The World Health Organization (WHO) grading system has a low prognostic value for early-stage oral tongue squamous cell carcinoma (OTSCC); greater prognostic power has been shown with tumor budding analysis. In this study, we combined tumor budding analysis with histopathologic grading according to WHO 2017. In our proposal, a revised Grade I tumor is defined as a "well differentiated cohesive tumor"; revised Grade II as a "moderately differentiated and/or slightly dissociated tumor"; and revised Grade III as a "poorly differentiated and/or dissociated tumor".We evaluated the prognostic value of this proposed grading system in a multicenter cohort of 311 cases of early OTSCC. The proposed grading system showed significant prognostic value in multivariable analysis for disease-specific survival (DSS) with a hazard ratio (HR) of 3.86 and a 95% confidence interval (CI) of 1.36 to 10.9 (P=0.001). For disease-free survival (DFS), the proposed grading system showed good predictive power in multivariable analysis (HR 2.07, 95% CI 1.00-4.27; P=0.009). The conventional WHO grading system showed a low prognostic value for DSS and DFS (P>0.05). In conclusion, the prognostic power of the WHO histopathologic grading improved significantly with incorporation of tumor budding. Our proposed grading system can be easily included in pathology reports.

Although there are many histopathologic prognosticators, grading of early oral tongue squamous cell carcinoma (OTSCC) is still based on morphological cell differentiation which has low prognostic value. Here we summarize the emerging histopathological markers showing powerful prognostic value, but are not included in pathology reports. Using PubMed, Scopus, Ovid Medline, and Web of Science databases, a systematic literature search was preformed to identify early OTSCC studies that investigated the prognostic significance of hematoxylin-eosin-based histopathologic markers. Our meta-analysis showed that tumor budding was associated with overall survival (hazard ratio[HR] 2.32; 95% CI 1.40-3.84; p < 0.01) and disease-specific survival (DSS) (1.89; 95% CI 1.13-3.15; p = 0.02). Worst pattern of invasion was associated with disease-free survival (DFS) (1.95; 95% CI 1.04-3.64; p = 0.04). Tumor-Alhadi Almangush and Tuula Salo jointly supervised this work.

Background The clinical significance of tertiary lymphoid structures (TLSs) is not well-documented in early oral tongue squamous cell carcinoma (OTSCC). Methods A total of 310 cases of early (cT1-2N0) OTSCC were included in this multicenter study. Assessment of TLSs was conducted on hematoxylin and eosin-stained sections. TLSs were assessed both in the central part of the tumor and at the invasive front area. Results The presence of TLSs associated with improved survival of early OTSCC as presented by Kaplan–Meier survival analyses for disease-specific survival (P = 0.01) and overall survival (P = 0.006). In multivariable analyses, which included conventional prognostic factors, the absence of TLSs associated with worse disease-specific survival with a hazard ratio (HR) of 1.96 (95% CI 1.09–3.54; P = 0.025) and poor overall survival (HR 1.66, 95% CI 1.11–2.48; P = 0.014). Conclusion Histological evaluation of TLSs predicts survival in early OTSCC. TLSs showed superior prognostic power independent of routine WHO grading and TNM staging system.