Leukoplakia

LEUKOPLAKIA

Leukoplakia is a keratotic plaque occurring on mucous membranes and is

considered a premalignant lesion. The World Health Organization defined leukoplakia

as "a white patch or plaque that cannot be characterized clinically or pathologically as

any other diseases” as with other keratotic lesions, it cannot be scraped off with a

tongue blade.3

The term leukoplakia was derived from the Greek word – ‘Leuko’ meaning

“white” and ‘Plax’ meaning “plaque”. Bazin and others first described the condition

as a type of lingual psoriasis, but it was Schwimmer in 1877, differentiated it from

psoriasis and described it under the present name.23

The WHO Collaborating Centre for Oral Precancerous Lesions in 1978 sought

to define ‘oral leukoplakia’ sufficiently tightly to provide an internationally accepted

system to characterize ‘white patches’ that carry an increased risk of malignant

potential. Over a 25year period researchers and clinicians alike, other working groups

and experts at several international seminars have quoted the WHO definition for

leukoplakia. 24

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” 25

Terminology and Definitions of OL

International attempts to define⁄refine WHO definition of OL are as follows:

Kramer (1978) had recognized the malignant potential of leukokeratosis and smokers

patch and its relationship to pipe smoking. Paget (1860) recognized an association

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between a white keratotic oral lesion and lingual carcinoma. Kramer (1978) suggested

the term leukoplakia describe white raised lesion involving oral mucosa. It was also

called as leukoma, smokers patch, leukokeratosis, and ichthyosis.

Butlin (1885) related these lesions to smoking and considered smokers patch

to be an early stage of a more advanced white raised lesion that he called as leukoma.

Axéll (1996) states leukoplakia as a white patch measuring 5 mm or more which

cannot be scrapped o and cannot be attributed to any other diagnostic disease.

The First International Conference on OL (1984) Malmo, Sweden: Described

leukoplakia as “A white patch or plaque that cannot be characterized clinically or

pathologically as any other disease and is not associated with any physical or

chemical causative agent except the use of tobacco.”

In a conference of Uppsala (1994), it was established that it would be the

“predominantly white lesion of the oral mucosa which could not be clinically or

pathologically characterized as another speci c entity.” As per the International

Symposium, Uppsala, Sweden (1996): It is “a predominantly white lesion of the oral

mucosa that cannot be characterized as any other de nable disease.”

The WHO (1997) described leukoplakia as “a predominantly white lesion of

the oral mucosa that cannot be characterized as any other de nable lesion.” According

to Warnakulasuriya et al. (2007), leukoplakia should be used to recognize white

plaques of questionable risk having excluded (other) known diseases or disorders that

carry no increased risk for cancer. Warnakulasuriya et al. (2007) de ned this lesion as

“a white plaque with an increasing questionable oral cancer risk after excluding other

known diseases and disorders that do not increase the risk.”26

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International attempts to define⁄refine the WHO definition of oral leukoplakia

are shown in

(Warnakulasuriya S et al 2007)27

Working group Definition

A white patch or plaque that cannot be

characterized clinically or pathologically
WHO (5) as any other disease

First International Conference on oral A white patch or plaque that cannot be

leukoplakia. Malmo, Sweden (6) characterized clinically or pathologically
as any other disease and is not associated
with any physical or chemical causative
agent except use of tobacco

International Symposium, Uppsala, A predominantly white lesion of the oral

Sweden (7) mucosa that cannot be characterized as
any other definable disease

WHO (8) A predominantly white lesion of the oral

mucosa that cannot be characterized as
any other definable lesion

WHO (1) Not defined – no distinction is made from

other white patches

Warnakulasuriya et al. (this report) Leukoplakia should be used to recognize

white plagues of questionable risk having
excluded (other) known
 diseases or
disorders that carry no increased risk for
cancer

