Pathology
Leukoplakia—A Diagnostic and Management Algorithm

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Oral white lesions are frequently encountered in daily practice. Most white lesions are benign (eg, reactive keratoses or keratoses from inflammatory conditions) and the diagnosis is usually evident from the clinical presentation and histopathology. Leukoplakia is a common condition characterized by an increased risk for malignant transformation. Histopathology of leukoplakia can disclose hyperkeratosis with dysplasia or carcinoma or hyperkeratosis or parakeratosis without dysplasia. Treatment depends on demographic, social, clinical, and histopathologic factors. This review focuses on the diagnosis and management of oral leukoplakia.

Section snippets

White Lesions in Genetic Diseases and Genodermatoses

These are extremely uncommon and all have specific and distinctive histopathologic features. Cannon white sponge nevus presents as diffuse bilateral white plaques of the oral mucosa and particularly the buccal mucosa and tongue and could involve esophageal and genital mucosa, but not the skin.5, 6 Similarly, hereditary benign intraepithelial dyskeratosis presents as bilateral thick white plaques of the oral mucosa and as gelatinous plaques of the conjunctiva without involvement of the skin.7, 8

White Lesions Caused by Local Injury

Lesions in this category include leukoedema, frictional keratoses, and contact injury, such as keeping mildly caustic substances for long periods at 1 site (eg, smokeless tobacco or chewing gum).

Leukoedema occurs in up to 90% of the population and can occur after exposure to mildly irritating substances (eg, mouthwash, toothpaste, and tobacco or marijuana smoke).11, 12 It presents as delicate gray-white lacy lines on the buccal mucosa or ventral tongue that disappear with stretching of the

White Lesions Caused by Infections

Oral candidiasis is the most common opportunistic fungal infection; it is usually caused by C albicans, a commensal present in 20 to 30% of patients.16 Oral lesions occur when the normal flora is altered (as in patients with hyposalivation, who wear dentures, who smoke, or who are on immunosuppressive agents). Additional contributing factors include anemia, diabetes mellitus, endocrine dysfunction, immunosuppression (eg, acquired immunodeficiency syndrome or human immunodeficiency virus [HIV]),

Immune-Mediated Keratotic Lesions

Oral lichen planus (OLP) is an immuno-mediated chronic condition present in 1 to 2% of the population, usually middle-age women.33 Of note, 10 to 15% of patients with OLP have cutaneous lesions. OLP can be idiopathic or secondary to local or systemic conditions and in particular to ingestion of medications such as antihypertensive and hypoglycemic agents.

Oral lesions are typically symmetric and bilateral and there is controversy regarding the clinical types. Although 6 distinct forms, namely

Leukoplakia

Leukoplakia is a potentially malignant lesion defined as a “white plaque of questionable risk having excluded (other) known diseases or disorders that carry no increased risk for cancer” (eg, frictional keratoses).3 Leukoplakia is a clinical term only; its definition is usually modified after a histopathologic evaluation. For example, a clinical impression of leukoplakia at biopsy examination might show candidiasis, bite keratosis, or lichen planus.

Management

White lesions with a histopathologic diagnosis of dysplasia or carcinoma in situ should be excised with clear margins, especially for cases of moderate or severe epithelial dysplasia93 (Fig 12). Of note, some cases of dysplasia (particularly mild dysplasia) have been reported to regress over time. However, it has been shown that several cases of mild dysplasia in reality could represent reactive epithelial atypia from trauma and therefore regression and recurrence would be expected.37

Reported

Conclusions and Future Directions

  • 1)

    Oral white lesions are common, but true leukoplakia has substantial potential to develop into cancer.

  • 2)

    Clinical features of leukoplakia, including partial demarcation, fissuring, and large size, and demographic information and social history guide the clinician in recognizing high-risk lesions; this is particularly true for PVL.

  • 3)

    Histopathologic examination is vitally important for the management of leukoplakia. Dysplastic lesions or carcinoma in situ should be excised with clear margins.

  • 4)

References (104)

  • M.D. Moura et al.

    A new topical treatment protocol for oral hairy leukoplakia

    Oral Surg Oral Med Oral Pathol Oral Radiol Endod

    (2010)
  • I. Al-Hashimi et al.

    Oral lichen planus and oral lichenoid lesions: Diagnostic and therapeutic considerations

    Oral Surg Oral Med Oral Pathol Oral Radiol Endod

    (2007)
  • Y.L. Cheng et al.

    Diagnosis of oral lichen planus: A position paper of the American Academy of Oral and Maxillofacial Pathology

    Oral Surg Oral Med Oral Pathol Oral Radiol

    (2016)
  • M.M. Schubert et al.

    Oral graft-versus-host disease

    Dent Clin North Am

    (2008)
  • S.G. Fitzpatrick et al.

    The malignant transformation of oral lichen planus and oral lichenoid lesions: A systematic review

    J Am Dent Assoc

    (2014)
  • I. Van der Waal

    Potentially malignant disorders of the oral and oropharyngeal mucosa; Present concepts of management

    Oral Oncol

    (2010)
  • S. Petti

    Pooled estimate of world leukoplakia prevalence: A systematic review

    Oral Oncol

    (2003)
  • I. Van der Waal

    Potentially malignant disorders of the oral and oropharyngeal mucosa; Terminology, classification and present concepts of management

    Oral Oncol

    (2009)
  • K.P. Schepman et al.

