Adjuvant radiation may be used to reduce the recurrence of high-risk cutaneous squamous cell carcinoma after resection. Adjuvant radiation can produce histologic changes in the skeletal muscle that mimic keratinocyte atypia, presenting a diagnostic challenge during subsequent resections. We present a case of cutaneous squamous cell carcinoma and histologic changes observed in a fresh frozen section that were consistent with degenerative changes of irradiated skeletal muscle that had a muscle-specific actin+, Melan-A-, and cytokeratin- immunophenotype on paraffin-embedded permanent sections. We also reviewed the literature of other similar reported findings on irradiated skeletal muscle.
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