Physical Examination

Most leukoplakias are smooth, white plaques (homogeneous leukoplakias), as shown in the image below.

Homogeneous leukoplakia.

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Most leukoplakias occur on the lip, the buccal mucosae, or the gingivae.

Some leukoplakias are white and warty (verrucous leukoplakia), as shown in the image below.

Verrucous or nodular leukoplakia.

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Some leukoplakias are mixed white and red lesions (erythroleukoplakias or speckled leukoplakias), as shown in the image below.

Erythroleukoplakia.

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Proliferative verrucous leukoplakia (PVL), the least common form of leukoplakia, is characterized by verruciform keratosis that are progressive and multifocal, exhibiting a high rate of recurrence and progression to carcinoma.

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. Note the image below.

Carcinoma referred to as a leukoplakia.

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A practical clinical tool for evaluating oral mucosal lesions has recently been developed. This tool is based on the grading of general clinical observations on a color scheme that reflects an increasing spectrum of concerns (green to red, or no concern to serious concern).^{[12, 13]}This tool is summarized in the table below, with the headers representing the green spectrum being “No Serious Concern”, the yellow being “Concern”, and the red being “Serious Concern”.

Table. Practical Clinical Tool for Evaluating Oral Mucosal Lesions (Open Table in a new window)

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

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: This includes smoked (including reverse smoking—lit end retained within the mouth) and smokeless (use of snuff and chewing tobacco); chewing tobacco likely contributes to oral leukoplakia more than smoking. ^[14]
Alcohol
Use of areca (betel) nut preparations, khat (qat), and similar products ^{[15, 16]}
Infections (eg, candidosis, syphilis, Epstein-Barr virus infection): Epstein-Barr virus infection causes a separate and distinct non–premalignant lesion termed oral hairy leukoplakia.
Chemicals (eg, sanguinaria) ^{[17, 18]}
Ultraviolet radiation (eg, actinic cheilitis)
Immune defects: Leukoplakias appear to be more common in transplant patients.

In cases of proliferative verrucous leukoplakia, the above risk factors are frequently absent; high-frequency allelic loss and high-risk allelic profiles noted in such lesions probably account for high-risk progression to dysplasia and malignancy.^[19]

Complications

Some leukoplakias are potentially malignant. Dysplasia currently appears to be the best predictor of malignant potential. As many as 25% of leukoplakias are dysplastic at the first visit. DNA ploidy and loss of heterozygosity (LOH) studies may help predict outcomes.^{[20, 21, 22]}Malignant change appears to be more frequent among nonsmokers than among smokers.

A poorer prognosis is noted in the following^{[22, 23, 24]}:

Nonsmokers
Females
Nonhomogenous appearance
Size larger than 200 mm
Moderate or severe epithelial dysplasia
LOH at 9p/3p and further increased risk if additional LOH at 4q and 17p
Lesions in high-risk sites, such as the floor of the mouth/tongue/soft palate

Differential Diagnoses

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Allen CL, Loudon J, Mascarenhas AK. Sanguinaria-related leukoplakia: epidemiologic and clinicopathologic features of a recently described entity. Gen Dent. 2001 Nov-Dec. 49(6):608-14. [QxMD MEDLINE Link].
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. 2000 Apr. 89(4):455-64. [QxMD MEDLINE Link].
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Bremmer JF, Brakenhoff RH, Broeckaert MA, et al. Prognostic value of DNA ploidy status in patients with oral leukoplakia. Oral Oncol. 2011 Oct. 47(10):956-60. [QxMD MEDLINE Link].
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Zhang L, Poh CF, Williams M, Laronde DM, Berean K, Gardner PJ, et al. Loss of heterozygosity (LOH) profiles--validated risk predictors for progression to oral cancer. Cancer Prev Res (Phila). 2012 Sep. 5 (9):1081-9. [QxMD MEDLINE Link].
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Media Gallery

Homogeneous leukoplakia.
Erythroleukoplakia.
Verrucous or nodular leukoplakia.
Carcinoma referred to as a leukoplakia.

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Table. Practical Clinical Tool for Evaluating Oral Mucosal Lesions

Table. Practical Clinical Tool for Evaluating Oral Mucosal Lesions

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

Back to List

Author

James J Sciubba, DMD, PhD Consultant, The Milton J Dance Head and Neck Center, Greater Baltimore Medical Center; Private Practice in Oral Medicine/Oral Pathology; Professor (Ret) of Otolaryngology-Head and Neck Surgery, Professor of Pathology, Professor of Dermatology, Johns Hopkins School of Medicine

James J Sciubba, DMD, PhD is a member of the following medical societies: American Academy of Oral and Maxillofacial Pathology, American Association for the Advancement of Science, American College of Dentists, American Dental Association, International Academy of Oral Oncology, International Association for Dental Research, International Association of Oral Pathologists, International College of Dentists, Sigma Xi, The Scientific Research Honor Society

Disclosure: Nothing to disclose.

Coauthor(s)

Narendran Andrew Robinson, BDS, MS Adjunct Senior Lecturer, Discipline of Oral and Maxillofacial Surgery, National University of Singapore; Visiting Specialist/Consultant, University Dental Cluster, National University Hospital

Narendran Andrew Robinson, BDS, MS is a member of the following medical societies: Singapore Dental Association

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Warren R Heymann, MD Head, Division of Dermatology, Professor, Department of Internal Medicine, Rutgers New Jersey Medical School

Warren R Heymann, MD is a member of the following medical societies: American Academy of Dermatology, American Society of Dermatopathology, Society for Investigative Dermatology

Disclosure: Nothing to disclose.

Chief Editor

William D James, MD Paul R Gross Professor of Dermatology, Vice-Chairman, Residency Program Director, Department of Dermatology, University of Pennsylvania School of Medicine

William D James, MD is a member of the following medical societies: American Academy of Dermatology, Society for Investigative Dermatology

Disclosure: Received income in an amount equal to or greater than $250 from: Elsevier; WebMD<br/>Served as a speaker for various universities, dermatology societies, and dermatology departments.

Additional Contributors

David P Fivenson, MD Associate Director, St Joseph Mercy Hospital Dermatology Program, Ann Arbor, Michigan

David P Fivenson, MD is a member of the following medical societies: American Academy of Dermatology, Michigan State Medical Society, Society for Investigative Dermatology, Photomedicine Society, Wound Healing Society, Michigan Dermatological Society, Medical Dermatology Society

Disclosure: Nothing to disclose.

Crispian Scully, MD, MRCS, PhD, MDS, CBE, FDSRCS(Eng), FDSRCPS, FFDRCSI, FDSRCSE, FRCPath, FMedSci, FHEA, FUCL, FSB, DSc, DChD, DMed(HC), Dr(HC) Emeritus Professor, University College London; Visiting Professor, Universities of Athens, BPP, Edinburgh, Granada, Helsinki and Plymouth

Crispian Scully, MD, MRCS, PhD, MDS, CBE, FDSRCS(Eng), FDSRCPS, FFDRCSI, FDSRCSE, FRCPath, FMedSci, FHEA, FUCL, FSB, DSc, DChD, DMed(HC), Dr(HC) is a member of the following medical societies: Academy of Medical Sciences, British Society for Oral Medicine, European Association for Oral Medicine, International Academy of Oral Oncology, International Association for Dental Research, International Association for Oral and Maxillofacial Pathology

Disclosure: Nothing to disclose.