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Leukoplakia – Differential diagnosis


Author: Sanketh DS, MDS


Diagnosis of leukoplakia is one of exclusion, meaning, a definitive diagnosis of leukoplakia is rendered only after other white lesions have been excluded. There are several white lesions that mimic leukoplakia.

Firstly, check if the lesions are removable with gauze. Chances are, it could be pseudomembranous candidiasis, if they are.


1. If the lesions are on sites prone to trauma from teeth, dentures or other appliances, they could be frictional keratotic lesions appearing due to mechanical trauma.

2. Lesions on the commissure could be hyperplastic candidiasis. Candidal hyphae, if present in cytology or biopsy could confirm diagnosis. Hyperplastic candidiasis could also occur on the tongue and is not scrapable unlike the pseudomembranous type.

3. Other unilateral lesions to be ruled out are chemical burns, linea alba and lichenoid lesions due to restorations.


1. Oral lichen planus characteristically manifests with reticular striae and occasionally plaques. Check for skin lesions and other clinical variants of OLP if in doubt.

2. White sponge nevus and hereditary benign intraepithelial dyskeratosis occurs most commonly on the buccal mucosa bilaterally. These lesions are shaggy, wrinkled, not well circumscribed and occur usually in early childhood.

3. Pale milky whiteness that disappears on stretching could be leukodema.

4. Also rule out cheek chewing, where patients have a chronic habit of chewing the buccal mucosa.

5. Presence of bilateral corrugated, wrinkled white lesions on the lateral border of the tongue could signify hairy leukoplakia. These are not true leukoplakias, are not potentially malignant and appear in HIV positive patients.


1. Nicotine stomatitis is a generalised white keratosis on the palate with scattered red spots representing inflamed minor salivary gland ducts. This lesion seems to be a response to the heat produced due to smoking and not to the chemical carcinogens within the smoke. It is not leukoplakia and is not potentially malignant.

2. Tobacco-pouch keratosis manifests as a fissured and wrinkled pouch with or without areas of white patches in the vestibule where the tobacco constituents are chronically pouched. This has a characteristic clinical appearance and should not be misdiagnosed as leukoplakia. It has very little potential to become malignant if any.

Besides clinically ruling out these lesions, biopsy must also reveal a diagnosis that is compatible with a clinical diagnosis of leukoplakia, meaning, the lesion under the microscope must not reveal any other microscopically definable lesion. Say, for example, if a plaque type oral lichen planus has been misdiagnosed as leukoplakia, microscopy would obviously reveal oral lichen planus.


In 2002, van der Waal and Axell proposed a system of reporting leukoplakia to maintain uniformity in diagnosis.

They recommended a distinction between provisional and a definitive diagnosis of leukoplakia.

A provisional diagnosis is made when the white lesion in question cannot be diagnosed as any other clinical entity on initial clinical examination applying only inspection and palpation.

A definitive diagnosis is made after elimination of  suspected etiological factors and other lesions during a follow-up of atleast 2-4 weeks and complemented by microscopic diagnosis where any other definable lesion is ruled out.

To make things clear, lets suppose a provisional diagnosis of leukoplakia has been made. If there are no possible etiological factors causing the lesion, it could be definitively diagnosed as leukoplakia. Now after eliminating possible etiological factors like habits or a source of trauma, keep the patient under follow-up for a minimum of 2-4 weeks to see if the lesion shows signs of regressing. If yes, chances are, it could have been a reactive lesion like frictional keratosis or a tobacco pouch keratosis.

If there are no signs of improvement, perform a biopsy to check for a histopathological diagnosis consistent with the clinical impression. Biopsy should reveal either a hyperkeratotic lesion without dysplasia or an epithelial dysplastic lesion. If it reveals any other definable lesion, then it has to be understood that clinically the lesion was misdiagnosed as leukoplakia.


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Brouns EREA, Baart JA, Bloemena E, Karagozoglu KH, van der Waal I. The relevance of uniform reporting in leukoplakia. Definition certainty factor and staging based on experience with 275 patients. Med Oral Pathol Oral Cir Bucal 2013;18(1):e19-26.

Warnakulasuriya S, Reibel J, Bouquot J, Dabelsteen E. Oral epithelial dysplasia classification systems: predictive value, utility, weaknesses and scope for improvement. J Oral Pathol Med 2008;37(3):127-133.


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