title: Significance of epidermal mitoses in challenging melanocytic proliferations.
abstract: BACKGROUND
  Accurate diagnosis of melanoma remains histologically challenging. Dermal mitoses support malignancy, but are only occasionally seen in melanomas. As melanomagenesis is thought to begin at the dermal-epidermal junction, we investigated the significance of epidermal melanocytic mitoses (EMM) in a spectrum of lesions with molecular characterization.
  
  
  METHODS
  Epidermal mitoses density (EMD) was evaluated in 46 straightforward lesions (24 benign and 22 malignant) and 30 challenging lesions with expert interpretation, fluorescence in situ hybridization and myPath-score characterization (12 favor-benign, 9 favor-malignant and 9 ambiguous). EMD was correlated with clinicopathologic parameters and myPath.
  
  
  RESULTS
  In straightforward cases, 25% nevi and 77% melanomas had EM. Median EMD was significantly lower in nevi vs. melanomas (0/mm vs. 0.04/mm, p = 0.001). EMD (0.01/mm-cutoff) had 77% sensitivity, 79% specificity discriminating melanomas from nevi. In challenging cases, 17% favor-benign, 67% favor-malignant and 78% ambiguous lesions had EM. EMD (0.01/mm-cutoff) had 67% sensitivity, 82% specificity on 21 non-ambiguous lesions, similar to myPath. EMD was less accurate in Spitzoid lesions, which have high EMD and dermal mitoses.
  
  
  CONCLUSIONS
  While EMD is not an adequate single criterion in diagnosing melanoma, our results validate its discriminatory potential, suggesting that EM should prompt closer investigation for malignancy. Expanded studies with clinical follow up are warranted to further assess the EM utility in classifying melanocytic lesions.
authors.affiliation: Department of Pathology, Cleveland Clinic, Cleveland, OH, USA.|Department of Dermatology, Cleveland Clinic, Cleveland, OH, USA.
authors.forename: Eugen C
authors.initials: EC
authors.lastname: Minca
authors.affiliation: Department of Pathology, Cleveland Clinic, Cleveland, OH, USA.|Department of Dermatology, Cleveland Clinic, Cleveland, OH, USA.
authors.forename: Steven D
authors.initials: SD
authors.lastname: Billings
authors.affiliation: Department of Pathology, Cleveland Clinic, Cleveland, OH, USA.|Department of Dermatology, Cleveland Clinic, Cleveland, OH, USA.|Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, OH, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Elson
authors.affiliation: Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, OH, USA.|Department of Pathology, MD Anderson Cancer Center, The University of Texas, Houston, TX, USA.
authors.forename: Michael T
authors.initials: MT
authors.lastname: Tetzlaff
authors.affiliation: Department of Pathology, MD Anderson Cancer Center, The University of Texas, Houston, TX, USA.|Department of Pathology, University of Michigan Medical Center, Ann Arbor, MI, USA.
authors.forename: Aleodor A
authors.initials: AA
authors.lastname: Andea
authors.affiliation: Department of Pathology, Cleveland Clinic, Cleveland, OH, USA.|Department of Dermatology, Cleveland Clinic, Cleveland, OH, USA.
authors.forename: Jennifer S
authors.initials: JS
authors.lastname: Ko
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D049109:Cell Proliferation; D004817:Epidermis / Q000473:pathology; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008544:Melanocytes / Q000473:pathology; D008545:Melanoma / Q000175:diagnosis* / Q000473:pathology; D008875:Middle Aged; D008938:Mitosis; D008940:Mitotic Index; D012680:Sensitivity and Specificity; D012878:Skin Neoplasms / Q000175:diagnosis* / Q000473:pathology; D055815:Young Adult
keywords: epidermal mitoses; junctional mitoses; melanoma; myPath