i Oral Precursor Lesions

8/13/2019 i Oral Precursor Lesions

1/51

EPITHELIUM

ORAL PRECURSOR LESIONS


2/51

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 LESIONSof the epithelial tissue in origin


3/51

Clinical Features

The majority of leukoplakias will not show dysplasiaand correspond to the hyperplasia category.The majority of leukoplakias may not undergo

malignant change and may even regress particularlyif apparent aetiologic factors are removed.Red and mixed lesions (speckled leukoplakia) show ahigher frequency of dysplasia, often of higher grade.


4/51


5/51

SQUAMOUS INTRAEPITHELIAL LESIONS

The term SILs has been proposed as an all-embracing expression of the whole spectrum ofepithelial changes ranging from squamous cellhyperplasia to carcinoma in situ.In their evolution, some cases of SIL are self-limitingand reversible, some persist, and some of themprogress to SCC in spite of treatment.


6/51

HISTOPATHOLOGIC PICTURE

The epithelium of precursor lesions maybe thick, butin the oral cavity it can also be atrophic.

By definition, there is no evidence of invasion.

The magnitude of surface keratinisation is of noimportance.


7/51

Architectural and Cytologic Features,MICROSCOPICALLY (OL)

HYPERPLASIAHyperplasia describes increased cell numbers.This may be in the spinous layer (acanthosis) and/or

in the basal/parabasal cell layers (progenitorcompartment), termed basal cell hyperplasia.The architecture shows regular stratification withoutcellular atypia.


8/51

Architectural and Cytologic Features

DYSPLASIA When architectural disturbance is accompanied bycytologic atypia , the term dysplasia applies.

Dysplasia is a spectrum and no criteria exist toprecisely divide this spectrum into mild, moderateand severe categories.


9/51

CRITERIA USED FOR DIAGNOSINGDYSPLASIA


10/51

MILD DYSPLASIA

Architectural disturbance limitedto the lower third of theepithelium accompanied bycytological atypia


11/51

MODERATE DYSPLASIA

Architectural disturbance extending intothe middle third of the epithelium.However, consideration of the degreeof cytologic atypia may requireupgrading.


12/51

MODERATE DYSPLASIA

Moderate dysplasia . Drop shapedrete ridges, dysplasia extending tomid-third and moderate cytologicalchanges


13/51

SEVERE DYSPLASIA

Recognition of severe dysplasia starts withgreater than two thirds of the epitheliumshowing architectural disturbance with

associated cytologic atypia . Architectural disturbance extending intothe middle third of the epithelium withsufficient cytologic atypia is upgraded frommoderate to severe dysplasia .


14/51

SEVERE DYSPLASIA

Severe dysplasia into upper thirdof epithelium with marked

cytological change


15/51

SEVERE DYSPLASIA

Severe dysplasia into upper third ofepithelium with prominent cytological

change including abnormal mitoses .


16/51

SIGNIFICANCE/RELEVANCE OF DYSPLASIA

It is reasonable to assume that the changes describedin dysplasia are due to genetic changes in theepithelium

It is unlikely that the mutations involved are thesame ones as are associated with development ofmalignancyMore severe dysplasia has been traditionally believed

to be associated with a greater likelihood ofprogression to malignancy


17/51

RELEVANCE OF DYSPLASIA

This might indicate that the greater theaccumulation of mutations in tissue, the greater thechance that the critical mutations for malignancy will be present.The corollary is also true in that malignancy canarise from non-dysplastic epithelium presumably because these critical mutations can be present in

the absence of the mutations causing dysplasia.


18/51

OTHER MICROSCOPIC FEATURES OFLEUKOPLAKIA

HYPERORTHOKERATOSIS Abnormal increase in the thickness of theorthokeratin layer or stratum corneum in a

particular locationModerate amount of orthokeratin present on thesurface of normal epithelium, vary slightly in amountfrom area to area depending upon frictional

irritation


19/51


HYPERPARAKERATOSISThis is presence of parakeratin in areas where it isnot usually found, or particularly , a thickening of the

parakeratin layerBut this can be a normal process in other certainareas of the oral cavity And it is also not unusual in the oral cavity to seealternating areas of orthokeratin and parakeratin


20/51

Parakeratin differs from orthokeratin in thepersistence of nuclei or nuclear remnants in thekeratin layer

The presence of a granular layer or stratumgranulosum is obvious only in orthokeratinized oralepitheliumThe granular layer is often thickened and extremely

prominent in cases of hyperkerorthokeratosis, but isseldom seen in severe cases of hyperparakeratosis


21/51


ACANTHOSISThis is the abnormal thickening of the spinous layerfor a particular location

Can be severe with elongation, thickening, blunting,and confluence of rete ridges, or may consists only oftheir elongation


22/51

GENETICS STUDY

There are no individual markers thatreliably predict malignant transformation

The molecular biology techniques which show mostpromise as predictors of development of SCC arelarge scale genomic status (DNA ploidy) andloss of heterozygosity (LOH) at defined loci


23/51

SUMMARY OF DIAGNOSTIC CYTOLOGICCRITERIA: Dysplasia

Increased and abnormal mitosesIndividual cell keratinizationEpithelial pearls within the spinous layer

Alterations in the N:C ratio (Normal ratio?)Loss of polarity and disorientation of cellsHyperchromatism of cellsLarge and prominent nucleoli

Dyskaryosis or nuclear atypism including giant cellDivision of nuclei without division of the cytoplasmBasilar hyperplasia


24/51

CARCINOMA-IN-SITU

Full or almost full thickness of the epithelium showsarchitectural disturbance, accompanied bypronounced cytological atypia.

Atypical mitotic figures and abnormal superficialmitoses are present.Malignant transformation has occurred butinvasion is not present.

