Management of periocular cutaneous squamous cell carcinoma with perineural invasion: a case series and literature review

Purpose: To review and elucidate the complex, multimodal management of periocular cutaneous squamous cell carcinoma (SCC) with perineural invasion (PNI), and offer practical, evidence-based patient care recommendations. Methods: Three exemplary cases of high-risk periocular cutaneous SCC with PNI were selected from a single surgeon's experience. The clinical courses, management, and clinical outcomes, with follow-up intervals of 19, 19, and 24 months after presentation, were reviewed. The English-language literature on PNI, with attention to the management of cutaneous SCC of the head and neck (SCCHN), was reviewed. Results: PNI of cutaneous SCCHN portends aggressive tumor behavior and a worsened prognosis. Treatment is multimodal, with varied combinations of surgical excision, radiotherapy (RT), and systemic chemotherapy. Retrospective reports from multiple institutions involve heterogenous patient populations, treatment strategies, and confounding variables that preclude formulation of a standardized treatment paradigm. Newer, comparative studies of advanced RT techniques (e.g., hyper-fractionation), novel systemic chemotherapeutic agents (e.g., cetuximab, cemiplimab), and varied integrative regimens are providing additional insights. Prompt initiation of adjuvant therapies (within 6-8 weeks of surgery), and careful evaluation of lymphatic basins can increase oncologic control. Utilizing deep-tissue fixation of advancement flaps and eyelid stabilization can enhance functional and aesthetic results. Conclusion: Management of cutaneous SCC with PNI remains complex and in most cases requires combined-modality therapy directed by a multidisciplinary tumor board. With novel therapies and new treatment patterns, optimal combinations and intensities of individual modalities require further elucidation. The oculofacial plastic surgeon plays a pivotal role - in diagnosis, coordination of interdisciplinary management, thoughtful surgical reconstruction, and postoperative surveillance.