{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T16:12:19Z","timestamp":1791994339546,"version":"4.4.0"},"reference-count":24,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2014,11,26]],"date-time":"2014-11-26T00:00:00Z","timestamp":1416960000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Almirall"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Acad Dermatol Venereol"],"published-print":{"date-parts":[[2015,5]]},"abstract":"Abstract<\/jats:title>Background<\/jats:title>Progression from actinic keratosis (AK) to invasive squamous cell carcinoma (iSCC<\/jats:styled-content>) 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<\/jats:styled-content> 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 \u2018differentiated pathway\u2019 of iSCC<\/jats:styled-content> of the vulva, oral cavity and other locations.<\/jats:p><\/jats:sec>Objective<\/jats:title>To evaluate the prevalence of classic and differentiated pathways in the development of cutaneous iSCC<\/jats:styled-content>.<\/jats:p><\/jats:sec>Methods<\/jats:title>The epidermis adjacent to and overlying iSCC<\/jats:styled-content>, assumed to be representative of pre\u2010existing lesions, was histologically studied in 196 skin biopsy specimens showing iSCC<\/jats:styled-content>.<\/jats:p><\/jats:sec>Results<\/jats:title>AK I, AK II and AK III lesions overlying iSCC<\/jats:styled-content> were present in 63.8%, 17.9% and 18.4% of cases respectively. The corresponding percentages in the epidermis adjacent to iSCC<\/jats:styled-content> were 77.9%, 6.6% and 8.3% respectively (stage could not be assessed in 8.1% of cases). Focal epidermal ulceration overlying iSCC<\/jats:styled-content> was seen in 32% of AK I, 28.6% of AK II and 33.3% of AK III instances. Adnexal involvement by atypical keratinocytes (proliferative AK) was present more frequently in cases with overlying AK I (39\/125, 31.2%) than with AK II (8\/35, 22.9%) and AKII I (5\/36, 13.9%).<\/jats:p><\/jats:sec>Conclusion<\/jats:title>Direct invasion from proliferating basaloid atypical keratinocytes limited to the epidermal basal layer (AK I), known as the differentiated pathway, was the most common form of progression to cutaneous iSCC<\/jats:styled-content> in our series. On the other hand, stepwise progression from AK I to AK II and AK III (classic pathway) was seen to be operative in a substantial proportion of iSCC<\/jats:styled-content> cases. All AK lesions, irrespective of intraepidermal neoplasia thickness, are therefore potentially invasive and tumour advance along adnexal structures might facilitate iSCC<\/jats:styled-content> development from AK I lesions.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jdv.12848","type":"journal-article","created":{"date-parts":[[2014,11,27]],"date-time":"2014-11-27T02:00:08Z","timestamp":1417053608000},"page":"991-997","source":"Crossref","is-referenced-by-count":209,"title":["Actinic keratosis with atypical basal cells (AK<\/scp> I) is the most common lesion associated with invasive squamous cell carcinoma of the skin"],"prefix":"10.1111","volume":"29","author":[{"given":"M.T.","family":"Fern\u00e1ndez\u2010Figueras","sequence":"first","affiliation":[{"name":"Department of Anatomic Pathology Hospital Universitari Germans Trias i Pujol Universitat Aut\u00f2noma de Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Carrato","sequence":"additional","affiliation":[{"name":"Department of Anatomic Pathology Hospital Universitari Germans Trias i Pujol Universitat Aut\u00f2noma de Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"X.","family":"S\u00e1enz","sequence":"additional","affiliation":[{"name":"Department of Anatomic Pathology Hospital Universitari Germans Trias i Pujol Universitat Aut\u00f2noma de Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6083-0952","authenticated-orcid":false,"given":"L.","family":"Puig","sequence":"additional","affiliation":[{"name":"Department of Dermatology Hospital de la Santa Creu i Sant Pau Universitat Aut\u00f2noma de Barcelona Barcelona 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