Controversies in the Evaluation and Management of Atypical Melanocytic Proliferations in Children, Adolescents, and Young Adults

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The rising incidence of melanoma in children has brought increased attention to the clinical and pathologic diagnosis of pigmented lesions in the pediatric age group. Although melanoma in infancy and early childhood is often associated with large congenital nevi, in older children and teenagers it is most often sporadic, occurring in patients with a low skin phototype and substantial sun exposure. The rarity of this potentially fatal disorder demands astute clinical attention and a high index of suspicion for atypical lesions in pediatric patients. The challenges include the difficult decision of whether to biopsy and an often equivocal pathologic diagnosis. These diagnostically challenging and equivocal lesions lead to a degree of uncertainty regarding additional workup, prognosis, potential therapy, and follow-up plans. Consultation with a specialty dermatopathologist can be very helpful, and advanced molecular diagnostic techniques may be used in selected circumstances. Although still controversial, good evidence exists to justify a role for sentinel lymph node biopsy. Patients with atypical melanocytic proliferations have a high rate of positive sentinel lymph nodes; however, their outcomes are clearly better than in similarly staged adults with conventional melanoma. With the multiple variables involved and the relative lack of prospectively derived evidence, clinical decision-making is challenging and patients and families may experience considerable stress. This article provides data and weighs the pros and cons of a rationale for decision-making in pediatric and young adult patients with diagnostically challenging melanocytic lesions.

Correspondence: Damon Reed, MD, Sarcoma Department, Moffitt Cancer Center, 12902 Magnolia Drive, FOB 1, Tampa, FL 33612. E-mail: Damon.Reed@moffitt.org
  • 1

    LewisKG. Trends in pediatric melanoma mortality in the United States, 1968 through 2004. Dermatol Surg2008;34:152-159.

  • 2

    WongJRHarrisJKRodriguez-GalindoCJohnsonKJ. Incidence of childhood and adolescent melanoma in the United States: 1973-2009. Pediatrics2013;131:846-854.

    • Search Google Scholar
    • Export Citation
  • 3

    ChaoMMSchwartzJLWechslerDS. High-risk surgically resected pediatric melanoma and adjuvant interferon therapy. Pediatr Blood Cancer2005;44:441-448.

    • Search Google Scholar
    • Export Citation
  • 4

    MoscarellaEZalaudekICerroniL. Excised melanocytic lesions in children and adolescents: a ten-year survey. Br J Dermatol2012;167:368-373.

    • Search Google Scholar
    • Export Citation
  • 5

    CeballosPIRuiz-MaldonadoRMihmMCJr. Melanoma in children. N Engl J Med1995;332:656-662.

  • 6

    HodiFSO'DaySJMcDermottDF. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med2010;363:711-723.

  • 7

    SosmanJAKimKBSchuchterL. Survival in BRAF V600-mutant advanced melanoma treated with vemurafenib. N Engl J Med2012;366:707-714.

  • 8

    TomWLHsuJWEichenfieldLFFriedlanderSF. Pediatric “STUMP” lesions: evaluation and management of difficult atypical Spitzoid lesions in children. J Am Acad Dermatol2011;64:559-572.

    • Search Google Scholar
    • Export Citation
  • 9

    ElderDEXuX. The approach to the patient with a difficult melanocytic lesion. Pathology2004;36:428-434.

  • 10

    LudgateMWFullenDRLeeJ. The atypical Spitz tumor of uncertain biologic potential: a series of 67 patients from a single institution. Cancer2009;115:631-641.

    • Search Google Scholar
    • Export Citation
  • 11

    MillsOLMarzbanSZagerJS. Sentinel node biopsy in atypical melanocytic neoplasms in childhood: a single institution experience in 24 patients. J Cutan Pathol2012;39:331-336.

    • Search Google Scholar
    • Export Citation
  • 12

    BarnhillRLArgenyiZBFromL. Atypical Spitz nevi/tumors: lack of consensus for diagnosis, discrimination from melanoma, and prediction of outcome. Hum Pathol1999;30:513-520.

    • Search Google Scholar
    • Export Citation
  • 13

    CerroniLBarnhillRElderD. 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 Pathol2010;34:314-326.

    • Search Google Scholar
    • Export Citation
  • 14

    TrozakDJRowlandWDHuF. Metastatic malignant melanoma in prepubertal children. Pediatrics1975;55:191-204.

