Oral Cancer

What to look for

How Do We Recognise Oral Cancer?

A multitude of mucosal disorders, mostly benign anomalies may be found when screening the oral mucosa. This makes it difficult to make a diagnosis of cancer or a potentially malignant disorder unless the practitioner is familiar with the clinical presentation. Sometimes malignant lesions seen in the early stage may be mistaken for a benign change.

Key entities considered in this section to help the practitioner with a differential diagnosis are:

  1. Cancer

  2. Potentially malignant disorders. These are listed below:

    • Leukoplakia
    • Erythroplakia
    • Erythroleukoplakia
    • Lichen planus
    • Oral submucous fibrosis
    • Discoid lupus erythematosus
    • Tertiary syphilis
    • Actinic keratosis of lip

We describe here the key features and further illustrations can be found in the Diagnostic Atlas:

Clinical Presentations of Cancer of the Oral Cavity

Any ulcer of the mucosa (a break in the surface lining) that fails to heal within two weeks with appropriate therapy (eg. removal of a frictional source) and for which no other diagnosis can be established (eg. major apthous ulcer) should be suspected of a malignant ulcer until confirmed otherwise.

The second feature suggestive of a cancer is an exophytic growth. A new growth for which no local cause can be found should be considered cancerous.

Often these two features ulcer and growth are found to co-exist at presentation.

Pain (deeper in the mucosa), could be an early symptom that differentiates a malignant ulcer particularly in the absence of erythema and acute infection of the surrounding area.

Clinical Presentations of Potentially Malignant Disorders

Disorders of the oral mucosa that may progress to cancer with time but not frankly malignant at the time of presentation, may present in a number of ways. These are now referred to as Oral Potentially Malignant Disorders (OPMD). Their clinical signs are likely to be less obvious than those from established carcinoma.

Please select from the tabs to the left for more detailed clinical presentations.

Introduction

Oral cancer could develop in a variety of presentations in the mouth, the two common forms being either as an ulcer or a new growth.

Malignant ulcer

An ulcer is the key sign of malignancy, particularly when it is persistent and does not respond to simple therapies. Malignant ulcers have “rolled borders” as shown here (Figures 6 & 7).

New growth

A new growth for which there is no explanation (e.g. trauma from teeth or denture trauma) should also be suspected of cancer. This may be an exophytic growth of tissue that produces a lump with a smooth, lobulated or corrugated surface covering (Figure 8). Fungation is common, due to central necrosis of a rapidly enlarging mass which outgrows its blood supply (Figure 9).

Induration is the key clinical sign of malignancy. This means that the surrounding mucosa or base of the lesion on palpation is firm/hard. It is therefore important that all areas with a visual abnormality are palpated to exclude the presence or absence of induration.

Fixation – as a cancer spreads the mucosa may be fixed to underlying tissues, with loss of normal mobility. Thus the tongue may lose its mobility or there could be limited mouth opening.

Fig.6Figure 6. A squamous cell carcinoma presenting as an ulcer on the floor of the mouth
Fig.7Figure 7. An ulcer of the buccal mucosa with a granular appearance at the base and part covered by an exudate
Fig.8
Figure 8. A lobulated mucosal swelling with a speckled appearance anterior to the tumour
Fig.9
Figure 9. An exophytic growth on the lateral margin of tongue with an ulcerated necrotic area posteriorly

Unexplained tooth mobility

Unexplained tooth mobility not associated with periodontal disease or failure of a tooth socket to heal should be investigated by imaging. Unexplained pain or paraesthesia of lip/tongue with no apparent cause also requires referral to a specialist.

Similarly dysphagia for which no other diagnosis can be made should be considered suspicious.

White and red patches

Some white and red patches of the mucosa (Figures 10 & 11) are considered as potentially malignant disorders (see next section), but occasionally they may be the clinical presentation of a malignancy. In a large case series in the USA 6% of the biopsies which were histologically squamous cell carcinomas presented to the clinician as a simple white patch, suggesting the necessity to biopsy and investigation to exclude malignancy. Red patches in particular could be cancerous even at the time of first presentation. Presence of induration again should make one suspicious of malignancy.

Lymph nodes

Lymph nodes of the head and neck (Figure 12a) should always be palpated as part of the clinical examination by every dentist. Enlargement of one or more nodes presenting with a primary in the mouth may indicate metastasis, especially if hard or fixed to skin or deeper structures (Figure 12b). The precise group of nodes likely to be affected depends on the location of the primary cancer, but submandibular, then upper, middle and lower deep cervical nodes are most commonly involved with intra-oral lesions; these are often referred to as levels I-IV, level V being the posterior triangle of neck (Figure 12a).

The greater the size of the enlarged nodes and the number of node groups involved, the more serious is the prognosis for the patient. The lower the level in the neck (levels III-V), the more extensive is the spread (UICC 2002).

