|Year : 2004 | Volume
| Issue : 2 | Page : 58-68
Oral leukoplakia (leukokeratosis): Compilation of facts and figures
Department of Oral Pathology, Government Dental College, Trivandrum, India
Department of Oral Pathology, Government Dental College, Dental Wing - Medical College, Trivandrum - 695 011
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Rajendran R. Oral leukoplakia (leukokeratosis): Compilation of facts and figures. J Oral Maxillofac Pathol 2004;8:58-68
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Rajendran R. Oral leukoplakia (leukokeratosis): Compilation of facts and figures. J Oral Maxillofac Pathol [serial online] 2004 [cited 2020 Apr 3];8:58-68. Available from: http://www.jomfp.in/text.asp?2004/8/2/58/40968
| Precancerous Lesions and Conditions|| |
Cancer being a genetic disorder involves multiple alterations of the genome progressively accumulated during a protracted period, the overall effects of which surpasses the inherent reparative ability of the cell. In the course of its progression, visible physical changes are taking place at the cellular level (atypia) and at the resultant tissue level (dysplasia). These alterations include genetic changes. epigenetic changes, surface alterations, and alterations in intercellular interactions. The sum total of these physical and morphological alterations arc of diagnostic and prognostic relevance and is designated as 'precancerous' changes. In many situations, the relationship between these changes and the progression towards neoplasia is not understood. Nevertheless, it seems probable that these changes are ultimately involved in driving cells further along the path to neoplastic transformation.
The diagnosis of precancers is primarily based on morphology and its grading on histology (dysplasia). Despite the fact that this estimation is subjective and therefore carries a low prognostic value of an impending malignancy, is still widely practiced to assess the risk of malignant potential of such lesions. Because of this inherent discrepancy, such lesions may well be designated as potentially malignant.
A premalignant phase in the development of oral cancer is predicated by the classic model of experimental epithelial carcinogenesis. Virtually all oral squamous cell carcinomas arise from a premalignant precursor, but it is difficult to specifically define the term premalignant. Oral pathologists use the term epithelial dysplasia to indicated microscopic features in a biopsy specimen that are associated with a risk of malignant change and then assign a grade of severity. There is good correlation between higher grades of dysplasia and increasing risk of cancer but less so with the lower grades.
| Definitions|| |
A morphologically altered tissue in which cancer is more likely to occur than in its apparently normal counterpart (WHO 1972). Examples of precancerous lesions are leukoplakia and erythroplakia.
A generalized state associated with a significantly increased risk of cancer. Examples of precancerous conditions arc sidcropenic dysphagia, submucous fibrosis and possibly, lichen planus.
The histologic connotation to premalignancy is marked by aberrant and uncoordinated cellular proliferation depicted basically at cellular level (atypia), reflections of which could he discerned at tissue levels too (dysplasia), Frequently it is the forerunner of cancer, the causation of this twilight zone in cellular transformation is by no means clear. Dysplasia is encountered principally in the epithelia. 'It comprises a loss in the uniformity of the individual cells, as well as a loss in their architectural orientation'. Dysplastic cells exhibit considerable pleomorphism (variation in size and shape) and often possessed deeply stained (hyperchromatic) nuclei, which are abnormally large for the size of the cell. The nuclear: cytoplasmic ratio increases from 1:4 to 1:1, at the expense of the cytoplasmic volume. Mitotic figures are more abundant than usual, although almost invariably they conform to normal pattern. Frequently, the mitoses appear in abnormal locations within epithelium and may appear at all levels rather than their usual basal location. The usual proliferative organization of the epithelium is lost and is replaced by a disorderly arranged scrample of cells with varying degrees of differentiation arrest.
'Dysplasia is characteristically associated with protracted chronic irritation or inflammation', of which oral cavity is a common site. Due to its peculiar anatomic location and its constant presence of endogenous and exogenous micro-organisins, a sustained state of chronic subclinical infection is maintained at the oral cavity. Overlying physical trauma consistently inflicted to the oral mucosa compound the existing situation.
