Melanoma pp 337-364 | Cite as

Primary Cutaneous Melanocytic Neoplasms

  • Pedram GeramiEmail author
Reference work entry


This chapter on primary cutaneous melanocytic neoplasms of the skin will discuss three major categories of benign melanocytic neoplasms: common acquired, congenital, and blue nevi. The predominant initiating genomic event in common acquired nevi is a mutation in BRAF, while a significantly smaller percentage have a mutation in NRAS. Mutations in NRAS occur far more frequently in congenital nevi; the ratio of NRAS to BRAF mutations in congenital nevi varies depending on the size of the congenital nevus. Giant congenital nevi are almost exclusively NRAS mutated. Blue nevi commonly have mutations in GNAQ and GNA11 and likely have a distinct melanocytic precursor cell compared to many, but not all, common acquired nevi. This chapter will highlight how specific mutations and melanocytic precursor cell types impact morphology of benign melanocytic nevi and how these factors can be integrated into a more reproducible classification system. The author also discusses two major subtypes of melanoma: those occurring on non-chronically sun-damaged skin, which have frequent BRAF mutations, and melanomas occurring in chronically sun-damaged skin, which have less frequent BRAF and NRAS mutations but have occasional mutations in c-Kit or NF1. Likewise, the author discusses how the mutation and cell of origin in these melanomas relate to morphology and ultimately can be used for a more robust classification system.


Nevi Common acquired Congenital Blue nevi Melanoma Genomics 


  1. Aalborg J, Morelli JG, Mokrohisky ST, Asdigian NL, Byers TE, Dellavalle RP, Box NF, Crane LA (2009) Tanning and increased nevus development in very-light-skinned children without red hair. Arch Dermatol 145(9):989–996PubMedPubMedCentralCrossRefGoogle Scholar
  2. Aalto Y, Eriksson L, Seregard S, Larsson O, Knuutila S (2001) Concomitant loss of chromosome 3 and whole arm losses and gains of chromosome 1, 6, or 8 in metastasizing primary uveal melanoma. Invest Ophthalmol Vis Sci 42(2):313–317PubMedGoogle Scholar
  3. Alikhan A, Ibrahimi OA, Eisen DB (2012) Congenital melanocytic nevi: where are we now? Part I. Clinical presentation, epidemiology, pathogenesis, histology, malignant transformation, and neurocutaneous melanosis. J Am Acad Dermatol 67(4):495–511PubMedCrossRefGoogle Scholar
  4. Azzola MF, Shaw HM, Thompson JF, Soong SJ, Scolyer RA, Watson GF, Colman MH, Zhang Y (2003) Tumor mitotic rate is a more powerful prognostic indicator than ulceration in patients with primary cutaneous melanoma: an analysis of 3661 patients from a single center. Cancer 97(6):1488–1498. Scholar
  5. Ball NJ, Golitz LE (1994) Melanocytic nevi with focal atypical epithelioid cell components: a review of seventy-three cases. J Am Acad Dermatol 30(5 Pt 1):724–729PubMedCrossRefGoogle Scholar
  6. Bastian BC (2014) The molecular pathology of melanoma: an integrated taxonomy of melanocytic neoplasia. Annu Rev Pathol 9:239–271. Scholar
  7. Bastian BC, Kashani-Sabet M, Hamm H, Godfrey T, Moore DH 2nd, Brocker EB, LeBoit PE, Pinkel D (2000) Gene amplifications characterize acral melanoma and permit the detection of occult tumor cells in the surrounding skin. Cancer Res 60(7):1968–1973PubMedGoogle Scholar
  8. Bastian BC, Xiong J, Frieden IJ, Williams ML, Chou P, Busam K, Pinkel D, LeBoit PE (2002) Genetic changes in neoplasms arising in congenital melanocytic nevi: differences between nodular proliferations and melanomas. Am J Pathol 161(4):1163–1169. Scholar
