Oral epithelial dysplasia grading: Comparing the binary system to the traditional 3‐tier system, an actuarial study with malignant transformation as outcome

Abstract

Background: Establishing the risk of malignant transformation (MT) in oral leukoplakia is usually based on grading oral epithelial dysplasia (OED) on biopsy tissue, for which two systems are proposed: a 3-tier and a binary system. Only very few actuarial studies have tested the accuracy of such methods in predicting MT, especially for the binary system. This study aimed to assess the accuracy of the two grading systems in predicting MT in a cohort of oral leukoplakia (OL) from Brazil, with follow-up data. Methods:The sample comprised 878 individuals diagnosed with OL from 2005 to 2018. Follow-up data were obtained both locally and from the regional cancer registry. All lesions were graded using both the 3-tier and the binary systems. Kaplan-Meier curves (Log-rank Mantel-Cox) were used to assess risk and kappa to assess interobserver agreement.Results: Thirty-five individuals underwent MT (4%). Both systems demonstrated prognostic value, though the 3-tier system proved superior, with OR 9.23 (3.42-23.69), PPV 0.152, NPV 0.98, compared to binary OR 3.49 (1.79-6.79), PPV 0.079, NPV 0.976. Interobserver agreement was also superior in the 3-tier system (0.47, p < 0.05) compared to the binary system (0.139, p = 0.39). Combining the two systems enhanced prognostic values (OR 14.28, PPV 0.217, NPV 0.981). Conclusion:The 3-tier system presented superior prognostic value to the binary system. Combining both systems to double-grade intermediate lesions might enhance risk assessment.

EZH2 Expression Correlates With T-Cell Infiltration in Oral Leukoplakia and Predicts Cancer Transformation

“…Interestingly, as mentioned above, EZH2-expressing cells were detected also in tissues without dysplasia. Assessment of the presence of dysplasia is associated with a certain degree of uncertainty (42), depending on the subjective evaluation of a pathologist. Also, an increase in EZH2 expression may precede visual signs of dysplasia that can be detected in routine histopathology.…”

The role of differentiated dysplasia in the prediction of malignant transformation of oral leukoplakia

“…We also investigated the inter‐observer agreement of dysplasia diagnosis in OL within the context of differentiated dysplasia. Dysplasia diagnosis in OL has long been a point of debate and although several updates in dysplasia grading have been proposed, the range in inter‐observer agreement between studies is ranging widely from slight (κ = 0.22) to substantial (κ = 0.78) 15–19 . Several explanations for the variation in dysplasia grading have been proposed such as the lack of standardization, lack of understanding clinical relevance and subjectivity 11,12,16,26 .…”

“…Dysplasia diagnosis in OL has long been a point of debate and although several updates in dysplasia grading have been proposed, the range in inter-observer agreement between studies is ranging widely from slight (κ = 0.22) to substantial (κ = 0.78). [15][16][17][18][19] Several explanations for the variation in dysplasia grading have been proposed such as the lack of standardization, lack of understanding clinical relevance and subjectivity. 11,12,16,26 We investigated the inter-observer agreement between experienced head and neck cancer pathologists using four categories including differentiated dysplasia, and report a moderate agreement of κ = 0.56.…”

“…Utilization of classic epithelial dysplasia as a marker for the prediction of MT of OL has been hampered by the lack of reproducibility 11,12 . There is a considerable variability in the inter‐observer agreement for classic epithelial dysplasia diagnosis in OL that ranges from fair (κ = 0.22) to substantial (κ = 0.78), especially in the absence of cytological changes 11,15–19 . As of now, there is no data on the inter‐observer agreement on the architectural aspects of differentiated dysplasia in the oral mucosa.…”

“…11,12 There is a considerable variability in the inter-observer agreement for classic epithelial dysplasia diagnosis in OL that ranges from fair (κ = 0.22) to substantial (κ = 0.78), especially in the absence of cytological changes. 11,[15][16][17][18][19] As of now, there is no data on the inter-observer agreement on the architectural aspects of differentiated dysplasia in the oral mucosa. In a recent study investigating differentiated dysplasia in vulvar epithelium, a moderate (κ = 0.42) inter-observer agreement between pathologists from multiple centers was reported.…”