This article is based on an original article in Swedish which can be found here

BACKGROUND

Tobacco is a medicinal plant that was originally cultivated in Central and South America and arrived in Europe in the 14th and 15th centuries through Columbus's voyages to the West Indies. In its unburned form, tobacco contains several thousand chemical substances, and in its burned form, it contains an additional several thousand. When tobacco and/or tobacco smoke come into contact with the mucous membranes of the mouth, various changes occur. The specific chemical substances or factors, such as smoke temperature, that cause these changes are not fully understood. Tobacco or tobacco smoke primarily affects the different tissue layers of the mucosa through direct contact, but there may also be indirect effects through tobacco's impact on blood vessels, particularly concerning the supporting tissues of the teeth, the periodontium. Periodontal changes will not be discussed in this overview.

DIAGNOSES

The following clinical changes will be described:

• Leukoplakia
• Smoker’s palate
• Smoker’s melanosis
• Leukedema
• Snus-induced changes
• Chewing tobacco-induced changes

LEUKOPLAKIA

Prevalence

During the 1970s and 1990s, the prevalence was estimated to be between 2 and 4%. As tobacco smoking has decreased in Sweden, the prevalence is likely now under 1%.

Classification

Leukoplakia, the term means white patch, is a potentially malignant change (previously referred to as precancerous) where a distinction is usually made between idiopathic and tobacco-associated changes. Tobacco-associated changes constitute the majority of changes but are not as prone to develop into a malignant change as idiopathic ones. Leukoplakia is a diagnosis of exclusion, meaning a whitish change is assigned that cannot be identified as another specific whitish change. Homogeneous (Image 1) and non-homogeneous (Image 2) changes are typically identified, where homogeneous changes have a relatively even whitish surface, and non-homogeneous changes exhibit a whitish surface with red elements or a significantly uneven surface structure. Non-homogeneous changes have a greater tendency to malignancy than homogeneous ones.

Diagnosis

If there is uncertainty regarding the diagnosis, a biopsy can and should be taken. The tissue analysis looks for various degrees of dysplasia or even cancer.

Differential Diagnoses

• Lichen planus, especially plaque lichen
• Friction-induced white changes
• Etching-induced changes
• Snus-induced changes
• White sponge nevus
• Morsicatio buccarum
• Leukedema

Treatment

Primarily, efforts should be made to encourage the patient to reduce or preferably completely cease tobacco smoking. Leukoplakia may then decrease or completely disappear. If this does not occur, the change is monitored with monthly check-ups initially, followed by semi-annual or annual intervals. Color photographs can be advantageously used as comparative material. Should non-homogeneous structures in the form of erythema be present, homogenization often occurs after antifungal treatment, after which the patient is scheduled for follow-up as mentioned above for monitoring purposes. If the change increases in extent or if the erythema expands, a biopsy is taken. If dysplasia is detected, leukoplakia can be removed with a scalpel or with the help of laser or cryotherapy. The value of removing the change has been debated recently. Removal has shown to hardly affect the tendency to malignancy. However, removal may be justified for ethical-psychological reasons or to demonstrate an already existing malignancy.

Prognosis

Transformation to malignancy occurs in approximately 5% of cases over a 10-year period. The risk appears to be greater for idiopathic than for tobacco-associated leukoplakias and for those exhibiting non-homogeneity and/or epithelial dysplasia. Previously, changes on the tongue, floor of the mouth, and lips were considered most risky from a cancer development perspective. Recently published studies have questioned whether these parameters have any significant importance. Instead, the extent has been proposed as a potential risk marker.

SMOKER’S PALATE

There is no really good Swedish term. Previously, the term nicotine stomatitis was used, but it is inadequate since nicotine likely does not play a significant etiological role.

Prevalence

In earlier Swedish studies, the prevalence has been reported as 1-3%, but this figure is likely now significantly lower as tobacco smoking has markedly decreased in the population.