"Dysplasia is reversible, and therefore presumably, a controlled, cellular proliferation. When the underlying inciting stimulus is removed, the dysplastic alterations revert to normal". However, this is an important and significant cellular change discerned at the morphological level which caution its likelihood of subsequent neoplastic transformation. The line of demarcation when the cell surpass the point of no return is rather faint and the underlying mechanism poorly defined. In short, dysplasia giving rise to neoplasia is akin to the cellular changes in response to a noxious stimulus. As it is evident, it transverses the stage of cellular adaptation, reversible damage, and finally irreversible cell death. When a susceptive cell is exposed to a carcinogen it probably tries to adapt to it, depending on the extent and duration of stimuli. An increase in cell proliferation, diminishing the cytosolic volume and the associated organellar load, could be an attempt in this direction. In the context of oral epithelium, an accelerated growth phase depicted by broadening the progenitor compartment (hyperplasia) is the earlier sequel of exposure to an irritant. When the irritant persists, the epithelium shows features of cellular atrophy, again a well characterized feature of adaptation (atrophy). At a later stage, when the stages of adaptation and reversible cell damage surpass, the cells progressively slip into a stage of irreversible cell damage: manifesting either as cell death or neoplastic transformation. It appears that some mysterious line is crossed, whereby dysplastic cells escape the normal homeostatic controls and assume the autonomy of a tumour cell. The accelerated pace of cell division noted at the earlier stages of transformation as part of an adaptive response (to replace the damaged cell pool) in a way facilitates the accumulation of further genetic damage, thereby driving the cells further along the path of transformation. As is apparent from the foregoing discussion, there is considerable overlap between the stages of cellular adaptation, reversible cell damage, and atypia. Precise morphologic and genetic criteria delineating this line of demarcation between atypia (reversible damage) and neoplasia is unfortunately unknown and is the scope of the study of tumor biology.
Proliferative organization of oral epithelium
Advances in our understanding of the proliferative organization in oral epithelium has been a slow process for several reasons. These include a lack of suitable experimental models to test hypotheses, difficulty in extrapolating from other renewing cell systems, and the need for new investigative techniques (W. J. Hume 1991). The earlier, rather mechanistic, concept envisages a uniform progenitor compartment occupying the basal layer, retained in a state of sustained replication readiness with roughly equal cell cycle times and their migration towards the surface layers, simply by physical process of forward push induced during waves of cell division. Experimental work to elucidate this underpinned these concepts and radical revisions are made (Leblond et al 1964).
Between 1969 and 1975, a number of workers showed that these concepts were too simple, which suggested that a complex pattern of migration from the basal layer to the surface had to occur to maintain this highly ordered and non-random cell stacking. This in turn focused attention on the pattern of cell proliferation in the basal layer and led to the concept of the existence of a number of proliferative sub-populations, of which the stem cell population seemed to be of particular importance for tissue homeostasis and disease. This concept envisages that not all cells in basal layer can divide, that a number are instead already differentiating, that cells capable of division comprise a number of sub-populations and finally, that cell migration is not caused by cell proliferation pressure but is an independent biological process.
The use of oral epithelium as a model for the investigation of the behaviour of proliferative subpopulations followed on from the work that had already begun in rodent skin. It is also true that because of its particular morphological structure and marked circadian (diurnal) variation in cell proliferation, it has contributed significantly to the development of an integrated cell proliferation model applicable also to bone marrow, intestine, testis, nematodes and also to developmental situations (W. J. Hume 1991).
| Leukoplakia (Leukokeratosis)|| |
Leukoplakia (white patch) is the most common potentially malignant lesion of the oral mucosa. However, its usage should be limited exclusively to the clinical context by the exclusion of other lesions, which present as oral white plaques. Such lesions are lichen planus (hypertrophic), chronic cheek bite (morsicatio), frictional keratosis, tobacco - induced keratosis (nicotine stomatitis), leukoedema, and white sponge nevus. When a biopsy is taken, the term leukoplakia should be replaced by the diagnosis obtained histologically. In other words, leukoplakia denotes a negative diagnosis obtained histologically. In other words, leukoplakia denotes a negative diagnosis based on exclusion criteria. It represents an area localized in distribution, hyperkeratotic in nature, and white in appearance due to wetting of the keratotic patch while in contact with saliva. It should be stressed that the diagnosis of leukoplakia denotes mainly, that (a) the mucosa is irritated by either mechanical, chemical or galvanic means and (b) the mucosa is trying to adapt to the noxious stimuli by undergoing hyperkeratinisation of its surface. Since leukoplakia is an adaptive response, offered by a viable and healthy oral mucosa against some forms of sustained, low-grade irritant, it is irrational to consider it as a disease entity (hence its assumption of a negative diagnostic state).
Definition and terminology
Oral leukoplakia has recently been redefined as "a predominantly white lesion of the oral mucosa that cannot be characterized as any other definable lesion; some oral leukoplakia will transform into cancer" (Axell T. 1996). A provisional diagnosis is made when a lesion at clinical examination cannot be clearly diagnosed as any other disease of the oral mucosa with a white appearance. A definitive diagnosis is made when it is histopathologically examined. The term preleukoplakia is sometimes used when the whiteness is not very distinct and should not be confused with leukoedema (a hereditary malformation of the oral mucosa).
