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ORAL PRECURSOR LESIONS

EPITHELIUM

Clinical Features
Principal oral and oropharyngeal lesions which may

be precursor lesions: 1. White patches (leukoplakia) 2. Red patches (erythroplasia/erythroplakia) 3. Mixed red and white lesions.
These are considered as PREMALIGNANT LESIONS

of the epithelial tissue in origin

Clinical Features
The majority of leukoplakias will not show dysplasia

and correspond to the hyperplasia category. The majority of leukoplakias may not undergo malignant change and may even regress particularly if apparent aetiologic factors are removed. Red and mixed lesions (speckled leukoplakia) show a higher frequency of dysplasia, often of higher grade.

SQUAMOUS INTRAEPITHELIAL LESIONS


The term SILs has been proposed as an all-

embracing expression of the whole spectrum of epithelial changes ranging from squamous cell hyperplasia to carcinoma in situ. In their evolution, some cases of SIL are self-limiting and reversible, some persist, and some of them progress to SCC in spite of treatment.

HISTOPATHOLOGIC PICTURE
The epithelium of precursor lesions maybe thick, but

in the oral cavity it can also be atrophic.


By definition, there is no evidence of invasion. The magnitude of surface keratinisation is of no

importance.

Architectural and Cytologic Features, MICROSCOPICALLY (OL)


HYPERPLASIA

Hyperplasia describes increased cell numbers.


This may be in the spinous layer (acanthosis) and/or

in the basal/parabasal cell layers (progenitor compartment), termed basal cell hyperplasia. The architecture shows regular stratification without cellular atypia.

Architectural and Cytologic Features


DYSPLASIA

When architectural disturbance is accompanied by

cytologic atypia, the term dysplasia applies. Dysplasia is a spectrum and no criteria exist to precisely divide this spectrum into mild, moderate and severe categories.

CRITERIA USED FOR DIAGNOSING DYSPLASIA

MILD DYSPLASIA

Architectural disturbance limited to the lower third of the epithelium accompanied by cytological atypia

MODERATE DYSPLASIA
Architectural disturbance extending into

the middle third of the epithelium.


However, consideration of the degree

of cytologic atypia may require upgrading.

MODERATE DYSPLASIA

Moderate dysplasia. Drop shaped

rete ridges, dysplasia extending to mid-third and moderate cytological changes

SEVERE DYSPLASIA
Recognition of severe dysplasia starts with

greater than two thirds of the epithelium showing architectural disturbance with associated cytologic atypia. Architectural disturbance extending into the middle third of the epithelium with sufficient cytologic atypia is upgraded from moderate to severe dysplasia.

SEVERE DYSPLASIA

Severe dysplasia into upper third of epithelium with marked cytological change

SEVERE DYSPLASIA

Severe dysplasia into upper third of epithelium with prominent cytological change including abnormal mitoses.

SIGNIFICANCE/RELEVANCE OF DYSPLASIA
It is reasonable to assume that the changes described

in dysplasia are due to genetic changes in the epithelium It is unlikely that the mutations involved are the same ones as are associated with development of malignancy More severe dysplasia has been traditionally believed to be associated with a greater likelihood of progression to malignancy

RELEVANCE OF DYSPLASIA
This might indicate that the greater the

accumulation of mutations in tissue, the greater the chance that the critical mutations for malignancy will be present. The corollary is also true in that malignancy can arise from non-dysplastic epithelium presumably because these critical mutations can be present in the absence of the mutations causing dysplasia.

OTHER MICROSCOPIC FEATURES OF LEUKOPLAKIA


HYPERORTHOKERATOSIS

Abnormal increase in the thickness of the

orthokeratin layer or stratum corneum in a particular location Moderate amount of orthokeratin present on the surface of normal epithelium, vary slightly in amount from area to area depending upon frictional irritation

OTHER MICROSCOPIC FEATURES OF LEUKOPLAKIA


HYPERPARAKERATOSIS

This is presence of parakeratin in areas where it is

not usually found, or particularly , a thickening of the parakeratin layer But this can be a normal process in other certain areas of the oral cavity And it is also not unusual in the oral cavity to see alternating areas of orthokeratin and parakeratin

