Histopathological predictor of the progression from actinic keratosis to squamous cell carcinoma: quantitative computer-aided image analysis

Background: The current histopathological classifications for actinic keratosis (AK) are subjective, and histopathological factors predicting the progression into invasive squamous cell carcinoma (SCC) remain unclear. Objectives: To quantitatively assess the histopathological findings of AK and to investigate the predisposing factors for malignant transformation of AK. Methods: A total of 502 AK specimens were retrospectively reviewed. The AK lesions were divided into the atrophic, intermediate, hypertrophic and bowenoid types. Histopathological features were quantitatively analysed using computer-aided image analysis. Results: The epidermal thickness excluding the horny layer increased with statistical significance (P < 0.001) in order of atrophic, intermediate, hypertrophic and bowenoid type. The proportion of keratinocytic atypia was not significantly different among subtypes, except for the bowenoid type. Five of 498 cases were confirmed to develop into SCC. Bowenoid type, epidermal thickening and higher proportion of keratinocytic atypia were significantly associated with progression to invasive SCC in univariate analysis (OR = 12.571, 95% CI: 1.392-113.57; OR = 1.004, 95% CI: 1.001-1.007; OR = 1.069, 95% CI: 1.011-1.130, respectively). In multivariate analysis, only the proportion of keratinocytic atypia was an independent predisposing factor for progression to invasive SCC (OR = 1.069; 95% CI: 1.011-1.130). Conclusions: Histopathological subtypes based on the essential change of the epidermis well correlated with the actual epidermal thickness excluding the horny layer. The overall severity of keratinocytic atypia might be an independent risk factor for malignant transformation of AK.

Automated summary

This study quantitatively assessed histopathological findings of actinic keratosis (AK) and identified bowenoid type, epidermal thickening, and higher proportion of keratinocytic atypia as significant factors associated with progression to invasive squamous cell carcinoma (SCC). Multivariate analysis revealed that the proportion of keratinocytic atypia was the only independent predisposing factor for SCC progression.