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.
•
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
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.
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
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.
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.