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Review
. 2017 Aug 1;153(8):781-788.
doi: 10.1001/jamadermatol.2017.1680.

Clinical and Incidental Perineural Invasion of Cutaneous Squamous Cell Carcinoma: A Systematic Review and Pooled Analysis of Outcomes Data

Pritesh S Karia  1   2 , Frederick C Morgan  1 , Emily Stamell Ruiz  1 , Chrysalyne D Schmults  1
Affiliations
Review

Clinical and Incidental Perineural Invasion of Cutaneous Squamous Cell Carcinoma: A Systematic Review and Pooled Analysis of Outcomes Data

Pritesh S Karia et al. JAMA Dermatol. .

Abstract

Importance: Perineural invasion (PNI) in cutaneous squamous cell carcinoma (CSCC) has been associated with an increased risk of poor outcomes. Patients with PNI may present with clinical symptoms and/or radiologic evidence of PNI (clinical PNI [CPNI]), yet most patients are asymptomatic and PNI is often found on histologic examination (incidental PNI [IPNI]). Evidence-based estimates of the risks of disease-related outcomes comparing IPNI and CPNI are limited in the dermatology literature.

Objectives: To review and synthesize outcomes data for patients with CSCC and CPNI or IPNI.

Data sources: A systematic review was conducted in MEDLINE and EMBASE for English-language articles published since inception to November 11, 2016.

Study selection: All studies that reported a disease-related outcome (local recurrence, nodal metastasis, distant metastasis, or disease-specific death) of CSCCs with CPNI and IPNI were included.

Data extraction and synthesis: Articles were screened for eligibility, and any possible discrepancies in this screening were resolved. Data extracted included study characteristics, tumor characteristics, treatments performed, and disease-related outcomes. Overall risks of disease-related outcomes were generated by pooling patients from eligible studies. χ2 Statistics and Fisher exact tests were used to evaluate differences in disease-related outcomes.

Main outcomes and measures: Risks of disease-related outcomes and 5-year recurrence-free, disease-specific, and overall survival.

Results: A total of 12 studies containing 241 patients with CPNI and 381 patients with IPNI were included in the systematic review and analysis. The overall risks of local recurrence and disease-specific death were significantly higher in patients with CSCC and CPNI compared with those with CSCC and IPNI (local recurrence, 37% vs 17%; P < .001; disease-specific death, 27% vs 6%; P < .001). The risks of nodal metastasis and distant metastasis did not differ significantly by PNI classification. Patients with CSCC and CPNI had poorer mean 5-year recurrence-free survival and disease-specific survival compared with patients with IPNI (recurrence-free survival, 61% vs 76%; P = .009; disease-specific survival, 70% vs 88%; P = .002).

Conclusions and relevance: Patients with CSCC and CPNI are at an increased risk of local recurrence and disease-specific death compared with patients with CSCC and IPNI and have a 30% risk of death. Patients with PNI may benefit from increased long-term surveillance. Further studies are needed to establish standardized guidelines on follow-up and dermatologic surveillance in this high-risk patient population.

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Conflict of interest statement

Conflict of Interest Disclosures: None reported.

Figures

Figure.
Figure.. Flowchart of Studies Included in the Systematic Review
PNI indicates perineural invasion.
See this image and copyright information in PMC

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