Practice Essentials
The World Health Organization (WHO) first defined oral leukoplakia as a white patch or plaque that could not be characterized clinically or pathologically as any other disease; therefore, conditions including, but not limited to, lichen planus, candidiasis, and white sponge nevus were excluded. At a 1983 international seminar, the following definition was proposed:
Leukoplakia is a whitish patch or plaque that cannot be characterized clinically or pathologically as any other disease and is not associated with any physical or chemical causative agent, except the use of tobacco.
A more recent WHO workshop [1] has amended the earlier WHO definition as follows: "The term leukoplakia should be used to recognize white plaques of questionable risk having excluded (other) known diseases or disorders that carry no risk for cancer.” It has also recommended abandoning the distinction between the terms "potentially malignant lesions" and "potentially malignant conditions" and to use the term "potentially malignant disorders" instead. Leukoplakia and erythroplakia are the most common potentially malignant disorders. These diagnoses are still defined by exclusion of other known white or red lesions. Not included in the discussion concerning leukoplakias are the rare inherited or genetically driven forms of oral white lesions, which include white sponge nevus, among others. [2]
Oral white lesions include leukoplakias (as defined above), keratoses, leukoplakias of clear infective origin (candidal, syphilitic, hairy leukoplakia associated with Epstein-Barr virus), candidosis, lichen planus, oral submucous fibrosis, lupus erythematosus, congenital lesions (eg, white sponge nevus, dyskeratosis congenita, pachyonychia congenita), and frank carcinomas.
Oral leukoplakia was formerly often called "snuff-dipper's lesion" and is still sometimes referred to as "tobacco pouch keratosis" in the literature. [3, 4]
Symptoms
Leukoplakias are white lesions that cannot be removed with a gauze swab. Leukoplakias are usually asymptomatic and are initially noticed by a dentist during a routine examination.
Diagnostics
Perform an oral lesional biopsy. Unfortunately, exclusion of dysplasia in a biopsy sample does not guarantee that elsewhere in the lesion there is not dysplasia or even carcinoma.
A number of adjunctive diagnostic aids can assist in the clinical assessment of oral mucosal pathology. These include oral brush biopsy, toluidine vital staining and various light-based detection systems (eg, VELscope), and oral spectroscopy. However, evidence of efficacy is lacking. A 2015 Cochrane review concludes that “none of the adjunctive tests can be recommended as a replacement for the currently used standard of a scalpel biopsy and histological assessment”. [5]
Treatment
Several management regimens have been suggested; however, no large trials have shown a definitive, reliable treatment. No evidence base exists on which to reliably recommend treatment. Indeed, current evidence suggests that no treatment is of reliable benefit. For suspicious oral leukoplakia, surgical removal is the gold standard treatment. [6]
Prognosis
Some leukoplakias culminate in oral squamous cell carcinoma (OSCC). [7, 8] Estimates of malignant transformation vary from 3-33% over a 10-year period. However, many innocuous leukoplakias are not always followed up in some centers, and the studies are often small. As many as 30% of leukoplakias can regress if habits are stopped.
Sundberg et al reviewed 180 oral leukoplakia patients who underwent surgical removal of the lesions. The total incidence of lesion recurrence was 45% after 4 years and 49% after 5 years. Among non-homogeneous oral leukoplakia lesions, 23 (56%) cases recurred. Among snuff-users, 8 (73%) cases recurred. The investigators concluded that having non-homogenous lesions and using tobacco snuff were risk factors for oral leukoplakia recurrence after surgical removal. [6]
Prevention
Counsel patients against tobacco use. The percentage of nonsmokers who develop malignancy in a leukoplakia is greater than the percentage of smokers who develop a malignancy in a leukoplakia; however, the condition is more common in smokers such that the overall number of malignancies that arise in leukoplakias is greater in smokers than the general population.
Advise patients to avoid alcohol use. Additionally, advise patients to eat a diet high in fresh fruits and vegetables.
Long-term monitoring
Examine patients with leukoplakias regularly at 3- to 6-month intervals. Detection of clinical changes, such as erosions or nodule formation, warrants a biopsy. An oral brush biopsy may be helpful in detecting dysplasia.
Patient education
For patient education resources, see the Cancer and Tumors Center, as well as Cancer of the Mouth and Throat.
Pathophysiology
No etiologic factor can be identified for most persistent oral white plaques (ie, idiopathic leukoplakia), although most white lesions are benign frictional keratoses. The histopathologic features of the group of leukoplakias are highly variable, ranging from hyperkeratosis and hyperplasia to atrophy and severe dysplasia.
Patients with idiopathic leukoplakia have the highest risk of developing cancer. In studies of these patients, 4-17% had malignant transformation of the lesions in less than 20 years. The risk of developing malignancies at lesion sites is 5 times greater in patients with leukoplakia than in patients without leukoplakia.
