variable. In mucous membranes, hyperkeratosis can be defined as "an increase in the thickness of the keratin layer of the epithelium, or the presence of such a layer in a site where none would normally be expected." In leukoplakia, the hyperkeratosis varies in thickness and may be either ortho- or para-keratosis, (depending upon whether cell nuclei are lost or retained in the superficial layers respectively), or a mixture of both in different areas of the lesion. The epithelium may show hypertrophy (e.g. acanthosis) or atrophy. Red areas within leukoplakia represent atrophic or immature epithelium which has lost the ability to keratinize. The transition between the lesion and normal surrounding mucosa may be well-demarcated, or poorly defined. Melanin, a pigment naturally produced in oral mucosa, can leak from cells and give a grey color to some leukoplakia lesions. Hyperkeratosis and altered epithelial thickness may be the only histologic features of a leukoplakia lesion, but some show dysplasia. The word "dysplasia" generally means "abnormal growth", and specifically, in the context of oral red or white lesions, refers to microscopic changes ("cellular atypia") in the mucosa that indicate a risk of malignant transformation. When dysplasia is present, there is generally an inflammatory cell infiltration in the lamina propria. The following are commonly cited as being possible features of epithelial dysplasia in leukoplakia specimens: Cellular pleomorphism, in which cells are of abnormal and different shapes. 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