Tumor budding and tumor-associated lymphocytic response as histopathological indicators of high-risk disease in head and neck cutaneous squamous cell carcinoma

Abstract

Tumor budding (TB) and tumor-associated lymphocytic response (TALR) have emerged as promising histopathological indicators of tumor aggressiveness across epithelial malignancies. Recent studies have suggested that both tumor invasive activity and host immune response contribute substantially to disease progression in cutaneous squamous cell carcinoma (cSCC). However, data evaluating their combined significance in head and neck cSCC remain limited. A retrospective cohort of 187 primary head and neck cSCC cases was analyzed. TB was graded using a three-tier system, and TALR was categorized into three inflammatory response patterns. Associations with clinicopathological characteristics were evaluated using univariate analyses. Multivariable logistic regression was performed to identify factors independently associated with high-risk disease, defined as advanced pathological stage (T3–T4). High-grade TB was significantly associated with adverse histopathological characteristics, including poor differentiation, increased depth of invasion, aggressive invasion pattern, perineural invasion, lymphovascular invasion, and advanced pathological stage (all p < 0.001). Weak TALR was associated with infiltrative growth characteristics and older age. In multivariable analysis, Grade 3 TB (OR 6.75, 95% CI 2.33–19.57), tumor depth > 6 mm (OR 4.03, 95% CI 2.03–8.38), poor differentiation (OR 2.64, 95% CI 1.06–6.61), aggressive invasion pattern (OR 3.07, 95% CI 1.43–6.60), and weak TALR (OR 2.29, 95% CI 1.12–4.69) remained independently associated with high-risk disease. Tumor budding and tumor-associated lymphocytic response were independently associated with histopathological features of high-risk disease in head and neck cSCC. Their combined assessment may provide additional information for pathological risk stratification and may support incorporation into routine histopathological evaluation. Prospective studies incorporating recurrence and survival outcomes are required before definitive prognostic conclusions can be established. What is known about this topic • Tumor budding reflects invasive tumor behavior and is increasingly recognized as a marker of aggressive disease in epithelial malignancies. • Host immune response influences tumor progression and may affect disease behavior in cutaneous squamous cell carcinoma. What this study adds • Demonstrates independent associations between tumor budding, lymphocytic response, and high-risk histopathological features. • Supports the complementary value of combined tumor–immune assessment in pathological risk stratification. • Provides additional evidence regarding the role of tumor microenvironment-related parameters in head and neck cSCC. Implications for practice • These parameters can be assessed using routine hematoxylin–eosin stained sections. • Combined evaluation may improve pathological risk assessment in head and neck cSCC. • Further prospective studies are required before routine prognostic implementation.