title: Grading of atypia in genital skin lesions: routine microscopic evaluation and use of p16 immunostaining.
abstract: p16 immunostaining has been used to aid and improve the histopathologic evaluation of equivocal cervical lesions with associated low-grade or high-grade dysplasia. However, the utility of p16 immunostaining in the diagnosis of atypical genital skin lesions remains debatable.
  
  
  
  We conducted a cross-sectional study of genital skin lesions with varying degrees of atypia. Four pathologists assessed lesional atypia and interpreted hematoxylin and eosin (H&E) staining and p16 immunostaining without knowledge of original diagnosis. Our primary outcomes were diagnostic agreement and test performance of p16 immunostaining compared to consensus H&E diagnosis.
  
  
  
  Our sample was comprised of 23 cases of atypical genital skin lesions. p16 immunostaining was negative in all cases of reactive atypia (n = 3) and the majority (n = 7 of 8; 88%) of low-grade squamous intraepithelial lesions (LSILs). The majority (n = 10 of 12; 83%) of high-grade squamous intraepithelial lesions (HSIL) were p16 positive. Diagnostic agreement for histopathologic assessment using H&E staining was moderate (kappa = 0.44), while inter-observer agreement of p16 immunostaining was excellent (kappa = 0.87). Compared to consensus diagnosis using H&E staining, p16 immunostaining performed well (sensitivity 83.3%; specificity 90.9%).
  
  
  
  p16 immunostaining may be a useful adjunctive marker for assessing dysplasia in genital skin lesions and increasing diagnostic agreement among pathologists.
authors.affiliation: Department of Dermatology, Yale School of Medicine, New Haven, CT, USA.
authors.forename: Harib
authors.initials: H
authors.lastname: Ezaldein
authors.affiliation: Department of Dermatology, Yale School of Medicine, New Haven, CT, USA.
authors.forename: Jason P
authors.initials: JP
authors.lastname: Lott
authors.affiliation: Department of Dermatology, Yale School of Medicine, New Haven, CT, USA.
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: McNiff
authors.affiliation: Department of Dermatology, Yale School of Medicine, New Haven, CT, USA.
authors.forename: Pei
authors.initials: P
authors.lastname: Hui
authors.affiliation: Department of Dermatology, Yale School of Medicine, New Haven, CT, USA.
authors.forename: Natalia
authors.initials: N
authors.lastname: Buza
authors.affiliation: Department of Dermatology, Yale School of Medicine, New Haven, CT, USA.
authors.forename: Christine J
authors.initials: CJ
authors.lastname: Ko
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis; D003430:Cross-Sectional Studies; D019941:Cyclin-Dependent Kinase Inhibitor p16; D005260:Female; D005836:Genitalia, Female / Q000378:metabolism / Q000473:pathology* / Q000821:virology; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis*; D015588:Observer Variation; D030361:Papillomavirus Infections / Q000378:metabolism / Q000473:pathology / Q000821:virology; D012680:Sensitivity and Specificity; D012871:Skin Diseases / Q000378:metabolism / Q000473:pathology* / Q000821:virology; D065310:Squamous Intraepithelial Lesions of the Cervix / Q000378:metabolism / Q000473:pathology / Q000821:virology; D002583:Uterine Cervical Neoplasms / Q000473:pathology / Q000821:virology
chemical_list: D014408:Biomarkers, Tumor; C000614131:CDKN2A protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; D009363:Neoplasm Proteins
keywords: HPV; HSIL; LSIL; dysplasia; p16