Table: Definitions of oral leukoplakia proposed in the past decades

Having considered all proposed definitions the working group agreed to

amend the original 1978 WHO definition to stand as: ‘The term leukoplakia should be

used to recognize white plaques of questionable risk having excluded (other) known

diseases or disorders that carry no increased risk for cancer’.23

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Furthermore leukoplakia is a clinical term and the lesion has no specific

histology. It may show atrophy or hyperplasia (acanthosis) and may or may not

demonstrate epithelial dysplasia. It has a variable behavioral pattern but with an

assessable tendency to malignant transformation. It must be noted that oral epithelial

dysplasia has no specific clinical appearance and the term should not be used as a

clinical descriptor of a white lesion.23

HISTORICAL ASPECT


In ancient literature, Shushruta first described leukoplakia, in 600 BC, who

called it as Sanipataj Rog.4 Sir James Paget of London wondered in 1851 about the

cancer-producing potential of pipe smoker's palate or "leukokeratosis," and in 1870 he

clearly implied that oral "ichthyosis" (white keratotic plaque) was a significant

precursor to lingual carcinoma.28

Katz et al (1985), they found the system to be of considerable value for

purposes of standardization and eliminated observer bias by the use of standardized

photographs. Nevertheless, they questioned the accuracy of the weightage given to

each of the histological characteristics. 28

Girod S.C. et al (1999) in his study classified the epithelial dysplastic lesions

and studied the expression of p53, PCNA and Ki-67 in different degrees of epithelial

dysplasia. The expression pattern correlated better with the different degrees of

dysplasia.29

EPIDEMIOLOGY

The estimated reported prevalence of oral leukoplakia worldwide is

approximately 2%. 2 However, when viewed in relation to an annual malignant

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transformation rate of 1%, this prevalence figure would result in development of oral

cancer in 20 per 100,000 populations per year. Obviously, this cancer incidence

figure, based on malignant transformation of oral leukoplakia alone is much too high.

Probably, the prevalence of oral leukoplakia has to be set at a more realistic figure of

less than 0.5%. There are some geographical differences with regard to the gender

distribution.

Leukoplakia is six times more common among smokers than among non-

smokers.29 Alcohol is an independent risk factor, regardless of beverage type or

drinking pattern. There are conflicting results of studies related to the possible role of

human papilloma virus infection. 3

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.14

Gender in this century the incidence of squamous cell carcinoma has favored

male over female patients by 4 to 1. Recently, this has fallen to an approximate ratio

of 2 to I or less. There may be a concomitant decrease in male patients with an

increase in female patients. However, the male to female ratios vary from site to site

in the oral cavity. For instance, carcinoma of the gingiva or alveolus is 1.5 times as

frequent in female patients. There appears to be an increase in the incidence of

carcinoma of the tongue in women, as wel1.The increased incidence of cancer in

female patients may relate to factors in addition to increased smoking and drinking

High-risk sites depicts the high-risk oval of the oral cavity. Basically the oral

soft tissues that contact a donut placed over the raised tongue represent the high
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frequency sites of squamous cell carcinoma: lower lip, floor of the mouth, ventral

surface and lateral borders of the tongue, retromolar regions, and soft palate. Tumors

of the tongue and floor of the mouth are the most common site by far, and the soft

palate is next. The clinician needs to examine these sites carefully and thoroughly

during the systematic clinical examination

Leukoplakic lesions are characteristically asymptomatic and are most often

discovered during a routine oral examination. Leukoplakia is a common lesion. It

represents 6.2% of all oral biopsy specimens and occurs in approx-7 
 imately 3% of

white Americans over 35 years of age. Most lesions occur between 40 and 70 years of

age and more commonly in men. Frequent sites are the lip vermilion, buccal mucosa,

mandibular gingiva, tongue, oral floor, hard palate, maxillary gingiva, lip mucosa, and

soft palate. The lesions may vary greatly in size, shape, and distribution. The borders

may be distinct or indistinct and smoothly contoured or ragged. The lesions may be

solitary, or multiple plaques may be scattered through the mouth

ETIOPATHOGENESIS:

