What is Leukoplakia?
Leukoplakia is a predominantly white patch or plaque of the oral mucosa that cannot be wiped away and cannot be clinically or histologically characterized as any other definable disorder. 1
Clinical Definition and Characteristics
Leukoplakia is a clinical diagnosis, not a histological entity – it describes the appearance of white lesions on mucosal surfaces that remain after attempting to remove them and cannot be attributed to other specific diseases 1, 2
The condition most commonly affects the oral cavity, appearing as white patches or plaques on the buccal mucosa, tongue, gingiva, or other oral mucosal surfaces 3
This is the most common oral mucosal lesion, affecting approximately 3% of adults, and represents up to 85% of all precancerous oral lesions 2
Patient Demographics and Risk Factors
Leukoplakia predominantly affects middle-aged to elderly adults, with most patients diagnosed over age 60 years 3, 4
Strong association with tobacco smoking and alcohol consumption – 75-81% of oral cancers are attributable to these risk factors 5
The condition can occur in both smokers and non-smokers, though tobacco use significantly increases risk 3
Some variants, such as proliferative verrucous leukoplakia, occur more frequently in women and elderly patients 3
Histological Features
The microscopic characteristics include: 2
- Hyperkeratosis (either orthokeratotic or parakeratotic type)
- Acanthosis (thickening of the epithelium)
- Chronic inflammatory infiltrates in the underlying connective tissue (lamina propria)
- Variable degrees of epithelial dysplasia, which is the critical feature determining malignant potential
Key dysplastic features that may be present include: 2
- Loss of normal cell polarity in the basal layer
- Increased nuclear-to-cytoplasmic ratio
- Irregular epithelial stratification
- Abnormal mitotic figures, particularly in superficial layers
- Cellular and nuclear pleomorphism
- Abnormal keratinization patterns
Clinical Variants and Malignant Potential
Non-homogeneous leukoplakia carries higher malignant transformation risk compared to homogeneous types 6
Clinical subtypes include: 7
- Leukoplakia simplex – flat, uniform white patches (typically with orthokeratosis)
- Verrucous leukoplakia – raised, wrinkled surface texture
- Erosive or speckled leukoplakia – nodular white excrescences on an erythematous base, most frequently associated with severe dysplasia and carcinoma 7
Overall malignant transformation risk is approximately 4%, though lesions with dysplasia may have transformation rates up to 16% 2
Critical Distinction: Erythroplakia
- Erythroplakia (red patches) carries significantly higher malignant transformation risk than leukoplakia and requires immediate surgical excision with histopathologic examination 5
Special Variant: Proliferative Verrucous Leukoplakia
This is a rare, aggressive variant that initially appears as simple hyperkeratosis but progresses to multifocal disease with exophytic, proliferative features 3
Characterized by high recurrence rates and high malignant transformation potential, making prognosis poor despite its initially benign appearance 3
Etiology remains unclear, and tobacco use does not appear to be a significant factor in this variant 3
Association with Systemic Conditions
In the context of telomere biology disorders (such as dyskeratosis congenita), oral leukoplakia is part of the classic mucocutaneous triad along with nail dystrophy and reticulated skin pigmentation 8
- These patients have significantly elevated risk of developing head and neck squamous cell carcinoma at younger ages (median onset in the 20s-30s) 8