, Leong SP, McMasters KM, Mihm MC Jr, Morton DL, Ross MI, Sondak VK (2013) Age as a prognostic factor in patients with localized melanoma and regional metastases. Ann Surg Oncol 20:3961–3968PubMedPubMedCentralCrossRefGoogle Scholar
  3. Balch CM, Thompson JF, Gershenwald JE, Soong SJ, Ding S, McMasters KM, Coit DG, Eggermont AM, Gimotty PA, Johnson TM, Kirkwood JM, Leong SP, Ross MI, Byrd DR, Cochran AJ, Mihm MC Jr, Morton DL, Atkins MB, Flaherty KT, Sondak VK (2014) Age as a predictor of sentinel node metastasis among patients with localized melanoma: an inverse correlation of melanoma mortality and incidence of sentinel node metastasis among young and old patients. Ann Surg Oncol 21:1075–1081PubMedPubMedCentralCrossRefGoogle Scholar
  4. Barnhill RL, Fleischli M (1995) Histologic features of congenital melanocytic nevi in infants 1 year of age or younger. J Am Acad Dermatol 33:780–785PubMedCrossRefPubMedCentralGoogle Scholar
  5. Bastian BC, Leboit PE, Pinkel D (2000) Mutations and copy number increase of HRAS in Spitz nevi with distinctive histopathological features. Am J Pathol 157:967–972PubMedPubMedCentralCrossRefGoogle Scholar
  6. Bisogno G, Ferrari A, Bien E, Brecht IB, Brennan B, Cecchetto G, Godzinski J, Orbach D, Reguerre Y, Stachowicz-Stencel T, Schneider DT (2012) Rare cancers in children – the EXPeRT Initiative: a report from the European Cooperative Study Group on Pediatric Rare Tumors. Klin Padiatr 224:416–420PubMedCrossRefPubMedCentralGoogle Scholar
  7. Bittencourt FV, Marghoob AA, Kopf AW, Koenig KL, Bart RS (2000) Large congenital melanocytic nevi and the risk for development of malignant melanoma and neurocutaneous melanocytosis. Pediatrics 106:736–741PubMedCrossRefPubMedCentralGoogle Scholar
  8. Brecht IB, Garbe C, Gefeller O, Pfahlberg A, Bauer J, Eigentler TK, Offenmueller S, Schneider DT, Leiter U (2015) 443 paediatric cases of malignant melanoma registered with the German Central Malignant Melanoma Registry between 1983 and 2011. Eur J Cancer 51:861–868PubMedCrossRefPubMedCentralGoogle Scholar
  9. Brecht IB, De Paoli A, Bisogno G, Orbach D, Schneider DT, Leiter U, Offenmueller S, Cecchetto G, Godzinski J, Bien E, Stachowicz-Stencel T, Ben-Ami T, Chiaravalli S, Maurichi A, De Salvo GL, Sorbara S, Bodemer C, Garbe C, Reguerre Y, Ferrari A (2018) Pediatric patients with cutaneous melanoma: a European study. Pediatr Blood Cancer 65:e26974PubMedCrossRefPubMedCentralGoogle Scholar
  10. Campbell LB, Kreicher KL, Gittleman HR, Strodtbeck K, Barnholtz-Sloan J, Bordeaux JS (2015) Melanoma incidence in children and adolescents: decreasing trends in the United States. J Pediatr 166:1505–1513PubMedCrossRefGoogle Scholar
  11. Castilla EE, Da Graca Dutra M, Orioli-Parreiras IM (1981) Epidemiology of congenital pigmented naevi: I. Incidence rates and relative frequencies. Br J Dermatol 104:307–315PubMedCrossRefGoogle Scholar
  12. Cerroni L, Barnhill R, Elder D, Gottlieb G, Heenan P, Kutzner H, Leboit PE, Mihm M Jr, Rosai J, Kerl H (2010) Melanocytic tumors of uncertain malignant potential: results of a tutorial held at the XXIX Symposium of the International Society of Dermatopathology in Graz, October 2008. Am J Surg Pathol 34:314–326PubMedCrossRefGoogle Scholar
  13. Chao C, Martin RC 2nd, Ross MI, Reintgen DS, Edwards MJ, Noyes RD, Hagendoorn LJ, Stromberg AJ, McMasters KM (2004) Correlation between prognostic factors and increasing age in melanoma. Ann Surg Oncol 11:259–264PubMedCrossRefGoogle Scholar
  14. Chao MM, Schwartz JL, Wechsler DS, Thornburg CD, Griffith KA, Williams JA (2005) High-risk surgically resected pediatric melanoma and adjuvant interferon therapy. Pediatr Blood Cancer 44:441–448PubMedCrossRefGoogle Scholar
