Recurrence Status, Perineural Invasion, and Hypothyroidism Are Associated With Lymph Node Metastasis in Cutaneous Squamous Cell Carcinoma: A Case–Control Study

Abstract

BACKGROUND Lymph node metastasis is a critical prognostic indicator for mortality in patients with cutaneous squamous cell carcinoma (SCC). OBJECTIVE To identify and characterize key risk factors for SCC lymph node metastasis. METHODS This was a multi-institutional, case-control study of 65 cutaneous SCCs with known lymph node metastasis matched with 195 cutaneous SCCs without lymph node metastasis (3:1 matching). The cases and controls were matched by anatomic location, age, and sex. Odds ratios (ORs) and their 95% confidence intervals (CIs) were generated to determine the association between specific risk factors and lymph node metastasis in a multivariate analysis. RESULTS Recurrent tumors (p , .001), perineural invasion (p , .001), lymphovascular invasion (p 5 .002), size of 2 cm or greater (p 5 .008), and hypothyroidism (p 5 .03) were significantly more common in the lymph node metastasis cohort. Recurrence (OR 6.3, 95% CI 2.6-15.3), perineural invasion (OR 4.5, 95% CI 1.7-11.8), and hypothyroidism (OR 2.7, 95% CI 1.04-7.0) remained significant on performing a multivariate analysis. CONCLUSION Lymph node metastasis in SCC is associated with recurrence, perineural invasion, lymphovascular invasion, size of 2 cm or greater, and hypothyroidism. Clinical consideration of these findings within the context of current staging systems may help improve patient outcomes.

Association of Patient Risk Factors, Tumor Characteristics, and Treatment Modality With Poor Outcomes in Primary Cutaneous Squamous Cell Carcinoma

“…After inclusion criteria were applied, the full text of 310 articles were assessed. Of these, 129 studies were included in final analysis (Figure 1). Study characteristics, including risk of bias, are described in eTable 1 in the Supplement.…”

“…Of these 129 studies, 114 studies assessed risk factors, with a total of 137 449 patients and 126 553 tumors. Of these, 87 studies with 122 484 tumors were included in the random effects analysis risk ratio, and 62 studies with 116 958 tumors were included in analysis of incidence data. Treatment modality was assessed by 28 studies…”

Lymphovascular Invasion in Cutaneous Squamous Cell Carcinoma

“…This phenomenon may be due to the fact that many tumors with LVI also often exhibit other high-risk features that portend a poor prognosis. 32 This observation highlights the dilemma as to whether LVI is a direct causative factor contributing to the poor outcomes noted in the literature, or whether tumors with poor outcomes demonstrate LVI because of their naturally more aggressive phenotype. The answer to this query likely lies somewhere between both theories, and further research is needed in this area to determine the exact role that LVI plays in the prognosis of cSCC.…”

“…31 In 2022, a case-control study compared 65 cSCC with lymph node metastasis to 195 matched controls without metastasis and found a significant increase of LVI in metastatic cases, 28%, compared with controls, 1.5%. 32 Most recently, in 2023, Rao and colleagues 33 reported that in a retrospective series of cSCC metastatic to the parotid gland, LVI along with immune status was predictive in multivariate analysis for overall survival (HR 5 2.38), disease-specific survival (HR 5 5.24), and disease-free survival (HR 5 2.60).…”