  9. Bauer J, Curtin JA, Pinkel D, Bastian BC (2007) Congenital melanocytic nevi frequently harbor NRAS mutations but no BRAF mutations. J Invest Dermatol 127(1):179–182PubMedCrossRefGoogle Scholar
  10. Bett BJ (2005) Large or multiple congenital melanocytic nevi: occurrence of cutaneous melanoma in 1008 persons. J Am Acad Dermatol 52(5):793–797PubMedCrossRefGoogle Scholar
  11. Betti R, Martino P, Vergani R, Gualandri L, Crosti C (2008) Nodular melanomas: analysis of the casistic and relationship with thick melanomas and diagnostic delay. J Dermatol 35(10):643–650. Scholar
  12. Broekaert SM, Roy R, Okamoto I, van den Oord J, Bauer J, Garbe C, Barnhill RL, Busam KJ, Cochran AJ, Cook MG, Elder DE, McCarthy SW, Mihm MC, Schadendorf D, Scolyer RA, Spatz A, Bastian BC (2010) Genetic and morphologic features for melanoma classification. Pigment Cell Melanoma Res 23(6):763–770. Scholar
  13. Cancer Genome Atlas N (2015) Genomic classification of cutaneous melanoma. Cell 161(7):1681–1696CrossRefGoogle Scholar
  14. 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(3):307–315PubMedCrossRefGoogle Scholar
  15. Connelly J, Smith JL Jr (1991) Malignant blue nevus. Cancer 67(10):2653–2657PubMedCrossRefGoogle Scholar
  16. Cook MG, Clarke TJ, Humphreys S, Fletcher A, McLaren KM, Smith NP, Stevens A, Theaker JM, Melia J (1996) The evaluation of diagnostic and prognostic criteria and the terminology of thin cutaneous malignant melanoma by the CRC melanoma pathology panel. Histopathology 28(6):497–512PubMedCrossRefGoogle Scholar
  17. Costa S, Byrne M, Pissaloux D, Haddad V, Paindavoine S, Thomas L, Aubin F, Lesimple T, Grange F, Bonniaud B, Mortier L, Mateus C, Dreno B, Balme B, Vergier B, de la Fouchardiere A (2016) Melanomas associated with blue nevi or mimicking cellular blue nevi: clinical, pathologic, and molecular study of 11 cases displaying a high frequency of GNA11 mutations, BAP1 expression loss, and a predilection for the scalp. Am J Surg Pathol 40(3):368–377PubMedCrossRefGoogle Scholar
  18. Curtin JA, Busam K, Pinkel D, Bastian BC (2006) Somatic activation of KIT in distinct subtypes of melanoma. J Clin Oncol 24(26):4340–4346PubMedCrossRefGoogle Scholar
  19. Dankort D, Curley DP, Cartlidge RA, Nelson B, Karnezis AN, Damsky WE Jr, You MJ, DePinho RA, McMahon M, Bosenberg M (2009) Braf(V600E) cooperates with Pten loss to induce metastatic melanoma. Nat Genet 41(5):544–552PubMedPubMedCentralCrossRefGoogle Scholar
  20. DeDavid M, Orlow SJ, Provost N, Marghoob AA, Rao BK, Wasti Q, Huang CL, Kopf AW, Bart RS (1996) Neurocutaneous melanosis: clinical features of large congenital melanocytic nevi in patients with manifest central nervous system melanosis. J Am Acad Dermatol 35(4):529–538PubMedCrossRefGoogle Scholar
  21. Dulon M, Weichenthal M, Blettner M, Breitbart M, Hetzer M, Greinert R, Baumgardt-Elms C, Breitbart EW (2002) Sun exposure and number of nevi in 5- to 6-year-old European children. J Clin Epidemiol 55(11):1075–1081PubMedCrossRefGoogle Scholar
  22. Ellerhorst JA, Greene VR, Ekmekcioglu S, Warneke CL, Johnson MM, Cooke CP, Wang LE, Prieto VG, Gershenwald JE, Wei Q, Grimm EA (2011) Clinical correlates of NRAS and BRAF mutations in primary human melanoma. Clin Cancer Res 17(2):229–235PubMedCrossRefGoogle Scholar
  23. Fernandes KJ, McKenzie IA, Mill P, Smith KM, Akhavan M, Barnabe-Heider F, Biernaskie J, Junek A, Kobayashi NR, Toma JG, Kaplan DR, Labosky PA, Rafuse V, Hui CC, Miller FD (2004) A dermal niche for multipotent adult skin-derived precursor cells. Nat Cell Biol 6(11):1082–1093PubMedCrossRefGoogle Scholar