The etiology of leukoplakia is still unclear. Even though various hypotheses

have been put forth, their association cannot be determined in most of the cases. Some

workers believe that the initiation of this lesion may depend upon intrinsic

predisposing factors. The factors most frequently thought to result in leukoplakia are

tobacco, alcohol, virus, vitamin deficiency, candida, syphilis, galvanism, endocrine

disturbances and local irritating factors. Although, tobacco seems to be the major

inducing factor, many cases diagnosed were without the habit of tobacco usage.31

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TOBACCO:


Tobacco consumption continues to prevail as the most important cancer risk

and tobacco accounts for millions of cancer deaths annually.32 The neoplastic diseases

caused by smoking include cancers of the lung, oral cavity, pharynx, larynx,

esophagus, urinary bladder, renal pelvis and pancreas.33 The oral consumption of

smokeless tobacco in various forms also causes cancer, particularly in the oral

cavity.33

Tobacco carcinogenicity is more evident and about one fourth of oral cancer

cases are attributable to cigarette smoking.34

Although the association between tobacco smoking and oral cancer is dose-

dependent, with the risk for cancer development proportional to the number of daily

smoked cigarettes and the duration of smoking, while heavy smokers are at manifest

higher risk. Indeed, head and neck cancer risk markedly increases when smoking

duration is greater than 20 years and the daily frequency of smoked cigarettes is

higher than 20 number.35

ALCOHOL

Alcohol has been strongly implicated in the development of oral cancer. Based

on the results of cohort and case-control studies, the consumption of alcoholic

beverages has been considered carcinogenic to humans causing in particular, tumors

of the oral cavity, pharynx, larynx, esophagus and liver, although ethanol per se has

not been proven carcinogenic in animal studies.36

Several epidemiologic studies, done and reported that, alcohol consumption

has been shown to act synergistically with tobacco in the increased risk of

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development of oral cancer.36

Hence, the role of alcohol as an independent factor in oral carcinogenesis is

still unclear albeit epidemiological evidence establishes the synergistic role played by

alcohol with tobacco.37

BETEL QUID

Betel quid chewing with different ingredients is the most common habit in

Southeast Asia especially in the Indian subcontinent. Betel quid with areca nut, slaked

lime and tobacco.38

Studies have shown the association of these tobacco-chewing products with

oral cancer development and precancer namely leukoplakia, erythroplakia and oral

submucous fibrosis for instance, shammah is associated with leukoplakia-like lesions

and oral cancer.39

In vitro studies have shown that reactive oxygen species (ROS), methylating

agents and reactive metabolic intermediates from betel quid induce various kinds of

DNA damage.40

NUTRITIONAL DEFICIENCY:

Dietary deficiencies are sometimes considered to play a contributory role in

the development of oral cancer. Interest here relates to the roles of iron, free radical or

antioxidant scavenging vitamins A, C, E, and trace elements such as zinc and

selenium, for which there is evidence of protective effect. The relationship between

sideropenic dysphagia and oral cancer is a well-recognized entity. 30

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GALVANISM:


Differences in the electrical potential between two dissimilar metal fillings

were believed to be important for causation of leukoplakia. Although such lesions

may be seen they should not be termed as leukoplakia.30

SANGUINARIA:

Herbal extract sanguinaria which is used in mouth washes and tooth pastes

was found to develop leukoplakia (Sanguinaria-associated keratosis). Even after

stopping usage of this product, the lesion did not subside. The commonest site was

maxillary vestibule and alveolar mucosa.41

CANDIDA:

Studies have been carried out find out the association between leukoplakia and

candida and in few leukoplakias, nitrosamine producing Candida species were found.

