A novel tumor budding and cell nest size-based grading system outperforms conventional methods in vulvar squamous cell carcinoma.

The tumor budding and tumor cell nest size-based (TBNS) grading scheme is an emerging prognostic indicator for squamous cell carcinoma (SCC) across various organs; however, its significance in vulvar SCC (VSCC) remains poorly investigated. In this study, we applied the TBNS grading system to an institutional cohort of 62 consecutive surgically resected VSCC cases (39 HPV-independent and 23 HPV-associated), excluding patients with neoadjuvant chemotherapy or FIGO stage IA disease. High tumor budding activity, small cell nest size, and high TBNS grade were significantly associated with reduced overall survival (OS) and disease-free survival (DFS) in VSCC, as well as with adverse clinicopathologic features such as lymphovascular space invasion, perineural involvement, lymph node metastasis, and advanced FIGO stage (p < 0.05). Multivariate analysis revealed that TBNS grade 3 was independently associated with reduced DFS (p < 0.05). In contrast, among the two conventional grading systems, only the Gynecology Oncology Group grading system showed a significant association with OS in univariate analysis (p < 0.05), but not in multivariate analysis (p > 0.05). We conclude that the TBNS grading system is a promising prognostic indicator for VSCC, outperforming conventional grading systems. Further validation in larger cohorts is needed to expand the clinical applicability of this grading system in VSCC.