It is not possible to recognize this morphologically.


25/51

CARCINOMA-IN-SITU

Three distinct morphologic characteristics areusually present:a) Loss of stratification or maturation of the

epithelium as a whole; however, the surface of theepithelium may be covered by one or at most a fewlayers of compressed, horizontally stratified, andsometimes keratinised cells.

b) Epithelial cells may show all the cytologiccharacteristics of invasive squamous cell carcinoma


26/51

CARCINOMA-IN-SITU

c) Mitotic figures are usually markedly increasedthroughout the whole epithelium, often more thanfive per high power field. Abnormal mitoses arefrequently seen. Hyaline bodies and dyskeratoticcells are present, often in high numbers


27/51

CARCINOMA-IN-SITU

Carcinoma in-situ. Abnormal cells seen

throughout the fullthickness of theepithelium


28/51


29/51

CLINICAL MANIFESTATIONS

EtiologyTobacco, whether smoked, chewed or used as snuff, which seems to be the major carcinogen

Smoking 20 or more cigarettes per day, particularlynon-filteredDrinking alcohol, particularly fortified wines andspiritsChewing habits, including betel quid, stronglycorrelate with oral precancer and cancerdevelopment


30/51

As For ETIOLOGY.

Tobacco is a stronger independent risk factor fororal SILs than alcohol Its synergistic effect with tobacco is particularly

evident !!!! .The risk of the development of oral dysplasia isincreased six to 15 times in smokers and heavydrinkers compared with non-smokers and non-

drinkers


31/51

TOBACCO

MANY of the chemical constituents of tobacco andits combustion end products (tobacco tar andresin ) => irritating to the oral mucosa => capable ofproducing or leukoplakic alterations in the oralmucosaMaterials which leach out of the tobacco whenchewed and are allowed to rest against the moist

mucosa => irritating to the oral mucosa


32/51

TOBACCO SMOKING

PIPE SMOKING IS MOST HARMFUL!!!Stomatitis nicotina ( pipesmokers palate) is seenamong heavy pipesmokers => redness and

inflammation of the palate, then palate developsdiffuse, grayish white, thickened, multinodular orpapular appearance, fissures and cracks may appear,producing a wrinkled and irregular surface


33/51

ALCOHOL

The risk of the development of oral dysplasia isincreased six to 15 times in smokers and heavydrinkers compared with non-smokers and non-drinkersPersons who habitually consume considerablequantities of alcohol are ALSO USUALLY inveteratesmokers!

ALCOHOL is also irritating to the mucosa


34/51

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)


35/51

Other Etiologic Factors

Chronic irritation - also extremely importantfactor e.g. mal occlusions and ill fitting dentures which can produce chronic cheek-biting habits, andalso sharp, broken-down teeth

SYPHILIS it has been found out that there ishigher incidence of leukoplakia among patients whohave had syphilitic glossitis

VITAMIN Deficiency deficiency of VIT A has been suggested with devt of leukoplakia =>induction of metaplasia and increased keratinizationof some epithelial structures


36/51

Other Etiologic Factors

VITAMIN Deficiency VIT B complex deficiencyhas been suggested as a predisposing factor =>related to alteration in the oxidation patterns of theepithelium, making it more susceptible to irritation=> treatment with brewers yeast is recommended CANDIDIASIS/CANDIDOSIS fungal invasionhas been associated with speckled type of

leukoplakia => invading Candida hyphae may beresponsible for a disorderly maturation of theepithelium


37/51

ORAL CLINICAL MANIFESTATIONS


38/51

DISTRIBUTION AS TO AGE AND SEX

GENERALLY leukoplakia is seen in patients over 40 years of ageOnly about 5% of px are under 30 yrs of age

Males (69%) more predisposed than women (31%)Slight trend for earlier occurrence of leukoplakia inFEMALES


39/51

DISTRIBUTION AS TO LOCATION

Renstrup report:top locations: buccal mucosa and commisuresin descending order: alveolar mucosa, tongue,lip, hard and soft palates, floor of the mouthand gingivaHobaek report:top locations: tongue and floor of the mouthin descending order : lower lip, buccal mucosa,

palate, and gingiva*** In this study of Hobaek, multiple areas ofinvolvement were common


40/51

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


41/51

LEUKOPLAKIA

Leukoplakia of the dorsaltongue. The microscopicdiagnosis was basal and

parabasal cell hyperplasia


42/51

LEUKOPLAKIA

The white appearance of OL (oral leukoplakia) ismost often related to an increase in the surfacekeratin layer.

The most common sites of lesions are the buccal andalveolar mucosa and the lower lip. Lesions in the floor of the mouth, lateral tongue andlower lip more often show epithelial atypia or even

malignant growthTWO TYPES: homogenous and nonhomogenous


43/51


44/51

LEUKOPLAKIA, HOMOGENOUS Type


45/51

LEUKOPLAKIA

NONHOMOGENOUS TYPE (a.k.aERYTHROLEUKOPLAKIA)

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 sharpprojections .

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.


46/51

LEUKOPLAKIA, NonHomogenous Type

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


47/51


48/51


49/51

LEUKOPLAKIA, NonHomogenous Type

PVL showing verrucous surface with hyperkeratosis,hypergranulosis and a denseinflammatory infiltrate in the

corium.

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


50/51

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 anincrease in subepithelial blood vessels, a lack ofsurface keratin and thinness of the epithelium

Although OE is a rare lesion, it is much more likelyto show dysplasia or carcinoma.


51/51

Take note.

In all red lesions of the oralmucosa that do not regresswithin 2 weeks of the removal of

possible aetiological factors,biopsy is, therefore,

Mandatory!!!!!

Documents

i Oral Precursor Lesions