They found that even after elimination of surface mycosis after administration of

antifungals, the leukoplakia persisted. They also noted that the malignant

transformation of candida infected leukoplakias was high, suggesting candida

association as a significant risk factor for oncogenesis.41

PAPILLOMA VIRUS:

Extensive molecular biology and virology studies have been carried out to find

out the role of Human Papilloma Virus (HPV) in the aetiology as well as oncogenesis

of oral leukoplakia. HPV type 16 was demonstrated in oral leukoplakias and

carcinomas. In a more aggressive variant of leukoplakia, Proliferative Verrucous

leukoplakia (PVL), HPV 16 and 18 were isolated.41

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EPSTEIN BARR VIRUS (EBV):

Even though EBV was found to be associated with aetiology of oral squamous

cell carcinomas, their role in oral leukoplakias was not found in any of the studies.

May be carrying out studies on a larger sample may help us if there is any role of

EBV in oral leukoplakias.41

ORAL EPITHELIAL ATROPHY

There is a tendency for leukoplakia to develop in atrophic epithelium.

Conditions which predispose to epithelial atrophy and leukoplakia include iron

deficiency, oral submucous fibrosis, tertiary syphilis, and possibly some vitamin

deficiencies. Sideropenic dysphagia (Patterson-Kelly or Plummer-Vinson syndrome)

is associated particularly with postcricoid carcinoma but may also be associated with

oral leukoplakia and oral squamous cell carcinoma.42

TUMOUR-SUPPRESSOR GENES

Tumour-suppressor genes are involved in regulation of the normal cell-

proliferation cycle. One of the best known is the p53 gene located on chromosome

17p. Mutation of the gene can result in inactivation of the normal suppressor activity

of the p53 protein leading to uncontrolled cell proliferation. Abnormalities of the p53

gene have been identified in a wide range of malignancies, including oral cancer and

in some leukoplakias, particularly those showing dysplasia and those associated with

heavy smoking and drinking. A variety of other genetic abnormalities have also been

detected involving areas of the genome thought to harbour other tumour-suppressor

genes. It is likely that the pattern and timing of these genetic changes are the key to

understanding the progression from normal mucosa to dysplasia and invasive

squamous cell carcinoma.42

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SYPHILIS

In the older literatures, syphilis was considered to be a very important

predisposing factor for the development of leukoplakia, especially the tertiary stage of

the disease, which presents mucous patches over the tongue and buccal mucosa.

However, recent reports indicate that the syphilitic infections play only a minor role in

the causation of leukoplakia.14

HORMONAL IMBALANCE

Imbalance or dysfunctions of both male and female sex hormones may induce

some keratogenic changes in the oral epithelium and these changes may ultimately

lead to the development of leukoplakia. 14

CHRONIC IRRITATION

Chronic irritation to the mucosa by illfitting dentures, sharp cuspal edges of

teeth and hot or spicy foods, etc. may cause leukoplakia.14

ACTINIC RADIATION

Actinic or solar radiation may bring about some hyperkeratotic changes in the

oral mucosa, especially the lip mucosa and this can be a predisposing factor for

leukoplakia in rare cases.14

XEROSTOMIA

Some conditions which can cause xerostomia may lead to leukoplakia. These

conditions are salivary gland diseases, anticholinergic drugs and radiation.43

CLINICAL CLASSIFICATION OF LEUKOPLAKIA

Leukoplakia is classified in two main types:
 Homogeneous
 Non-Homogeneous

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CLINICAL TYPES OF LEUKOPLAKIA

 Homogeneous type


 Speckled type


 White and red patches

 Verrucous type

Classification According to clinical description.43

• Homogenous—itiscompletelywhitishlesion.

• Flat—ithassmoothsurface.

• Corrugated—likeabeachatebbingtide.

• Pumicelike—withapatternoffinelines(cristae).

• Wrinkled—likedry,crackedmudsurface.

• Non-homogenous

• Nodular or speckled—characterized by white specks or nodules on erythematous

base.