  24. Elder DE (2016) Melanoma progression. Pathology 48(2):147–154PubMedCrossRefGoogle Scholar
  25. Francken AB, Shaw HM, Thompson JF, Soong SJ, Accortt NA, Azzola MF, Scolyer RA, Milton GW, McCarthy WH, Colman MH, McGovern VJ (2004) The prognostic importance of tumor mitotic rate confirmed in 1317 patients with primary cutaneous melanoma and long follow-up. Ann Surg Oncol 11(4):426–433. Scholar
  26. George E, McClain SE, Slingluff CL, Polissar NL, Patterson JW (2009) Subclassification of desmoplastic melanoma: pure and mixed variants have significantly different capacities for lymph node metastasis. J Cutan Pathol 36(4):425–432PubMedCrossRefGoogle Scholar
  27. Gerami P, Cook RW, Russell MC, Wilkinson J, Amaria RN, Gonzalez R, Lyle S, Jackson GL, Greisinger AJ, Johnson CE, Oelschlager KM, Stone JF, Maetzold DJ, Ferris LK, Wayne JD, Cooper C, Obregon R, Delman KA, Lawson D (2015a) Gene expression profiling for molecular staging of cutaneous melanoma in patients undergoing sentinel lymph node biopsy. J Am Acad Dermatol 72(5):780–785. e783. Scholar
  28. Gerami P, Cook RW, Wilkinson J, Russell MC, Dhillon N, Amaria RN, Gonzalez R, Lyle S, Johnson CE, Oelschlager KM, Jackson GL, Greisinger AJ, Maetzold D, Delman KA, Lawson DH, Stone JF (2015b) Development of a prognostic genetic signature to predict the metastatic risk associated with cutaneous melanoma. Clin Cancer Res 21(1):175–183. Scholar
  29. Gershenwald JE, Scolyer RA, Hess KR, Sondak VK, Long GV, Ross MI, Lazar AJ, Faries MB, Kirkwood JM, McArthur GA, Haydu LE, Eggermont AMM, Flaherty KT, Balch CM, Thompson JF, for members of the American Joint Committee on Cancer Melanoma Expert Panel and the International Melanoma Database and Discovery Platform (2017) Melanoma staging: evidence-based changes in the American joint committee on Cancer eighth edition cancer staging manual. CA Cancer J Clin 67(6):472–492. Scholar
  30. Goldgar DE, Cannon-Albright LA, Meyer LJ, Piepkorn MW, Zone JJ, Skolnick MH (1991) Inheritance of nevus number and size in melanoma and dysplastic nevus syndrome kindreds. J Natl Cancer Inst 83(23):1726–1733PubMedCrossRefGoogle Scholar
  31. Gutzmer R, Herbst RA, Mommert S, Kiehl P, Matiaske F, Rutten A, Kapp A, Weiss J (2000) Allelic loss at the neurofibromatosis type 1 (NF1) gene locus is frequent in desmoplastic neurotropic melanoma. Hum Genet 107(4):357–361PubMedCrossRefGoogle Scholar
  32. Gyorki DE, Busam K, Panageas K, Brady MS, Coit DG (2003) Sentinel lymph node biopsy for patients with cutaneous desmoplastic melanoma. Ann Surg Oncol 10(4):403–407PubMedCrossRefGoogle Scholar
  33. Harbour JW, Chao DL (2014) A molecular revolution in uveal melanoma: implications for patient care and targeted therapy. Ophthalmology 121(6):1281–1288PubMedPubMedCentralCrossRefGoogle Scholar
  34. Harbour JW, Onken MD, Roberson ED, Duan S, Cao L, Worley LA, Council ML, Matatall KA, Helms C, Bowcock AM (2010) Frequent mutation of BAP1 in metastasizing uveal melanomas. Science 330(6009):1410–1413PubMedPubMedCentralCrossRefGoogle Scholar
  35. Haugh AM, Zhang B, Quan VL, Garfield EM, Bubley JA, Kudalkar E, Verzi AE, Walton K, VandenBoom T, Merkel EA, Lee CY, Tan T, Isales MC, Kong BY, Wenzel AT, Bunick CG, Choi J, Sosman J, Gerami P (2018) Distinct patterns of Acral melanoma based on site and relative sun exposure. J Invest Dermatol 138(2):384–393. Scholar
  36. Heenan PJ, Matz LR, Blackwell JB, Kelsall GR, Singh A, ten Seldam RE, Holman CD (1984) Inter-observer variation between pathologists in the classification of cutaneous malignant melanoma in western Australia. Histopathology 8(5):717–729PubMedCrossRefGoogle Scholar