Parakeratin differs from orthokeratin in the

persistence of nuclei or nuclear remnants in the keratin layer The presence of a granular layer or stratum granulosum is obvious only in orthokeratinized oral epithelium The granular layer is often thickened and extremely prominent in cases of hyperkerorthokeratosis, but is seldom seen in severe cases of hyperparakeratosis

OTHER MICROSCOPIC FEATURES OF LEUKOPLAKIA


ACANTHOSIS

This is the abnormal thickening of the spinous layer

for a particular location Can be severe with elongation, thickening, blunting, and confluence of rete ridges, or may consists only of their elongation

GENETICS STUDY
There are no individual markers that

reliably predict malignant transformation


The molecular biology techniques which show most

promise as predictors of development of SCC are large scale genomic status (DNA ploidy) and loss of heterozygosity (LOH) at defined loci

SUMMARY OF DIAGNOSTIC CYTOLOGIC CRITERIA: Dysplasia


Increased and abnormal mitoses

Individual cell keratinization


Epithelial pearls within the spinous layer Alterations in the N:C ratio (Normal ratio?) Loss of polarity and disorientation of cells Hyperchromatism of cells Large and prominent nucleoli Dyskaryosis or nuclear atypism including giant cell Division of nuclei without division of the cytoplasm Basilar hyperplasia

CARCINOMA-IN-SITU
Full or almost full thickness of the epithelium shows

architectural disturbance, accompanied by pronounced cytological atypia. Atypical mitotic figures and abnormal superficial mitoses are present. Malignant transformation has occurred but invasion is not present. It is not possible to recognize this morphologically.

CARCINOMA-IN-SITU
Three distinct morphologic characteristics are

usually present: a) Loss of stratification or maturation of the epithelium as a whole; however, the surface of the epithelium may be covered by one or at most a few layers of compressed, horizontally stratified, and sometimes keratinised cells. b) Epithelial cells may show all the cytologic characteristics of invasive squamous cell carcinoma

CARCINOMA-IN-SITU
c) Mitotic figures are usually markedly increased

throughout the whole epithelium, often more than five per high power field. Abnormal mitoses are frequently seen. Hyaline bodies and dyskeratotic cells are present, often in high numbers

CARCINOMA-IN-SITU

Carcinoma in-situ. Abnormal cells seen throughout the full thickness of the epithelium

CARCINOMA-IN-SITU

Carcinoma in situ. The lesion shows loss of stratification, malignant cells with increased mitotic activity replace the entire epithelial thickness

CLINICAL MANIFESTATIONS
Etiology

Tobacco, whether smoked, chewed or used as snuff,

which seems to be the major carcinogen Smoking 20 or more cigarettes per day, particularly non-filtered Drinking alcohol, particularly fortified wines and spirits Chewing habits, including betel quid, strongly correlate with oral precancer and cancer development

As For ETIOLOGY.
Tobacco is a stronger independent risk factor for

oral SILs than alcohol Its synergistic effect with tobacco is particularly evident !!!!. The risk of the development of oral dysplasia is increased six to 15 times in smokers and heavy drinkers compared with non-smokers and nondrinkers

TOBACCO
MANY of the chemical constituents of tobacco and

its combustion end products (tobacco tar and resin) => irritating to the oral mucosa => capable of producing or leukoplakic alterations in the oral mucosa Materials which leach out of the tobacco when chewed and are allowed to rest against the moist mucosa => irritating to the oral mucosa

TOBACCO SMOKING
PIPE SMOKING IS MOST HARMFUL!!!

Stomatitis nicotina (pipesmokers palate) is seen

among heavy pipesmokers => redness and inflammation of the palate, then palate develops diffuse, grayish white, thickened, multinodular or papular appearance, fissures and cracks may appear, producing a wrinkled and irregular surface

ALCOHOL
The risk of the development of oral dysplasia is

increased six to 15 times in smokers and heavy drinkers compared with non-smokers and nondrinkers Persons who habitually consume considerable quantities of alcohol are ALSO USUALLY inveterate smokers! ALCOHOL is also irritating to the mucosa

Other ETIOLOGICAL FACTORS


Industrial pollution, chronic infections,

vitamin deficiency (Vit A and B complex), and hormonal/endocrine disturbances, galvanism, actinic radiation Infections ( syphilis and fungal e.g. Candidiasis)