• Verrucous—slow growing, papillary proliferations above the mucosal surface that

may be heavily keratinized. Extensive lesion of this type is called as ‘oral
florid papillomatosis’.

• Ulcerated—lesionexhibitsredareaattheperipheryof which white patches are present.

• Erythroleukoplakia—leukoplakia is present in asso- ciation with erythroplakia.

According to risk of future development of oral cancer

• Highrisksites

• Floorofmouth

• Lateralorventralsurfaceoftongue

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• Softpalate

• Lowrisksites

• Dorsumoftongue

• Hardpalate

• Intermediategroup

• Allothersitesororalmucosa

According to histology

• Dysplastic

• Non-dysplastic

According to extent

• Localized

• Diffuse

According to Banoczy

• Leukoplakiasimplex—auniformraisedplaqueformation, varying in size, with

regular edges. It corresponds to homogenous type of leukoplakia.

• Leukoplakia erosiva—a lesion with slightly raised, rounded, red and/or

whitish excrescence, that may be described as granules or nodules.

• Leukoplakiaverrucosa—itischaracterizedbyverrucous proliferation raised

above the mucosal surface.

Leukoplakia is classified in two main types:

• Homogeneous
• Non-Homogeneous

Homogeneous type which appears as a flat white lesion and non-homogeneous

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type which includes speckled, nodular and verrucous leukoplakia. The homogeneous

leukoplakia is a uniform, thin white area altering or not with normal mucosa. The

speckled type is a white and red lesion, with a predominantly white surface.

Verrucous leukoplakia has an elevated, proliferative or corrugated surface

appearance. The nodular type has small polypoid outgrowths, rounded predominantly

white excrescences.

Proliferative verrucous leukoplakia is a sub type of verrucous leukoplakia

characterized by an aggressive evolution, a multifocal appearance, resistance to

treatment, higher degree of recurrence and a high rate of malignant transformation.

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Wood and Goaz (1989) divided leukoplakia into four basic clinical appearances:3

1. Homogeneous white plaques have no red component but have a fine, white,

grainy texture or a more mottled, rough appearance

2. Speckled leukoplakias are composed of white and red flecks of fine or coarse

variety

3. Combination white and red patches demonstrate segregation of the red and

white components and are basically erythroleukoplakic lesions

4. Verrucous leukoplakias possess red and white components, but the white

components are much thicker and protrude above the surface mucosa

Red components of leukoplakias represent dysplasias, carcinomas in situs, and

invasive carcinomas, providing that the red component is not a traumatic erosion or

traumatic ulcer. Banoczy presented impressive evidence that each of these clinical

types has some potential to change from one type to another.

Histologically classification

Histologically, leukoplakias have been classified as simple orthokeratosis;

parakeratosis with epithelial hyperplasia and minimum in ammation; and

hyperkeratosis with different degrees of dysplasia (16% of the cases). Epithelial

dysplasia has been categorized as mild, moderate, and severe; the latter known as in

situ carcinoma due to its location within the layer of epithelial cells.44

Various Forms of Leukoplakia

Proliferative verrucous leukoplakia (PVL): Hansen et al. (1985) rst

described PVL is a distinct clinical form of OL. PVL has a high rate of malignant

transformation which was described by the WHO. It is multifocal progressive lesions,

found in women. Most frequently a ected area was the lower gingival, tongue, buccal
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mucosa, and alveolar ridge.45 


Oral erythroleukoplakia (OEL) is a non-homogenous lesion of mixed white

and red components. It is de ned as a ery red patch that cannot be characterized

clinically or pathologically as any other de nable disease’. OEL shows a higher

malignant transformation potential than homogeneous leukoplakia.45


Sublingual keratosis: It is a soft white plaque in the sublingual region with a

wrinkled surface, an irregular but well-de ned outline and sometimes a butter y

shape.45 


Candidal leukoplakia (CL) is a chronic, discrete elevated lesions that are

palpable, translucent, whitish areas to large, dense, opaque plaques, hard and rough to

the touch45


Oral hairy leukoplakia (OHL) otherwise known as Greenspan lesion. In

1984, Greenspan et al. rst described OHL characterized by whitish patches with a

corrugated or hairy surface and most commonly present on the lateral borders of the

tongue. It is caused by the reactivation of a previous Epstein-Barr virus infection. 45 


