Advertisement

Skin, Melanocytic Neoplasms

  • Kristen M. Paral
  • Thomas Krausz
Chapter
Part of the Molecular Pathology Library book series (MPLB)

Abstract

There has been an explosion of molecular data on melanocytic neoplasms in recent years, emerging from studies utilizing a variety of methods that include whole genome or exome sequencing, targeted sequencing, comparative genomic hybridization (CGH), and fluorescence in situ hybridization (FISH). These data have greatly enhanced our understanding of melanocytic tumor biology and have resulted in new therapeutic targets. Nevertheless, the role for molecular diagnostic testing of melanocytic lesions remains undefined, and histopathological analysis remains of primary importance in the diagnosis and management of melanocytic neoplasms. This chapter presents the relevant molecular data and indications for its use as a diagnostic aid within the context of clinical and histopathologic findings.

Keywords

Melanoma Nevus BRAF p16 NRAS HRAS BAP1 Melanocytosis GNAQ Spitz Spitzoid Kinase 

References

  1. 1.
    Lu C, Zhang J, Nagahawatte P, Easton J, Lee S, Liu Z, et al. The genomic landscape of childhood and adolescent melanoma. J Invest Dermatol. 2015;135(3):816–23.CrossRefPubMedGoogle Scholar
  2. 2.
    Bauer J, Curtin JA, Pinkel D, Bastian BC. Congenital melanocytic nevi frequently harbor NRAS mutations but no BRAF mutations. J Invest Dermatol. 2007;127(1):179–82.CrossRefPubMedGoogle Scholar
  3. 3.
    Gray-Schopfer VC, Cheong SC, Chong H, Chow J, Moss T, Abdel-Malek ZA, et al. Cellular senescence in naevi and immortalisation in melanoma: a role for p16? Br J Cancer. 2006;95(4):496–505.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Pollock PM, Harper UL, Hansen KS, Yudt LM, Stark M, Robbins CM, et al. High frequency of BRAF mutations in nevi. Nat Genet. 2003;33(1):19–20.CrossRefPubMedGoogle Scholar
  5. 5.
    Soo JK, Mackenzie Ross AD, Kallenberg DM, Milagre C, Heung Chong W, Chow J, et al. Malignancy without immortality? Cellular immortalization as a possible late event in melanoma progression. Pigment Cell Melanoma Res. 2011;24(3):490–503.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Wiesner T, Kutzner H, Cerroni L, Mihm MC Jr, Busam KJ, Murali R. Genomic aberrations in spitzoid melanocytic tumours and their implications for diagnosis, prognosis and therapy. Pathology. 2016;48(2):113–31.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Lynch HT, Shaw TG. Familial atypical multiple mole melanoma (FAMMM) syndrome: history, genetics, and heterogeneity. Familial Cancer. 2016;15(3):487–91.CrossRefPubMedGoogle Scholar
  8. 8.
    Pappo AS. Melanoma in children and adolescents. Eur J Cancer. 2003;39(18):2651–61.CrossRefPubMedGoogle Scholar
  9. 9.
    Wong JR, Harris JK, Rodriguez-Galindo C, Johnson KJ. Incidence of childhood and adolescent melanoma in the United States: 1973–2009. Pediatrics. 2013;131(5):846–54.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Cordoro KM, Gupta D, Frieden IJ, McCalmont T, Kashani-Sabet M. Pediatric melanoma: results of a large cohort study and proposal for modified ABCD detection criteria for children. J Am Acad Dermatol. 2013;68(6):913–25.CrossRefPubMedGoogle Scholar
  11. 11.
    Bett BJ. Large or multiple congenital melanocytic nevi: occurrence of cutaneous melanoma in 1008 persons. J Am Acad Dermatol. 2005;52(5):793–7.CrossRefPubMedGoogle Scholar
  12. 12.
    Bittencourt FV, Marghoob AA, Kopf AW, Koenig KL, Bart RS. Large congenital melanocytic nevi and the risk for development of malignant melanoma and neurocutaneous melanocytosis. Pediatrics. 2000;106(4):736–41.CrossRefPubMedGoogle Scholar
