Limited literature exists regarding whether intraoperative analysis of frozen debulk specimens during Mohs micrographic surgery (MMS) improves identification of high-risk features (HRF) of cutaneous squamous cell carcinoma (CSCC).

Primary: identification of new HRF on debulk specimens. Secondary: CSCC upstaged after considering debulk data.

A single-center, retrospective cohort study of patients with biopsy-proven CSCC treated by MMS with intraoperative frozen debulk analysis. Restricted (poor differentiation, new perineural invasion ≥0.1 mm, and Breslow depth >6 mm) and nonrestricted (any worsened tumor differentiation, any new perineural invasion, and Breslow depth >2 mm) analyses were performed.

In restricted analysis, 3.94% of cases had 1 new HRF on debulk analysis. In nonrestricted analysis, 32.9% of cases had ≥1 new HRF; 7.6% increased by 2 HRF. Approximately 2.0% of cases were upstaged by American Joint Committee on Cancer system, eighth edition criteria, 1.4% by Brigham and Women's Hospital. Tumor size ≥2 cm, male sex, and moderate differentiation on biopsy were significantly associated with new HRF identified on debulk analysis.

Intraoperative frozen debulk analysis can reveal HRF of CSCC not seen on biopsy or MMS stages, particularly among tumors ≥2 cm. American Joint Committee on Cancer system, eighth edition T2 tumors were most likely to be upstaged. Identification of new HRF on debulk analysis can improve CSCC staging and may impact patient treatment and follow-up.