(ChemotherapyAdvisor) – Squamous cell carcinoma (SCC) with large-caliber nerve invasion is associated with an elevated risk of nodal metastasis and death, in part due to multiple risk factors, results of a retrospective cohort study reported in the January 2013 issue of JAMA Dermatology.

Perineural invasion (PNI), one of the new additions to the American Joint Committee on Cancer (AJCC) staging system, occurs in approximately 2.5% to 5% of primary SCCs, reported Joi B. Carter, MD, of the Department of Dermatology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, and colleagues.

“Perineural invasion portends poor outcomes with reported risks of lymph node metastasis and distant metastasis of 35% and 15%, respectively, compared with SCC without PNI,” the authors wrote. They reviewed 114 cases of adults with perineural SCC diagnosed from 1998 to 2008 to identify factors associated with poor outcomes.

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“Only a single local recurrence occurred in cases with no risk factors other than nerve invasion,” Dr. Carter stated, adding that “tumors with large nerve (≥0.1 mm in caliber) invasion were significantly more likely to have other risk factors, including diameters of 2 cm or greater (P<0.001), invasion beyond the subcutaneous fat (P<0.003), multiple nerve involvement (P<0.001), infiltrative growth (P=0.01), or lymphovascular invasion (P=0.01).”

On univariate analysis, large nerve invasion was associated with increased risk of nodal metastasis (hazard ratio [HR] 5.6; 95% CI: 1.1-27.9) and death from disease (HR 4.5; 95% CI: 1.2-17.0).

The investigators found that on multivariate analysis, tumor diameter of 2 cm or greater predicted local recurrence; more than one risk factor predicted nodal metastasis; and lymphovascular invasion predicted both death from disease and overall death, the latter of which was also predicted by invasion beyond subcutaneous fat.

Of the cases, all but two involved unnamed nerves. The authors concluded that a larger study is needed to estimate the specific prognostic impact of nerve caliber.