Premalignant lesions

The association of oral carcinoma and other oral mucosal lesions has been recognised for many years. Often these lesions are in the form of white plaques (‘leucoplakia’) or bright red velvety plaques (‘erythroplakia’). They may be present for periods of months to years prior to the onset of malignant change and often they will he present together with the carcinoma at presentation. Because of this association the assumption was made that such lesions led directly to invasive carcinoma and hence were themselves premalignant.

Some white plaques do undoubtedly have a potential to undergo malignant transformation, and an examination of established carcinomas will show many to exist in

association with white plaques. However, the majority of oral carcinomas is not preceded by or is associated with leucoplakia.

Although historically oral ‘leucoplakia’ has been recognised as premalignant, the risk of malignant transformation is not as great as was previously thought. Early literature sug­gested a 30 per cent or higher incidence of malignant transformation of these lesions whereas more recent authors quote an incidence of between 3 and 6 per cent.

The following oral lesions are now definitely considered to carry a potential for malignant change:

       leucoplakia;

       erythroplakia;

       chronic hyperplastic candidiasis.

 A further group of conditions, although not themselves premalignant, are associated with a higher than normal incidence of oral cancer:

oral submucous fibrosis;

syphilitic glossitis;

sideropenic dysphagia.

There remains a further group of oral conditions about which there is still some doubt as to whether their association with oral cancer is causal or casual:

oral lichen planus;

discoid lupus erythematosus;

  dyskeratosis congenita.

Leucoplakia

Using the term leucoplakia (Fig. 41.2) either in a histological or clinical context is a matter of defining what one means by the term. The World Health Organisation (WHO) has defined leucoplakia as ‘any white parch or plaque that cannot be characterised clinically or pathologically as any other disease’. This definition has no histological connotation.

Clinical features

Clinically leucoplakia may vary from a small circumscribed white plaque to an extensive lesion involving wide areas of the oral mucosa. The surface may be smooth or it may be wrinkled, and many lesions are traversed by cracks or fis­sures. The colour of the lesion may be white, yellowish or grey, with some being homogeneous whilst others are nodular or speckled on an erythematous base. Many lesions are soft whereas other thicker lesions feel crusty. Induration suggests malignant change and is an indication for immediate biopsy. It is important to recognise that it is the speckled or nodular leucoplakias which are the most likely to undergo malignant change.

Potential for malignant change

It has been shown that the incidence of ultimate malignant change in oral leucoplakia increases with the age of the lesion. One study showed a 2.4 per cent malignant transformation rate at 10 years which increased to 4 per cent at 20 years. It also showed that as the age of the patient increased so did the risk of malignant transformation: for patients younger than 50 years it was I per cent whereas for those between 70 and 89 years it was 7.5 per cent during a 5-year observation period. Studies have shown that, in southern England, leucoplakia of the floor of the mouth and ventral surface of the tongue has a particularly high incidence of malignant change. This study suggested that this occurrence was due to pooling of soluble carcinogens in the ‘sump’ of the floor of the mouth.

Aetiology

Tobacco smoking and chewing are undoubtedly important aetiological factors. In Indians who smoke or chew tobacco (often as a component of the betel quid) the incidence of leucoplakia in those of 60 years of age is 20 per cent, whereas in those who neither smoke not chew tobacco the incidence is 1 per cent.

The role of alcohol in the development of oral leucoplakia is difficult to assess. Few studies have been reported, but it has been shown that in patients with leucoplakia the incidence of excessive alcohol consumption is greater than in those free of leucoplakia.

Management

In any patient presenting for the first time with oral leucoplakia a careful history — particularly looking for aetiological factors — and a detailed clinical examination should precede the histological examination of biopsies of any suspicious areas. Suspicion should be aroused by any areas of ulceration or induration or where the underlying tissues are bright red and hyperemic.

If there is a history of tobacco consumption then the patient should be persuaded to stop immediately. It has been shown that if the patient stops smoking entirely for 1 year the leucoplakia will disappear in 60 per cent of the cases.

Whenever severe epithelial dysplasia or carcinoma in situ is present, surgical excision or carbon dioxide laser excision of the lesions is mandatory. Small lesions may be excised, the margins of the adjacent mucosa undermined and the defect closed by advancing the margins. For larger defects the area

should be left to epithelialise spontaneously or alternatively the area can be skin grafted. On the tongue the graft is quilted on to the raw area, whereas on the cheek, floor of mouth or palate the graft can be retained in place by suturing a suitable pack overlying it.

When only mild to moderate epithelial dysplasia is present the patient should be followed up at 4-monthly intervals and the lesions recorded in the notes either photographically or diagrammatically.

Erythroplakia

Erythroplakia (Fig. 41.3) is defined as ‘any lesion of the oral mucosa that presents as bright red velvety plaques which cannot be characterised clinically or pathologically as any other recognisable condition’. Such lesions are usually irreg­ular in outline, although clearly demarcated from adjacent normal epithelium. The surface may be nodular. In some cases erythroplakia coexists with areas of leucoplakia. The incidence of malignant change in erythroplakias is 17-fold higher than in leucoplakia. In every case of erythroplakia there are areas of epithelial dysplasia, carcinoma in situ or invasive carcinoma. Clearly, all erythroplakic areas must be completely excised either surgically or with a carbon dioxide laser, and the specimens submitted for careful pathological examination.

