Cutaneous squamous cell carcinoma with subtle perineural invasion detected with cytokeratin and epithelial membrane antigen immunohistochemistry

Perineural invasion (PNI), the infiltration of tumor within the perineural space, is an independent risk factor for adverse outcomes in cutaneous squamous cell carcinoma (cSCC) including recurrence, metastasis, and death.1,2 During microscopically controlled excision, histopathologic features seen on intraoperative tissue sections can present challenges in assessing the presence of PNI. Benign findings such as normal perineurium may mimic PNI in routine sections. Conversely, subtle PNI may be mistaken for benign findings.