  • 15

    LangeJRPalisBEChangDC. Melanoma in children and teenagers: an analysis of patients from the National Cancer Data Base. J Clin Oncol2007;25:1363-1368.

    • Search Google Scholar
    • Export Citation
  • 16

    MillsOMessinaJL. Pediatric melanoma: a review. Cancer Control2009;16:225-233.

  • 17

    Ruiz-MaldonadoRTamayoLLaterzaAMDuranC. Giant pigmented nevi: clinical, histopathologic, and therapeutic considerations. J Pediatr1992;120:906-911.

    • Search Google Scholar
    • Export Citation
  • 18

    ParadelaSFonsecaEPrietoVG. Melanoma in children. Arch Pathol Lab Med2011;135:307-316.

  • 19

    BergPWennbergAMTuominenR. Germline CDKN2A mutations are rare in child and adolescent cutaneous melanoma. Melanoma Res2004;14:251-255.

  • 20

    BradfordPTGoldsteinAMTamuraD. Cancer and neurologic degeneration in xeroderma pigmentosum: long term follow-up characterises the role of DNA repair. J Med Genet2011;48:168-176.

    • Search Google Scholar
    • Export Citation
  • 21

    FerrariABonoABaldiM. Does melanoma behave differently in younger children than in adults? A retrospective study of 33 cases of childhood melanoma from a single institution. Pediatrics2005;115:649-654.

    • Search Google Scholar
    • Export Citation
  • 22

    BichakjianCKHalpernACJohnsonTM. Guidelines of care for the management of primary cutaneous melanoma. American Academy of Dermatology. J Am Acad Dermatol2011;65:1032-1047.

    • Search Google Scholar
    • Export Citation
  • 23

    CoitDGAndtbackaRAnkerCJ. Melanoma. J Natl Compr Canc Netw2012;10:366-400.

  • 24

    WoodJButlerCCHoodK. Antibiotic prescribing for adults with acute cough/lower respiratory tract infection: congruence with guidelines. Eur Respir J2011;38:112-118.

    • Search Google Scholar
    • Export Citation
  • 25

    CerroniLBarnhillRElderD. 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 Pathol2010;34:314-326.

    • Search Google Scholar
    • Export Citation
  • 26

    CasperDJRossKIMessinaJL. Use of anti-phosphohistone H3 immunohistochemistry to determine mitotic rate in thin melanoma. Am J Dermatopathol2010;32:650-654.

    • Search Google Scholar
    • Export Citation
  • 27

    KapurPSelimMARoyLC. Spitz nevi and atypical Spitz nevi/tumors: a histologic and immunohistochemical analysis. Mod Pathol2005;18:197-204.

    • Search Google Scholar
    • Export Citation
  • 28

    VollmerRT. Use of Bayes rule and MIB-1 proliferation index to discriminate Spitz nevus from malignant melanoma. Am J Clin Pathol2004;122:499-505.

    • Search Google Scholar
    • Export Citation
  • 29

    NasrMREl-ZammarO. Comparison of pHH3, Ki-67, and survivin immunoreactivity in benign and malignant melanocytic lesions. Am J Dermatopathol2008;30:117-122.

    • Search Google Scholar
    • Export Citation
  • 30

    Al DhaybiRAgoumiMGagneI. p16 expression: a marker of differentiation between childhood malignant melanomas and Spitz nevi. J Am Acad Dermatol2011;65:357-363.

    • Search Google Scholar
    • Export Citation
  • 31

    ZedekDCMcCalmontTH. Spitz nevi, atypical spitzoid neoplasms, and spitzoid melanoma. Clin Lab Med2011;31:311-320.

  • 32

    ZembowiczAYangSEKafanasALyleSR. Correlation between histologic assessment and fluorescence in situ hybridization using MelanoSITE in evaluation of histologically ambiguous melanocytic lesions. Arch Pathol Lab Med2012;136:1571-1579.

    • Search Google Scholar
    • Export Citation
  • 33

    ZimmermannAKHirschmannAPfeifferD. FISH analysis for diagnostic evaluation of challenging melanocytic lesions. Histol Histopathol2010;25:1139-1147.

    • Search Google Scholar
    • Export Citation
  • 34

    GeramiPZembowiczA. Update on fluorescence in situ hybridization in melanoma: state of the art. Arch Pathol Lab Med2011;135:830-837.

