keratoses and related disorders of oral mucosa ii (slide 4 + 5 + 6)

8/2/2019 Keratoses and Related Disorders of Oral Mucosa II (slide 4 + 5 + 6)

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Dent 355Dent 355KeratosesKeratoses and Related Disordersand Related Disorders

of Oral Mucosa IIof Oral Mucosa II

Dr. Rima SafadiDr. Rima SafadiModified from Dr. HudaModified from Dr. Huda HammadHammad lectureslecturesReference: Oral pathology book byReference: Oral pathology book by SoamsSoams andand

SouthamSoutham


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Leukoplakia: Pathology, Epithelial DysplasiaLeukoplakia: Pathology, Epithelial Dysplasia

Wide range in histological appearances reflectsWide range in histological appearances reflectsvarying degreesvarying degrees of:of:

keratosiskeratosis,, epithelialepithelial thicknessthickness,, epithelialepithelial dysplasiadysplasia,, chronicchronic inflammationinflammation in the laminain the lamina propriapropria..


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It is important to remember that:It is important to remember that:LeukoplakiaLeukoplakia is ais a clinical diagnosisclinical diagnosis

arrived at after exclusion of otherarrived at after exclusion of otherdiseases and isdiseases and is notnot based on anybased on anyspecificspecific histopathologicalhistopathological features,features,i.e. the termi.e. the term leukoplakialeukoplakia hashas nono

histological connotation.histological connotation.


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Hyperkeratosis may be due to orthokeratosis,Hyperkeratosis may be due to orthokeratosis,parakeratosis, or both.parakeratosis, or both.


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Epithelium may be hyperplasticEpithelium may be hyperplasticor atrophic.or atrophic.

Areas of erythroplakia areAreas of erythroplakia areoften associated with epithelialoften associated with epithelialatrophy.atrophy.


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The junction betweenThe junction betweennormal and abnormalnormal and abnormalepithelium may beepithelium may beabrupt or there mayabrupt or there maybe gradual transition.be gradual transition.


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2 features are highly2 features are highlysuggestive of smoking as ansuggestive of smoking as anetiological factor:etiological factor:

1. presence of chevron peaks in1. presence of chevron peaks inkeratin.keratin.

2. increased melanin production2. increased melanin productionin basal keratinocytesin basal keratinocytes andandleakage of melanin into theleakage of melanin into the

underlying connective tissueunderlying connective tissue(melanin incontinence).(melanin incontinence).


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In some leukoplakias, keratosis and change in thickness are the onlyIn some leukoplakias, keratosis and change in thickness are the onlyabnormal features.abnormal features.

Other cases show features of epithelial dysplasia.Other cases show features of epithelial dysplasia.

When dysplasia is present, not all dysplastic features are necessarily seen inWhen dysplasia is present, not all dysplastic features are necessarily seen inany one case.any one case.


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The degree of dysplasia isThe degree of dysplasia issubjectively assessedsubjectively assessed using termsusing termssuch assuch as mild, moderate andmild, moderate andseveresevere based on thebased on the thicknessthickness ofofepithelium involved.epithelium involved.

Mild (grade I) dysplasiaMild (grade I) dysplasiademonstrates proliferation ofdemonstrates proliferation ofatypical or immature basal cellsatypical or immature basal cellsabove theabove the parabasalparabasal region butregion butnot extending beyond the lowernot extending beyond the lowerthird of the epithelium.third of the epithelium.

Moderate (grade II) dysplasiaModerate (grade II) dysplasiademonstrates a similardemonstrates a similarproliferation into theproliferation into the middle onemiddle one--thirdthird of the epithelial crossof the epithelial cross--section.section.

The term severe (grade III)The term severe (grade III)dysplasia is reserved for abnormaldysplasia is reserved for abnormalproliferation from the basal layerproliferation from the basal layerinto the upper third of theinto the upper third of the

epithelium.epithelium.


