Grading of atypia in genital skin lesions: routine microscopic evaluation and use of p16 immunostaining

J Cutan Pathol. 2015 Aug;42(8):519-26. doi: 10.1111/cup.12525. Epub 2015 Jun 8.

Abstract

Background: 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.

Methods: 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.

Results: 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%).

Conclusions: p16 immunostaining may be a useful adjunctive marker for assessing dysplasia in genital skin lesions and increasing diagnostic agreement among pathologists.

Keywords: HPV; HSIL; LSIL; dysplasia; p16.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / analysis
  • Cross-Sectional Studies
  • Cyclin-Dependent Kinase Inhibitor p16
  • Female
  • Genitalia, Female / metabolism
  • Genitalia, Female / pathology*
  • Genitalia, Female / virology
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Neoplasm Proteins / analysis*
  • Observer Variation
  • Papillomavirus Infections / metabolism
  • Papillomavirus Infections / pathology
  • Papillomavirus Infections / virology
  • Sensitivity and Specificity
  • Skin Diseases / metabolism
  • Skin Diseases / pathology*
  • Skin Diseases / virology
  • Squamous Intraepithelial Lesions of the Cervix / metabolism
  • Squamous Intraepithelial Lesions of the Cervix / pathology
  • Squamous Intraepithelial Lesions of the Cervix / virology
  • Uterine Cervical Neoplasms / pathology
  • Uterine Cervical Neoplasms / virology

Substances

  • Biomarkers, Tumor
  • CDKN2A protein, human
  • Cyclin-Dependent Kinase Inhibitor p16
  • Neoplasm Proteins