Diagnosis

The diagnosis is based almost exclusively on the clinical picture and is seen only in smokers. There is a uniformly increased degree of whiteness in the palate with red spots indicating inflamed ducts from salivary glands in the palatal mucosa. In advanced cases, small hyperplasias may be seen around the openings of the ducts.

Differential Diagnoses

• Dariers disease
• Change caused by frequent intake of hot beverages such as coffee or tea

Treatment and Prognosis

The change does not need treatment. If the patient quits smoking, it usually disappears within a few weeks. There is no risk of malignancy.

SMOKER’S MELANOSIS

Tobacco smoking seems to stimulate melanin production in the oral mucosa. The higher the tobacco consumption, the more common it is for the smoker to have smoker’s melanos.

Prevalence

1-3% in previous Swedish studies.

Diagnosis

Seen as brown hyperpigmentation primarily in the buccal gingiva of the lower front, but sometimes occurs in both the buccal and floor of the mouth mucosa.

Differential Diagnoses

• Addison's disease
• Drug-induced pigmentation – (antimalarial agents, cancer chemotherapy, etc.)
• Amalgam pigmentation

Treatment and Prognosis

The pigmentation does not need treatment. It slowly regresses if the patient quits smoking. However, this may take up to a couple of years.

LEUKEDEMA

A milky, white, and veil-like surface film primarily seen in the cheeks. The pathogenesis is not clarified. It is likely a normal condition. The film may possibly consist of fluid that seeps through the mucosa combined with a saliva-generated pellicle. Leukedema significantly increases with various types of mechanical or chemical influence. Primarily, a pronounced leukedema is seen in tobacco smokers, including those who smoke water pipes. However, it is not seen in snus users. Leukedema may also be prominent in those who chew on their mucosa, morsicatio.

Prevalence

Almost 50%. Over 70% in heavy smokers compared to under 40% in non-smokers.

Diagnosis

When the mucosa is stretched, the leukedema temporarily disappears only to almost immediately return when the mucosa regains its resting state.

Differential Diagnoses

• White sponge nevus

Treatment and Prognosis

No treatment is necessary. Leukedema likely decreases if the patient quits smoking or chewing on the mucosa.

SNUS-INDUCED CHANGE

Sweden may be the country in the world where the habit of using unburned tobacco (smokeless tobacco) is most widespread among the population. The sale of snus is not allowed within the EU, but Sweden has received an exemption in the EU tobacco directive, the latest from February 2015.

Prevalence

Almost 10% in the adult population, significantly more common among men than women.

Diagnosis

Clinically, a fairly varied picture is seen. Usually, a snus pouch is placed under the upper lip, less often inside the lower lip, inside the cheek, or under the tongue. Depending on how frequently the contact is between the snus and the mucosa, changes can range from a slight, wrinkled redness to a thick, furrowed whitish change. The change is more pronounced in those who use loose snus compared to those who use so-called portioned snus. The latter packaging has been available in Sweden for a few decades but has only been sold in increasing amounts over the last ten years, now surpassing the sales of loose snus. In addition to causing less pronounced damage to the mucosa, the use of the product results in less extensive damage to the gums. Loose snus causes such damage, gingival recessions, in up to 25%, while portioned snus causes it in just under 5%. A biopsy is rarely indicated but may occasionally be performed for various reasons (ulcer, patient’s request, etc.). Histologically, a vacuolated surface layer with an underlying acanthotic epithelium is seen, separated from the vacuolated layer by a demarcation zone/line. In the connective tissue, a mild to moderate chronic inflammatory picture is observed. Occasionally, homogeneous/hyaline connective tissue structures and atrophied gland packages may be found. Epithelial dysplasias are extremely rare.