  • 35

    GeramiPJewellSSMorrisonLE. Fluorescence in situ hybridization (FISH) as an ancillary diagnostic tool in the diagnosis of melanoma. Am J Surg Pathol2009;33:1146-1156.

    • Search Google Scholar
    • Export Citation
  • 36

    MoreyALMuraliRMcCarthySW. Diagnosis of cutaneous melanocytic tumours by four-colour fluorescence in situ hybridisation. Pathology2009;41:383-387.

    • Search Google Scholar
    • Export Citation
  • 37

    BastianBCOlshenABLeBoitPEPinkelD. Classifying melanocytic tumors based on DNA copy number changes. Am J Pathol2003;163:1765-1770.

  • 38

    HarvellJDKohlerSZhuS. High-resolution array-based comparative genomic hybridization for distinguishing paraffin-embedded Spitz nevi and melanomas. Diagn Mol Pathol2004;13:22-25.

    • Search Google Scholar
    • Export Citation
  • 39

    AliLHelmTCheneyR. Correlating array comparative genomic hybridization findings with histology and outcome in spitzoid melanocytic neoplasms. Int J Clin Exp Pathol2010;3:593-599.

    • Search Google Scholar
    • Export Citation
  • 40

    VanisonCTannaNMurthyAS. Comparative genomic hybridization for the diagnosis of melanoma. Eur J Plast Surg2010;33:45-48.

  • 41

    BraunRPGutkowicz-KrusinDRabinovitzH. Agreement of dermatopathologists in the evaluation of clinically difficult melanocytic lesions: how golden is the 'gold standard'?Dermatology2012;224:51-58.

    • Search Google Scholar
    • Export Citation
  • 42

    WongJYSondakVK. Unanswered questions about margin recommendations for primary cutaneous melanoma. J Natl Compr Canc Netw2012;10:357-365.

    • Search Google Scholar
    • Export Citation
  • 43

    CoitDGAndtbackaRBichakjianCK. Melanoma. J Natl Compr Canc Netw2009;7:250-275.

  • 44

    KellMRRidgeJAJosephNSigurdsonER. PET CT imaging in patients undergoing sentinel node biopsy for melanoma. Eur J Surg Oncol2007;33:911-913.

    • Search Google Scholar
    • Export Citation
  • 45

    Schmid-WendtnerMHPaerschkeGBaumertJ. Value of ultrasonography compared with physical examination for the detection of locoregional metastases in patients with cutaneous melanoma. Melanoma Res2003;13:183-188.

    • Search Google Scholar
    • Export Citation
  • 46

    VoitCAvan AkkooiACSchafer-HesterbergG. Rotterdam Criteria for sentinel node (SN) tumor burden and the accuracy of ultrasound (US)-guided fine-needle aspiration cytology (FNAC): can US-guided FNAC replace SN staging in patients with melanoma?J Clin Oncol2009;27:4994-5000.

    • Search Google Scholar
    • Export Citation
  • 47

    PearceMSSalottiJALittleMP. Radiation exposure from CT scans in childhood and subsequent risk of leukaemia and brain tumours: a retrospective cohort study. Lancet2012;380:499-505.

    • Search Google Scholar
    • Export Citation
  • 48

    HanDZagerJSHanG. The unique clinical characteristics of melanoma diagnosed in children. Ann Surg Oncol2012;19:3888-3895.

  • 49

    MillsOLMarzbanSZagerJS. Sentinel node biopsy in atypical melanocytic neoplasms in childhood: a single institution experience in 24 patients. J Cutan Pathol2012;39:331-336.

    • Search Google Scholar
    • Export Citation
  • 50

    Howman-GilesRShawHMScolyerRA. Sentinel lymph node biopsy in pediatric and adolescent cutaneous melanoma patients. Ann Surg Oncol2010;17:138-143.

    • Search Google Scholar
    • Export Citation
  • 51

    MuELangeJRStrouseJJ. Comparison of the use and results of sentinel lymph node biopsy in children and young adults with melanoma. Cancer2012;118:2700-2707.

    • Search Google Scholar
    • Export Citation
  • 52

    RoatenJBPartrickDAPearlmanN. Sentinel lymph node biopsy for melanoma and other melanocytic tumors in adolescents. J Pediatr Surg2005;40:232-235.