  37. Huang FW, Hodis E, Xu MJ, Kryukov GV, Chin L, Garraway LA (2013) Highly recurrent TERT promoter mutations in human melanoma. Science 339(6122):957–959PubMedPubMedCentralCrossRefGoogle Scholar
  38. Hussein MR, Wood GS (2002) Molecular aspects of melanocytic dysplastic nevi. J Mol Diagn 4(2):71–80. Scholar
  39. Ichii-Nakato N, Takata M, Takayanagi S, Takashima S, Lin J, Murata H, Fujimoto A, Hatta N, Saida T (2006) High frequency of BRAFV600E mutation in acquired nevi and small congenital nevi, but low frequency of mutation in medium-sized congenital nevi. J Invest Dermatol 126(9):2111–2118PubMedCrossRefGoogle Scholar
  40. Illig L, Weidner F, Hundeiker M, Gartmann H, Biess B, Leyh F, Paul E (1985) Congenital nevi less than or equal to 10 cm as precursors to melanoma. 52 cases, a review, and a new conception. Arch Dermatol 121(10):1274–1281PubMedCrossRefGoogle Scholar
  41. Kinsler VA, Chong WK, Aylett SE, Atherton DJ (2008) Complications of congenital melanocytic naevi in children: analysis of 16 years’ experience and clinical practice. Br J Dermatol 159(4):907–914PubMedCrossRefGoogle Scholar
  42. Kinsler VA, Thomas AC, Ishida M, Bulstrode NW, Loughlin S, Hing S, Chalker J, McKenzie K, Abu-Amero S, Slater O, Chanudet E, Palmer R, Morrogh D, Stanier P, Healy E, Sebire NJ, Moore GE (2013) Multiple congenital melanocytic nevi and neurocutaneous melanosis are caused by postzygotic mutations in codon 61 of NRAS. J Invest Dermatol 133(9):2229–2236PubMedPubMedCentralCrossRefGoogle Scholar
  43. Landi MT, Bauer J, Pfeiffer RM, Elder DE, Hulley B, Minghetti P, Calista D, Kanetsky PA, Pinkel D, Bastian BC (2006) MC1R germline variants confer risk for BRAF-mutant melanoma. Science 313(5786):521–522PubMedCrossRefGoogle Scholar
  44. Landow SM, Gjelsvik A, Weinstock MA (2017) Mortality burden and prognosis of thin melanomas overall and by subcategory of thickness, SEER registry data, 1992-2013. J Am Acad Dermatol 76(2):258–263. Scholar
  45. Larsen TE, Little JH, Orell SR, Prade M (1980) International pathologists congruence survey on quantitation of malignant melanoma. Pathology 12(2):245–253PubMedCrossRefGoogle Scholar
  46. Lee S, Duffy DL, McClenahan P, Lee KJ, McEniery E, Burke B, Jagirdar K, Martin NG, Sturm RA, Soyer HP, Schaider H (2016) Heritability of naevus patterns in an adult twin cohort from the Brisbane twin registry: a cross-sectional study. Br J Dermatol 174(2):356–363PubMedCrossRefGoogle Scholar
  47. Lee JH, Choi JW, Kim YS (2011) Frequencies of BRAF and NRAS mutations are different in histological types and sites of origin of cutaneous melanoma: a meta-analysis. Br J Dermatol 164(4):776–784. Scholar
  48. Liu W, McArthur GA, Trivett M, Murray WK, Wolfe R, Kelly JW (2008) Correlation of subjective self-reported melanoma growth rate with objective tumor proliferation markers. Arch Dermatol 144(4):555–556. Scholar
  49. Maldonado JL, Fridlyand J, Patel H, Jain AN, Busam K, Kageshita T, Ono T, Albertson DG, Pinkel D, Bastian BC (2003) Determinants of BRAF mutations in primary melanomas. J Natl Cancer Inst 95(24):1878–1890PubMedCrossRefGoogle Scholar
  50. Mar V, Roberts H, Wolfe R, English DR, Kelly JW (2013) Nodular melanoma: a distinct clinical entity and the largest contributor to melanoma deaths in Victoria, Australia. J Am Acad Dermatol 68(4):568–575. Scholar
  51. Marghoob AA, Dusza S, Oliveria S, Halpern AC (2004) Number of satellite nevi as a correlate for neurocutaneous melanocytosis in patients with large congenital melanocytic nevi. Arch Dermatol 140(2):171–175PubMedCrossRefGoogle Scholar
