Laboratory Studies
Idiopathic lesions and dysplastic lesions do not have any specific clinical appearance. Therefore, in any case, the clinical appearance is not a guide to the underlying microscopic characteristics. A definitive diagnosis of oral leukoplakia is made when any etiologic cause other than tobacco/areca nut use has been excluded and histopathology has not confirmed any other specific disorder. [4]
Procedures
Biopsy obtainment, repeated as necessary, is essential.
Histologic Findings
The plaque may show hyperorthokeratosis or hyperparakeratosis. The granular layer is often thickened and extremely prominent in cases of hyperorthokeratosis, but it is seldom observed in even severe cases of hyperparakeratosis. Acanthosis, which refers to the abnormal thickening of the prickle cell layer, may also be observed. Epithelial changes suggestive of premalignancy include the following:
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Nuclear hyperchromatism
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Loss of polarity
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Increased number of mitotic figures
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Nuclear pleomorphism
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Altered nuclear-to-cytoplasmic ratio
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Deep cell keratinization
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Loss of differentiation
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Loss of intercellular adherence
Yang et al analyzed the relationship between clinical features of OL using endoscopy with narrow-band imaging histopathology. They concluded that flexible endoscopy can be a successful tool for examining OL. [12]
Molecular markers that may indicate an increased likelihood of malignant transformation are (1) Mutations in the p53 gene, (2) Inappropriate expression of oncogenes (eg, cyclin D1), keratins, blood-group antigens and other cell-surface carbohydrates, and (3) DNA aneuploidy (when the amount of DNA is not an exact multiple of the diploid number). The latter emerges as one of the most promising prognostic indicators since oral cancer with poor survival consistently developed in human subjects with aneuploid dysplastic OL. [13, 14]
A study by Sakata et al indicated that a combination of low expression of the tumor suppressor SMAD4 and high stromal lymphocyte infiltration is predictive for the malignant transformation of OL. [15]
A study by von Zeidler et al suggested that reductions in the amount of epithelial cadherin (E-cadherin), a cellular adhesion protein, signal an increased risk of malignant transformation by OL. The investigators found that the amount of E-cadherin expressed in tissue differed between normal oral mucosa and low-risk OL, between low-risk and high-risk OL, and between high-risk OL and squamous cell carcinoma of the oral cavity with cervical lymph node metastasis. [16]
A study by Habiba et al indicated that expression of aldehyde dehydrogenase 1 and the transmembrane protein podoplanin are associated with a 3.02- and 2.62-fold increase, respectively, in the likelihood that OL will progress to oral cancer. [17] In addition, a report by Grochau et al indicated that expression of podoplanin in OL correlates with the leukoplakia’s degree of dysplasia (as indicated by the lesion’s squamous intraepithelial neoplasia classification). [18] A study by Gissi et al also found evidence of a relationship between podoplanin expression and dysplasia in OL. [19]