Other Etiologic Factors


Chronic irritation - also extremely important

factor e.g. mal occlusions and ill fitting dentures which can produce chronic cheek-biting habits, and also sharp, broken-down teeth SYPHILIS it has been found out that there is higher incidence of leukoplakia among patients who have had syphilitic glossitis VITAMIN Deficiency deficiency of VIT A has been suggested with devt of leukoplakia => induction of metaplasia and increased keratinization of some epithelial structures

Other Etiologic Factors


VITAMIN Deficiency VIT B complex deficiency

has been suggested as a predisposing factor => related to alteration in the oxidation patterns of the epithelium, making it more susceptible to irritation => treatment with brewers yeast is recommended CANDIDIASIS/CANDIDOSIS fungal invasion has been associated with speckled type of leukoplakia => invading Candida hyphae may be responsible for a disorderly maturation of the epithelium

ORAL CLINICAL MANIFESTATIONS

DISTRIBUTION AS TO AGE AND SEX


GENERALLY leukoplakia is seen in patients over 40

years of age Only about 5% of px are under 30 yrs of age Males (69%) more predisposed than women (31%) Slight trend for earlier occurrence of leukoplakia in FEMALES

DISTRIBUTION AS TO LOCATION
Renstrup report:

top locations: buccal mucosa and commisures


in descending order: alveolar mucosa, tongue,

lip, hard and soft palates, floor of the mouth and gingiva Hobaek report: top locations: tongue and floor of the mouth in descending order: lower lip, buccal mucosa, palate, and gingiva *** In this study of Hobaek, multiple areas of involvement were common

DISTRIBUTION AS TO LOCATION
Waldron and Shafer report:

top locations: mandibular alveolar ridge,

gingiva or mucobuccal folds in descending order: buccal mucosa, lower lip (low frequency), and tongue ***In this study of Shafer, tongue is the least frequent site for males and females *** Also in this study of Shafer, no lesions in the upper lip was found

LEUKOPLAKIA

Leukoplakia of the dorsal tongue. The microscopic


diagnosis was basal and parabasal cell hyperplasia

LEUKOPLAKIA
The white appearance of OL (oral leukoplakia) is

most often related to an increase in the surface keratin layer. The most common sites of lesions are the buccal and alveolar mucosa and the lower lip. Lesions in the floor of the mouth, lateral tongue and lower lip more often show epithelial atypia or even malignant growth TWO TYPES: homogenous and nonhomogenous

LEUKOPLAKIA
HOMOGENOUS TYPE Characterized as a uniform, flat, thin lesion with a

smooth or wrinkled surface showing shallow cracks, but a constant texture throughout

LEUKOPLAKIA, HOMOGENOUS Type

LEUKOPLAKIA
NONHOMOGENOUS TYPE (a.k.a

ERYTHROLEUKOPLAKIA)

A predominantly white or white and red lesion that may

be irregularly flat, nodular or exophytic. Nodular lesions have slightly raised rounded, red and/or whitish excrescences. Exophytic lesions have irregular blunt or sharp projections . The term non-homogenous is applicable to the aspect of both colour (a mixed white and red lesion) and texture (exophytic, papillary or verrucous) of the lesions.

LEUKOPLAKIA, NonHomogenous Type

Erythroleukoplakia of the buccal mucosa. The microscopic diagnosis was atypical hyperplasia.

LEUKOPLAKIA, NonHomogenous Type

Proliferative verrucous leukoplakia. Extensive, thick, white plaques.

LEUKOPLAKIA, NonHomogenous Type


PVL showing verrucous surface with hyperkeratosis, hypergranulosis and a dense inflammatory infiltrate in the corium.

Same case as shown above, two years later showing more florid verrucous hyperplasia illustrating the progressive nature of the condition.

ERYTHROLEUKOPLAKIA (OE)
Oral intraepithelial lesions that are intermixed with

white areas Also called speckled mucosa and are believed to behave similarly to pure leukoplakia. The red appearance of OE may be related to an increase in subepithelial blood vessels, a lack of surface keratin and thinness of the epithelium Although OE is a rare lesion, it is much more likely to show dysplasia or carcinoma.

Take note.
In all red lesions of the oral

mucosa that do not regress within 2 weeks of the removal of possible aetiological factors, biopsy is, therefore, Mandatory!!!!!