    • Search Google Scholar
    • Export Citation
  • 53

    BerkDRLaBuzEDadrasSS. Melanoma and melanocytic tumors of uncertain malignant potential in children, adolescents and young adults—the Stanford experience 1995-2008. Pediatr Dermatol2010;27:244-254.

    • Search Google Scholar
    • Export Citation
  • 54

    CerratoFWallinsJSWebbML. Outcomes in pediatric atypical spitz tumors treated without sentinel lymph node biopsy. Pediatr Dermatol2012;29:448-453.

    • Search Google Scholar
    • Export Citation
  • 55

    AldrinkJHSelimMADiesenDL. Pediatric melanoma: a single-institution experience of 150 patients. J Pediatr Surg2009;44:1514-1521.

  • 56

    HungTPirisALoboA. Sentinel lymph node metastasis is not predictive of poor outcome in patients with problematic spitzoid melanocytic tumors. Hum Pathol2013;44:87-94.

    • Search Google Scholar
    • Export Citation
  • 57

    WongSLBalchCMHurleyP. Sentinel lymph node biopsy for melanoma: American Society of Clinical Oncology and Society of Surgical Oncology joint clinical practice guideline. J Clin Oncol2012;30:2912-2918.

    • Search Google Scholar
    • Export Citation
  • 58

    FariesMBThompsonJFCochranA. The impact on morbidity and length of stay of early versus delayed complete lymphadenectomy in melanoma: results of the Multicenter Selective Lymphadenectomy Trial (I). Ann Surg Oncol2010;17:3324-3329.

    • Search Google Scholar
    • Export Citation
  • 59

    WongSLMortonDLThompsonJF. Melanoma patients with positive sentinel nodes who did not undergo completion lymphadenectomy: a multi-institutional study. Ann Surg Oncol2006;13:809-816.

    • Search Google Scholar
    • Export Citation
  • 60

    KirkwoodJMStrawdermanMHErnstoffMS. Interferon alfa-2b adjuvant therapy of high-risk resected cutaneous melanoma: the Eastern Cooperative Oncology Group Trial EST 1684. J Clin Oncol1996;14:7-17.

    • Search Google Scholar
    • Export Citation
  • 61

    KirkwoodJMManolaJIbrahimJ. A pooled analysis of Eastern Cooperative Oncology Group and intergroup trials of adjuvant high-dose interferon for melanoma. Clin Cancer Res2004;10:1670-1677.

    • Search Google Scholar
    • Export Citation
  • 62

    KirkwoodJMIbrahimJLawsonDH. High-dose interferon alfa-2b does not diminish antibody response to GM2 vaccination in patients with resected melanoma: results of the multicenter Eastern Cooperative Oncology Group phase II trial E2696. J Clin Oncol2001;19:1430-1436.

    • Search Google Scholar
    • Export Citation
  • 63

    KirkwoodJMIbrahimJGSondakVK. High- and low-dose interferon alfa-2b in high-risk melanoma: first analysis of intergroup trial E1690/S9111/C9190. J Clin Oncol2000;18:2444-2458.

    • Search Google Scholar
    • Export Citation
  • 64

    KirkwoodJMIbrahimJGSosmanJA. High-dose interferon alfa-2b significantly prolongs relapse-free and overall survival compared with the GM2-KLH/QS-21 vaccine in patients with resected stage IIB-III melanoma: results of intergroup trial E1694/S9512/C509801. J Clin Oncol2001;19:2370-2380.

    • Search Google Scholar
    • Export Citation
  • 65

    MocellinSPasqualiSRossiCRNittiD. Interferon alpha adjuvant therapy in patients with high-risk melanoma: a systematic review and meta-analysis. J Natl Cancer Inst2010;102:493-501.

    • Search Google Scholar
    • Export Citation
  • 66

    NavidFFurmanWLFlemingM. The feasibility of adjuvant interferon alpha-2b in children with high-risk melanoma. Cancer2005;103:780-787.

  • 67

    GibbsPMooreARobinsonW. Pediatric melanoma: are recent advances in the management of adult melanoma relevant to the pediatric population. J Pediatr Hematol Oncol2000;22:428-432.

    • Search Google Scholar
    • Export Citation
  • 68

    EggermontAMSuciuSSantinamiM. Adjuvant therapy with pegylated interferon alfa-2b versus observation alone in resected stage III melanoma: final results of EORTC 18991, a randomised phase III trial. Lancet2008;372:117-126.

    • Search Google Scholar
    • Export Citation
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