Clonal highlights: Clonal seborrheic keratoses often demonstrates p16 expression

Abstract

Background: At times, distinguishing Bowen disease (BD) and benign seborrheic keratosis (SK) is histologically challenging, especially when SK shows clonal features (clonal seborrheic keratosis [CSK]). While p16 is often reported as positive in BD and negative in SK, p16 expression in CSK is rarely studied. Here we investigate p16 immunohistochemistry in CSK, SK, and BD.Methods: p16 immunohistochemistry with pattern of expression was noted for 14 CSK, 12 SK, and 18 BD. The degree of inflammation among lesions with respect to p16 expression was also noted.Results: When examining p16 staining in clonal nests of CSK, 57% showed diffuse or patchy/ diffuse positivity, 21% showed patchy positivity, and 21% showed clusters of single positive cells. 67% of BD showed diffuse positivity, 11% showed patchy/diffuse positivity, 17% showed patchy positivity, and 6% were negative. 25% of SK showed focal areas of patchy to full thickness positivity, 25% showed moderate number of positive single cells with or without patchy staining, and 50% showed negative/scattered single cell positivity.Conclusion: Our findings support that p16 positivity limited to clonal nests in CSK is normal. p16 positivity in clonal nests of CSK in isolation without concurrent atypical histologic features should not be used to support a diagnosis of BD. K E Y W O R D Sclonal, seborrheic keratosis, Bowen disease, immunohistochemistry, p16

The diagnostic value of p63, p16, and p53 immunohistochemistry in distinguishing seborrheic keratosis, actinic keratosis, and Bowen's disease

“…Almost no case showed staining at the level of the basal keratinocytes, except three cases which exhibited positive staining. In one of these three cases, the basal layer was obscured by inflammation, while in the other two cases at least 30% and 50% of the basal keratinocytes did not stain and 23.1% of the BD cases were completely negative; this number was 6% in another study 15 . Although reported staining patterns of p16 differed between previous studies, we can deduce that scattered single and patches of positive cells were the dominant patterns of staining in SK and AK cases in our and other studies alike 9,11,13‐15,18,20 .…”

“…The basal cells were spared in some and stained in others. [13][14][15][17][18][19] According to our grading system, 38.5% of the BD cases were diffusely positive with p16.…”

“…This is also reported by others. 9,[13][14][15]18 The negative results might be related to non-sunexposed lesions. According to several studies, higher expression of p16 in Bowenoid AK compared with other types of AK might result in a worse prognosis.…”

“…In our study, 13.3% of SK cases were negative with p16. Other studies found this percentage to be between 35% and 83%, in which the most common patterns were scattered patches of positive cells 9,13‐15 . One study has shown a connection between the intensity of p16 expression and the number of a patient's SK lesions 16 .…”

Recent advances in managing and understanding seborrheic keratosis

“…Clonal nests of SKs can show a diffuse or patchy positivity for p16. A p16 positivity in clonal nests of SKs without concurrent atypical histologic features is typical for SK and not for pagetoid Bowen’s disease 31 .…”