Toluidine Blue Stain Variation and Malignant Progression of Oral Dysplasia

Objectives: Oral cancer has a poor survival rate mainly due to late stage diagnosis. Early detection is vital to the improvement of this prognosis. High-grade oral dysplasia (severe dysplasia/ carcinoma-in-situ) is a good predictor for progression to malignancy. However, the ability to predict outcome in low-grade (mild/moderate) dysplasia is challenging, as the majority will not progress. Finding markers to predict which low-grade dysplasia will progress has the potential to guide the clinical management of these lesions and improve patient outcomes. In this study, we look at the temporal changes in toluidine blue (TB) uptake during follow-up to determine if changes to TB status over time in low-grade dysplasia can predict patterns of progression.
Methods: Subjects in this study were accrued from the Oral Cancer Prediction Longitudinal (OCPL) study. Patients with a histologically confirmed mild or moderate oral dysplasia and no history of head and neck cancer were examined and followed at 6-month intervals (n=251). Demographic data, habit information and clinicopathological features of the lesions, including temporal TB positivity, and were collected. Outcome was considered to be progression to severe dysplasia, carcinoma-in-situ, or squamous cell carcinoma.
Results: Out of 251 subjects, 30 (12%) progressed. The median time to progression was 36.7 months (2.9 – 115.8). Age at diagnosis, gender, ethnicity, tobacco history, and tobacco use at time of diagnosis, were not associated with progression. Lesion presence in a high-risk site (floor of mouth or ventrolateral tongue) was significantly associated with progression (P<0.05). A lesion being ever positive to TB staining was associated with progression (P<.001). Further temporal clinicopathological data are currently being analyzed.
Conclusions: Understanding whether the persistence or appearance of TB staining during follow-up signal a change in risk, may aid in clinician decision-making regarding the need for further biopsy. Temporal clinicopathological pattern changes in TB positivity in low-grade dysplasia may predict progression.