para>Malignant transformation to carcinoma is more common in older patients. ‚
ETIOLOGY AND PATHOPHYSIOLOGY
Hyperkeratosis or dyskeratosis of the oral squamous epithelium ‚
- Tobacco use in any form
- Alcohol consumption/alcoholism
- Oral infections
- Candida albicans infection may induce dysplasia and increase malignant transformation (2)[B].
- Human papillomavirus, types 11 and 15
- Sunlight
- Vitamin deficiency
- Syphilis
- Dental restorations/prosthetic appliances
- Estrogen therapy
- Chronic trauma or irritation
- Epstein-Barr virus (oral hairy leukoplakia)
- Areca nut/betel (Asian populations)
- Mouthwash preparations and toothpaste containing the herbal root extract sanguinaria
Genetics
- Dyskeratosis congenital and epidermolysis bullosa increase the likelihood of oral malignancy (1)[B].
- P53 overexpression correlates with leukoplakia and particularly squamous cell carcinoma (3)[B].
RISK FACTORS
- 70 " “90% of oral leukoplakia is related to tobacco, particularly smokeless tobacco or areca/betel nut use.
- Alcohol increases risk 1.5-fold
- Repeated or chronic mechanical trauma from dental appliances or cheek biting
- Chemical irritation to oral regions
- Diabetes
- Age
- Socioeconomic status
- Risk factors for malignant transformation of leukoplakia
- Female
- Long duration of leukoplakia
- Nonsmoker (idiopathic leukoplakia)
- Located on tongue or floor of mouth
- Size >200 mm2
- Nonhomogenous type
- Presence of epithelial dysplasia
GENERAL PREVENTION
- Avoid tobacco of any kind, alcohol, habitual cheek biting, tongue chewing.
- Use well-fitting dental prosthesis.
- Regular dental check-ups to avoid bad restorations
- Diet rich in fresh fruits and vegetables may help to prevent cancer.
- HPV vaccination may be preventive.
COMMONLY ASSOCIATED CONDITIONS
- HIV infection is closely associated with hairy leukoplakia.
- Erythroplakia in association with leukoplakia, "speckled leukoplakia, " ť or erythroleukoplakia is a marker for underlying dysplasia.
DIAGNOSIS
Leukoplakia is an asymptomatic white patch on the oral mucosa. ‚
HISTORY
- Usually asymptomatic
- History of tobacco or alcohol use or oral exposure to irritants
PHYSICAL EXAM
- Location
- 50% on tongue, mandibular alveolar ridge, and buccal mucosa
- Also seen on maxillary alveolar ridge, palate, and lower lip
- Infrequently seen on floor of the mouth and retromolar areas
- Floor of mouth, ventrolateral tongue, and soft palate complex are more likely to have dysplastic lesions.
- Appearance
- Varies from homogeneous, nonpalpable, faintly translucent white areas to thick, fissured, papillomatous, indurated plaques
- May feel rough or leathery
- Lesions can become exophytic or verruciform.
- Color may be white, gray, yellowish white, or brownish gray.
- Cannot be wiped or scraped off
- World Health Organization classification (1)
- Homogeneous refers to color
- Flat, corrugated, wrinkled, or pumice
- Nonhomogeneous refers to color and texture (more likely to be dysplastic or malignant).
- Erythroleukoplakia (mixture of red and white)
- Exophytic: papillary or verrucous texture
DIFFERENTIAL DIAGNOSIS
- White oral lesions that can be wiped away: acute pseudomembranous candidiasis
- White oral lesions that cannot be rubbed off (1)
- Morsicatio buccarum (habitual cheek-biting), generally benign (4)[C]
- Chemical injury
- Acute pseudomembranous candidiasis
- Traumatic or frictional keratosis (e.g., linea alba)
- Leukoedema (benign milky opaque lesions that disappear with stretching)
- Aspirin burn (from holding aspirin in cheek)
- Lichen planus (bilateral fairly symmetric lesions, reticular pattern of slightly raised gray-white lines)
- Lichenoid reaction
- Verrucous carcinoma
- Discoid lupus erythematosus
- Skin graft (known history)
- Squamous cell carcinoma
- Oral hairy leukoplakia, commonly on the lateral border of the tongue with a bilateral distribution (in HIV patients with Epstein-Barr virus infection)
- Smoker 's palate (leukokeratosis nicotina palati)
- White sponge nevus (congenital benign spongy lesions)
- Syphilitic oral lesion
- Dyskeratosis congenita (a rare inherited multisystem disorder)
DIAGNOSTIC TESTS & INTERPRETATION
Biopsy to rule out carcinoma if lesion is persistent, changing, or unexplained ‚
Initial Tests (lab, imaging)
- Laboratory tests generally are not indicated
- Consider saliva culture if C. albicans infection is suspected.
