title: Characteristics and associations of high-mitotic-rate melanoma.
abstract: OBJECTIVE
  Mitotic rate is now recognized as having independent prognostic significance in melanoma survival. However, its clinicopathologic associations have not been the focus of any previous study.
  
  
  OBJECTIVE
  To identify a set of patient and tumor characteristics associated with high-mitotic-rate melanoma with the aim of facilitating the earlier detection of aggressive primary invasive melanoma.
  
  
  METHODS
  Cross-sectional study of patients from a multidisciplinary melanoma clinic based in a public hospital. A total of 2397 cases from January 2006 to December 2011 were reviewed by the Victorian Melanoma Service, and 1441 patients with 1500 primary invasive melanomas were included in the study.
  
  
  METHODS
  Mitotic rate was measured as number of mitoses per mm2 and analyzed as ordered categories (0, <1, 1 and <2, 2, 3-4, 5-9, and ≥10) according to patient demographics, phenotypic markers, historical data, tumor presentation, and histopathologic features.
  
  
  RESULTS
  Melanomas with higher mitotic rates were more likely to occur in men (odds ratio [OR], 1.5; 95% CI, 1.3-1.8), patients 70 years or older (OR, 2.1; 95% CI, 1.7-2.8), and those with a history of solar keratosis (OR, 1.3; 95% CI, 1.1-1.6). These melanomas occurred more frequently on the head and neck (OR, 1.4; 95% CI, 1.0-1.9) and presented more often as amelanotic (OR, 1.9; 95% CI, 1.4-2.5) and rapidly growing (≥2 mm/mo) lesions (OR, 12.5; 95% CI, 8.4-18.5). An association was seen with the nodular melanoma subtype (vs superficial spreading [reference]) (OR, 2.5; 95% CI, 1.8-3.4), greater tumor thickness (vs ≤1 mm [reference]) (>1-4 mm: OR, 4.5; 95% CI, 3.2-6.1; >4 mm: OR, 12.6; 95% CI, 7.5-21.1), and ulceration (OR, 2.0; 95% CI, 1.5-2.7). These histopathologic features, along with amelanosis and rate of growth, remained as significant associations with high mitotic rate in the overall multivariate analysis.
  
  
  CONCLUSIONS
  High-mitotic-rate primary cutaneous melanoma is associated with aggressive histologic features and atypical clinical presentation. It has a predilection for the head and neck region and is more likely to be seen in elderly men with a history of cumulative solar damage who present clinically with rapidly developing disease.
authors.affiliation: Victorian Melanoma Service, Alfred Hospital, Victoria, Australia2Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Australia.
authors.forename: Sarah
authors.initials: S
authors.lastname: Shen
authors.affiliation: Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Australia.
authors.forename: Rory
authors.initials: R
authors.lastname: Wolfe
authors.affiliation: Department of Anatomical Pathology, Alfred Hospital, Victoria, Australia.
authors.forename: Catriona A
authors.initials: CA
authors.lastname: McLean
authors.affiliation: Victorian Melanoma Service, Alfred Hospital, Victoria, Australia.
authors.forename: Martin
authors.initials: M
authors.lastname: Haskett
authors.affiliation: Victorian Melanoma Service, Alfred Hospital, Victoria, Australia.
authors.forename: John W
authors.initials: JW
authors.lastname: Kelly
mesh_terms: D000367:Age Factors; D000368:Aged; D049109:Cell Proliferation; D003430:Cross-Sectional Studies; D005260:Female; D006258:Head and Neck Neoplasms / Q000453:epidemiology / Q000473:pathology*; D006801:Humans; D055623:Keratosis, Actinic / Q000453:epidemiology; D008297:Male; D018328:Melanoma, Amelanotic / Q000453:epidemiology / Q000473:pathology*; D008875:Middle Aged; D008940:Mitotic Index; D012737:Sex Factors; D012878:Skin Neoplasms / Q000453:epidemiology / Q000473:pathology*; D047368:Tumor Burden; D014739:Victoria / Q000453:epidemiology