eMedicine Specialties > Dermatology > Diseases of the Oral Mucosa
Leukoplakia, Oral
Updated: Oct 17, 2008
Introduction
Background
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, 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 workshop1 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.
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..
Pathophysiology
No etiologic factor can be identified for most persistent oral white plaques (ie, idiopathic leukoplakia). The histopathologic features 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.
Dysplastic lesions do not have any specific clinical appearance; however, where erythroplakia is present, 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 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.2
Frequency
United States
Oral leukoplakia is uncommon, possibly occurring in less than 1% of adults.
International
The rates are the same as those in the United States.
Mortality/Morbidity
Some leukoplakias culminate in oral squamous cell carcinoma (OSCC).3,4
Race
An increased prevalence is observed in communities and races with high tobacco use, such as Southeast Asia.
Sex
Males have the highest incidence of leukoplakias.
Age
Leukoplakias are usually seen in adults older than 40 years.
Clinical
History
Leukoplakias are usually asymptomatic and are initially noticed by a dentist during a routine examination.
Physical
Leukoplakias are white lesions that cannot be removed with a gauze swab.
- Most leukoplakias are smooth, white plaques (homogeneous leukoplakias).
- Most leukoplakias occur on the lip, the buccal mucosae, or the gingivae.
- Some leukoplakias are white and warty (verrucous leukoplakia).
- Some leukoplakias are mixed white and red lesions (erythroleukoplakias or speckled leukoplakias).
- Dysplastic lesions do not have any specific clinical appearance; however, where erythroplasia is present, dysplasia, carcinoma in situ, and frank carcinomas are more likely to be seen.
- The site of the lesion is relevant; leukoplakias on the floor of the mouth or on the ventrum of the tongue and the lip are sinister.
- The size of the lesion appears to be irrelevant. Even small dysplastic lesions may lead to multiple carcinomas and a fatal outcome.
Causes
No etiologic factor can be identified for most persistent oral leukoplakias (idiopathic leukoplakia).
- Known causes of leukoplakia include the following:
- Trauma (eg, chronic trauma from a sharp or broken tooth or from mastication may cause keratosis)
- Tobacco use: Chewing tobacco is probably worse than smoking.5
- Alcohol
- Infections (eg, candidosis, syphilis, Epstein-Barr virus infection): Epstein-Barr virus infection causes a separate and distinct non–premalignant lesion termed hairy leukoplakia.
- Chemicals (eg, sanguinaria)6,7
- Immune defects: Leukoplakias appear to be more common in transplant patients.
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References
Warnakulasuriya S, Johnson NW, van der Waal I. Nomenclature and classification of potentially malignant disorders of the oral mucosa. J Oral Pathol Med. Nov 2007;36(10):575-80. [Medline].
Bouquot JE, Weiland LH, Kurland LT. Leukoplakia and carcinoma in situ synchronously associated with invasive oral/oropharyngeal carcinoma in Rochester, Minn., 1935-1984. Oral Surg Oral Med Oral Pathol. Feb 1988;65(2):199-207. [Medline].
Bagan JV, Jimenez Y, Sanchis JM, Poveda R, Milian MA, Murillo J, et al. Proliferative verrucous leukoplakia: high incidence of gingival squamous cell carcinoma. J Oral Pathol Med. Aug 2003;32(7):379-82. [Medline].
Bagán JV, Murillo J, Poveda R, Gavaldá C, Jiménez Y, Scully C. Proliferative verrucous leukoplakia: unusual locations of oral squamous cell carcinomas, and field cancerization as shown by the appearance of multiple OSCCs. Oral Oncol. Apr 2004;40(4):440-3. [Medline].
Fisher MA, Bouquot JE, Shelton BJ. Assessment of risk factors for oral leukoplakia in West Virginia. Community Dent Oral Epidemiol. Feb 2005;33(1):45-52. [Medline].
Allen CL, Loudon J, Mascarenhas AK. Sanguinaria-related leukoplakia: epidemiologic and clinicopathologic features of a recently described entity. Gen Dent. Nov-Dec 2001;49(6):608-14. [Medline].
Eversole LR, Eversole GM, Kopcik J. Sanguinaria-associated oral leukoplakia: comparison with other benign and dysplastic leukoplakic lesions. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. Apr 2000;89(4):455-64. [Medline].
Jiang WW, Fujii H, Shirai T, Mega H, Takagi M. Accumulative increase of loss of heterozygosity from leukoplakia to foci of early cancerization in leukoplakia of the oral cavity. Cancer. Nov 1 2001;92(9):2349-56. [Medline].
Garewal HS, Katz RV, Meyskens F, Pitcock J, Morse D, Friedman S, et al. Beta-carotene produces sustained remissions in patients with oral leukoplakia: results of a multicenter prospective trial. Arch Otolaryngol Head Neck Surg. Dec 1999;125(12):1305-10. [Medline].
Chiesa F, Tradati N, Sala L, Costa L, Podrecca S, Boracchi P, et al. Follow-up of oral leukoplakia after carbon dioxide laser surgery. Arch Otolaryngol Head Neck Surg. Feb 1990;116(2):177-80. [Medline].
Chiesa F, Sala L, Costa L, Moglia D, Mauri M, Podrecca S, et al. Excision of oral leukoplakias by CO2 laser on an out-patient basis: a useful procedure for prevention and early detection of oral carcinomas. Tumori. Jun 30 1986;72(3):307-12. [Medline].
