Oral leukoplakia is a white patch or plaque that develops in the oral cavity and is strongly associated with tobacco smoking. More importantly, it is widely recognized as a precancerous lesion of oral squamous carcinoma. Oral leukoplakia has a wide differential diagnosis, which is why an extensive workup is necessary to rule out other etiologies.
The definition of oral leukoplakia has undergone numerous revisions from its introduction in the medical literature. It is now defined as a white plaque that is diagnosed after excluding all other potential diagnoses that are not predisposing lesions for a malignant disease  . The lesion is either flat or elevated, homogeneous or non-homogeneous, and often has an irregular surface and border . Furthermore, non-homogeneous oral leukoplakia can be further divided into speckled, nodular (the formation of polyploids is observed) and verrucous (the most proliferative type), based on its appearance on clinical examination  . The overall prevalence rate is estimated around 2%. Its appearance is primarily seen in adults over 40 years of age and is significantly associated with cigarette smoking    . In fact, cigarette smoking was confirmed as a factor in the pathogenesis of this oral lesion after studies confirmed that cessation of smoking leads to complete resolution of oral leukoplakia . Other potential risk factors include alcohol consumption and deficiency of beta-carotene, which is related to poor nutrition  . This lesion can appear at any location within the oral cavity and its presence is much more frequently noted in males . Although it is painless and may seem as a benign occurrence, many studies have reported that it has potential for malignant transformation into oral squamous carcinoma in 1-36% cases   . For this reason, early recognition is pivotal.
Oral leukoplakia has a broad differential diagnosis, and the most important conditions that need to be excluded during workup are: early stages of oropharyngeal candidiasis (thrush), hairy leukoplakia (a constitutive feature of human immunodeficiency virus - HIV infection), lichen planus, lupus erythematosus, secondary syphilis, leukoedema, frictional keratosis, and aspirin burns  . For these conditions to be excluded, a detailed patient history and a thorough physical examination of the entire body is mandatory. Physicians must inspect the entire oral cavity, particularly the sublingual region where this lesion potentially develops and is often missed. The current diagnostic criteria, in addition to clinical findings and exclusion of other potential diagnoses, rely on obtaining a biopsy sample and subsequent histopathological examination, an essential step to confirm the diagnosis   . Epithelial dysplasia, and its severity, ranging from absent (P0) to severe (P2, which may be even classified as carcinoma in situ and thus can lead to oral squamous carcinoma) determines the stage of oral leukoplakia  . Together with the size of the lesion (the diameter of either one or multiple leukoplakias < 2cm, 2-4 cm or > 4 cm are designated as L1, L2, and L3), oral leukoplakias are staged from 1 (L1 and P0) to 4 (L3 and P1 or L of any stage and P2) .