INCORPORATION OF DIFFERENTIATED DYSPLASIA IMPROVES PREDICTION OF ORAL LEUKOPLAKIA AT INCREASED RISK OF MALIGNANT PROGRESSION

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<h3>Background</h3> Oral leukoplakia is the most common oral potentially malignant disorder with a transformation rate into oral squamous cell carcinoma (SCC) of 1%-3% annually. The World Health Organization (WHO) defined dysplasia as an important histologic marker for malignant transformation risk assessment, but it is not sufficiently accurate to personalize treatment and surveillance. Differentiated dysplasia, known from differentiated vulvar intraepithelial neoplasia, is hitherto not used in oral dysplasia grading. <h3>Objective</h3> We hypothesized that assessing differentiated dysplasia besides WHO-defined (classic) dysplasia will improve oral leukoplakia malignant transformation risk assessment. <h3>Methods</h3> We investigated a retrospective cohort consisting of 84 oral leukoplakia patients for dysplasia and the expression of CK13 and CK17, known to be dysregulated in dysplastic vulvar mucosa. <h3>Results</h3> In dysplastic oral lesions, differentiated dysplasia is as common as classic dysplasia. In 25 of 84 patients (30%), SCC of the upper aerodigestive tract developed during follow-up. Considering only classic dysplasia, 11 of 56 patients (20%) with nondysplastic lesions experienced progression. With the incorporation of differentiated dysplasia, only 2 of 30 (7%) patients with nondysplastic lesions progressed. Risk of progression increased from a hazard ratio of 3.26 (<i>P</i> = .002) when only classic dysplasia was considered to 7.43 (<i>P</i> = .001) when classic and differentiated dysplasia were combined. Loss of CK13 combined with presence of dysplasia is associated with greater risk of malignant progression (<i>P</i> = .006). <h3>Conclusions</h3> This study demonstrates that differentiated dysplasia should be recognized as a separate type of dysplasia and that its distinction from classic dysplasia is of significance, since it is a strong (co)prognostic histopathological marker for oral malignant transformation. In oral lesions without dysplasia and retained CK13 staining, the risk for progression is very low.