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Cutaneous squamous cell carcinoma (cSCC) of the vermilion lip may carry a higher-risk of metastasis, according to a retrospective study.

A fivefold greater risk of nodal metastasis was seen among cSCCs of the vermilion lip compared with cSCCs of the cutaneous lip (7.6% versus 1.5%, P=0.01), reported Chrysalyne D. Schmults, MD, MSCE, of Brigham and Women's Hospital (BWH) and Harvard Medical School in Boston, and colleagues.

"For cSCCs of the lip, local recurrence occurs in up to 22% of tumors compared with 3% for cSCCs of all locations," the authors wrote in . "Vermilion involvement appears responsible for the increased risk," and "may merit radiologic nodal staging and inclusion in future tumor staging."

Schmults' group also found that nodal metastasis was associated with invasion beyond the fascia or vermilion lip (subhazard ratio 4.4, 95% CI, 1.3-14.9) and with vermilion lip location (subhazard ratio 5.0, 95% CI 1.1-23.8) in a multivariable analysis. But the latest American Joint Committee on Cancer (AJCC 8) staging system has vermilion lip cSCC lumped together with cutaneous lip cSCC.

"This finding suggests that the recently updated AJCC 8 criteria and BWH cSCC staging may not adequately account for the increased risk inherent to vermilion lip location," the team explained.

The researchers looked at 310 primary cSCCs (138 cutaneous lip, 172 vermilion lip) from 303 patients diagnosed from 2000 to 2015 at two care centers in Boston.

Other outcomes of interest did not reach statistical significance (vermilion versus cutaneous cSCCs):

• local recurrence, 6.4% versus 2.9%
• distant metastasis, 0.6% versus 0.7%
• disease-specific death, 3.5% versus 2.9%
• all-cause death, 26.7% versus 29.0%

"This study is very important for formally defining this risk factor of the anatomic origin on the vermilion lip," Bryan T. Carroll, MD, PhD, of the University of Pittsburgh School of Medicine, told MedPage Today, noting that cSCCs in the vermilion lip are common in his practice.

The definition of lip cSCCs as cutaneous, vermilion, or mucosal lip is not consistent across previous studies, said Carroll, who was not involved in the study. This ambiguity is further confounded by larger tumors extending across all three zones of the lip.

"The novelty of their approach is in their definition of vermilion lip SCC," Carroll explained. "While most tumor locations were evident from the clinical record, inconclusive locations were confirmed by histologic evidence of vermilion features (the presence of superficial muscle without hair follicles nor fat)."

And tumors that involved both vermilion and cutaneous locations were classified as vermilion lip cSCCs.

Patients in the study were evenly divided between men and women (50.5% versus 49.5%). The median age at diagnosis was 68 years (27-93), and 173 patients (57.1%) had a history of skin cancer. A number of patients (26.1%) had immunosuppression.

Vermilion lip cSCCs were more often located on the lower (81%) compared with the upper lip (19%), but there was no significant difference in terms of nodal involvement (7.9% versus 6.3%, P>0.99).

Limitations of the study include its retrospective nature, the authors noted. A fifth of cases had to be excluded due to lack of risk factor or outcomes data, and factors such as tobacco or herpes -- which could contribute to worse outcomes -- were unavailable.