title: Dysplastic naevi with moderate to severe histological dysplasia: a risk factor for melanoma.
abstract: BACKGROUND
  The risk of malignant melanoma associated with histologically dysplastic naevi (HDN) has not been defined. While clinically atypical naevi appear to confer an independent risk of melanoma, no study has evaluated the extent to which HDN are predictive of melanoma.
  
  
  OBJECTIVE
  To estimate the risk of melanoma associated with HDN. Secondarily, the risk associated with number of naevi and large naevi is estimated.
  
  
  METHODS
  We enrolled 80 patients with newly diagnosed melanoma along with 80 spousal controls. After obtaining information on melanoma risk factors and performing a complete cutaneous examination, the most clinically atypical naevus was biopsied in both cases and controls. Histological dysplasia was then assessed independently by 13 dermatopathologists (0, no dysplasia; 1, mild dysplasia; 2, moderate dysplasia; 3, severe dysplasia). The dermatopathologists were blinded as to whether the naevi were from melanoma subjects or controls. Multivariate analyses were performed to determine if there was an independent association between the degree of histological dysplasia in naevi and a personal history of melanoma.
  
  
  RESULTS
  In persons with naevi receiving an average score of > 1 (i.e. naevi considered to have greater than mild histological dysplasia), there was an increased risk of melanoma [odds ratio (OR) 2.60, 95% confidence interval (CI) 0.99-6.86] which persisted after adjustment for confounders (OR 3.99, 95% CI 1.02-15.71). Very few dermatopathologists reliably graded naevi of subjects with melanoma as being more dysplastic than naevi of control subjects. Among the entire group, the interobserver reliability associated with grading histological dysplasia in naevi was poor (weighted kappa 0.28).
  
  
  CONCLUSIONS
  HDN do appear to confer an independent risk of melanoma. However, this result may add more to our biological understanding of melanoma risk than to clinical assessment of risk, because HDN assessed by a single pathologist generally cannot be used to assess risk of melanoma. Future studies should be directed at establishing reproducible, predictive criteria for grading naevi.
authors.affiliation: Cancer Prevention, Fred Hutchinson Cancer Research Center, Seattle, WA, USA. ashors@u.washington.edu
authors.forename: A R
authors.initials: AR
authors.lastname: Shors
authors.forename: S
authors.initials: S
authors.lastname: Kim
authors.forename: E
authors.initials: E
authors.lastname: White
authors.forename: Z
authors.initials: Z
authors.lastname: Argenyi
authors.forename: R L
authors.initials: RL
authors.lastname: Barnhill
authors.forename: P
authors.initials: P
authors.lastname: Duray
authors.forename: L
authors.initials: L
authors.lastname: Erickson
authors.forename: J
authors.initials: J
authors.lastname: Guitart
authors.forename: M G
authors.initials: MG
authors.lastname: Horenstein
authors.forename: L
authors.initials: L
authors.lastname: Lowe
authors.forename: J
authors.initials: J
authors.lastname: Messina
authors.forename: M S
authors.initials: MS
authors.lastname: Rabkin
authors.forename: B
authors.initials: B
authors.lastname: Schmidt
authors.forename: C R
authors.initials: CR
authors.lastname: Shea
authors.forename: M J
authors.initials: MJ
authors.lastname: Trotter
authors.forename: M W
authors.initials: MW
authors.lastname: Piepkorn
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D018450:Disease Progression; D004416:Dysplastic Nevus Syndrome / Q000473:pathology*; D005260:Female; D006801:Humans; D008297:Male; D008545:Melanoma / Q000209:etiology / Q000473:pathology*; D008875:Middle Aged; D015588:Observer Variation; D010858:Pigmentation; D012307:Risk Factors; D012720:Severity of Illness Index; D012878:Skin Neoplasms / Q000209:etiology / Q000473:pathology*