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

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.