Differential Diagnoses

• Damage caused by tobacco/nicotine-free snus
• Damage caused by regularly and long-term placing a tablet or other substance against the mucosa

Treatment

Withdrawal, although this is often very difficult to achieve. Nicotine dependence after using snus seems to be at least as great as with smoking, if not greater. To reduce damage to the mucosa and gums, the patient may be advised to change the application site from time to time. Loose snus users may be advised to switch to portioned snus.

Prognosis

If snus use ceases, the snus change regresses in most cases to a completely normal mucosa within a few weeks. For many years, the question of cancer development in snus-induced changes has been discussed. In several Scandinavian epidemiological studies, no correlation between snus use and oral cancer has been demonstrated. It has been pointed out that snus could cause cancer in the pancreas, but the scientific evidence for this is weak. Thus, while the cancer risk from snus use is extraordinarily low and epidemiological studies cannot demonstrate such a risk, it cannot be completely ruled out that one or a few isolated cases may occur, likely in individuals who have used loose snus for a long time.

CHEWING TOBACCO-INDUCED CHANGE

Prevalence

Approximately 0.3%.

Photo: Gunilla Andersson

Diagnosis

At the site where chewing tobacco is applied, a whitish veil-like change is seen, sometimes combined with an appearance similar to a mildly pronounced snus-induced change.

 Differential Diagnosis

• Leukedema
• Snus-induced change

Treatment and Prognosis

The change is likely to be significantly reduced if the habit ceases. No apparent risk for cancer development.

BETEL CHEWING-INDUCED CHANGE

Background

With ongoing globalization, several tobacco habits typical of countries other than Sweden can be seen among foreign-born patients. An example of changes caused by unburned tobacco/chewing tobacco is those seen with betel chewing. After regular daily chewing of a so-called betel pan (areca nut, slaked lime, and often tobacco wrapped in a betel leaf), discolored teeth and a "Betel chewer’s mucosa," which is a patchy reddish chewing injury in the cheeks (Image 11), can be observed. After many years of daily use, a condition known as submucous fibrosis may develop. This is characterized by a thin epithelium and underlying fibrotic connective tissue (Image 12). Dorsally in the buccal mucosa, fibrous bands may sometimes be palpated in advanced stages, significantly reducing the ability to open the mouth.

Treatment and Prognosis

Unfortunately, the changes are largely irreversible, although simpler forms may regress if the habit can be stopped. Submucous fibrosis is considered a potentially malignant change, and cancer development is not uncommon (Image 13).

REFERENCES

Andersson G. Snuff-induced changes associated with the use of loose and portion-bag-packed Swedish moist snuff. A clinical, histological and follow-up study.Thesis. Swed Dent J, Suppl 75, 1991

Axéll T. Munslemhinnan vid hälsa och sjukdom. Klinisk diagnostik och behandling. Gothia förlag 2009.ISBN 978-91-7205-654-1

Axéll T, Hedin CA. Epidemiologic study of excessive oral melanin pigmentation with special reference to the influence of tobacco habits. Scand J Dent Res 1982;90:434-42

Axéll T, Henricsson V. Leukoedema – an epidemiologic study with special reference to the influence of tobacco habits.Community Dent Oral Epidemiol 1981;9:142-6

Axéll T, Mølbach J. Oral mucosal lesions – Digital Tree Net. www.oralmedicine.se

Holmstrup P, Vedtofte P, Reibel J, Stoltze K. Long-term treatment outcome of oral premalignant lesions. Oral Oncol 2006;43:461-74

Salonen L, Axéll T, Helldén L. Occurrence of oral mucosal lesions, the influence of tobacco habits and estimate of treatment time in an adult Swedish population.J Oral Pathol Med 1990;19:170-6

Zain RB, Ikeda N, Gupta PC, Warnakulasuriya S, van Wyk CW, Shrestha P, Axéll TOral mucosal lesions associated with betel quid, areca nut and tobacco chewing habits: consensus from a workshop held in Kuala Lumpur, Malaysia, November 25-27, 1996.J Oral Pathol Med 1999;1:1-4.