    Malignant transformation of oral leukoplakia: A follow-up study of a hospital-based population of 166 patients with oral leukoplakia from The Netherlands

    Oral Oncol

    (1998)
  • J.J. Lee et al.

    Carcinoma and dysplasia in oral leukoplakias in Taiwan: Prevalence and risk factors

    Oral Surg Oral Med Oral Pathol Oral Radiol Endod

    (2006)
  • S.B. Woo et al.

    Keratosis of unknown significance and leukoplakia: A preliminary study

    Oral Surg Oral Med Oral Pathol Oral Radiol

    (2014)
  • T. Saito et al.

    High malignant transformation rate of widespread multiple oral leukoplakias

    Oral Dis

    (1999)
  • H. Lumerman et al.

    Oral epithelial dysplasia and the development of invasive squamous cell carcinoma

    Oral Surg Oral Med Oral Pathol Oral Radiol Endod

    (1995)
  • I. Van der Waal et al.

    Oral leukoplakia: A proposal for uniform reporting

    Oral Oncol

    (2002)
  • J.G. Batsakis et al.

    Proliferative verrucous leukoplakia and its related lesions

    Oral Oncol

    (1999)
  • P. Holmstrup et al.

    Long-term treatment outcome of oral premalignant lesions

    Oral Oncol

    (2006)
  • J.J. Lee et al.

    Factors associated with underdiagnosis from incisional biopsy of oral leukoplakic lesions

    Oral Surg Oral Med Oral Pathol Oral Radiol Endod

    (2007)
  • T.J. Siebers et al.

    Chromosome instability predicts the progression of premalignant oral lesions

    Oral Oncol

    (2013)
  • V. Kulkarni et al.

    Concurrent hypermethylation of multiple regulatory genes in chewing tobacco associated oral squamous cell carcinomas and adjacent normal tissues

    Oral Oncol

    (2004)
  • A.P. Graveland et al.

    Molecular screening of oral precancer

    Oral Oncol

    (2013)
  • S.B. Woo et al.

    Human papillomavirus-associated oral intraepithelial neoplasia

    Mod Pathol

    (2013)
  • R. Kuffer et al.

    Premalignant lesions of the oral mucosa. A discussion about the place of oral intraepithelial neoplasia (OIN)

    Oral Oncol

    (2002)
  • V. Jayaprakash et al.

    Human papillomavirus types 16 and 18 in epithelial dysplasia of oral cavity and oropharynx: A meta-analysis, 1985-2010

    Oral Oncol

    (2011)
  • L.L. Patton et al.

    Adjunctive techniques for oral cancer examination and lesion diagnosis: A systematic review of the literature

    J Am Dent Assoc

    (2008)
  • M.W. Lingen et al.

    Critical evaluation of diagnostic aids for the detection of oral cancer

    Oral Oncol

    (2008)
  • N. Vigneswaran et al.

    Epidemiologic trends in head and neck cancer and aids in diagnosis

    Oral Maxillofac Surg Clin North Am

    (2014)
  • J.J. Pindborg et al.

    Studies in oral leukoplakia: A preliminary report on the period prevalence of malignant transformation in leukoplakia based on a follow-up study of 248 patients

    J Am Dent Assoc

    (1968)
  • P. Vedtofte et al.

    Surgical treatment of premalignant lesions of the oral mucosa

    Int J Oral Maxillofac Surg

    (1987)
  • A. Mogedas-Vegara et al.

    Oral leukoplakia treatment with the carbon dioxide laser: A systematic review of the literature

    J Craniomaxillofac Surg

    (2016)
  • F. Vohra et al.

    Efficacy of photodynamic therapy in the management of oral premalignant lesions. A systematic review

    Photodiagnosis Photodyn Ther

    (2015)
  • S. Warnakulasuriya et al.

    Nomenclature and classification of potentially malignant disorders of the oral mucosa

    J Oral Pathol Med

    (2007)
  • F.G. Aloi et al.

    White sponge nevus with epidermolytic changes

    Dermatologica

    (1988)
  • R. Morris et al.

    White sponge nevus. Diagnosis by light microscopic and ultrastructural cytology

    Acta Cytol

    (1988)
  • B.C. Jham et al.

    Hereditary benign intraepithelial dyskeratosis: A new case?

    J Oral Pathol Med

    (2007)
  • M.M. Nico et al.

    Oral mucosal manifestations in some genodermatoses: Correlation with cutaneous lesions

    Eur J Dermatol

    (2013)
  • T. Heyl et al.

    Sucking pads (sucking calluses) of the lips in neonates: A manifestation of transient leukoedema

    Pediatr Dermatol

    (1987)
  • G.E. Gurvits et al.

    Black hairy tongue syndrome

    World J Gastroenterol

    (2014)
  • S. Tejani et al.

    Candidal carriage predicts candidiasis during topical immunosuppressive therapy: A preliminary retrospective cohort study

    Oral Surg Oral Med Oral Pathol Oral Radiol

    (2016)
  • U. Nair et al.

    Alert for an epidemic of oral cancer due to use of the betel quid substitutes gutkha and pan masala: A review of agents and causative mechanisms

    Mutagenesis

    (2004)
  • I. Stepanov et al.

    New and traditional smokeless tobacco: Comparison of toxicant and carcinogen levels

    Nicotine Tob Res

    (2008)
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    Conflict of Interest Disclosures: None of the authors have any relevant financial relationship(s) with a commercial interest.

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