Fig.10Figure 10. An extensive white patch (leukoplakia) affecting the commisure and buccal mucosa. The central area shows erythema and superficial ulceration.
Fig.11Figure 11. A patch of leukoplakia on the ventrolateral margin of tongue
Fig.12aFigure 12a. A diagram of the neck illustrating where nodal metastasis may be situated
Fig.12b
Figure 12b. Lymphadenopathy associated with metastasis from a primary oral carcinoma

Leukoplakia

Leukoplakia (Figure 13) is the most common OPMD. The term leukoplakia has long been used rather loosely by clinicians specialising in oral, throat and even genital diseases. Dentists have tended to follow the WHO (1977) definition of leukoplakia as, ‘a white patch which cannot be rubbed off and cannot be characterised clinically or histologically as any other disorder’. It is now recommended that the term is used as a clinical descriptor of a white patch or plaque that cannot be diagnosed as otherwise, and is confirmed by histological information to exclude other possible disorders. A more recent definition from the WHO Collaborating Centre for Oral Cancer (2005) states: ‘The term leukoplakia should be used to recognize predominantly white plaques of questionable risk having excluded (other) known diseases or disorders that carry no increased risk for cancer’. It is recommended that the term leukoplakia is used as a clinical diagnosis, guided by the above definition.

Biopsy of such lesions is essential to establish diagnosis and to estimate the degree of epithelial dysplasia which has some value for predicting malignant potential.

A biopsy will indicate whether cancer is already present or not. Histology may lead to diagnosis of a specific lesion which can present as a white plaque, such as lichen planus, chronic candidiasis, or lupus erythematosis. The clinician should characterise tobacco-induced lesions and assist in differentiating these from the idiopathic white plaques in which no causal factor is evident from history or examination.

Leukoplakia appears as a predominantly white patch of slightly raised mucosa and plaque anywhere in the mouth (Figure 14). The mucosal surface may be smooth or cracked. In Western Europe, the floor of the mouth, lateral or ventral tongue, are high risk sites for oral leukoplakia.

An example of idiopathic keratosis (in a never smoker) presenting as a homogenous leukoplakia on the floor of the mouth and ventral surface of the tongue is shown in Figure 15. This being in an non-smoker, is considered a high-risk lesion.

Some leukoplakias have a white granular (nodular) surface. They may often be associated with Candida albicans infection (Figure 16).

A key to clinical diagnosis of oral leukoplakia is given by Warnakulasuriya et al. (2007).

Fig.13Figure 13. A white plaque on lateral tongue which by definition is a leukoplakia
Fig.14Figure 14. Leukoplakia of gingiva
Fig.15Figure 15. Sublingual keratosis – a patch of leukoplakia on the floor of mouth bordering ventral tongue
Fig.16Figure 16. Leukoplakia of oral commisure associated with candida

Erythroplakia

Erythroplakia appears as a well-defined fiery red, velvety patch of oral mucosa and situated 0.1-0.2 mm suppressed below the surrounding oral mucosa. While some have a smooth surface others may have a granular appearance, interspersed with white or yellow nodules. Often there is a well defined margin to this red patch. Erythroplakias are not wide spread and appear localised. Generally soft to palpation unless transformed to malignancy. Common sites are the buccal mucosa, mandibular gingiva and palate. Tongue is rarely affected by erythroplakia (Figure 18).

Erythroplakia has a greater malignant potential than leukoplakia. Histologically there are changes ranging from moderate to severe dysplasia to micro invasive squamous cell carcinoma in over 50% of ‘red patches’ diagnosed in specialist clinics.

Erythroleukoplakia

An erythroleukoplakia has combined red and white elements in the plaque together with an irregular surface texture, and is most commonly found in the oral commisures (Figure 19). It is synonymous with but has replaced the term speckled leukoplakia in the new WHO classification (2007).

Fig.17Figure 17. Red patch on palate; erythroplakia
Fig.18Figure 18. Erythroplakia of the tongue
Fig.19Figure 19. Erythroleukoplakia of the buccal commissure extending onto the buccal mucosa

Candidal leukoplakia

A candidal leukoplakia (Figure 16) is a hyperkeratotic lesion that is superficially infected by fungus, most commonly Candida albicans. The term can only be used after histological examination. Most so-called candidal leukoplakias are clinically erythroleukoplakias (speckled; Figure 19).

It is well established that the presence of fungi increases the long-term risk of malignant transformation. Appropriate anti-fungal therapy is therefore an important component of the management of such cases.

Verrucous leukoplakia

A verrucous leukoplakia is a white patch with a warty corrugated surface (Figures 20a & 20b).

Proliferative verrucous leukoplakia (Figure 21) is a white patch with a warty hyperplastic surface. Multiple and widespread leukoplakias are present in this condition. These tend to recur on removal. A very high proportion of patients develop oral cancer following the diagnosis of this condition.

Fig.20aFigure 20a. Thick white plaques with a corrugated surface – verrucous leukoplakia (verrucous carcinoma should be excluded in biopsy)
Fig.20bFigure 20b. Thick corrugated white plaques on labial alveolar mucosa spreading to sulcus
Fig.21Figure 21. Proliferative verrucous leukoplakia: widespread and multiple areas of keratoses of palate and gingiva

Verrucous Hyperplasia

A new entity referred to as Verrucous Hyperplasia has been described in Asian bete-quid chewers with a malignant potential. These are elevated plaques that are white or exophytic growths that are pink in colour.