  15. Chisholm JC, Suvada J, Dunkel IJ, Casanova M, Zhang W, Ritchie N, Choi Y, Park J, Das Thakur M, Simko S, Wan Rachel Tam N, Ferrari A (2018) BRIM-P: a phase I, open-label, multicenter, dose-escalation study of vemurafenib in pediatric patients with surgically incurable, BRAF mutation-positive melanoma. Pediatr Blood Cancer 65:e26947PubMedPubMedCentralCrossRefGoogle Scholar
  16. Chuk MK, Mulugeta Y, Roth-Cline M, Mehrotra N, Reaman GH (2017) Enrolling adolescents in disease/target-appropriate adult oncology clinical trials of investigational agents. Clin Cancer Res 23:9–12PubMedCrossRefGoogle Scholar
  17. Cordoro KM, Gupta D, Frieden IJ, Mccalmont T, Kashani-Sabet M (2013) Pediatric melanoma: results of a large cohort study and proposal for modified ABCD detection criteria for children. J Am Acad Dermatol 68:913–925PubMedCrossRefGoogle Scholar
  18. Crotty KA, Scolyer RA, Li L, Palmer AA, Wang L, McCarthy SW (2002) Spitz naevus versus Spitzoid melanoma: when and how can they be distinguished? Pathology 34:6–12PubMedCrossRefGoogle Scholar
  19. Davar D, Lin Y, Kirkwood JM (2015) Unfolding the mutational landscape of human melanoma. J Invest Dermatol 135:659–662PubMedPubMedCentralCrossRefGoogle Scholar
  20. Davis KL, Fox E, Reid JM et al (2017) ADVL1412: initial results of a phase I/II study of nivolumab and ipilimumab in pediatric patients with relapsed/refractory solid tumors – a COG study. J Clin Oncol 35:10526CrossRefGoogle Scholar
  21. De Vries E, Steliarova-Foucher E, Spatz A, Ardanaz E, Eggermont AM, Coebergh JW (2006) Skin cancer incidence and survival in European children and adolescents (1978–1997). Report from the Automated Childhood Cancer Information System project. Eur J Cancer 42:2170–2182PubMedCrossRefGoogle Scholar
  22. De David M, Orlow SJ, Provost N, Marghoob AA, Rao BK, Huang CL, Wasti Q, Kopf AW, Bart RS (1997) A study of large congenital melanocytic nevi and associated malignant melanomas: review of cases in the New York University Registry and the world literature. J Am Acad Dermatol 36:409–416CrossRefGoogle Scholar
  23. Ferrari A, Bono A, Baldi M, Collini P, Casanova M, Pennacchioli E, Terenziani M, Marcon I, Santinami M, Bartoli C (2005) Does melanoma behave differently in younger children than in adults? A retrospective study of 33 cases of childhood melanoma from a single institution. Pediatrics 115:649–654PubMedCrossRefGoogle Scholar
  24. Ferrari A, Bisogno G, Cecchetto G, Santinami M, Maurichi A, Bono A, Vajna De Pava M, Pierani P, Bertolini P, Rossi CR, De Salvo GL (2014) Cutaneous melanoma in children and adolescents: the Italian rare tumors in pediatric age project experience. J Pediatr 164:376–382.e2PubMedCrossRefGoogle Scholar
  25. Garbe C, Peris K, Hauschild A, Saiag P, Middleton M, Bastholt L, Grob JJ, Malvehy J, Newton-Bishop J, Stratigos AJ, Pehamberger H, Eggermont AM, European Dermatology Forum, European Association of Dermato-Oncology, European Organisation for Research & Treatment of Cancer (2016) Diagnosis and treatment of melanoma. European consensus-based interdisciplinary guideline – update 2016. Eur J Cancer 63:201–217PubMedCrossRefGoogle Scholar
  26. Geoerger B, Bergeron C, Gore L, Sender L, Dunkel IJ, Herzog C, Brochez L, Cruz O, Nysom K, Berghorn E, Simsek B, Shen J, Pappo A (2017) Phase II study of ipilimumab in adolescents with unresectable stage III or IV malignant melanoma. Eur J Cancer 86:358–363PubMedCrossRefGoogle Scholar
  27. Geoerger B, Moertel CL, Whitlock J et al (2018) Phase 1 trial of trametinib alone and in combination with dabrafenib in children and adolescents with relapsed solid tumors or neurofibromatosis type 1 progressive plexiform neurofibromas. J Clin Oncol 36:10537CrossRefGoogle Scholar
  28. Gerami P, Li G, Pouryazdanparast P, Blondin B, Beilfuss B, Slenk C, Du J, Guitart J, Jewell S, Pestova K (2012) A highly specific and discriminatory Fish assay for distinguishing between benign and malignant melanocytic neoplasms. Am J Surg Pathol 36:808–817PubMedCrossRefGoogle Scholar
