The degree of hyperkeratosis, epithelial thickness (acanthosis/atrophy), dysplasia and inflammatory cell infiltration in the underlying lamina propria are 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.
bilirubin in hyperbilirubinemia or hemosiderin in hemochromatosis, or exogenous pigments such as heavy metals can be introduced into the mucosa, e.g. in an amalgam tattoo. Almost all white patches are benign, i.e. non-malignant. The differential diagnosis of a white lesion in the mouth can be considered according to a surgical sieve (see table).Leukoplakia cannot be rubbed off the mucosa, distinguishing it readily from white patches such as pseudomembraneous candidiasis, where a white layer can be removed to reveal an erythematous, sometimes bleeding surface underneath. The white color associated with leukoedema disappears when the mucosa is stretched. A frictional keratosis will generally be adjacent to a sharp surface such as a broken tooth or rough area on a denture and will disappear when the causative factor is removed. Some have a suggested as general rule that any lesion that does not show signs of healing within 2 weeks should be biopsied. Morsicatio buccarum and linea alba are located at the level of the occlusal plane (the level at which the teeth meet). A chemical burn has a clear history of placing an aspirin tablet (or other caustic substance such as eugenol) against the mucosa in an attempt to relieve toothache. Developmental white patches usually are present from birth or become apparent earlier in life, whilst leukoplakia generally affects middle aged or elderly people. Other causes of white patches generally require pathologic examination of a biopsy specimen to distinguish with certainty from leukoplakia.