Definable white lesions
(a) Hyperplastic candidiasis (Candidal leukoplakia) When dealing with a hyperplastic epithelial lesion in which the presence of candida albicans is demonstrated, it is referred to as candida-associated leukoplakia or others prefer the term hyperplastic candidiasis. In the absence of clinical response to antifungal treatment, it seems preferable to consider such lesion as leukoplakia. (Vander Waal, 1997).
(b) Hairy leukoplakia (Greenspan lesion)
The term hairy leukoplakia is a misnomer due to several reasons. First of all, hairy leukoplakia is a definable lesion. Furthermore, the lesion is not premalignant in nature. Therefore the use of the term should be abandoned. As an alternative, the term "Greenspan lesion" has been suggested.
(c) Tobacco-induced white lesions
Smoker's palate (leukokeratosis nicotina palati), palatal keratosis in reverse smokers, and snuff dippers lesions are clearly related to tobacco use and, therefore, are usually listed as "tobacco-induced lesions". These lesions are being regarded as "definable lesions" and are traditionally not described as leukoplakia. Nevertheless, some of these lesions may transform into cancer.
(d) Tobacco-associated leukoplakia
The aetiological rote of tobacco in patients who smoke cigarettes, cigars or pipes is less obvious. Therefore, preference has been given to the term "tobaccoassociated leukoplakia" (leukoplakia in smokers) over the term "tobacco-inducted white lesions".
(e) Idiopathic leukoplakia
One also recognizes non-tobacco associated leukoplakia (leukoplakia in non smokers), often referred to as idiopathic leukoplakia.
As a premalignant / potentially malignant lesion
In two studies from India (Gupta PC et al 1980, Silvennan S et al 1976), rather low annual malignant transformation rates of oral leukoplakia have been reported, 0.3% and 0.06% respectively. In reports from Western Countries, usually based on hospital material, some what higher figures have been mentioned (Axell T 1987). One must take into account, when studying precentages of malignant transformation rates of oral leukoplakia
(a) The length of observation period
(b) The type of study population
(c) The therapeutic approach.
On the basis of the lowest reported annual malignant transformation rate of oral leukoplakia, it can be calculated that patients with oral leukoplakia carry a 5fold higher risk of developing oral cancer than controls. Recently the role(s) of dietary factors in determining the precancerous nature of oral leukoplakia among tobacco habitues revealed interesting results (Gupta PC et al 1998).
A population based case control study in the Bhavnagar District, Gujarat, India estimated nutrient intake in blinded, house-to-house interviews. Among 5018 male tobacco users, 318 were diagnosed as cases. An equal number of controls matched on age (± 5 years), sex, village, and use of tobacco were selected. Odd ratios (OR), a measure of the relative risk of malignant transformation of individual lesions were calculated from multiple logistic regression analysis controlling for relevant variables (type of tobacco use and economic status), a protective effect of fibre was observed for both oral submucous fibrosis (OSF) and leukoplakia; with 10% reduction in risk per g day (p<0.05). Ascorbic acid (vitamin C) appeared to be protective against leukoplakia with the halving of associated risk of malignant transformation (OR=0.46; p<0.10). It is apparent that in addition to tobacco use, intake of specific nutrients and their deficiency may have a role in the development and progression of oral precancerous lesions.
The prevalence of this lesion in Ernakulam District, Kerala, India was 17 per 1000; it was higher (61 per 1000) among people with mixed habits. The annual age adjusted incidence rate was 2.1 per 1000 among men and 1.3 per 1000 among women; the highest incidence (6.0 per 1000) was among men who both chewed and smoked. In an adult Swedish population, a 3.6% prevalence rate was recorded (Axell T 1976). Almost all leukoplakia in India occur in tobacco users. A definite dose-response relationship between leukoplakia and various forms of tobacco use in this area has been demonstrated. The dose-response relationship was stronger for smoking habit than for chewing habit and remained significant after taking account of age, sex and type of tobacco habit.
Age and Gender
The onset of leukoplakia usually takes place after the age of 30 years; resulting in a peak incidence above the age of 50 years. The gender distribution in most studies varies, ranging from a strong male predominance in different parts in India, to almost 1: 1 in the western world.
