title: De Novo vs Nevus-Associated Melanomas: Differences in Associations With Prognostic Indicators and Survival.
abstract: Although 20% to 30% of melanomas are histopathologically 'nevus associated,' the majority of melanomas arise de novo, ie, in clinically normal skin with no associated nevus. We examined whether these forms of melanoma differed in their associations with clinical and histopathologic features and patient survival.
  
  
  
  We analyzed two prospective cohorts from our institution with protocol-driven follow-up information (NYU1, n = 1024; NYU2, n = 1125). We used univariate and multivariable analyses to examine associations between de novo vs nevus-associated melanoma classification and age, anatomic site, tumor thickness, tumor ulceration, mitotic index, histological subtype, clinical stage, and survival. We tested the associations identified in NYU1 using NYU2 as a replication cohort. All tests of statistical significance were two-sided.
  
  
  
  In NYU1, de novo melanomas were associated with tumor thickness greater than 1.0 mm (odds ratio [OR] = 1.96, 95% confidence interval [CI] = 1.43 to 2.70, P < .001), ulceration (OR = 1.65, 95% CI = 1.10 to 2.54, P = .02), nodular subtype (OR = 3.26, 95% CI = 1.70 to 7.11, P = .001), greater than stage I (OR = 2.35, 95% CI = 1.65 to 3.40, P < .001), older age (OR = 1.64, 95% CI = 1.18 to 2.30, P = .004), and shorter overall survival (HR = 1.63, 95% CI = 1.22 to 2.18, P < .001). In NYU2, de novo melanoma was again statistically significantly associated with thickness greater than 1.0 mm (OR = 2.24, 95% CI = 1.72 to 2.93, P < .001), ulceration (OR = 2.88, 95% CI = 1.95 to 4.37, P < .001), nodular subtype (OR = 2.41, 95% CI = 1.75 to 3.37, P < .001), greater than stage I (OR = 2.42, 95% CI = 1.80 to 3.29, P < .001), older age (OR = 1.68, 95% CI = 1.31 to 2.17, P < .001), and shorter overall survival (HR = 2.52, 95% CI = 1.78 to 3.56, P < .001). In multivariable analysis, de novo classification was an independent, poor prognostic indicator in NYU2 (HR = 1.70, 95% CI = 1.19 to 2.44, P = .004). Male patients had a statistically significantly worse survival than female patients if their melanoma was de novo (NYU1, P < .001; NYU2, P < .001); unexpectedly, there was no sex difference in survival among patients with nevus-associated tumors.
  
  
  
  These data suggest that de novo melanomas are more aggressive than nevus-associated melanomas. This classification scheme may also provide a useful framework for investigations into sex differences in melanoma outcomes.
authors.affiliation: Affiliations of authors: The Ronald O. Perelman Department of Dermatology (RMC, ECM, LAP, IO, DP) and Department of Population Health (YS, KW, YZ), New York University School of Medicine; Laura and Isaac Perlmutter Cancer Center, NYU Langone Medical Center, New York, NY (YS, IO, DP).
authors.forename: Rachel M
authors.initials: RM
authors.lastname: Cymerman
authors.affiliation: Affiliations of authors: The Ronald O. Perelman Department of Dermatology (RMC, ECM, LAP, IO, DP) and Department of Population Health (YS, KW, YZ), New York University School of Medicine; Laura and Isaac Perlmutter Cancer Center, NYU Langone Medical Center, New York, NY (YS, IO, DP).
authors.forename: Yongzhao
authors.initials: Y
authors.lastname: Shao
authors.affiliation: Affiliations of authors: The Ronald O. Perelman Department of Dermatology (RMC, ECM, LAP, IO, DP) and Department of Population Health (YS, KW, YZ), New York University School of Medicine; Laura and Isaac Perlmutter Cancer Center, NYU Langone Medical Center, New York, NY (YS, IO, DP).
authors.forename: Kun
authors.initials: K
authors.lastname: Wang
authors.affiliation: Affiliations of authors: The Ronald O. Perelman Department of Dermatology (RMC, ECM, LAP, IO, DP) and Department of Population Health (YS, KW, YZ), New York University School of Medicine; Laura and Isaac Perlmutter Cancer Center, NYU Langone Medical Center, New York, NY (YS, IO, DP).
authors.forename: Yilong
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Affiliations of authors: The Ronald O. Perelman Department of Dermatology (RMC, ECM, LAP, IO, DP) and Department of Population Health (YS, KW, YZ), New York University School of Medicine; Laura and Isaac Perlmutter Cancer Center, NYU Langone Medical Center, New York, NY (YS, IO, DP).
authors.forename: Era C
authors.initials: EC
authors.lastname: Murzaku
authors.affiliation: Affiliations of authors: The Ronald O. Perelman Department of Dermatology (RMC, ECM, LAP, IO, DP) and Department of Population Health (YS, KW, YZ), New York University School of Medicine; Laura and Isaac Perlmutter Cancer Center, NYU Langone Medical Center, New York, NY (YS, IO, DP).
authors.forename: Lauren A
authors.initials: LA
authors.lastname: Penn
authors.affiliation: Affiliations of authors: The Ronald O. Perelman Department of Dermatology (RMC, ECM, LAP, IO, DP) and Department of Population Health (YS, KW, YZ), New York University School of Medicine; Laura and Isaac Perlmutter Cancer Center, NYU Langone Medical Center, New York, NY (YS, IO, DP).
authors.forename: Iman
authors.initials: I
authors.lastname: Osman
authors.affiliation: Affiliations of authors: The Ronald O. Perelman Department of Dermatology (RMC, ECM, LAP, IO, DP) and Department of Population Health (YS, KW, YZ), New York University School of Medicine; Laura and Isaac Perlmutter Cancer Center, NYU Langone Medical Center, New York, NY (YS, IO, DP).
authors.forename: David
authors.initials: D
authors.lastname: Polsky
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D002471:Cell Transformation, Neoplastic / Q000473:pathology; D002648:Child; D005260:Female; D006801:Humans; D008297:Male; D008545:Melanoma / Q000150:complications / Q000401:mortality* / Q000473:pathology*; D008875:Middle Aged; D009367:Neoplasm Staging; D009508:Nevus, Pigmented / Q000150:complications / Q000473:pathology*; D009518:New York / Q000453:epidemiology; D011379:Prognosis; D011446:Prospective Studies; D012737:Sex Factors; D012878:Skin Neoplasms / Q000150:complications / Q000401:mortality* / Q000473:pathology*; D012883:Skin Ulcer / Q000209:etiology; D015996:Survival Rate; D055815:Young Adult