Lichen planus

Lichen planus presents as keratotic striae; the characteristic reticular form is illustrated in Figures 22 and 23. The presentation is often bilateral. On the dorsal surface of the tongue lichen planus presents as white plaques (Figure 24). Erythematous lichen planus appears as atrophic, erosive red areas of the oral mucosa. When particularly affecting gingivae it is referred to as desquamative gingivitis.

Ulcerative lesions of lichen planus can occur on buccal mucosa or lateral tongue and are often associated with surrounding keratotic striae.

Ulcerative areas cause pain and discomfort to the patient, especially upon contact with acidic or spicy foodstuffs. Ulcerative lichen planus must be treated for symptoms.

Lichen planus in whatever form (reticular, ulcerative or plaque form) should be monitored regularly (at least annually) as a small proportion of patients may develop oral cancer.

Recent evidence suggests that lichenoid contact lesions (associated with dental amalgam restorations) may also carry an increased risk of malignancy.

Fig.22Figure 22. Reticular lichen planus
Fig.23Figure 23. Reticular lichen planus
Fig.24Figure 24. Plaque-type lichen planus

Fig.25Figure 25. Oral submucous fibrosis

Oral submucous fibrosis

Oral submucous fibrosis (OSF) (Figure 25) presents as a loss of elasticity of the mucosa, with fibrous bands causing limitation of opening of the mouth. Early signs may include blanching and stiffening of the mucosa and a leathery feeling.

A burning sensation in the mouth or throat may be an early symptom. The tongue shows loss of papillae, firmness and a lack of mobility. This condition is found exclusively in Asian and Taiwanese patients who chew areca nut, whether chewed alone or as a component of quids with or without tobacco. Prevalence of OSF is increasing in Asian or Chinese communities due to the availability and use of betel quid in commercially packaged freeze-dried forms (pan masala/gutkha).

Hundreds of thousands of people suffer from this condition worldwide, particularly in south Asia and in immigrant communities from that region. A large reservoir of undetected disease exists amongst Asian populations who chew areca products. It has one of the highest rates of malignant transformation amongst potentially malignant oral disorders.

Fig.26Figure 26. Discoid lupus erythematosus

Discoid lupus erythematosus

Discoid lupus erythematosus of the oral mucosa may or may not be associated with skin lesions elsewhere on the body. Oral lesions appear as an area of atrophy or erosion, surrounded by a white keratotic halo (Figure 26).

Soreness is often present. This is an uncommon condition but when present, the buccal mucosa palate, and lips are most likely to be involved. Biopsy of a representative site is essential to confirm the diagnosis, coupled with haematological examination to exclude systemic lupus erythematosus (SLE). Most patients will be found to have a raised anti nuclear antibody titre in their serum. There is little quantitative information on the risk of malignant transformation, but most reports of cancer development in cases with DLE often involve the lips.

Fig.27Figure 27. Syphillis

Syphilis

Syphilis is seen less frequently these days because the earlier stages are amenable to treatment with antibiotics. Nevertheless syphilis is still a common disease worldwide. The keratotic plaque of tertiary syphilis appears on the dorsum of the tongue and may occasionally be associated with the development of oral cancer at this site (Figure 27). Special investigations to detect Treponema pallidum organisms and serological tests are essential to establish a diagnosis.

Actinic keratosis

Actinic keratosis may be characterised by atrophy, erosion and white or brown crusting of the vermilion of the lower lip. It is caused by exposure to ultraviolet light, particularly from strong sunlight. This condition and cancer of the lip itself are thus more common in outdoor workers such as fishermen and farmers, particularly in latitudes close to the equator, and in those with fair complexions. Within Europe, the prevalence of this condition is high in Southern Spain. Avoidance of sunburn and chronic exposure by the wearing of broad-brimmed hats and the use of topical sunscreens should be advised.

The world is experiencing an epidemic of skin cancer, particularly malignant melanoma due to an over exposure to sun.

Mucosal atrophy

Mucosal atrophy is often a feature with pallor as a clinical sign and may be associated with malignant change in the oral cavity and pharynx. The condition may predispose to candidiasis and ulceration of the oral mucosa. Paterson Kelly (Plummer-Vinson) Syndrome is the combination of iron deficiency anaemia with dysphasia and glossitis. Spooning of finger nails (koilonychia) may be seen. Indeed, correction of anaemia whatever its type, and of any other nutritional deficiencies present in the patient, is a fundamental aspect of management.

What to look for during surveillance

High risk oral leukoplakias and erythroplakias are generally excised (by surgery or laser) as part of their management. Those of low risk (mild or no dysplasia on biopsy) are carefully followed up. During follow up it is important to look for any new changes such as redness, ulceration or development of exophytic areas. Examples of malignant changes seen in existing leukoplakias during follow-up are shown in Figures 28 and 29. It is important to carefully establish follow-up intervals, appropriate to the risk status of the case.

Fig.28Figure 28. Gingival carcinoma on a patch of verrucous leukoplakia

Fig.29

Figure 29. Carcinoma developing on an existing patch of leukoplakia of the buccal mucosa detected at follow up

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