Sudbø J, Lippman SM, Lee JJ, Mao L, Kildal W, Sudbø A, et al. The influence of resection and aneuploidy on mortality in oral leukoplakia. N Engl J Med. Apr 1 2004;350(14):1405-13. [Medline].
Sudbø J, Kildal W, Risberg B, Koppang HS, Danielsen HE, Reith A. DNA content as a prognostic marker in patients with oral leukoplakia. N Engl J Med. Apr 26 2001;344(17):1270-8. [Medline].
Abdel-Salam M, Mayall BH, Chew K, Silverman S Jr, Greenspan JS. Prediction of malignant transformation in oral epithelial lesions by image cytometry. Cancer. Nov 1 1988;62(9):1981-7. [Medline].
Bouquot JE, Whitaker SB. Oral leukoplakia--rationale for diagnosis and prognosis of its clinical subtypes or "phases". Quintessence Int. Feb 1994;25(2):133-40. [Medline].
Bánóczy J. Follow-up studies in oral leukoplakia. J Maxillofac Surg. Feb 1977;5(1):69-75. [Medline].
Ikeda N, Ishii T, Iida S, Kawai T. Epidemiological study of oral leukoplakia based on mass screening for oral mucosal diseases in a selected Japanese population. Community Dent Oral Epidemiol. Jun 1991;19(3):160-3. [Medline].
Jaber MA, Porter SR, Speight P, Eveson JW, Scully C. Oral epithelial dysplasia: clinical characteristics of western European residents. Oral Oncol. Sep 2003;39(6):589-96. [Medline].
Kramer IR, Lucas RB, Pindborg JJ, Sobin LH. Definition of leukoplakia and related lesions: an aid to studies on oral precancer. Oral Surg Oral Med Oral Pathol. Oct 1978;46(4):518-39. [Medline].
Kulasegaram R, Downer MC, Jullien JA, Zakrzewska JM, Speight PM. Case-control study of oral dysplasia and risk habits among patients of a dental hospital. Eur J Cancer B Oral Oncol. Jul 1995;31B(4):227-31. [Medline].
Lumerman H, Freedman P, Kerpel S. Oral epithelial dysplasia and the development of invasive squamous cell carcinoma. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. Mar 1995;79(3):321-9. [Medline].
Marley JJ, Linden GJ, Cowan CG, Lamey PJ, Johnson NW, Warnakulasuriya KA, et al. A comparison of the management of potentially malignant oral mucosal lesions by oral medicine practitioners and oral & maxillofacial surgeons in the UK. J Oral Pathol Med. Nov 1998;27(10):489-95. [Medline].
McCarthy FP. Etiology, pathology and treatment of leukoplakia buccalis with a report of 316 cases. Arch Dermatol Syph. 1936;6:612-23.
Pentenero M, Carrozzo M, Pagano M, Galliano D, Broccoletti R, Scully C, et al. Oral mucosal dysplastic lesions and early squamous cell carcinomas: underdiagnosis from incisional biopsy. Oral Dis. Mar 2003;9(2):68-72. [Medline].
Sankaranarayanan R, Nair MK, Mathew B, Balaram P, Sebastian P, Dutt SC. Recent results of oral cancer research in Kerala, India. Head Neck. Mar-Apr 1992;14(2):107-12. [Medline].
Schepman K, der Meij E, Smeele L, der Waal I. Concomitant leukoplakia in patients with oral squamous cell carcinoma. Oral Dis. Jul 1999;5(3):206-9. [Medline].
Schepman KP, van der Waal I. A proposal for a classification and staging system for oral leukoplakia: a preliminary study. Eur J Cancer B Oral Oncol. Nov 1995;31B(6):396-8. [Medline].
Sciubba JJ. Oral leukoplakia. Crit Rev Oral Biol Med. 1995;6(2):147-60. [Medline].
Scully C, Cawson RA. Potentially malignant oral lesions. J Epidemiol Biostat. 1996;1:3-12.
Scully C, Sudbø J, Speight PM. Progress in determining the malignant potential of oral lesions. J Oral Pathol Med. May 2003;32(5):251-6. [Medline].
Silverman S Jr, Gorsky M, Lozada F. Oral leukoplakia and malignant transformation. A follow-up study of 257 patients. Cancer. Feb 1 1984;53(3):563-8. [Medline].
Szpirglas H. [Detection of oral cancers and current conception of precancerous conditions]. Rev Prat. Apr 1 1995;45(7):831-7. [Medline].
van der Waal RI, Pas HH, Nousari HC, Schulten EA, Jonkman MF, Nieboer C, et al. Paraneoplastic pemphigus caused by an epithelioid leiomyosarcoma and associated with fatal respiratory failure. Oral Oncol. Jul 2000;36(4):390-3. [Medline].
Waldron CA, Shafer WG. Leukoplakia revisited. A clinicopathologic study 3256 oral leukoplakias. Cancer. Oct 1975;36(4):1386-92. [Medline].
Wright JM. Oral precancerous lesions and conditions. Semin Dermatol. Jun 1994;13(2):125-31. [Medline].
Zavras AI, Laskaris C, Kittas C, Laskaris G. Leukoplakia and intraoral malignancies: female cases increase in Greece. J Eur Acad Dermatol Venereol. Jan 2003;17(1):25-7. [Medline].
Further Reading
Keywords
oral leukoplakia, leukoplakia, oral cancer, mouth cancer, smokeless tobacco, keratosis,
