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

Abstract

ObjectiveOral leukoplakia is the most common oral potentially malignant disorder. Malignant transformation of oral leukoplakia occurs at an annual rate of 1%–7%. WHO‐defined classic epithelial dysplasia is an important predictor of malignant transformation of oral leukoplakia, but we have previously shown in a proof of concept study that prediction improves by incorporation of an architectural pattern of dysplasia, also coined as differentiated dysplasia. We aimed to analyze this finding in a larger cohort of patients.MethodFor this retrospective study 176 oral leukoplakia patients were included. Biopsies for all patients were assessed for the presence of dysplasia and analyzed for cytokeratin 13 and 17 expression. Moreover, the inter‐observer agreement for the diagnosis of differentiated dysplasia was determined.ResultsIn total, 33 of 176 patients developed oral squamous cell carcinoma during follow‐up. Presence of classic epithelial dysplasia increased cancer risk two‐fold (HR = 2.18, p = 0.026). Lesions without classic epithelial dysplasia could be further risk‐stratified by the presence of differentiated dysplasia (HR = 7.36, p < 0.001). Combined classic epithelial and differentiated dysplasia imparted a seven‐fold increased risk of malignant transformation (7.34, p = 0.001). Inter‐observer agreement for the diagnosis of dysplasia, including differentiated dysplasia, was moderate (κ = 0.56, p < 0.001).DiscussionThis study emphasizes the importance of the recognition of the architectural pattern of differentiated dysplasia as a separate entity for risk prediction of malignant transformation of oral leukoplakia. Presence of any pattern of dysplasia results in accurate prediction of malignant transformation risk of oral leukoplakia.

Unraveling the Keratin Expression in Oral Leukoplakia: A Scoping Review

“…Eighty studies were assessed for eligibility ( Figure 1 ). Of these, 42 studies fulfilled the inclusion and exclusion criteria, and 1 additional article was included, which was found by searching the reference list of the articles [ 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 ] ( Table 2 ). The year of publication ranged from 1989 to 2024.…”

“…Seven different dysplasia grading systems were represented. Nine studies [ 31 , 32 , 33 , 38 , 41 , 42 , 43 , 52 , 56 ] used WHO 1978 [ 69 ], two studies [ 55 , 68 ] used WHO 1997 [ 70 ], seven studies [ 27 , 36 , 45 , 48 , 50 , 53 , 62 ] used WHO 2005 [ 71 ], five studies [ 28 , 40 , 54 , 65 , 66 ] used WHO 2017 [ 72 ], two studies [ 36 , 67 ] used SIN system [ 71 ], two studies [ 46 , 61 ] used Kramer 1980 [ 73 ], and one study [ 64 ] used Grassel-Pietrusky and Hornstein 1982 [ 74 ] ( Table 2 ). Six studies [ 26 , 29 , 30 , 34 , 39 , 58 ] graded dysplasia without providing details of the criteria used, and seven studies [ 35 , 37 , 44 , 49 , 51 , 59 , 60 ] identified the presence of dysplasia without providing the details of the criteria used.…”

“…All 43 studies explored various keratins and their expression in OLK and dysplasia, and 5 investigated their prognostic potential with regard to MT [ 26 , 28 , 65 , 66 , 67 ]. No studies evaluated keratins as a diagnostic adjunct or predictive tool.…”

“…The third study [ 65 ] investigated K13 and K17, with a follow up time of 11–183 months for patients who had MT of their OLK (median 51 months) and 109–258 months (median 148 months) for their non-progressors. The fourth study [ 66 ] investigated K13 and K17 as well, with a follow up time of 12–300 months (median 63 months). The fifth study [ 28 ] investigated K13 and K17, with a follow up time of 4–290 months (median 52 months).…”

“…The prognostic studies have provided varied results, but most suggest that loss of K4 and particularly K13 did not predict MT. However, K13 loss may indicate a shorter MT, and K13 retention in OLK may be protective of MT, and as such, it may be utilized in other ways, such as less-intensive surveillance [ 66 ].…”