Cutaneous Squamous Cell Carcinoma of the Head and Neck: Pathological Features and What They Mean for Prognosis and Treatment

Simple Summary Cutaneous squamous cell carcinoma (cSCC) of the head and neck, although treatable, can be highly aggressive. Certain pathological features of cSCC can drastically impact prognosis. Therefore, the presence of a few such features is considered in both staging and treating cSCC. In this review, we summarize the current literature regarding pathological prognostic indicators of cSCC, including depth of invasion, surgical margins, perineural invasion, lymphovascular invasion, extranodal extension, tumor grade, tumor subtype, premalignant lesions, and molecular markers. Furthermore, we characterize the impact of each indicator on clinical outcomes of head and neck cSCC, their role in dictating adjuvant therapy for this tumor, and their incorporation or lack thereof into current staging and treatment guidelines.Abstract Cutaneous squamous cell carcinoma (cSCC) is one of the most common cancers worldwide, with an incidence that has increased over the past 30 years. Although usually curable with excision, cSCC can become widely metastatic and aggressive with poor outcomes. Whereas the clinical and radiographic extent of any cancer will always guide selection of treatment modality, pathological features of cSCC also play an important role in determining prognosis and, subsequently, the need for further therapy. Therefore, reviewing and summarizing the current literature regarding pathological prognostic indicators of cSCC is essential to improving clinical outcomes. The present literature review yielded depth of invasion, surgical margins, perineural invasion, extranodal extension, lymphovascular invasion, tumor grade, tumor subtype, premalignant lesions, and molecular markers as key prognostic indicators, all with varying recommendations for adjuvant therapy. Notably, some of these factors have not been incorporated into either the American Joint Committee on Cancer staging system (8th edition) or National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology for cSCC. This review highlights a need for further research into these prognostic indicators and their role in determining the need for adjuvant treatment in head and neck cSCC.