Leukoplakia

A white patch adhering to mucosa that cannot be removed by rubbing. Usually a diagnosis of exclusion. The term should be exclusively reserved for idiopathic lesions when investigations fail to reveal any cause. The term carries no histological association.

It is considered a pre-malignant lesion. The transformation rate in various studies and locations ranging from 0.6 to 20%.¹
Factors most frequently blamed for the development of idiopathic leukoplakia include tobacco use, alcohol consumption, chronic irritation, candidiasis, vitamin A or B deficiency and endocrine disturbances.
It may also be associated with other conditions such as;

• Lichen planus.
• Secondary syphilis.
• Ill-fitting dentures.
• Human papilloma virus infection.

Oral "hairy" leukoplakia is seen in HIV-positive individuals.²

• Prevalence - occurs in fewer than 1% of individuals.
• Most cases of leukoplakia occur at age 50-70 years. Approximately 80% of patients are older than 40.
• Leukoplakia is more common in men than in women, with a male-to-female ratio of 2:1.

• Occurs on mucous membranes in the mouth or vulva .
• Oral leukoplakia is most commonly found on the tongue.
• It is seen as patches that are bright white and sharply defined.
• The surfaces of the patches are slightly raised above the surrounding mucosa.
• Individuals are not symptomatic.

1. The earliest lesion is non-palpable, faintly translucent, and has white discolouration.
2. Next, localized or diffuse, slightly elevated plaques with an irregular outline develop. These lesions are opaque white and may have a fine, granular texture.
3. In some instances, the lesions progress to thickened, white lesions, showing induration, fissuring, and ulcer formation.

Any suspicious areas should be biopsied.

The patient should abstain from alcohol and tobacco.

• Surgical excision of leukoplakia may be considered.
• Frequent clinical observation accompanied by photographic records is recommended. Because of the unpredictable behaviour of dysplastic lesions, immediately obtain a biopsy on any areas that are suggestive, or that change in appearance.
• Cryotherapy ablation and carbon dioxide laser ablation are also used.
• The area heals rapidly, and apparently healthy mucosa is left behind.
• However, uncertainty remains regarding the risk of invasive carcinomas subsequently arising in sites previously treated. However a study from Japan showed only 1.2% malignant transformation, where the cases had non-keritinised epithelia i.e., the tongue and buccal mucosa.⁴

Systemic retinoids may be effective, but they have toxic effects.
Studies investigating the use of a high-dose induction followed by low-dose systemic isotretinoin report stabilization of the majority of lesions, a more effective response than beta-carotene in preventing malignant changes, and no toxicity.⁵
Studies have reported that beta-carotene produced sustained remissions in patients with leukoplakia, with a durable response for at least 1 year.⁶
Oral lycopene ( a carotenoid) appeared, from a small RCT conducted over 5 months, to be effective in the treatment and management of oral leukoplakia.⁷ Further evaluation is required.
Low-dose fenretinide, a synthetic retinoid, has recently been found to be clinically active in a 3 month trial in patients with resistance or relapse with natural retinoids.⁸ It produced a small increase in apoptosis.

• Approximately 10% of patients who develop leukoplakia have invasive carcinoma in the lesion (6%) or will develop carcinoma (4%).⁹
• Despite excision, small dysplastic lesions can be followed by multiple carcinomas and a fatal outcome.
• In addition, some dysplastic lesions may have a worse prognosis than isolated carcinomas without leukoplakia.
• However, dysplastic lesions can regress spontaneously. Therefore the behaviour of dysplastic lesions is unpredictable. There is currently no reliable management protocol.
• Prolonged and close follow-up care is essential, but the prognosis may still be poor.