Histologic study Leukoplakias may be histologically divided into two main

categories those that show no atypia (dysplasia) and those that show different degrees

of atypia. From 20% to 25% of leukoplakias show atypia. A lesion may show severe

atypia with malignant change throughout the depth of the epithelial layer, but its

basement membrane may still be intact. Such a lesion is referred to as carcinoma in

situ or intraepithelial carcinoma.3

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When an intraepithelial carcinoma breaks through the basement membrane, it

becomes an invasive Sec. The investigator must study microscopic sections from

various areas of a biopsy of leukoplakia, since the complete spectrum of

histopathologic features from increased keratosis to invasive scc may be found in the

surgical specimen from one lesion. Invasive scc developed in l6% of cases of

epithelial dysplasia in a mean of 33.6 months after biopsy.3

Reversible or irreversible types

Leukoplakia may also be divided into two types according to whether it

spontaneously disappears after the chronic irritant has been eliminated. Lesions that

disappear are referred to as reversible leukoplakias, whereas the persistent lesions are

termed irreversible leukoplakias. In one large study, 62% of the lesions were

completely or partially irreversible.3

Malignant potential

It has been reported that the malignant change in leukoplakia ranges between

39c and 7%.6,7,12 However, it is very difficult to establish a percentage rate for

malignant change for leukoplakias in general because so many variables exist. The

statistics depend on clinical type, site, etiology, and patient's gen- der and age. It is

helpful to consider just the homogeneous type here and assign all lesions with red or

verrucous components to a high suspicion index. These latter lesions should be

managed with aggressive removal and follow-up. Therefore the homogeneous variety.

which clearly has a much lower rate of malignant change, is left. Even these vary

greatly in the percentage of malignant change. Those situated in the high-risk oval,

such as the floor of the mouth, ventral surface of the tongue, margins of the tongue,

and retromolar region. have a much higher than those occurring else- where, such as

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the crest of the ridge where the malignant potential may approach zero.3

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Clinical Variants

Pindborg classied leukoplakia into two main types

Homogeneous leukoplakia 


Non homogeneous leukoplakia 


Bailoor and Nagesh divided leukoplakia in to

 Speckled leukoplakia and non speckeled leukoplakia

 Homogenous, Ulcerative, Speckled
 Reversible / irreversible

WHO (1980) subdivided leukoplakia into various forms

Homogeneous leukoplakia/leukoplakia simplex: Lesions are uniformly at,

thin and predominantly white in colour. The surface of the lesion may be smooth,

wrinkled or corrugated and with a consistent texture throughout. These lesions are

asymptomatic and show a very low risk of malignant transformation.41

Non homogeneous leukoplakia/Erythroleukoplakia: Mixed white and red

lesions associated with an erythematous component. Patients complain of pain,

itching and discomfort. These show a high risk for malignant transformation.41

Proliferative Verrucous leukoplakia (PVL): PVL is an aggressive variant of

leukoplakia, rst described by Hansen et al., in 1985. It shows a female preponderance

in contrast to other subtypes of leukoplakia with female to male ratio of about 4:1. In

patients with PVL, smoking and drinking were not found to be significant. The

commonest site in females was buccal mucosa whereas in males tongue was

frequently involved. The significance of PVL is that the lesions show high risk for

malignant transformation, treatment resistant and show high recurrence rates. Hence

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such lesions require early and aggressive treatment. HPV 16 was found to be

associated with this lesion. Four stages have been described in its development,

initially as a simple hyperkeratosis without epithelial dysplasia, followed by

verrucous hyperplasia, verrucous carcinoma, and nally conventional carcinoma.41

Ghazali et al., suggested the following criteria for the diagnosis of PVL:

