Outcomes of primary cutaneous squamous cell carcinoma with perineural invasion: an 11-year cohort study

JAMA Dermatol. 2013 Jan;149(1):35-41. doi: 10.1001/jamadermatol.2013.746.


Objective: To identify factors associated with poor outcomes in perineurally invasive squamous cell carcinoma.

Design: Retrospective cohort study.

Setting: Two academic hospitals in Boston, Massachusetts.

Patients: Adults with perineural SCC diagnosed from 1998 to 2008.

Main outcome measures: Hazard ratios (HRs) for local recurrence, nodal metastasis, death from disease, and overall death, adjusted for known prognostic factors.

Results: A total of 114 cases were included, all but 2 involving unnamed nerves. Only a single local recurrence occurred in cases with no risk factors other than nerve invasion. 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<.001), invasion beyond the subcutaneous fat (P<.003), multiple nerve involvement (P<.001), infiltrative growth (P=.01), or lymphovascular invasion (P=.01). On univariate analysis, large nerve invasion was associated with increased risk of nodal metastasis (HR, 5.6 [95% CI, 1.1-27.9]) and death from disease (HR, 4.5 [95% CI, 1.2-17.0]). On multivariate analysis, tumor diameter of 2 cm or greater predicted local recurrence (HR, 4.8 [95% CI, 1.8-12.7]), >1 risk factor predicted nodal metastasis (2 factors: HR, 4.1 [95% CI, 1.0-16.6]), lymphovascular invasion predicted death from disease (HR, 15.3 [95% CI, 3.7-62.8]), and overall death (HR, 1.1 [95% CI, 1.0-1.1]). Invasion beyond subcutaneous fat also predicted overall death (HR, 2.1 [95% CI, 1.0-4.3]).

Conclusions: Squamous cell carcinoma involving unnamed small nerves (<0.1 mm in caliber) may have a low risk of poor outcomes in the absence of other risk factors. Large-caliber nerve invasion is associated with an elevated risk of nodal metastasis and death, but this is due in part to multiple other risk factors associated with large-caliber nerve invasion. A larger study is needed to estimate the specific prognostic impact of nerve caliber.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Carcinoma, Squamous Cell / pathology*
  • Cohort Studies
  • Female
  • Follow-Up Studies
  • Humans
  • Lymphatic Metastasis
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Neoplasm Invasiveness
  • Neoplasm Recurrence, Local
  • Outcome Assessment, Health Care*
  • Peripheral Nerves / pathology*
  • Prognosis
  • Retrospective Studies
  • Risk Factors
  • Skin Neoplasms / pathology*
  • Subcutaneous Fat / pathology*