- No imaging is indicated.
Follow-Up Tests & Special Considerations
- Biopsy is necessary to rule out carcinoma if lesion is persistent, changing, or unexplained (1).
- Consider CBC, rapid plasma reagin (RPR).
Diagnostic Procedures/Other
- Oral cytology is superior to conventional oral examination (5)[A].
- Computer-assisted cytology or liquid-based cytology is not superior to oral cytology (5)[A].
- Noninvasive brush biopsy and analysis of cells with DNA " “image cytometry constitute a sensitive and specific screening method.
- Patients with dysplastic or malignant cells on brush biopsy should undergo more formal excisional biopsy (1).
- Excisional biopsy is definitive procedure.
Test Interpretation
- Biopsy specimens range from hyperkeratosis to invasive carcinoma.
- At initial biopsy, 6% are invasive carcinoma.
- 0.13 " “6% subsequently undergo malignant transformation
- Location is important: 60% on floor of mouth or lateral border of tongue are cancerous; buccal mucosal lesions are generally not malignant but require biopsy if not resolving.
TREATMENT
- All oral leukoplakias should be treated.
- Treatment may include the following:
- For 2 to 3 circumscribed lesions, surgical excision
- For multiple or large lesions where surgery would cause unacceptable deformity, consider cryosurgery or laser surgery (6)[C].
- Removal of predisposing habits (alcohol and tobacco)
- Complete excision is standard treatment for dysplasia or malignancy.
- After treatment, up to 30% of leukoplakia recurs, and some leukoplakia still transforms to squamous cell carcinoma (6)[B].
- Oral hairy leukoplakia may be treated with podophyllin with acyclovir cream (7)[A].
GENERAL MEASURES
- Eliminate habitual lip biting.
- Correct ill-fitting dental appliances, bad restorations, or sharp teeth.
- Stop smoking and using alcohol.
- Some small lesions may respond to cryosurgery.
- Ž ˛-carotene, lycopene, retinoids, and cyclooxygenase 2 (COX-2) inhibitors may cause partial regression.
- For hairy tongue: tongue brushing
MEDICATION
Carotenoids, vitamins A, C, and K, bleomycin, and photodynamic therapy ineffective to prevent malignant transformation and recurrence (8)[A] ‚
ISSUES FOR REFERRAL
Consider otolaryngologist or oral surgery referral for extensive disease ‚
SURGERY/OTHER PROCEDURES
- Scalpel excision, laser ablation, electrocautery, or cryoablation
- Cryotherapy slightly less effective than photodynamic therapy response (73% vs. 90%) and recurrence (27% vs. 24%) (9)[A]
- CO2 laser had 20% recurrence and 10% malignant transformation within 5 years (10)[B].
INPATIENT CONSIDERATIONS
Admission Criteria/Initial Stabilization
- Eliminate etiologic factors.
- Reevaluate in 7 to 14 days.
- Biopsy if lesion is persistent.
ONGOING CARE
FOLLOW-UP RECOMMENDATIONS
Patient Monitoring
- Regular, close follow-up, even after successful treatment
- Biopsy as needed
DIET
Regular ‚
PATIENT EDUCATION
- If biopsy is negative, stress importance of periodic and careful follow-up.
- Initiate a dental referral to eliminate dental factors.
- Stress importance of stopping tobacco and alcohol use.
- Encourage participation in smoking cessation program.
PROGNOSIS
- Most leukoplakia is benign.
- Leukoplakia may regress, remain stable, or progress.
- 0.13 " “6% of initially benign lesions subsequently develop into cancer.
- More likely to be cancerous if on floor of mouth or lateral border of tongue
COMPLICATIONS
- New lesions may develop after treatment.
- Risk of malignant transformation to squamous cell carcinoma is approximately 5 " “17% (11)[B].
- Larger lesions and nonhomogeneous leukoplakia are associated with higher rates of malignant transformation.
