A Proposal to Revise the Histopathologic Grading System of Early Oral Tongue Cancer Incorporating Tumor Budding.

Amr Elseragy,Ricardo D Coletta,Pentti Nieminen,Antti A Mäkitie,Caj Haglund,Luiz P Kowalski,Tuula Salo,Alhadi Almangush,Ilmo Leivo

doi:10.1097/pas.0000000000001241

Abstract

The World Health Organization (WHO) grading system has a low prognostic value for early-stage oral tongue squamous cell carcinoma; 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 oral tongue squamous cell carcinoma. The proposed grading system showed significant prognostic value in multivariable analysis for disease-specific survival with a hazard ratio of 3.86 and a 95% confidence interval of 1.36-10.9 (P=0.001). For disease-free survival, the proposed grading system showed good predictive power in multivariable analysis (hazard ratio, 2.07; 95% confidence interval, 1.00-4.27; P=0.009). The conventional WHO grading system showed a low prognostic value for disease-specific survival and disease-free survival (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.

Highlights

Oral tongue squamous cell carcinoma (OTSCC) is one of the most common cancers in the oral cavity
It is known that such features do not have reliable prognostic power for oral carcinomas especially at early stages histopathologic parameters such as perineural invasion (PNI) and lymphovascular invasion (LVI)
Our proposed grade showed a statistically significant increase in cancer-related mortality for tumours with revised Grade III in univariable (HR 3.42, 95% confidence interval (CI) 1.23-9.56; P=0.001) and multivariable analysis (HR 3.86; 95% CI 1.36-10.9; P=0.001)

Summary

Introduction

Oral tongue squamous cell carcinoma (OTSCC) is one of the most common cancers in the oral cavity. OTSCC is known for its unpredictable spread and metastasis. Many biomarkers have been introduced for prognostication of OTSCC, none of them can be approved for daily practice 1. The previously published biomarkers are not routinely performed. The traditional histopathologic features (e.g., mitotic activity) are usually evaluated in some epithelial tumors 2. It is known that such features do not have reliable prognostic power for oral carcinomas especially at early stages histopathologic parameters such as perineural invasion (PNI) and lymphovascular invasion (LVI)

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Conclusion