Yogesh and Aswath point out that deletion of the glutathione S-transferase mu 1 (GSTM1) gene, especially with homozygosity (GSTM1 null), is associated with increased oral squamous cell carcinoma. This genetic abnormality may partially account for varying oral carcinoma incidence among smokeless tobacco users with oral leukoplakia. [9]
Dysplastic lesions do not have any specific clinical appearance; however, where erythroplakia is present as an additional clinical component, dysplasia is likely.
Dysplasia is evident in 17-25% of biopsy samples of leukoplakias. Erythroleukoplakias, verrucous leukoplakias, and nodular leukoplakias show an increasing frequency of dysplastic histologic changes or aneuploidy.
Leukoplakias that are speckled, or erythroleukoplakic, are usually dysplastic or frank carcinomas. Nodular or verrucous lesions are also sinister, but homogenous and so-called "thin" leukoplakias are far less likely to be potentially malignant.
Most idiopathic leukoplakias are homogenous leukoplakias and show little evidence of dysplastic histologic changes or aneuploidy. However, studies have revealed carcinoma or severe dysplasia in the excision specimens of approximately 5% of leukoplakias excised when the diagnostic biopsy specimens had revealed no dysplasia.
Carcinoma in situ is a controversial term used for severe dysplasia in which the abnormalities extend throughout the thickness of the epithelium. All the cellular abnormalities characteristic of malignancy may be present; only invasion of the underlying connective tissue is absent. Top-to-bottom epithelial dysplasia, like other dysplastic lesions, has no characteristic clinical appearance, although erythroplasia often proves to be carcinoma in situ or early invasive carcinoma. [10]
Epidemiology
Oral leukoplakia is uncommon, possibly occurring in less than 1% of adults, with worldwide, nation-by-nation prevalence varying widely, based on cultural and dietary factors. [11] An increased prevalence is observed in communities and races with high tobacco use, such as Southeast Asia. Males have the highest incidence of leukoplakias, and leukoplakias are usually seen in adults older than 40 years.
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Homogeneous leukoplakia.
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Erythroleukoplakia.
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Verrucous or nodular leukoplakia.
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Carcinoma referred to as a leukoplakia.
Tables
Issue |
|
No Serious Concern |
Concern: Consider Referral to Specialist if Clinician or Patient Concerned, Especially if Multiple Issues Apply |
Serious Concern: Referral to a Specialist |
Historical Features |
Size |
No change |
No reduction in size, even after eliminating trauma to lesion after 10-14 days |
Increasing size, even after eliminating trauma to lesion after 10-14 days |
|
Chronology |
Lesion heals |
No resolution over brief observation period |
Rapid symptom onset Solitary lesion or change in one area of lesion Lesion persisting 3 weeks or longer Persistent ulceration Persistent swelling Loosening of a tooth Nonhealing tooth extraction socket |
|
Neurological |
None |
Lack of pain |
Pain Dysphagia Odynophagia Otalgia Numbness/paresthesia Speech or voice change |
|
Weight |
Normal |
No weight loss |
Weight loss |
History |
Lifestyle Habits |
None |
Tobacco consumption mild/moderate Betel quid or khat consumption mild/moderate Marijuana consumption mild/moderate UV light exposure mild/moderate (lip surface exposure Late-onset sexual debut Few or moderate numbers of lifetime sexual partners |
Tobacco consumption high Betel quid or khat consumption high Alcohol consumption high Marijuana consumption mild/moderate UV light exposure high Early sexual debut Numerous lifetime sexual partners |
|
Medical History |
Clear |
Deficiencies of iron or vitamins A, C, or E Diabetes Discoid lupus erythematosus Dyskeratosis congenita Epidermolysis bullosa Fanconi anemia High-risk human papillomavirus infection Immune defects, including HIV/AIDS or chronic candidosis Medications: Immunosuppressants, antihypertensives Periodontitis, poor hygiene Plummer-Vinson syndrome Scleroderma Xeroderma pigmentosum |
Deficiencies of iron or vitamins A, C, or E Diabetes Discoid lupus erythematosus Dyskeratosis congenita Epidermolysis bullosa Fanconi anemia High-risk human papillomavirus infection Immune defects, including HIV/AIDS or chronic candidosis Medications: Immunosuppressants, antihypertensives Periodontitis, poor hygiene Plummer-Vinson syndrome Scleroderma Xeroderma pigmentosum |
Examination and Imaging |
Potentially Malignant Disorder |
None |
Leukoplakia Lichen planus/lichenoid mucositis Oral submucous fibrosis |
Erythroplakia Leukoplakia; speckled or verrucous Lichen planus/lichenoid mucositis; unilateral |
|
Lesion Features |
Equivocal |
White patch (leukoplakia) Lichen/lichenoid Oral submucous fibrosis |
Red patch (erythroplakia) Mixed red and white patch (erythroleukoplakia/speckled leukoplakia) Granular surface Rolled, elevated margins Ulceration Induration |
|
Cervical Lymph Nodes |
No enlargement |
Possible enlargement |
Enlarged, firm, fixed, nontender, asymmetric |
|
Imaging |
No abnormality |
Any bone density change |
Poorly defined, uncorticated, irregular radiolucency Lamina dura loss Teeth displaced and/or resorbed Pathological fracture |