1. The lesion should start as homogeneous leukoplakia with histopathological

ndings of dysplasia
2. Later in it should show verrucous areas
3. From single lesion it should progress to multiple lesions at the same or
different site
4. It should progress later into different histological stages.
5. It should show recurrence after treatment

Oral hairy leukoplakia (ohl): OHL is a white lesion related to pstein-Barr virus

(EBV). It is usually associated with AIDS. OHL is seen on lateral border of the

tongue, rarely on the buccal mucosa, with slightly raised and corrugated hairy surface.

Like leukoplakia these lesions are also white in colour, cannot be rubbed off and

asymptomatic. But OHL must not be considered as a variant of leukoplakia as its

aetiological factor is EBV virus.41

Histopathological Aspects.14

Histopathological features of epithelial dysplasia

1. Loss of polarity of the basal cells

2. Presence of more than one layer of cells having a basaloid appearance

3. Increased nuclear cytoplasmic ratio

4. Drop-shaped rete processes

5. Irregular epithelial stratification

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6. Increased number of mitotic figures (a few abnormal mitoses may be present)

7. Presence of mitotic figures in the superficial half of the epithelium

8. Cellular pleomorphism

9. Nuclear hyperchromatism

10. Enlarged nucleoli

11. Reduction of cellular cohesion

12. Keratinization of single cells or cell groups in the prickle layer

Grading of Epithelial Dysplasia. Epithelial dysplasia is usually assessed

subjectively and considerable interobserver variability exists in its interpretation.

Principally, what is lacking in this exercise is 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 dyplasia 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 shows a greater disposition for malignant

transformation than in the absence of dysplastic features, carcinomatous

transformation may also take place in non-dysplastic leukoplakias.14

HIGH-RISK LEUKOPLAKIAS

• Red component


• Raised component


• Presence in high-risk oval


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• Tobacco and alcohol use


• Nonsmoker and unknown etiology of lesion

• Nonreversible type


• Microscopic atypia

Management

Not all leukoplakias are the same. A conservative approach is indicated for

those that do not share the characteristics listed in the box on p. 101, left, and thus fall

into the low-risk group.3

For low-risk lesions, every effort must be made to identify local and chronic

causative irritants. The cause may be obvious from the location of the lesion (e.g., a

white patch on an edentulous ridge directly beneath an occluding maxillary molar not

in direct line with the course of the smoke from a pipe held in the smoker's favorite

position or in contact with a fractured crown). These irritants must be eliminated and

the patient reexamined biweekly to determine whether the lesion is regressing. If

evidence of regression is not detectable within 2 weeks (color photographs are useful

as records for comparison), the lesion should be completely excised. A simple

procedure for small lesions is, a relatively complicated operation if the lesions are

large, involve many surfaces, or are in a surgically delicate site. A "ridge callus" is an

exception and would not require excision in most cases.3

If the lesions are large or widespread, stripping procedures must be used-in

stages with free grafts or with allowance for the denuded surface to epithelialize by

secondary healing. Approximately 6% of the irreversible leukoplakial lesions undergo

malignant transformation to SCC.There seems to be little doubt that irreversible

leukoplakial lesions should be completely excised with careful postsurgical follow-up.

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If the microscopic diagnosis is SCC, the patient should be referred to a clinician who

is competent in treating oral cancers.3

High-risk leukoplakias should be referred promptly on detection to a tumor

board or clinician who is competent to treat oral cancer.3

Chemopreventive agents are currently in field trials. Basically researchers are

attempting to eliminate leukoplakial lesions with local and systemic agents.

Table : Drugs used in tobacco dependence.

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Treatment Modalities. Apart from the surgical excision, various treatment

modalities are available, such as cryosurgery, CO2- 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.14

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