  13. 13.
    Krengel S, Hauschild A, Schafer T. Melanoma risk in congenital melanocytic naevi: a systematic review. Br J Dermatol. 2006;155(1):1–8.CrossRefPubMedGoogle Scholar
  14. 14.
    Pappo AS. Pediatric melanoma: the whole (genome) story. Am Soc Clin Oncol Educ Book. 2014:e432–5.Google Scholar
  15. 15.
    Bastian BC, Olshen AB, LeBoit PE, Pinkel D. Classifying melanocytic tumors based on DNA copy number changes. Am J Pathol. 2003;163(5):1765–70.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Bauer J, Bastian BC. Distinguishing melanocytic nevi from melanoma by DNA copy number changes: comparative genomic hybridization as a research and diagnostic tool. Dermatol Ther. 2006;19(1):40–9.CrossRefPubMedGoogle Scholar
  17. 17.
    Jang S, Atkins MB. Which drug, and when, for patients with BRAF-mutant melanoma? Lancet Oncol. 2013;14(2):e60–9.CrossRefPubMedGoogle Scholar
  18. 18.
    Lee S, Barnhill RL, Dummer R, Dalton J, Wu J, Pappo A, et al. TERT promoter mutations are predictive of aggressive clinical behavior in patients with spitzoid melanocytic neoplasms. Sci Rep. 2015;5:11200.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Mooi WK, Krausz T. Pathology of melanocytic disorders. Boca Raton: CRC Press; 2007.Google Scholar
  20. 20.
    Alikhan A, Ibrahimi OA, Eisen DB. Congenital melanocytic nevi: where are we now? Part I. Clinical presentation, epidemiology, pathogenesis, histology, malignant transformation, and neurocutaneous melanosis. J Am Acad Dermatol. 2012;67(4):495-e1–495-e17.CrossRefGoogle Scholar
  21. 21.
    Nguyen TL, Theos A, Kelly DR, Busam K, Andea AA. Mitotically active proliferative nodule arising in a giant congenital melanocytic nevus: a diagnostic pitfall. Am J Dermatopathol. 2013;35(1):e16–21.CrossRefPubMedGoogle Scholar
  22. 22.
    Yelamos O, Arva NC, Obregon R, Yazdan P, Wagner A, Guitart J, et al. A comparative study of proliferative nodules and lethal melanomas in congenital nevi from children. Am J Surg Pathol. 2015;39(3):405–15.CrossRefPubMedGoogle Scholar
  23. 23.
    Zembowicz A, Phadke PA. Blue nevi and variants: an update. Arch Pathol Lab Med. 2011;135(3):327–36.PubMedGoogle Scholar
  24. 24.
    Franceschini D, Dinulos JG. Dermal melanocytosis and associated disorders. Curr Opin Pediatr. 2015;27(4):480–5.CrossRefPubMedGoogle Scholar
  25. 25.
    Gerami PG, Gammon B, Murphy M. Melanocytic neoplasms I: molecular diagnostics in dermatology and dermatopathology. In: Giordano A, editor. Current clinical pathology. New York: Springer; 2011.Google Scholar
  26. 26.
    Paral KF, Furtado L, Long, B, Zhen, C, Krausz, T. Blue nevus with malignant transformation: a detailed account with molecular analysis–poster presentation at the annual meeting of the American Society of Dermatopathology, San Fransisco. 2015.Google Scholar
  27. 27.
    Wiesner T, He J, Yelensky R, Esteve-Puig R, Botton T, Yeh I, et al. Kinase fusions are frequent in Spitz tumours and spitzoid melanomas. Nat Commun. 2014;5:3116.CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Wu G, Barnhill RL, Lee S, Li Y, Shao Y, Easton J, et al. The landscape of fusion transcripts in spitzoid melanoma and biologically indeterminate spitzoid tumors by RNA sequencing. Mod Pathol. 2016;29(4):359–69.CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Patterson J. Weedon’s skin pathology. London: Elsevier; 2015.Google Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Duke University Medical CenterDurhamUSA
  2. 2.University of Chicago MedicineChicagoUSA

Personalised recommendations