Examples include nicotine stomatitis, which is keratosis in response to heat from tobacco smoking (rather than a response to the carcinogens in tobacco smoke). The risk of malignant transformation is similar to normal mucosa. Mechanical trauma, e.g. caused by a sharp edge on a denture, or a broken tooth, may cause white patches which appear very similar to leukoplakia. However, these white patches represent a normal hyperkeratotic reaction, similar to a callus on the skin, and will resolve when the cause is removed. Where there is a demonstrable cause such as mechanical or thermal trauma, the term idiopathic leukoplakia should not be used. Pathophysiology
Tumor suppressor genes
Tumor suppressor genes are genes involved in the regulation of normal cell turnover and apoptosis (programmed cell death). One of the most studied tumor suppressor genes is p53, which is found on the short arm of chromosome 17. Mutation of p53 can disrupt its regulatory function and lead to uncontrolled cell growth. Mutations of p53 have been demonstrated in the cells from areas of some leukoplakias, especially those with dysplasia and in individuals who smoke and drink heavily. Diagnosis
Definition
Leukoplakia is a diagnosis of exclusion, meaning that which lesions are included depends upon what diagnoses are currently considered acceptable. Accepted definitions of leukoplakia have changed over time and are still controversial. It is possible that the definition will be further revised as new knowledge becomes available.
Nuclear atypia, in which the nuclei of cells varies in size, any may be increased in size relative to the cytoplasm, shape, and may stain more intensely. There may also be more prominent nucleoli. Increased number of cells seen undergoing mitosis, including both normal and abnormal mitoses. Abnormal mitosis may be abnormally located, e.g. occurring in suprabasal cells (cell layers more superficial to the basal cell layer) or of abnormal form, e.g. "tri-radiate mitoses" (a cell splitting into 3 daughter cells rather than only 2)
Loss the normal organization of the epithelial layers. The distinction between the epithelial layers may be lost. Normally stratified squamous epithelium shows progressive changes in the form of cells from the basal to the superficial layers, with cells becoming more flat ("squames") towards the surface as a continuous maturation process. In dysplastic epithelium, cells may become vertically orientated rather than becoming flat towards the surface. There may be abnormal keratinization, where keratin is formed below the normal keratin layer. This can occur in individual cells or groups of cells, forming an intraepithelial keratin pearl. There may be an increase in the number of basal cells, and they may lose their cellular orientation (losing their polarity and long axis). Alteration of the normal epithelial-connective tissue architecture - the rete pegs may become "drop shaped". wider at their base than more superficially.Generally, dysplasia is subjectively graded by pathologists into mild, moderate or severe dysplasia. This requires experience as it is a difficult skill to learn.