Leukoplakia occurs more frequently in smokers of tobacco than in non-smokers. There is a dose-response relationship between tobacco usage and the prevalence of oral leukoplakia. Reducing or cessation of tobacco use may result in the regression or disappearance of oral leukoplakia (Gupta et al 1995). On the other hand, disappearance of oral leukoplakia has occasionally been reported in patients who continued to smoke (Silverman and Rozen 1968). Tobacco was most often chewed as an ingredient in betal quid (smokeless tobacco) in India (Pan). The pan chewers lesion consists of a thick, brownish-black encrustation on the buccal mucosa at the site of placement of betal quid. It is often seen in heavily addicted betal quid chewers. It could be scraped off with a piece of gauze (leukoplakia?); it regresses spontaneously when the habit is discontinued. Due to these reasons the pan chewers lesion doesn't deserve the designation - leukoplakia. This is a specific entity and rarely progresses to leukoplakia. Whether the use of alcohol by itself is an independent actiological factor in the development of oral leukoplakia, is still questionable. Its effect, at best, may be synergistic to other well known aetiological factors (physical irritants). The role of Candida albicans as a possible aetiological factor in leukoplakia and its possible role in malignant transformation is still unclear. About 10% of oral leukoplakia satisfy the clinical and histological criteria for chronic hyperplastic candidiasis (candidal leukoplakia). Epithelial dysplasia is reported to occur four to five times more frequently in candida leukoplakia than in leukoplakia in general. However, this change is more common in the speckled variant than in homogeneous leukoplakia and carcinomatous change is more a characteristic of the speckled lesion than that of candidal super-infection. Various evidence has been presented to justify an aetiologic role for candida in neoplastic transformation, which includes among others the catalytic transformation in-vitro of the carcinogenic nitrasamine, N-nitrosobenzyl-methylamine, by stains of C. albicans demonstrated to be selectively associated with leukoplakia. The possible contributory role of viral agents (human papillorna virus strains 16, 18) in the pathogenesis of oral leukoplakia has also been discussed, particularly with regard to exophytic verrucous Ieukoplakia (Palefsky JM et al 1995). In a study from India, serum levels of vitamin A, B12, C, betacarotene, and folic acid were significantly decreased in patients with oral leukoplakia compared to controls, whereas, serum vitamin E was not (Ramaswamy G et al 1996). Relatively little is yet known with regard to possible genetic factors in the development of oral leukoplakia.
Preleukoplakia is defined as a low grade or very mild reaction of the oral mucosa, appearing as a grey or greyish-white, but never completely white area with a slightly lobular pattern and with indistinct borders blending into the adjacent normal mucosa (Pindborg et al 1968).
It is desirable to record separately the various forms of leukoplakia and for this purpose, the following subdivisions are recommended (WHO 1980):
Lesions that are uniformly white.
Lesions in which part of the lesion is white and rest appears reddened.
Alternatively, a more elaborate sub-division may be used such as:
(b) Furrowed (fissured)
2. Non-homogeneous nodulo - speckled
Well demarcated raised white areas, interspersed with reddened areas. When recording leukoplakia, space has been allowed in the recording form for three different sub-divisions:
1. Homogenous - Smooth and fissued
2. Homogenous - Ulcerated
3. Non homogenous - nodulo-speckled
(Adapted from Community Dentistry and Oral Epidemiology 1980; 8: 1-26).
The adjective non-homogeneous is applicable both to the aspect of colour i.e. mixture of white and red changes (erythroleukoplakia) and to the aspect of texture i.e exophytic, papillary or verrucous. With regard to the latter lesions, no reproducible clinical criteria can be provided to distinguish proliferative verrucous leukoplakia from the clinical aspect of verrucous hyperplasia or verrucous carcinoma. The homogenous type is usually otherwise asymptomatic, whereas the non-homogeneous (mixed white and red) leukoplakia are often associated with mild complaints of localized pain or discomfort. In the presence of redness or palpable induration, malignancy may already be present.[Figure 1],[Figure 2],[Table 1]
Proliferative verrucous leukoplakia and its related lesions
Proliferative verrucous leukoplakia (PVL) and verrucous hyperplasia (VII) are two related oral mucosal lesions. The terms, however, are not clinically or pathologically interchangeable. The term PVL is preferably a clinical one, but the diagnosis of VH, on the otherhand, must be made histologically.
First described by Hansen et al in 1985, PVL continues to be yecognizcd as a particularly aggressive form of oral idiopathic leukoplakia that has a considerable morbidity and a strong potential for malignant transformation Diagnosis is often made late in the protracted course of PVL with the disease in an advanced stage when it is especially refractory to treatment. Within the histologic spectrum that is seen in PVL, usually as a function of time, are: (1) verrucous hyperplasia (VH), a histologically defined lesion, (2) varying degrees of dysplasia, and (3) three forms of squamous eel: carcinoma: verrucous, conventional and according to some, papillary squamous cell carcinoma.