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Although it is not possible toAlthough it is not possible topredict the presence and severitypredict the presence and severityof dysplasia from clinicalof dysplasia from clinicalappearance lesion,appearance lesion,

erythroplakiaserythroplakias and nonand non--homogeneoushomogeneous leukoplakiasleukoplakias arearemore likely to be dysplastic (ormore likely to be dysplastic (oreven malignant) thaneven malignant) thanhomogeneoushomogeneous leukoplakiasleukoplakias..

Several studies showed only aboutSeveral studies showed only about10% of homogeneous10% of homogeneousleukoplakiasleukoplakias to be dysplastic, asto be dysplastic, asopposed toopposed to 50% or more of non50% or more of non--homogeneous typeshomogeneous types..

SpeckledSpeckled leukoplakiasleukoplakias show a veryshow a veryhigh incidence of dysplasia, whichhigh incidence of dysplasia, whichapproaches 100%approaches 100% as specklingas specklingincreases and as the clinicalincreases and as the clinical

features more closely resemblefeatures more closely resembleerythroplakiaerythroplakia..


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The individualThe individualcellular changescellular changes

(cellular(cellular atypiaatypia))seen in dysplasticseen in dysplasticepithelium reflectepithelium reflectabnormalities inabnormalities inproliferationproliferation,,maturationmaturation, and, anddifferentiation ofdifferentiation ofepithelial cells.epithelial cells.


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LeukoplakiaLeukoplakia: Pathology, Epithelial Dysplasia: Pathology, Epithelial Dysplasia--

Features of Epithelial DysplasiaFeatures of Epithelial Dysplasia

1.1. Increased and abnormal mitoses.Increased and abnormal mitoses.2.2. Basal cell hyperplasia.Basal cell hyperplasia.3.3. DropDrop--shapedshaped reterete ridges.ridges.4.4. Disturbed polarity of basal cells or loss of cellular orientation.Disturbed polarity of basal cells or loss of cellular orientation.5.5. Increase in nuclear/cytoplasmic ratio.Increase in nuclear/cytoplasmic ratio.6.6. Nuclear hyperchromatism.Nuclear hyperchromatism.7.7. Prominent and enlarged nucleoli.Prominent and enlarged nucleoli.8.8. Irregular epithelial stratification or disturbed maturation.Irregular epithelial stratification or disturbed maturation.

9.9. Nuclear and cellularNuclear and cellular pleomorphismpleomorphism..10.10. AbnormalAbnormal keratinizationkeratinization..11.11. Loss or reduction of intercellular adhesion.Loss or reduction of intercellular adhesion.First 7 features represents abnormal proliferation while last 4First 7 features represents abnormal proliferation while last 4

represents abnormal maturation/differentiationrepresents abnormal maturation/differentiation


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Leukoplakia: Pathology, Epithelial DysplasiaLeukoplakia: Pathology, Epithelial Dysplasia--


1. Increased and abnormal mitoses.1. Increased and abnormal mitoses.


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2. Basal cell hyperplasia.2. Basal cell hyperplasia.


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3. Drop3. Drop--shaped rete ridges.shaped rete ridges.


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4. Disturbed polarity of basal cells or loss of4. Disturbed polarity of basal cells or loss ofcellular orientation.cellular orientation.


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5. Increase in nuclear/ cytoplasmic ratio.5. Increase in nuclear/ cytoplasmic ratio.


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6. Nuclear hyperchromatism.6. Nuclear hyperchromatism.


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Features of Epithelial DysplasiaFeatures of Epithelial Dysplasia7. Prominent and enlarged nucleoli.7. Prominent and enlarged nucleoli.


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9. Nuclear and cellular pleomorphism.9. Nuclear and cellular pleomorphism.


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10. Abnormal keratinization (dyskeratosis).10. Abnormal keratinization (dyskeratosis).


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LeukoplakiaLeukoplakia: Pathology, Epithelial Dysplasia: Pathology, Epithelial Dysplasia--


11. Loss or reduction of intercellular adhesion.11. Loss or reduction of intercellular adhesion.


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Epithelial DysplasiaEpithelial Dysplasia

CellularCellular atypiaatypia of minor degree may beof minor degree may beseen in reaction to inflammation inseen in reaction to inflammation in

conditions such as lichenconditions such as lichen planusplanus andandcandidosiscandidosis (reactive cellular(reactive cellular atypiaatypia))


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Leukoplakia: PrognosisLeukoplakia: Prognosis

Unpredictable tendency to undergo malignant transformation.Unpredictable tendency to undergo malignant transformation.

