Redefining Perineural Invasion in Head and Neck Cutaneous Squamous Cell Carcinoma

Abstract

Objective Perineural invasion (PNI) negatively affects disease-specific survival in patients with head and neck cutaneous squamous cell carcinoma (HNcSCC). We aim to analyze the prognostic implications of PNI-related features. Study Design Retrospective cohort study. Setting Academic tertiary care hospital. Methods Retrospective chart review was performed on 104 patients diagnosed with HNcSCC between January 2011 and October 2019 who underwent resection, parotidectomy, and neck dissection with more than 1 year of follow-up. PNI was classified as incidental (identified on histopathology alone) or clinical (present on radiography and/or physical exam). Primary outcome measures were overall survival and disease-free survival (DFS). Kaplan-Meier analysis, logistic regression, and Cox regression were performed. Results The overall 5-year DFS was 57.9%. Sixty-one patients had PNI. On histopathology, 28 lesions showed complete nerve encirclement, 10 involved >5 nerves, and 12 involved named nerves. Patients with facial weakness ( P = .026) and positive margins ( P = .0029) had a higher likelihood of histopathologic PNI, and positive margins retained significance on multivariable analysis ( P = .0079). Worse DFS was seen in patients with PNI ( P = .004), advanced tumor stage ( P = .049), positive margins ( P = .014), and >5 nerves involved ( P = .0061). Furthermore, histopathologic PNI was a predictor of DFS (hazard ratio [HR], 3.07; 95% CI, 0.33-1.38; P = .0061) overall and in the clinical PNI cohort (HR, 3.43; 95% CI, 1.65-7.10; P = .00091). Conclusion DFS was significantly worse in patients with PNI, facial nerve weakness, advanced T stage, positive margins, and multiple nerve involvement. Further characterization of PNI features may help improve prognostic predictions and identify patients who may benefit from more aggressive treatment.

Dickkopf‐1 drives perineural invasion via PI3K–AKT signaling pathway in head and neck squamous cancer

“…5 The prognosis of HNSCC patients with PNI is very poor, and the occurrence of PNI always leads to shortened 5-year disease-free survival (DFS), tumor progression, marginal invasion, and so forth. 6,7 Furthermore, the American Joint Committee on Cancer (AJCC) guidelines classified HNSCC patients with PNI as stage T3, indicating that PNI is of great significance for the treatment and prognosis of HSNCC patients. 8 However, the mechanism of PNI is still unclear, and there are no specific treatment strategies for patients with PNI.…”

“…Because of the special anatomical location of HNSCC, HNSCC can invade into motor nerves, sensory nerves, and even brain, which may lead to pain and/or some cranial neuropathies, such as voice hoarseness and loss of cutaneous and mucosal sensation 5 . The prognosis of HNSCC patients with PNI is very poor, and the occurrence of PNI always leads to shortened 5‐year disease‐free survival (DFS), tumor progression, marginal invasion, and so forth 6,7 . Furthermore, the American Joint Committee on Cancer (AJCC) guidelines classified HNSCC patients with PNI as stage T3, indicating that PNI is of great significance for the treatment and prognosis of HSNCC patients 8 .…”

Extensive Perineural Invasion vs Nerve Caliber to Assess Cutaneous Squamous Cell Carcinoma Prognosis

“…Involvement of multiple nerves, also referred to as extensive PNI (ePNI), has similarly been associated with poor outcomes in CSCC. 8,[12][13][14] However, the literature on this topic is heterogeneous, with various numbers of involved nerves used as thresholds for poorer CSCC outcomes (including >2, 12 ≥3, 8 and >5 13,14 nerves) and inconsistent methodologies employed for assessment of involved nerve counts. Indeed, no definition for what constitutes ePNI is provided by the NCCN.…”