This is a forerunner of verrucous carcinoma [Figure 2] and the transition is so consistent that the hyperplasia, once diagnosed, should be treated like verrucous carcinoma.[Figure 3]
It should be emphasized that leukoplakia is a clinical term, and its use carries no implications with regard to the histological findings. However, it is recommended that a histological report should always include a statement on the presence or absence of epithelial dysplasia and, if present, the assessment of its severity. The hallmark of the histopathological aspects of leukoplakia are epithelial hyperplasia and surface hyperkeratosis. Epithelial dysplasia, if present, may range from mild to severe. In some instances, carcinoma in situ and even squamous cell carcinoma are encountered histologically. The various cellular changes that may occur in epithelial dysplasiaare listed in the [Table 1].
The clinical significance of human papilloma virus - associated epithelial dysplasia, so called koilocytic dysplasia remains to be investigated. The term lichenoid dysplasia is sometimes used when the dysplastic epithelium may show features that to some extent resemble those of lichen planus. The term chevron type of keratinisation is used when it is associated with use of tobacco. Micro-abscesses may be observed in the superficial layers of the epithelium in the presence of C. albicans and inflammatory cell infiltration is commonly seen. Some of the exophytic, verrucous or papillomatous lesions, inspite of the absence of epithelial dysplasia, may in time progress to squamous cell carcinoma and then long term follow-up should be considered. The final diagnosis of a white lesion of the oral mucosa can often only be made through a close dialogue between the clinician and the pathologist. Even then, cases may remain unsettled.
Grading of epithelial dysplasia
Epithelial dysplasia is usually assessed subjectively and considerable inter-observer variability exists in its interpretation. What is lacking in this exercise is principally objectivity and lack of reproducibility. A consensus decision is, by and large, adopted in the management of individual lesions and based on the presence of dysplastic features, epithelial dysplasia is usually divided into three categories; mild, moderate, and severe. It is recommended that the histological report of a leukoplakia should include a statement on the absence or presence of epithelial dysplasia and an assessment of its severity. The practical value of the grading of epithelial dysplasia is questionable. Although leukoplakia with moderate or severe epithelial dysplasia show a greater disposition for malignant transformation than in the absence of dysplastic features, carcinomatous transformation may also take place in non-dysplastic leukoplakias.
A modified classification and staging system for oral leukoplakia
A proposal for a modified classification and staging system for oral leukoplakia (OLEP) has been presented by van der Waal et al 2000 in which the size of the leukoplakia and the presence or absence of epithelial dysplasia are taken into account. Altogether four stages are recognized.
(L Size of leukoplakia)
L 1 - size of leukoplakia is < 2cm
L2 - size of leukoplakia is 2 - 4 cm
L3 - size ofleukoplakiais>4cm
Lx - size ofleukoplakia is not specified.
(P - Pathology)
PO - No epithelial dysplasia
P1 - Distinct epithelial dysplasia
Px - Dysplasia not specified in pathology report
OLEP Staging System
Stage I - L 1 PO
Stage II - L2 PO
Stage III - L3 PO or L1 L2 PI
Stage IV - L3 P 1[Table 2],[Table 3]
The proposed system should facilitate uniform reporting of treatment or management results of OLEPs in which a biopsy has become available. The system can easily be adjusted by replacing the histopathological criteria of epithelial dysplasia by a clinical sub-division in homogeneous and non-homogeneous leukoplakia for cases in which no biopsy is available. It also could serve as a means for epidemiological studies. It has yet to be shown whether such staging system may also be helpful in providing guidelines for the management of oral leukoplakias.
Elimination of possible cause(s)
The clinician should first try to rule out any of the definable white lesions before accepting a definitive clinical diagnosis ofleukoplakia.
In homogeneous leukoplakia, the value of histological examination might to some extent be questioned. The occurrence of epithelial dysplasia is rather low in this clinical subtype, as is the risk of future malignant transformation. But this cannot be taken as the dictum in all cases since atleast in few cases it proves to be otherwise. Therefore, the taking of a biopsy in homogeneous leukoplakia should be the standard rule. If treatment consists of C02 - laser evaporation, it is mandatory to have a biopsy taken prior to such treatment. In non-homogeneous leukoplakia, biopsy should be taken at the site of symptoms, if present, and / or at a site of redness or induration. Diagnostic methods other than histological examination, such as the use of toluidine blue staining or Lugol's iodine and exfoliative cytology are of limited value when dealing with leukoplakia.
Apart from the surgical excision, various treatment modalities are available, such as cryosurgery, C02 - laser surgery, retinoids and other drugs, and recently photodynamic therapy. The last is a rather recent application with regard to oral leukoplakia, therefore does not deserve comment on long term results.