Chronic hyperplastic candidiasis

In chronic hyperplastic candidiasis (Fig. 41.4), dense chalky plaques of keratin are formed, the plaques being thicker and more opaque than in noncandidal leucoplakia. Such lesions are particularly common at the oral commissures extending on to the adjacent skin of the face.

In 1969 Cawson drew attention to the high incidence of malignant transformation in these candidal leucoplakias, suggesting that the invasive candidal infection is the cause of the leucoplakia and not merely a superimposed infection. It has also been suggested that in such patients there may be an immunological defect which allows the Candida albicans to invade the epithelium and may render the patient susceptible to malignant change. It is thought that treatment with nystatin, amphotericin or miconazole to eliminate the candidal infection will reduce the risk of malignant change. However, treatment may be necessary for many months to eliminate the organisms and reinfection is a constant problem. Surgical excision is recommended for persistent lesions.

Oral submucous fibrosis

Oral submucous fibrosis (Fig. 41.5) is a progressive disease in which fibrous bands form beneath the oral mucosa. These bands progressively contract so that ultimately opening is severely limited. Tongue movements may also be limited. The condition is almost entirely confined to Asians. Histologically it is characterised by juxta-epithelial fibrosis with atrophy or hyperplasia of the overlying epithelium which also shows areas of epithelial dysplasia. Paymaster in 1956 first discussed the precancerous nature of submucous fibrosis. He noted the onset of a slowly growing squamous cell carcinoma in one-third of such patients. The aetiology is obscure. Hyper­sensitivity to chilli, betel nut, tobacco and vitamin deficiencies have been implicated. Canniff has investigated the various enzyme components of the constituents of the ‘betel quid’, and has characterised some alkaloids and collagenases that may be responsible for the connective tissue changes which lead to epithelial atrophy and ultimate malignant degeneration. Tissue culture experiments have shown that alkaloids in the betel nut — particularly arecoline — stimulate collagen synthesis and the proliferation of buccal mucosal fibroblasts. Tannins also present in the betel nut stabilise the collagen fibrils and render them resistant to degradation by collagenase.

The scar bands of submucous fibrosis which result in difficulty in opening can be treated either by intralesional injection of steroids or by surgical excision and grafting, but this has little effect in preventing the onset of squamous cell carcinoma in the generally atrophic oral mucosa. Any aetiological factors should, of course, be eliminated.

Syphilitic glossitis

Prior to the antibiotic era, syphilis was an important predisposing factor in the development of oral leucoplakia and oral cancer. The syphilitic infection produces an interstitial glossitis with an endarteritis which results in atrophy of the overlying epithelium. This atrophic epithelium appears to be more vulnerable to those other irritants which cause oral cancer or oral leucoplakia. As these changes are irreversible there is no specific treatment, although active syphilis must be treated. Regular follow-up is essential. It should be noted that squamous cell carcinomas may arise in syphilitic glossitis even in the absence of leucoplakia.

Sideropenic dysphagia (Plummer—Vinson syndrome, Paterson—Kelly syndrome)

In 1936 Ahlbom showed the relation between sideropenic dysphagia and oral cancer. Sideropenic dysphagia (Fig. 41.6) is particularly common in Swedish women, and this accounts for the high incidence of cancer of the upper alimentary tract in this group and the higher incidence of women with oral cancer in Sweden. of women with oral cancer in Sweden, 25 per cent were sideropenic.

The pathogenesis of oral cancer in such patients may he similar to that of syphilitic glossitis. The sideropenic dysphagia leads to epithelial atrophy, which in itself is excessively vulnerable to carcinogenic irritants. Although the anaemia will respond to treatment with iron supplements, it is not known whether such treatment reduces the risk of subsequent malignant change. There have been some reports that in erosive or atrophic lichen planus (Fig. 41.7) there is a risk of malignant transformation. If there is an association between lichen planus and oral cancer the relation only exists with atrophic or erosive lichen planus. All patients with erosive or atrophic lichen planus should be carefully reviewed. Erosive lichen planus should be treated with topical steroids and, in severe cases, systemic steroids may be necessary.

Discoid lupus erythematosus

The oral lesions of discoid lupus erythematosus consist of circumscribed, somewhat elevated, white patches usually surrounded by a telangiectatic halo. Epithehial dysplasia may be seen on histological examination and this may lead to malignant transformation. Malignant change usually occurs in those lesions of the labial mucosa adjacent to the vermilion border, and occurs more often in men than in women. Such patients with discoid lupus erythematosus should be advised to avoid bright sunlight and when in the open air to apply an ultraviolet barrier cream to the lips.

Dyskeratosis congenita

This syndrome is characterised by reticular atrophy of the skin with pigmentation, nail dystrophy and oral leucoplakia. Eventually, the oral mucosa becomes atrophic and the tongue loses its papillae. Finally, the mucosa becomes thickened, fissured and white.