Proliferative verrucous leukoplakia: a clinicopathological comparative study.

A retrospective clinicopathological analysis was performed to compare 35 proliferative verrucous leukoplakia (PVL), 40 leukoplakia without dysplasia (LK), 48 oral lichen planus (OLP)/oral lichenoid lesions (OLL), and 11 verrucous carcinoma (VC) (N = 134). The PVL group comprised 24 female and 11 male patients (mean age 66.5 years), with two to six sites involved (mean 3.1 sites) and multiple biopsies over time (mean 7.1/case). All PVL cases developed malignancy: 77.1% squamous cell and 40% verrucous carcinoma; 68.6% had multiple sites of malignancy. None showed local or distant metastatic spread. Five-year disease-specific survival was 88.6%. In LK and OLP/OLL, malignant transformation was significantly lower than in PVL (2.5% and 2.1%, respectively). Invasive squamous cell carcinoma was not reported in any conventional VC. Immunohistochemical histomorphometric analysis for p53, COX-2, and podoplanin showed no significant differences between the groups. PVL may overlap with LK, OLP/OLL, and VC, but has a persistent aggressive behaviour and high malignant transformation rate. The overlapping features may delay recognition as PVL. The results emphasize the need for a detailed clinicopathological definition of PVL, and long-term close monitoring to ensure progression to PVL and malignancy are recognized in time. The management of this persistent aggressive condition is challenging.