Abstract

The precursor lesion of SCC is the actinic keratosis (AK), and the risk of progression from a single AK to SCC is 0.025–16% per year. Previous studies demonstrate that AKs adjacent to invasive squamous cell carcinoma are more commonly proliferative AKs. When comparing clinical outcomes, it is not known whether proliferative AKs have a greater risk for progression to invasive SCC than non-proliferative AKs. We retrospectively examined histopathologic features of 134 tissue specimens of proliferative AKs (n=77, 25.3% female, mean age of 83 years) and ordinary AKs including hypertrophic AKs (n=57, 49.1% female, mean age of 80 years). Proliferative actinic keratoses were significantly more associated with adnexal extension and adverse clinical behavior compared to actinic keratoses without proliferative features. After controlling for adnexal extension with ordinal logistic regression analysis, the odds of having an increased clinical score (i.e., 3 or 2 or 1 versus 0) was 7.8 times higher (95% CI: 1.8-57.1, P-value = 0.02) in patients with a diagnosis of proliferative actinic keratosis compared to patients with a diagnosis of actinic keratosis without proliferative features. These results demonstrate that proliferative AKs have a more aggressive clinical behavior than ordinary AKs and are also more likely to demonstrate adnexal extension. There is also some degree of clinical evidence to suggest that AKs with a downward pattern of growth (the so-called “differentiated pathway”) portend a greater risk for malignant transformation than an upward spread of cellular atypia (the so-called “classical pathway”).

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