This overview demonstrates that tobacco smoking and betal-quid chewing are detrimental to oral health, as they are strongly associated with oral leukoplakia, oral cancer, and other mucosal pathologies. In view of these findings, specific studies for primary and secondary prevention of these lesions are warranted. Prevention was found to be feasible and effective (Gupta et al 1980) by timely diagnosis and management of oral precancerous lesions like leukoplakia and by measures like habit alleviation. Effort in this direction will take us a long way in to the overall control and management of potentially malignant oral mucosal lesions.
| Erythroplakia (Erythroplasia)|| |
Whilst leukoplakia is a relatively common condition, crythroplakia is rare. In contrast to leukoplakia, crythroplakia is almost always associated with premalignant changes histologically and is therfore a more important precancerous lesion. The term crythroplakia is used analogously to leukoplakia to designate lesions of the oral mucosa that present as bright red velvety plaques which cannot be characterized clinically or pathologically as due to any other condition. Just as there are many oral lesions that present clinically as white patches on the mucosa, so there are a number of conditions that appear as red areas. These include some dermatoses, inflammatory conditions due to local infection, or a more general subacute or chronic stomatitis associated with the presence of dentures, tuberculosis, fungal infection, and other conditions. Some red plaques prove to be early squamous cell carcinomas. The red patches that cannot be classified in any of these classes fall into the group of Erythroplakia (a negative diagnosis - refer leukoplakia). The term erythroplasia was originally used by Queyrat to describe a precancerous red lesion that develops on the penis. Oral erythroplakia is clinically and histopathologically similar to the genital process. Whereas red lesion of the oral mucosa have been noted for many years, the use of the term erythroplakia in this context was scanty. Erythroplakia lesions are easily overlooked and the true prevalence of the condition is not known. This blatant under-reporting probably reflects that fact that leukoplakias are more likely to be biopsied and emphasizes the lack of appreciation of the significance of erythroplakia clinically. Several clinical variants of erythroplakia have been described by different investigators, but there is no general agreement on the classification. Shear (1972) described homogenous erythroplakia, erythroplakia interspersed with patches of leukoplakia, and granular or speckled crythroplakia (the last category identical to speckled leukoplakia). The suggestion has also been made to change the term speckled leukoplakia to speckled erythroplakia, to emphasize the frequency with which this particular lesion is associated with cellular atypia. Many of these lesions are irregular in outline, and some contain islands of normal mucosa within areas off erythroplakia, a phenomenon that has been attributed to coalescence of a number of precancerous foci. The high rate of premalignant and malignant changes noticed of crythroplakia is true for all clinical varieties of this lesion and not solely a feature of speckled erythroplakia. Different studies have demonstrated that 80% to 90% of erythroplakias are histopathologically either severe epithelial dysplasia, carcinoma-in-situ, or invasive carcinoma. Erythroplakia has no apparent sex predilection; most cases reported have occurred in the sixth and seventh decades. The aetiology of erythroplakia is unknown, although it seems likely that smoking and alcohol abuse are important aetiological factors.
The epithelium shows a lack of keratin production and often is atrophic, but it may be hyperplastic. This lack of keratinization, especially when combined with epithelial thinness, allows the underlying microvasculature to show through, thereby causing the red colour. The underlying connective tissue often demonstrates chronic inflammation. Differentiation of erythroplakia with malignant change and other early squamous cell carcinomas from benign inflammatory lesions of the oral mucosa can be enhanced by use of 1% toluidine blue (tolonium chloride) solution applied topically with a swab or as an oral rinse. This technique gives excellent results in detecting epithelial dysplasia with falsenegative (under-diagnosis) and false prositive (overdiagnosis) rates of well below 10%.
It should follow the same principles outlined for leukoplakia. Observation for one to two weeks following elimination of suspected irritants is acceptable. Prompt biopsy is thereafter mandatory for lesions that persist. Surgical excision gives excellent results and a recurrences rate of less than 5% is reported.
Classification of oral mucosal lesions on different habits, can be grouped broadly as shown below
Predominently associated with smoking
Leukokeratosis nicotina palati
Central papillary atrophy of tongue
Predominantly associated with chewing
Pan chewers lesion
Oral lichen planus - like lesion
Oral submucous fibrosis
Associated with smoking and chewing (mixed habit)
Leukoplakia and Pre-leukoplakia
Oral lichen planus
Oral squamous carcinomas
| Leukoedema|| |
This is a chronic mucosal condition in which the oral mucosa has a grey, opaque appearance. When the mucosa is stretched the lesion disappears, only to reappear when it is relaxed.
