Histopathologic progression of proliferative verrucous leukoplakia

Objectives: Proliferative verrucous leukoplakia (PVL) is a spectrum of premalignant lesions that show an increased rate of progression into squamous cell carcinoma. This project aims to define the histopathologic features of PVL to aid in early identification and management. Evaluation of specimens from many subjects may help in defining the progression of histopathologic changes. Methods: A search query of the Laboratory Information System of the Surgical Oral Pathology Laboratory at the University of Iowa was created to identify all cases that suggest PVL. The common histopathologic features were catalogued and recorded for each case. Results: Microscopic examination and review of clinical features of 161 cases exhibited a possible continuum of characteristics common to this complex lesion. Results show the early microscopic features of PVL to include diminished rete ridges, a darkly staining granular layer, spinous atrophy, and an abrupt change from parakeratin to orthokeratin. Some single specimens displayed multiple aspects of the spectrum, including dysplasia or verrucous hyperplasia. This may allow extrapolation on how some lesions lead to papillary squamous cell carcinoma. Seven of the 161 cases examined represented recurrent or persistent lesions. All 7 subjects originally presented with an abrupt change from parakeratinization to orthokeratinization. In 5 of the 7 subjects progression towards the “more premalignant” end of the PVL spectrum was noted. The abrupt start-stop phenotype was noted in numerous specimens among the 161. Conclusions: This study may be the first to define the abrupt start-stop transition from parakeratin to orthokeratin as an early indicator of PVL disease progression. Future studies will focus on the relationship between the histopathologic and clinical presentation of PVL in order to better understand the biologic behavior promoting the progression of PVL to carcinoma.