REFERENCES
11 Warnakulasuriya ‚ S, Johnson ‚ NW, van der Waal ‚ I. Nomenclature and classification of potentially malignant disorders of the oral mucosa. J Oral Pathol Med. 2007;36(10):575 " “580.22 Cao ‚ J, Liu ‚ HW, Jin ‚ JQ. The effect of oral candida to development of oral leukoplakia into cancer [in Chinese]. Zhonghua Yu Fang Yi Xue Za Zhi. 2007;41(Suppl):90 " “93.33 Duarte ‚ EC, Ribeiro ‚ DC, Gomez ‚ MV, et al. Genetic polymorphisms of carcinogen metabolizing enzymes are associated with oral leukoplakia development and p53 overexpression. Anticancer Res. 2008;28(2A):1101 " “1106.44 Cam ‚ K, Santoro ‚ A, Lee ‚ JB. Oral frictional hyperkeratosis (morsicatio buccarum): an entity to be considered in the differential diagnosis of white oral mucosal lesions. Skinmed. 2012;10(2):114 " “115.55 Fuller ‚ C, Camilon ‚ R, Nguyen ‚ S, et al. Adjunctive diagnostic techniques for oral lesions of unknown malignant potential: systematic review with meta-analysis. Head Neck. 2015;37(5):755 " “762. doi:10.1002/hed.23667.66 Feller ‚ L, Lemmer ‚ J. Oral leukoplakia as it relates to HPV infection: a review. Int J Dent. 2012;2012:540561.77 Moura ‚ MD, Haddad ‚ JP, Senna ‚ MI, et al. A new topical treatment protocol for oral hairy leukoplakia. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2010;110(5):611 " “617.88 Ribeiro ‚ AS, Salles ‚ PR, da Silva ‚ TA, et al. A review of the nonsurgical treatment of oral leukoplakia. Int J Dent. 2010;2010:186018.99 Kawczyk-Krupka ‚ A, Wa … ›kowska ‚ J, Raczkowska-Siostrzonek ‚ A, et al. Comparison of cryotherapy and photodynamic therapy in treatment of oral leukoplakia. Photodiagnosis Photodyn Ther. 2012;9(2):148 " “155.1010 Jerjes ‚ W, Upile ‚ T, Hamdoon ‚ Z, et al. CO2 laser of oral dysplasia: clinicopathological features of recurrence and malignant transformation. Lasers Med Sci. 2012;27(1):169 " “179.1111 Rhodus ‚ NL, Kerr ‚ AR, Patel ‚ K. Oral cancer: leukoplakia, premalignancy, and squamous cell carcinoma. Dent Clin North Am. 2014;58(2):315 " “340.
ADDITIONAL READING
- Nair ‚ DR, Pruthy ‚ R, Pawar ‚ U, et al. Oral cancer: premalignant conditions and screening " ”an update. J Cancer Res Ther. 2012;8(Suppl 1):S57 " “S66.
- Reamy ‚ BV, Derby ‚ R, Bunt ‚ CW. Common tongue conditions in primary care. Am Fam Physician. 2010;81(5):627 " “634.
- Warnakulasuriya ‚ S, Dietrich ‚ T, Bornstein ‚ MM, et al. Oral health risks of tobacco use and effects of cessation. Int Dent J. 2010;60(1):7 " “30.
- Yardimci ‚ G, Kutlubay ‚ Z, Engin ‚ B, et al. Precancerous lesions of oral mucosa. World J Clin Cases. 2014;2(12):866 " “872.
SEE ALSO
Infectious Mononucleosis, Epstein-Barr Virus Infections; HIV/AIDS ‚
CODES
ICD10
- K13.21 Leukoplakia of oral mucosa, including tongue
- K13.3 Hairy leukoplakia
ICD9
528.6 Leukoplakia of oral mucosa, including tongue ‚
SNOMED
- 414603003 Leukoplakia of oral mucosa
- 414952002 oral hairy leukoplakia (disorder)
CLINICAL PEARLS
- Excisional biopsy is indicated for any undiagnosed leukoplakia.
- After treatment, up to 30% of leukoplakia recurs, and some leukoplakia still transforms to squamous cell carcinoma; thus, long-term surveillance is essential.
- To lessen risk of malignant transformation, encourage tobacco and alcohol cessation and consider C. albicans eradication.