Extensive Perineural and Intraneural Invasion of a Squamous Cell Carcinoma Arising in an Epidermal Inclusion Cyst.

A 75-year-old man presented with a three-year history of a non-healing papule on the left eyebrow. Initial biopsy demonstrated vascular ectasia and chronic inflammation. Two years later, repeat sampling revealed poorly differentiated cutaneous squamous cell carcinoma (SCC). Mohs micrographic surgery (MMS) was subsequently performed and required seven stages. The final stage of frozen section interpretation was limited due to dense perineural inflammation. Permanent sections from the main lesion demonstrated SCC arising from the wall of an epidermal inclusion cyst (EIC) with deep dermal and subcutaneous extension, and additional en face margins submitted for permanents showed extensive perineural invasion and intraneural invasion involving multiple larger-caliber nerves. p40 immunostaining highlighted tumor nests and delineated their extension into the deep dermis and subcutaneous tissue. The patient underwent wide local excision with parotidectomy, selective neck dissection, and free-flap reconstruction, followed by adjuvant radiation. Follow-up at four months showed no recurrence. This case highlights the rarity of SCC arising within an EIC, with both extensive perineural and intraneural invasion. Frozen section interpretation was limited by dense perineural inflammation, while permanent levels and selective immunohistochemistry clarified margins and informed escalation from MMS to otolaryngologic management and adjuvant radiotherapy. These findings underscore the importance of multidisciplinary care in high-risk disease.