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

Abstract

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.

Histopathological changes in tumor budding between biopsy and resected specimens from patients treated with preoperative S‐1 chemotherapy for oral cancer

“…The World Health Organization (WHO) histopathologic grading system focuses on tumor differentiation only. Elseragy et al reported that well‐differentiated tumors tend to invade in large islands, but this is not always the case because small clusters of cancer cells can also be present in well‐differentiated tumors. We agree with these findings because some of our cases had well‐differentiated tumor nests with tumor budding at the invasive front of the tumor, and these cases had a poor prognosis.…”

“…We agree with these findings because some of our cases had well‐differentiated tumor nests with tumor budding at the invasive front of the tumor, and these cases had a poor prognosis. Recently, a new improved histopathologic grading system for oral cancer that incorporated tumor budding into the WHO histopathologic grading system and showed good prognostic value has been proposed …”

Hallmarks of cancer: Tumor budding as a sign of invasion and metastasis in head and neck cancer

“…Boxberg et al proposed a histopathologic grading system based on the evaluation of tumor budding and cell nest size in OSCC, 49 and later on the same system was applied for laryngeal and hypopharyngeal cancers and showed a significant prognostic impact. 50 Of note, incorporating tumor budding in grading systems has also been suggested in other cancers including esophageal cancer, 51 lung cancer, 52 and colorectal cancer. 50 Of note, incorporating tumor budding in grading systems has also been suggested in other cancers including esophageal cancer, 51 lung cancer, 52 and colorectal cancer.…”

“…35 Our group has recently introduced a proposal that incorporates tumor budding in the histopathologic grading of early OTSCC and this showed a prognostic power superior to the traditional grading system. 50 Of note, incorporating tumor budding in grading systems has also been suggested in other cancers including esophageal cancer, 51 lung cancer, 52 and colorectal cancer. 53 Therefore, it seems that tumor budding is a prognostic parameter eligible for being included in a histopathologic grading system for routine reporting in daily practice also in HNSCC.…”

Prognostic value of blood and lymphatic vessel markers in tongue cancer: A systematic review

“…For example, the TNM staging scheme shows little or no prognostic value in early TSCC . Therefore, it is important to supplement the TNM staging system with new histological features and biomarkers . TSCC currently lacks reliable prognosticators that can predict outcome and response to therapy.…”