A large population based survey conducted in Ernakulam District of Kerala among 10,287 villagers ages 15 years and over, selected by random sampling recorded a prevalence of 0.4%. About 16 (62%) and the 26 leukoedema were seen among bidi smokers and the rest in people who smoked and chewed (Mehta FS et al 1971). The annual age-adjusted incidence rate of this lesion was 2.5 per 1000; it was 3.8 per 1000 among smokers.
Leukoedema was characterized by accumulation of spongy vacuolated cells (intracellular oedema) in the superficial epithelial layer, with pyknotic nuclei.
Ballooning of cells in the stratum spinosum and epithelial hyperplasia with broad and elongated rate ridges are seen. The epithelial surface is frequently parakeratinized but without cellular atypia.
Of the 87 leukoedemas followed-up over a 10 year period, 64% remained stationary and 32% regressed; no malignant transformation was observed. (Gupta PC et al 1980).
| Leukokeratosis Nicotina Palati|| |
This lesion which is commonly seen among conventional smokers consists of a grayish-white palate with small nodular excrescences having small central red spots corresponding to the inflamed orifices of the minor salivary glands (Murti et al 1992).
The prevalence of this lesion among Indians was 0.3%; 52% of the 31 lesions occurred among bidi smokers (Mehta ES et al 1971). The annual age adjusted incidence rate among smokers was 1.7 per 1000; it was 0.7 per 1000 in those who smoked and chewed (Gupta PC et al 1950).
Over a longer period 66% of the 44 lesions remained stationary, 34% regressed spontaneously and none showed malignant transformation. Palatal changes in reverse smokers (smoke with the burning end of a cigar / cigarette within the oral cavity) on the other hand must be distinguished from this lesion and are multi-morphic and pre-cancerous, whereas leukokeratosis nicotina palati exhibits neither great variability nor malignant transformation.
| Palatal Changes Associated with Reverse Smoking|| |
Reverse chutta (crude form of cigar) smoking practised especially among females of Srikakulam District of Andhra Pradesh, recorded prevalence of 8.8% of leukoplakia, 4.6% pre-leukoplakia and 17.9% leukokcratosis nicotina palati (Daftary et al 1992). Palatal involvement was noted in 422 (85%) of the 497 leukoplakia cases and in 168 (57%) of the 296 preleukoplakias, and of course in all of the cases of leukokeratosis nicotina palati. Palatal changes associated with reverse smoking thus exhibited spectrum of clinical changes, and it was not satisfactory to group them under leukoplakia, pre-leukoplakia or leukokeratosis nicotina palati. Accordingly, a new classification for palatal changes encompassing the entire spectrum of clinical components was proposed by Mehta FS et al, 1977.
The annual age adjusted incidence rates of palatal changes (encompassing all components) was 24.9 per 1000 men and 39.6 per 1000 among women and the peak incidence was in the 55-64 year age group (Srikakulam data).
Palatal changes comprise several components. (1) Keratosis - diffuse whitening of the entire palatal mucosa, (2) Excrescences - 1-3 mm elevated nodules, often with central red spots; (3) Patches - well defined, elevated white plaques, (4) Red areas - well defined reddening of the palatal mucosa, (5) Ulcerated areas - crater like areas covered by fibrin, and (6) Nonpigmented areas of palatal mucosa that are devoid of pigmentation.
Hyperorthokeratosis, epithelial dysplasia and inflammatory cells in the connective tissue were observed in 87%, 23% and 55% of the biopsies collected from Srikakulam district (Dallary et al 1992). Melanin deposits were noted in the lamina propria of most of them. The epithelium was atrophic in 60% of biopsies from red areas. Epithelial dysplasia was observed in 52% of red areas, 25% of excrescences, 20% of ulcerations. 10% of patches and in 19% of nonpigmented areas.
In a six-year follow up study, palatal changes remained stationary in 75% of individuals; regressed in 14% and were variable in 1 l % i.e. They regressed, recurred and regressed again (Gupta PC et al 1980). The regression rates were higher when the habit was discontinued or reduced substantially. Malignant transformation was observed for 0.3% of the palatal lesions. In a 10-year intervention study in the same area, the malignant potential of various components of palatal changes was evaluated: red areas and patches were found to exhibit a high potential for malignant transformation.
| Palatal Erythema|| |
This lesion is marked by a diffused erythematous hard palate, occasionally extending to the soft palate.
Of the 69 lesions observed among 7216 tobacco users, 87% occurred among smokers, especiallybidi smokers.
This lesion occurs either independently or sometimes with other lesions. About 10% of the lesions were associated with palatal papillary hyperplasia and 25% with central papillary atrophy of the tongue and bilateral commissural leukoplakias. This triad of lesions is comparable to the `multifcal candidiasis' described in western literature.
