There is range of potentially malignant disorders known. This article focuses on the most important – erythroplakia (erythroplasia), leukoplakia, and lichenoid lesions. Others such as actinic cheilitis, submucous fibrosis, Fanconi anaemia (syndrome) (table 1) are less common in the UK. The risk of malignant transformation in the potentially malignant disorders is approximately as shown in box 1.
Potentially malignant lesions are initially usually symptomless, so any symptoms should raise the index of suspicion of malignant change.
Erythroplakia
Erythroplakia (erythroplasia) is a rare red patch, usually related to tobacco and alcohol use, and seen in the middle aged and the older patient. Defined as a “fiery red patch that cannot be characterised clinically or pathologically as any other definable disease”, the clinical appearance is often of a flat or even depressed erythematous area of mucosa (fig 1). It is usually a solitary lesion. In some, there is a mixture of red and white changes - when the lesion is categorised as ‘erythroleukoplakia’, ‘non- homogeneous’ or ‘speckled’ leukoplakia. Histopathologically, erythroplakia typically shows at least moderate or severe dysplasia. Epithelial dysplasia is in general regarded as the most important indicator of malignant potential.
The majority of erythroplakias will undergo malignant transformation, so they need to be removed by surgery, either by cold knife (scalpel) or by laser excision, but there are no reliable data about the prognosis or recurrence rate.
Leukoplakia
Leukoplakia is much more common than erythroplakia and it also is associated mainly with tobacco and alcohol. Defined as “A white plaque of questionable risk having excluded (other) known diseases or disorders that carry no increased risk for cancer”, it can clinically be confused with other oral white lesions, such as lichenoid lesions. By definition the term excludes entities such as frictional keratosis or smokers keratosis. Leukoplakia can appear as:
? homogeneous leukoplakia (flat, thin, uniform white in colour)
? non-homogeneous leukoplakiaeither
– a white-and-red lesion (“erythroleukoplakia”), that may be eitherirregularly flat (speckled) or
– nodular, or
– verrucous. Proliferative verrucous leukoplakia (PVL) is a special subtype of verrucous leukoplakia, characterised by multifocal lesions, and a high malignant transformation rate.
An annual malignant transformation rate of about one to two per cent over 10 years is probably a realistic figure for leukoplakias overall. In dysplastic leukoplakias however, the malignant transformation may reach 30 per cent. Sadly, a number of studies have shown that the reliability of dysplasia grading and histopathological examination cannot be guaranteed; pathologists can differ in their diagnosis one from another and even the same pathologist can sometimes give a different view at different times.
There are certain other indicators that may help predict malignant change (box 2), but it is not possible at present to reliably predict which lesions will progress to carcinoma nor to be absolutely certain that a lesion has malignant potential or not.
Over the last few years, much effort has gone into identifying the genetic changes that underlie oral carcinoma and to find biomarkers such as DNA ploidy, and changes in the tumour suppressor gene p53, and changes called loss of heterozygosity in chromosomes 3 and 9 that might predict malignant change. Despite considerable progress in such molecular biology, there is as still no single marker or set of markers that reliably predicts malignant transformation of leukoplakia in an individual patient, though the presence of dysplasia and of other changes such as genetic changes, are suggestive.
There is also no scientific evidence that treatment truly prevents the possible future development of a carcinoma. Possible aetiological factors should be removed, and an observation of two to four weeks seems acceptable to observe any possible regression.
Since some potentially malignant lesions which on initial biopsy have shown no serious pathology have, on excision, been shown to contain cancers in up to 10 per cent, it is probably best to remove all oral leukoplakias if feasible, especially if there is epithelial dysplasia on biopsy, rather than so-called ‘watchful waiting’. The efficacy of continuous follow-up of oral leukoplakia patients is virtually unknown. Nevertheless, recurrence rates after any form of treatment may be up to 30 per cent, probably mainly depending on the duration of follow-up. The most commonly used treatments are surgical excision or CO2 laser therapy and the specimen must be sent for histopathological examination. For widespread leukoplakias, photodynamic therapy may be considered. The evidence from systematic reviews is that medical therapies are not reliably effective: topical anticancer agents such as podophyllin or bleomycin or retinoids have only temporary efficacy, and perhaps their best indication is when the location or extent of the lesion prevent adequate surgical removal.
Lichen planus/lichenoid lesions
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Summary
Sadly, the evidence base in this field is not ideal. Thus it is not possible yet to reliably define the risk of malignant transformation of a potentially malignant oral lesion nor to reliably predict the effects of any interventions. Future directions are hopeful and leading to increased reliability of prognostic factors as shown in box 3, most of which rely on molecular studies under development.
References available on request.