  29. Gibbs P, Moore A, Robinson W, Walsh P, Golitz L, Gonzalez R (2000) Pediatric melanoma: are recent advances in the management of adult melanoma relevant to the pediatric population. J Pediatr Hematol Oncol 22:428–432PubMedCrossRefGoogle Scholar
  30. Gosain AK, Santoro TD, Larson DL, Gingrass RP (2001) Giant congenital nevi: a 20-year experience and an algorithm for their management. Plast Reconstr Surg 108:622–636PubMedCrossRefGoogle Scholar
  31. Hargrave DR, Moreno L, Broniscer A et al (2018) Dabrafenib in pediatric patients with BRAF V600-positive high-grade glioma. J Clin Oncol 36:10505CrossRefGoogle Scholar
  32. Howman-Giles R, Shaw HM, Scolyer RA, Murali R, Wilmott J, McCarthy SW, Uren RF, Thompson JF (2010) Sentinel lymph node biopsy in pediatric and adolescent cutaneous melanoma patients. Ann Surg Oncol 17:138–143PubMedCrossRefPubMedCentralGoogle Scholar
  33. Indini A, Brecht I, Del Vecchio M, Sultan I, Signoroni S, Ferrari A (2018) Cutaneous melanoma in adolescents and young adults. Pediatr Blood Cancer 65:e27292PubMedCrossRefPubMedCentralGoogle Scholar
  34. Kadonaga JN, Frieden IJ (1991) Neurocutaneous melanosis: definition and review of the literature. J Am Acad Dermatol 24:747–755PubMedCrossRefPubMedCentralGoogle Scholar
  35. Karlsson PM, Fredrikson M (2007) Cutaneous malignant melanoma in children and adolescents in Sweden, 1993–2002: the increasing trend is broken. Int J Cancer 121:323–328PubMedCrossRefPubMedCentralGoogle Scholar
  36. Kieran MW, Bouffet E, Broniscer A et al (2018) Efficacy and safety results from a phase I/IIa study of dabrafenib in pediatric patients with BRAF V600–mutant relapsed refractory low-grade glioma. J Clin Oncol 36:10506CrossRefGoogle Scholar
  37. Kinsler VA, O’Hare P, Bulstrode N, Calonje JE, Chong WK, Hargrave D, Jacques T, Lomas D, Sebire NJ, Slater O (2017) Melanoma in congenital melanocytic naevi. Br J Dermatol 176:1131–1143PubMedPubMedCentralCrossRefGoogle Scholar
  38. Kraemer KH, Lee MM, Andrews AD, Lambert WC (1994) The role of sunlight and DNA repair in melanoma and nonmelanoma skin cancer. The xeroderma pigmentosum paradigm. Arch Dermatol 130:1018–1021PubMedCrossRefPubMedCentralGoogle Scholar
  39. Lallas A, Kyrgidis A, Ferrara G, Kittler H, Apalla Z, Castagnetti F, Longo C, Moscarella E, Piana S, Zalaudek I, Argenziano G (2014) Atypical Spitz tumours and sentinel lymph node biopsy: a systematic review. Lancet Oncol 15:e178–e183PubMedCrossRefPubMedCentralGoogle Scholar
  40. Lange JR, Palis BE, Chang DC, Soong SJ, Balch CM (2007) Melanoma in children and teenagers: an analysis of patients from the National Cancer Data Base. J Clin Oncol 25:1363–1368PubMedCrossRefPubMedCentralGoogle Scholar
  41. Leiter U, Eigentler T, Garbe C (2014) Epidemiology of skin cancer. Adv Exp Med Biol 810:120–140PubMedGoogle Scholar
  42. Lewis KG (2008) Trends in pediatric melanoma mortality in the United States, 1968 through 2004. Dermatol Surg 34:152–159PubMedCrossRefGoogle Scholar
  43. Lu C, Zhang J, Nagahawatte P, Easton J, Lee S, Liu Z, Ding L, Wyczalkowski MA, Valentine M, Navid F, Mulder H, Tatevossian RG, Dalton J, Davenport J, Yin Z, Edmonson M, Rusch M, Wu G, Li Y, Parker M, Hedlund E, Shurtleff S, Raimondi S, Bhavin V, Donald Y, Mardis ER, Wilson RK, Evans WE, Ellison DW, Pounds S, Dyer M, Downing JR, Pappo A, Bahrami A (2015) The genomic landscape of childhood and adolescent melanoma. J Invest Dermatol 135:816–823PubMedCrossRefGoogle Scholar
  44. Merchant MS, Wright M, Baird K, Wexler LH, Rodriguez-Galindo C, Bernstein D, Delbrook C, Lodish M, Bishop R, Wolchok JD, Streicher H, Mackall CL (2016) Phase I clinical trial of ipilimumab in pediatric patients with advanced solid tumors. Clin Cancer Res 22:1364–1370PubMedCrossRefGoogle Scholar
