Aims Cutaneous squamous cell carcinoma in situ (SCCis) can be classified histopathologically into four subtypes: full-thickness (FT), hypertrophic actinic keratosis (HAK), Bowenoid, and acantholytic types. 3%–5% of SCCis lesions progress to invasive squamous cell carcinoma (iSCC), however progression risk by subtype has not been assessed. Aim one of this study is to quantitatively assess the risk of iSCC associated with each histological subtype of SCCis. Aim two is to evaluate if the histological grade of iSCC differs among subtypes of the associated SCCis.

Methods The pathology information system at our institution was queried for cutaneous SCCis cases with and without associated iSCC from 2020 to 2022. The study group consisted of 65 cases of SCCis with associated iSCC and control group 65 randomly selected cases of SCCis without invasion. For each case SCCis subtype was classified as FT, HAK, Bowenoid or acantholytic type. iSCCs were classified as low grade if well to moderately differentiated (LG) and high grade (HG) if moderately to poorly differentiated.

Results iSCC was most often associated with HAK-type SCCis, followed by acantholytic and FT-type SCCis, with Bowenoid type rarely associated with iSCC. 41% (14/34) of iSCCs associated with HAK-type SCCis were HG compared with 84% (21/25) for FT-type SCCis.

Conclusions iSCC is most often associated with HAK-type SCCis, followed by acantholytic and FT-types, and rarely with Bowenoid type. HG invasive SCC is most often associated with FT-type, and LG with HAK-type SCCis. Stratifying SCCis by subtype can inform clinical management.