78 of the 10,707 tumors included had lymphovascular invasion. Of these, there was significantly higher incidence of local recurrence, metastasis, and disease specific death in low stage tumors. High stage tumors with lymphovascular invasion had a higher incidence of metastasis and disease-specific death, but not local recurrence.
Clinical Pearls
This 20-year, multi-center retrospective study of 10,707 cutaneous squamous cell carcinomas aimed to determine the effect of lymphovascular invasion on tumor outcomes. The effect of lymphovascular invasion on cutaneous squamous cell carcinoma was further stratified based on if tumors were low stage (BWH stage T1/T2a) or high stage (BWH T2b/T3).
78 of the 10,707 tumors included had lymphovascular invasion. Of these, there was significantly higher incidence of local recurrence, metastasis, and disease specific death in low stage tumors. High stage tumors with lymphovascular invasion had a higher incidence of metastasis and disease-specific death, but not local recurrence.
Overall, lymphovascular invasion in cutaneous squamous cell carcinomas was associated with higher rates of metastasis and death at 5 years, even in the absence of other risk factors.
Discussion:
Lymphovascular invasion is a relatively rare finding in cutaneous squamous cell carcinoma. However, when present, it is a high-risk feature associated with metastatic disease and disease-specific death. The presence of lymphovascular invasion has not yet demonstrated independent prognostic significance. Thus, lymphovascular invasion is excluded from staging systems. This study aimed to address this issue by evaluating the direct impact of lymphovascular invasion on cutaneous squamous cell carcinoma tumor outcomes.
This study included patients diagnosed with cutaneous squamous cell carcinoma at Brigham and Women’s Hospital from January of 2000 to December of 2017 and at The Cleveland Clinic Foundation from March 1999 to October 2020. Patient demographics in addition to tumor, treatment, and outcomes data was collected from this multi-center cohort.
The authors found BWH T1/T2a tumors with lymphovascular invasion were more likely to have moderate or poor differentiation (66% vs 13%; P<.01) and more likely to metastasize (15% vs <1%; P<.01) than tumors without lymphovascular invasion. Lymphovascular invasion was also associated with an increased disease-specific death in these tumors (19% vs <1%; P<.01)
The authors also found that BWH T2b/T3 tumors with lymphovascular invasion were more likely to have bone invasion (31% vs 12%; P=.02), more likely to metastasize (25% vs 5%; p=.05), and more likely to result in death (25% vs 13%; p=.02) than tumors without lymphovascular invasion.
Multivariable analyses were additionally performed by the authors, showing significant associations between lymphovascular invasion and local recurrence (SHR12.2 [95% CI: 5.1-29.3], p<.01), metastasis (SHR 9.9 [95% CI: 2.9-34.0], p<.01), and disease-specific death (SHR 41.4 [95% CI: 9.1-188.9], p<.01) for BWH T1/T2a tumors. The same analysis for BWH T2b/T3 tumors found a significant association between lymphovascular invasion and disease specific death (SHR 2.0 [95%CI: 1.1-3.6], p=.03). The association with BWH T2b/T3 tumors and metastasis trended towards significance (SHR 1.8 [95%CI:1.0-3.5], p=.06), while no difference was found when looking at local recurrence in this particular analysis (SHR 1.0 [95%CI: 0.5-2.2], p=.11)
Overall, this was the largest and first multi-center study to evaluate the impact of lymphovascular invasion on cutaneous squamous cell carcinoma outcomes. The authors found that lymphovascular invasion independently influenced local recurrence and metastasis in low-stage tumors while affecting disease related death in both low and high-stage tumors.
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