The highest percentage of persistent lesions (60%) was seen among people who did not give up their smoking habits, while the highest percentage (75%) of regressed lesions occurred among those who discontinued or reduced smoking substantially. These observations clearly indicate that palatal crythema is caused by smoking, particularly bidi smoking. None of the lesions progressed to cancer.
| Central Papillary Atrophy of the Tongue|| |
This lesion has also been described in the literature as median rhomboid glossitis and localised atrophy of the tongue papillae. It consists of a well-defined, oval, pink area in the centre of the dorsum of tongue devoid of lingual papillae.
The prevalence of this lesion in the general population was 1 %; it was present among 2.2% bidi smokers, 1.6% cigarette smokers and 0.3% of non-smokers of tobacco. In a 10-year follow up study from India, the annual age adjusted incidence rate among smokers was 1.5 per 1000 as compared to 0.8 per 1000 among non-smokers.
It is considered to be due to candidal infection, smoking or both (bidi smoking). Interestingly, very few women had this lesion due perhaps to the rarity of smoking among women.
This lesion was marked by the absence of tongue papillae, the presence of slight parakeratinisation of the epithelial surface, long slender rete ridges and occasional pseudo-epitheliomatous hyperplasia. Chronic inflammatory cell infiltrate, chiefly of lymphocytes, was usually present within the epithelium and in the lamina propria. Candidal hyphae were observed in the superficial layers of epithelium in the majority of cases.
The higher percentage of regressed lesions (87%) was seen in those who stopped their habits. None of the lesions progressed to cancer.
Lesions associated with betel-quid chewing
| Pan-Chewer's Lesion|| |
This lesion consists of thick brownish black encrustation on the buccal mucosa at the site of placement of the buccal quid. It is often seen among heavily addicted betel-quid chewers. It could be scrapped off with a piece of gauze; it regresses pontaneously, more frequently when the habit is discontinued.
The annual age adjusted incidence rate of this lesion was 28 per 1000 among male chewers and 17.4 per 1000 among female chewers (Gupta PC et al 1980).
These lesions showed pale staining parakeratin - like surface layers of epithelium, containing round nuclear remnants, ballooning and vacuolated cells and epithelial hyperplasia.
It is a specific entity and rarely progresses to leukoplakia. Malignant transformation was not observed in these lesions.
| Oral Lichen Planus - Like Lesion (Lichenoid Reaction)|| |
A characteristic lesion consisting of white, wavy, parallel, non-elevated striae that do not criss-corss (as in lichen planus) is observed in habitual betel quid chewers. Sometimes, these striae radiate from a central crythematous area at the site of placement of the betel quid.
The prevalence of this lesion among 5099 individuals in Ernakulam, Kerala was 0.7%. About 89% of the lesion occurred among betel quid chewers and 11% among people with mixed habits. The annual age-adjuster incidence rates among men and women were 0.7 and 2.2 per 1000 respectively. The peak incidence for women was in the 45 - 54 year age group. The incidence was zero among smokers and non-users of tabacco; 4.3 per 1000 among women who chewed. This lesion is thus entirely associated with betel quid chewing.
The lesions always occurs on the buccal mucosa and mandibular groove, locations which are in intimate contact with the betel quid.
The lesion shows parakeratinized, atrophic epithelium, liquefaction degeneration of the basal cell layer and a band-like inflammatory cell infiltrate containing lymphocytes and plasma cells. Unlike lichen planus, this lesion shows hyperparakeratosis, and plasma cells in the juxta epithelial region.
Although features are similar to those of oral lichen planus, in view of its complete association with betel quid chewing, it is regarded as a specific entity. No malignant transformation reported.
| References|| |
|1.||WHO: Guide to epidemiology and diagnosis of oral mucosal diseases and conditions. Community Dentistry and Oral Epidemiology 1980; 8: 1-26. |
|2.||van der Waal I, Schepman KR van der Meii; Smcele LE. Oral leukoplakia: a clinicopathological review. Oral Oncology 1997; 33:291-301. |
|3.||Batsakis JG, Suarez P, FI-Naggar AK. Proliferative verrucous leukoplakia and its related lesions - Review Oral Oncology 1999; 35:354-359. |
|4.||Rajendran R. Oral submucous fibrosis: etiology, Pathogenesis and future research - Review. Bulletin WHO 1994,72:985-996. |
|5.||Gupta PC, Hamner JE, Murti PR (Eds). Control of tobacco - related cancers and other diseases. Ox ford University Press, 1992, Bombay. |
[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2], [Table 3]