  52. Marks R, Dorevitch AP, Mason G (1990) Do all melanomas come from “moles”? A study of the histological association between melanocytic naevi and melanoma. Australas J Dermatol 31(2):77–80PubMedCrossRefGoogle Scholar
  53. Moon KR, Choi YD, Kim JM, Jin S, Shin MH, Shim HJ, Lee JB, Yun SJ (2018) Genetic Alterations in Primary Acral Melanoma and Acral Melanocytic Nevus in Korea: Common Mutated Genes Show Distinct Cytomorphological Features. J Invest Dermatol 138(4):933–945. Scholar
  54. Nguyen LP, Emley A, Wajapeyee N, Green MR, Mahalingam M (2010) BRAF V600E mutation and the tumour suppressor IGFBP7 in atypical genital naevi. Br J Dermatol 162(3):677–680PubMedCrossRefGoogle Scholar
  55. Oliveria SA, Yagerman SE, Jaimes N, Goodwin AI, Dusza SW, Halpern AC, Marghoob AA (2013) Clinical and dermoscopic characteristics of new naevi in adults: results from a cohort study. Br J Dermatol 169(4):848–853PubMedCrossRefGoogle Scholar
  56. Pan Y, Adler NR, Wolfe R, McLean CA, Kelly JW (2017) Nodular melanoma is less likely than superficial spreading melanoma to be histologically associated with a naevus. Med J Aust 207(8):333–338PubMedCrossRefGoogle Scholar
  57. Pawlik TM, Ross MI, Prieto VG, Ballo MT, Johnson MM, Mansfield PF, Lee JE, Cormier JN, Gershenwald JE (2006) Assessment of the role of sentinel lymph node biopsy for primary cutaneous desmoplastic melanoma. Cancer 106(4):900–906PubMedCrossRefGoogle Scholar
  58. Phadke PA, Rakheja D, Le LP, Selim MA, Kapur P, Davis A, Mihm MC Jr, Hoang MP (2011) Proliferative nodules arising within congenital melanocytic nevi: a histologic, immunohistochemical, and molecular analyses of 43 cases. Am J Surg Pathol 35(5):656–669PubMedCrossRefGoogle Scholar
  59. Pollock PM, Harper UL, Hansen KS, Yudt LM, Stark M, Robbins CM, Moses TY, Hostetter G, Wagner U, Kakareka J, Salem G, Pohida T, Heenan P, Duray P, Kallioniemi O, Hayward NK, Trent JM, Meltzer PS (2003) High frequency of BRAF mutations in nevi. Nat Genet 33(1):19–20PubMedPubMedCentralCrossRefGoogle Scholar
  60. Pouryazdanparast P, Brenner A, Haghighat Z, Guitart J, Rademaker A, Gerami P (2012a) The role of 8q24 copy number gains and c-MYC expression in amelanotic cutaneous melanoma. Mod Pathol 25(9):1221–1226PubMedCrossRefGoogle Scholar
  61. Pouryazdanparast P, Cowen DP, Beilfuss BA, Haghighat Z, Guitart J, Rademaker A, Gerami P (2012b) Distinctive clinical and histologic features in cutaneous melanoma with copy number gains in 8q24. Am J Surg Pathol 36(2):253–264PubMedCrossRefGoogle Scholar
  62. Rhodes AR, Albert LS, Weinstock MA (1996) Congenital nevomelanocytic nevi: proportionate area expansion during infancy and early childhood. J Am Acad Dermatol 34(1):51–62PubMedCrossRefGoogle Scholar
  63. Rigel DS, Friedman RJ, Kopf AW, Polsky D (2005) ABCDE–an evolving concept in the early detection of melanoma. Arch Dermatol 141(8):1032–1034PubMedCrossRefGoogle Scholar
  64. Ruiz-Maldonado R, Tamayo L, Laterza AM, Duran C (1992) Giant pigmented nevi: clinical, histopathologic, and therapeutic considerations. J Pediatr 120(6):906–911PubMedCrossRefGoogle Scholar
  65. Scalzo DA, Hida CA, Toth G, Sober AJ, Mihm MC Jr (1997) Childhood melanoma: a clinicopathological study of 22 cases. Melanoma Res 7(1):63–68PubMedCrossRefGoogle Scholar
  66. Shaikh WR, Dusza SW, Weinstock MA, Oliveria SA, Geller AC, Halpern AC (2016) Melanoma thickness and survival trends in the United States, 1989 to 2009. J Natl Cancer Inst 108(1).
