Initial biopsies of cutaneous squamous cell carcinomas (cSCCs) may not reveal aggressive histologic features, which would otherwise inform appropriate surgical management and patient education.

To assess the incidence of, and risk factors for, histopathologic upgrading of cSCC during Mohs micrographic surgery (MMS).

This was a retrospective cohort study of invasive cSCCs treated with MMS between 2017 and 2019 at 1 academic institution. An “upgrade” was defined as a lesser degree of differentiation (poor or moderate) and/or bony or perineural invasion identified during MMS that was not reported in histopathologic evaluation of the initial biopsy.

Of the 1558 tumors studied, 115 (7.4%) were upgraded during MMS. In multivariate logistic regression analysis, male sex, prior field treatment, location on the ear/lip, rapid growth of cSCC, and tumor diameter ≥2 cm were significant predictors of tumor upgrading. Upgraded tumors were more likely to require ≥3 MMS stages to clear, complicated closure (flap or graft), or outside (referral) repairs.

Single-center study, retrospective, and inter-rater variability.

A significant proportion of cSCCs is histopathologically upgraded with more aggressive features during MMS. Routinely documented patient and tumor characteristics can predict tumor upgrading and assist clinicians in directing the management of potentially high-risk cSCC patients.