  45. Navid F, Furman WL, Fleming M, Rao BN, Kovach S, Billups CA, Cain AM, Amonette R, Jenkins JJ, Pappo AS (2005) The feasibility of adjuvant interferon alpha-2b in children with high-risk melanoma. Cancer 103:780–787PubMedCrossRefGoogle Scholar
  46. Offenmueller S, Leiter U, Bernbeck B, Garbe C, Eigentler T, Borkhardt A, Friedrich Classen C, Corbacioglu S, Dirksen U, Ebetsberger-Dachs G, Heinzerling L, Jorch N, Kuhlen M, Lawlor J, Niggli F, Streiter M, Schneider DT, Brecht I (2017) Clinical characteristics and outcome of 60 pediatric patients with malignant melanoma registered with the German Pediatric Rare Tumor Registry (Step). Klin Padiatr 229:322–328PubMedCrossRefGoogle Scholar
  47. Pappo AS (2003) Melanoma in children and adolescents. Eur J Cancer 39:2651–2661PubMedCrossRefPubMedCentralGoogle Scholar
  48. Pappo AS, Kaste SC, Rao BN, Pratt CB (1998) Childhood melanoma. In: Balch CM, Houghton AN, Sober AJ, Soong SJ (eds) Cutaneous melanoma, 3rd edn. Quality Medical Publishing, St. Louis, p 177Google Scholar
  49. Prose NS, Laude TA, Heilman ER, Coren C (1987) Congenital malignant melanoma. Pediatrics 79:967–970PubMedPubMedCentralGoogle Scholar
  50. Rhodes AR (2011) Prognostic usefulness of sentinel lymph node biopsy for patients who have clinically node negative, localized, primary invasive cutaneous melanoma: a Bayesian analysis using informative published reports. Arch Dermatol 147:408–415PubMedCrossRefGoogle Scholar
  51. Richardson SK, Tannous ZS, Mihm MC Jr (2002) Congenital and infantile melanoma: review of the literature and report of an uncommon variant, pigment-synthesizing melanoma. J Am Acad Dermatol 47:77–90PubMedCrossRefGoogle Scholar
  52. Roaten JB, Partrick DA, Pearlman N, Gonzalez RJ, Gonzalez R, McCarter MD (2005) Sentinel lymph node biopsy for melanoma and other melanocytic tumors in adolescents. J Pediatr Surg 40:232–235PubMedCrossRefGoogle Scholar
  53. Saenz NC, Saenz-Badillos J, Busam K, Laquaglia MP, Corbally M, Brady MS (1999) Childhood melanoma survival. Cancer 85:750–754PubMedCrossRefGoogle Scholar
  54. Shah NC, Gerstle JT, Stuart M, Winter C, Pappo A (2006) Use of sentinel lymph node biopsy and high-dose interferon in pediatric patients with high-risk melanoma: the Hospital for Sick Children experience. J Pediatr Hematol Oncol 28:496–500PubMedCrossRefGoogle Scholar
  55. Strouse JJ, Fears TR, Tucker MA, Wayne AS (2005) Pediatric melanoma: risk factor and survival analysis of the surveillance, epidemiology and end results database. J Clin Oncol 23:4735–4741PubMedCrossRefGoogle Scholar
  56. Whiteman DC, Milligan A, Welch J, et al. (1997). Germline CDKN2A mutations in childhood melanoma. J Natl Cancer Inst 89:1460.PubMedCrossRefGoogle Scholar
  57. Wong JR, Harris JK, Rodriguez-Galindo C, Johnson KJ (2013) Incidence of childhood and adolescent melanoma in the United States: 1973–2009. Pediatrics 131:846–854PubMedPubMedCentralCrossRefGoogle Scholar
  58. Wouters MW, Michielin O, Bastiaannet E, Beishon M, Catalano O, Del Marmol V, Delgado-Bolton R, Dendale R, Trill MD, Ferrari A, Forsea AM, Kreckel H, Lovey J, Luyten G, Massi D, Mohr P, Oberst S, Pereira P, Prata JPP, Rutkowski P, Saarto T, Sheth S, Spurrier-Bernard G, Vuoristo MS, Costa A, Naredi P (2018) ECCO essential requirements for quality cancer care: melanoma. Crit Rev Oncol Hematol 122:164–178PubMedCrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Department of Pediatric Oncology and HematologyEberhard Karls UniversityTuebingenGermany
  2. 2.Department of PediatricsMemorial Sloan-Kettering Cancer CenterNew YorkUSA
  3. 3.Centre for DermatooncologyEberhard Karls UniversityTuebingenGermany

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