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Oral Leukoplakia Workup

  • Author: Christopher M Harris, MD, DMD; Chief Editor: Arlen D Meyers, MD, MBA  more...
Updated: Mar 31, 2015

Laboratory Studies

Idiopathic lesions and dysplastic lesions do not have any specific clinical appearance. Therefore, in any case, the clinical appearance is not a guide to the underlying microscopic characteristics. A definitive diagnosis of oral leukoplakia is made when any etiological cause other than tobacco/areca nut use has been excluded and histopathology has not confirmed any other specific disorder.[4]



Biopsy obtainment, repeated as necessary, is essential.


Histologic Findings

The plaque may show hyperorthokeratosis or hyperparakeratosis. The granular layer is often thickened and extremely prominent in cases of hyperorthokeratosis, but it is seldom observed in even severe cases of hyperparakeratosis. Acanthosis, which refers to the abnormal thickening of the prickle cell layer, may also be observed. Epithelial changes suggestive of premalignancy include the following:

  • Nuclear hyperchromatism
  • Loss of polarity
  • Increased number of mitotic figures
  • Nuclear pleomorphism
  • Altered nuclear-to-cytoplasmic ratio
  • Deep cell keratinization
  • Loss of differentiation
  • Loss of intercellular adherence

Yang et al analyzed the relationship between clinical features of OL using endoscopy with narrow-band imaging histopathology. They concluded that flexible endoscopy can be a successful tool for examining OL.[5]

Molecular markers that may indicate an increased likelihood of malignant transformation are (1) Mutations in the p53 gene, (2) Inappropriate expression of oncogenes (eg, cyclin D1), keratins, blood-group antigens and other cell-surface carbohydrates, and (3) DNA aneuploidy (when the amount of DNA is not an exact multiple of the diploid number). The latter emerges as one of the most promising prognostic indicators since oral cancer with poor survival consistently developed in human subjects with aneuploid dysplastic OL.[6, 7]

A study by von Zeidler et al suggested that reductions in the amount of epithelial cadherin (E-cadherin), a cellular adhesion protein, signal an increased risk of malignant transformation by oral leukoplakia. The investigators found that the amount of E-cadherin expressed in tissue differed between normal oral mucosa and low-risk oral leukoplakia, between low-risk and high-risk oral leukoplakia, and between high-risk oral leukoplakia and squamous cell carcinoma of the oral cavity with cervical lymph node metastasis.[8]

Contributor Information and Disclosures

Christopher M Harris, MD, DMD Residency Program Director, Department of Oral and Maxillofacial Surgery, Maxillofacial Tumor and Reconstruction, Naval Medical Center Portsmouth

Christopher M Harris, MD, DMD is a member of the following medical societies: American Association of Oral and Maxillofacial Surgeons, American 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.

Nader Sadeghi, MD, FRCSC Professor, Otolaryngology-Head and Neck Surgery, Director of Head and Neck Surgery, George Washington University School of Medicine and Health Sciences

Nader Sadeghi, MD, FRCSC is a member of the following medical societies: American Head and Neck Society, American Thyroid Association, American Academy of Otolaryngology-Head and Neck Surgery, Royal College of Physicians and Surgeons of Canada

Disclosure: Nothing to disclose.

Chief Editor

Arlen D Meyers, MD, MBA Professor of Otolaryngology, Dentistry, and Engineering, University of Colorado School of Medicine

Arlen D Meyers, MD, MBA is a member of the following medical societies: American Academy of Facial Plastic and Reconstructive Surgery, American Academy of Otolaryngology-Head and Neck Surgery, American Head and Neck Society

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Cerescan;RxRevu;SymbiaAllergySolutions<br/>Received income in an amount equal to or greater than $250 from: Symbia<br/>Received from Allergy Solutions, Inc for board membership; Received honoraria from RxRevu for chief medical editor; Received salary from Medvoy for founder and president; Received consulting fee from Corvectra for senior medical advisor; Received ownership interest from Cerescan for consulting; Received consulting fee from Essiahealth for advisor; Received consulting fee from Carespan for advisor; Received consulting fee from Covidien for consulting.

Additional Contributors

David J Terris, MD, FACS Porubsky Professor and Chairman, Department of Otolaryngology, Medical College of Georgia, Georgia Regents University

David J Terris, MD, FACS is a member of the following medical societies: American Association for the Advancement of Science, Federation of American Societies for Experimental Biology, International Association of Endocrine Surgeons, Alpha Omega Alpha, Triological Society, Radiation Research Society, American Academy of Otolaryngology-Head and Neck Surgery, American Bronchoesophagological Association, American College of Surgeons, American Head and Neck Society, Phi Beta Kappa, Society of University Otolaryngologists-Head and Neck Surgeons

Disclosure: Nothing to disclose.

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