Prognostic Impact of Perineural Invasion in Cutaneous Squamous Cell Carcinoma: Results of a Prospective Study of 1,399 Tumors

Perineural infiltration (PNI) and desmoplasia are believed to be high-risk factors in the prognosis of squamous cell carcinoma (SCC). In the literature, dependences between PNI, de-differentiation, and desmoplasia remain unclear. The aim of this study was to analyze the respective prognostic impact of these factors in regard to local recurrence and metastasis. Between 2005 and 2015, 1,399 unselected primary SCCs of 1,434 patients were diagnosed. If a patient had multiple tumors, the tumor with the highest risk profile was selected. Histological sections of all tumors with a tumor thickness of >6 mm and desmoplastic SCC with a tumor thickness of 2.1-5.9 mm were re-examined for PNI. Median follow-up was 36.5 months. PNI was present exclusively within tumors of the desmoplastic type (14.5%). PNI was present significantly more often in patients developing lymph node metastasis (3% all non-desmoplastic SCC, 17% desmoplastic SCC, and 29% desmoplastic SCC with PNI) and local recurrence (3%, 26%, and 64%) and associated with overall tumor-specific death (4%, 25%, and 54%). Using a multivariate model of disease recurrence, tumor thickness >6 mm, tumor horizontal size >20 mm, immunosuppression, desmoplasia, and PNI remained significant factors. In conclusion, PNI was found to be an additional marker indicative of an unfavorable prognosis and an independent high-risk factor within the desmoplastic type of SCC.