  67. Shain AH, Yeh I, Kovalyshyn I, Sriharan A, Talevich E, Gagnon A, Dummer R, North J, Pincus L, Ruben B, Rickaby W, D'Arrigo C, Robson A, Bastian BC (2015) The genetic evolution of melanoma from precursor lesions. N Engl J Med 373(20):1926–1936PubMedCrossRefGoogle Scholar
  68. Shors AR, Kim S, White E, Argenyi Z, Barnhill RL, Duray P, Erickson L, Guitart J, Horenstein MG, Lowe L, Messina J, Rabkin MS, Schmidt B, Shea CR, Trotter MJ, Piepkorn MW (2006) Dysplastic naevi with moderate to severe histological dysplasia: a risk factor for melanoma. Br J Dermatol 155(5):988–993. Scholar
  69. Siegel RL, Miller KD, Jemal A (2016) Cancer statistics, 2016. CA Cancer J Clin 66(1):7–30CrossRefGoogle Scholar
  70. Singh P, Kim HJ, Schwartz RA (2016) Superficial spreading melanoma: an analysis of 97 702 cases using the SEER database. Melanoma Res 26(4):395–400. Scholar
  71. Swerdlow AJ, English JS, Qiao Z (1995) The risk of melanoma in patients with congenital nevi: a cohort study. J Am Acad Dermatol 32(4):595–599PubMedCrossRefGoogle Scholar
  72. Thomas NE, Edmiston SN, Alexander A, Millikan RC, Groben PA, Hao H, Tolbert D, Berwick M, Busam K, Begg CB, Mattingly D, Ollila DW, Tse CK, Hummer A, Lee-Taylor J, Conway K (2007) Number of nevi and early-life ambient UV exposure are associated with BRAF-mutant melanoma. Cancer Epidemiol Biomark Prev 16(5):991–997CrossRefGoogle Scholar
  73. Thompson JF, Soong SJ, Balch CM, Gershenwald JE, Ding S, Coit DG, Flaherty KT, Gimotty PA, Johnson T, Johnson MM, Leong SP, Ross MI, Byrd DR, Cascinelli N, Cochran AJ, Eggermont AM, McMasters KM, Mihm MC Jr, Morton DL, Sondak VK (2011) Prognostic significance of mitotic rate in localized primary cutaneous melanoma: an analysis of patients in the multi-institutional American joint committee on Cancer melanoma staging database. J Clin Oncol 29(16):2199–2205. Scholar
  74. Tsao H, Bevona C, Goggins W, Quinn T (2003) The transformation rate of moles (melanocytic nevi) into cutaneous melanoma: a population-based estimate. Arch Dermatol 139(3):282–288PubMedCrossRefGoogle Scholar
  75. Tsao H, Goel V, Wu H, Yang G, Haluska FG (2004) Genetic interaction between NRAS and BRAF mutations and PTEN/MMAC1 inactivation in melanoma. J Invest Dermatol 122(2):337–341. Scholar
  76. Tucker MA, Fraser MC, Goldstein AM, Struewing JP, King MA, Crawford JT, Chiazze EA, Zametkin DP, Fontaine LS, Clark WH Jr (2002) A natural history of melanomas and dysplastic nevi: an atlas of lesions in melanoma-prone families. Cancer 94(12):3192–3209PubMedCrossRefGoogle Scholar
  77. Tucker MA, Halpern A, Holly EA, Hartge P, Elder DE, Sagebiel RW, Guerry D t, Clark WH Jr (1997) Clinically recognized dysplastic nevi. A central risk factor for cutaneous melanoma. JAMA 277(18):1439–1444PubMedCrossRefGoogle Scholar
  78. Unna PG (1893) Nevi and nevocarcinome. Berl Klin Wochenschr 30:14–16Google Scholar
  79. Van Raamsdonk CD, Bezrookove V, Green G, Bauer J, Gaugler L, O'Brien JM, Simpson EM, Barsh GS, Bastian BC (2009) Frequent somatic mutations of GNAQ in uveal melanoma and blue naevi. Nature 457(7229):599–602PubMedCrossRefGoogle Scholar
  80. Van Raamsdonk CD, Fitch KR, Fuchs H, de Angelis MH, Barsh GS (2004) Effects of G-protein mutations on skin color. Nat Genet 36(9):961–968PubMedCrossRefGoogle Scholar
