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Progression from actinic keratosis (AK) to invasive squamous cell carcinoma (iSCC) of the skin is thought to occur after the development of full thickness epidermal neoplasia, as in the classic pathway of cervical cancer. Nevertheless, cutaneous iSCC may also directly arise from a proliferation of atypical basaloid cells limited mostly to the epidermal basal layer (AK I), akin to what happens in the ‘differentiated pathway’ of iSCC of the vulva, oral cavity and other locations.

To evaluate the prevalence of classic and differentiated pathways in the development of cutaneous iSCC.

The epidermis adjacent to and overlying iSCC, assumed to be representative of pre‐existing lesions, was histologically studied in 196 skin biopsy specimens showing iSCC.

AK I, AK II and AK III lesions overlying iSCC were present in 63.8%, 17.9% and 18.4% of cases respectively. The corresponding …