  81. Van Raamsdonk CD, Griewank KG, Crosby MB, Garrido MC, Vemula S, Wiesner T, Obenauf AC, Wackernagel W, Green G, Bouvier N, Sozen MM, Baimukanova G, Roy R, Heguy A, Dolgalev I, Khanin R, Busam K, Speicher MR, O'Brien J, Bastian BC (2010) Mutations in GNA11 in uveal melanoma. N Engl J Med 363(23):2191–2199PubMedPubMedCentralCrossRefGoogle Scholar
  82. Verzi AE, Quan VL, Walton KE, Martini MC, Marghoob AA, Garfield EM, Kong BY, Isales MC, VandenBoom T, Zhang B, West DP, Gerami P (2018) The diagnostic value and histologic correlate of distinct patterns of shiny white streaks for the diagnosis of melanoma: A retrospective, case-control study. J Am Acad Dermatol 78(5):913–919. PMID: 29138058PubMedCrossRefGoogle Scholar
  83. Viros A, Fridlyand J, Bauer J, Lasithiotakis K, Garbe C, Pinkel D, Bastian BC (2008) Improving melanoma classification by integrating genetic and morphologic features. PLoS Med 5(6):e120. Scholar
  84. Wachsmuth RC, Gaut RM, Barrett JH, Saunders CL, Randerson-Moor JA, Eldridge A, Martin NG, Bishop TD, Newton Bishop JA (2001) Heritability and gene-environment interactions for melanocytic nevus density examined in a U.K. adolescent twin study. J Invest Dermatol 117(2):348–352PubMedCrossRefGoogle Scholar
  85. Whiteman DC, Baade PD, Olsen CM (2015) More people die from thin melanomas (1 mm) than from thick melanomas (>4 mm) in Queensland, Australia. J Invest Dermatol 135(4):1190–1193. Scholar
  86. Wiecker TS, Luther H, Buettner P, Bauer J, Garbe C (2003) Moderate sun exposure and nevus counts in parents are associated with development of melanocytic nevi in childhood: a risk factor study in 1,812 kindergarten children. Cancer 97(3):628–638PubMedCrossRefGoogle Scholar
  87. Yelamos O, Arva NC, Obregon R, Yazdan P, Wagner A, Guitart J, Gerami P (2015a) A comparative study of proliferative nodules and lethal melanomas in congenital nevi from children. Am J Surg Pathol 39(3):405–415PubMedCrossRefGoogle Scholar
  88. Yelamos O, Busam KJ, Lee C, Meldi Sholl L, Amin SM, Merkel EA, Obregon R, Guitart J, Gerami P (2015b) Morphologic clues and utility of fluorescence in situ hybridization for the diagnosis of nevoid melanoma. J Cutan Pathol 42(11):796–806PubMedCrossRefGoogle Scholar
  89. Yelamos O, Merkel EA, Sholl LM, Zhang B, Amin SM, Lee CY, Guitart GE, Yang J, Wenzel AT, Bunick CG, Yazdan P, Choi J, Gerami P (2016) Non-overlapping clinical and mutational patterns in melanomas from the female genital tract and atypical genital nevi. J Invest Dermatol 136(9):1858–1865PubMedCrossRefGoogle Scholar
  90. Zager JS, Gastman BR, Leachman S, Gonzalez RC, Fleming MD, Ferris LK, Ho J, Miller AR, Cook RW, Covington KR, Meldi-Plasseraud K, Middlebrook B, Kaminester LH, Greisinger A, Estrada SI, Pariser DM, Cranmer LD, Messina JL, Vetto JT, Wayne JD, Delman KA, Lawson DH, Gerami P (2018) Performance of a prognostic 31-gene expression profile in an independent cohort of 523 cutaneous melanoma patients. BMC Cancer 18(1):130. Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Feinberg School of MedicineNorthwestern UniversityChicagoUSA

Section editors and affiliations

  • Boris C. Bastian
    • 1
  • Hensin Tsao
    • 2
    • 3
  1. 1.Departments of Dermatology and Pathology, Helen Diller Family Comprehensive Cancer CenterUniversity of California, San FranciscoSan FranciscoUSA
  2. 2.AuburndaleUSA
  3. 3.Harvard-MIT Health Sciences and TechnologyCambridgeUSA

Personalised recommendations