Marked variation in reported rates from different countries.Marked variation in reported rates from different countries.

Differences in diagnostic criteria and etiological factors.Differences in diagnostic criteria and etiological factors.

Transformation times vary from one to several years.Transformation times vary from one to several years.

Combining results from several studies, a rate of ~14% over aCombining results from several studies, a rate of ~14% over a

period of up to 20 years has been reported.period of up to 20 years has been reported.


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LeukoplakiaLeukoplakia: Prognosis: Prognosis

Potential for malignantPotential for malignanttransformation is greatertransformation is greaterin high risk sites (ventralin high risk sites (ventral

tongue, FOM, lingualtongue, FOM, lingualaspect of lower alveolaraspect of lower alveolarmucosa).mucosa).

Lesions in these areas areLesions in these areas aredesignated asdesignated as sublingualsublingualkeratosiskeratosis to drawto drawattention to these sites.attention to these sites. 25% showed invasive SCC25% showed invasive SCC

in some studiesin some studies


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Dysplastic lesions carry an increased risk of malignantDysplastic lesions carry an increased risk of malignanttransformation (30%).

The more severe the dysplastic features, the greater theThe more severe the dysplastic features, the greater therisk, but no clear correlation.risk, but no clear correlation.

The majority of dysplastic lesions remain unchangedThe majority of dysplastic lesions remain unchangedduring observation period.during observation period.

A proportion of these will improve or regress.A proportion of these will improve or regress.


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Speckled and other nonSpeckled and other non--homogeneous types have anhomogeneous types have anincreased rate of malignaincreased rate of malignantnttransformation.transformation.

ErythroplakiaErythroplakia alone or as partalone or as partof speckledof speckled leukoplakialeukoplakia showsshowsinvasive carcinoma orinvasive carcinoma orcarcinoma icarcinoma in situ on ~n situ on ~ 50% o50% off

initial biopsies, and most of theinitial biopsies, and most of theremaining show severeremaining show severedysplasia.dysplasia.


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CandidalCandidal leukoplakialeukoplakia

has a highhas a high incidenceincidenceof dysplasia orof dysplasia ormalignantmalignanttransformationtransformation

(~30%).(~30%).


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Epithelial dysplasiaEpithelial dysplasia

DysplasticDysplastic leukoplakialeukoplakia-- higher rate tohigher rate toprogress than non neoplastic (10progress than non neoplastic (10--30%)30%)

More severe dysplasiaMore severe dysplasia higher riskhigher risk

Majority of dysplasia remain unchangedMajority of dysplasia remain unchanged

May progress or improveMay progress or improve

No clearNo clear corelationcorelation between histology andbetween histology andclinical:clinical:

SublingualSublingual keratosiskeratosis even with mild dysplasiaeven with mild dysplasia

is high riskis high risk


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Malignant transformation likely to be due to progressiveMalignant transformation likely to be due to progressiveaccumulation of genetic changes over time.accumulation of genetic changes over time.

Recent studies show thatRecent studies show that leukoplakiasleukoplakias with abnormalwith abnormalDNA content of epithelial cells are more likely toDNA content of epithelial cells are more likely toundergo malignant transformation.undergo malignant transformation.

This may become an important prognostic indicator inThis may become an important prognostic indicator in

the future.the future.


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LeukoplakiaLeukoplakia PrognosisPrognosis

DNA content is related to number of chromosomes:DNA content is related to number of chromosomes:

Malignant cells haveMalignant cells have abonormalabonormal number of chromosomes (deletionsnumber of chromosomes (deletionsreplications etc..)replications etc..)

Variation in number of chromosomes:Variation in number of chromosomes: aneuoploidyaneuoploidy

Duplication of chromosomes:Duplication of chromosomes: tetraploidytetraploidy

Normal cells with 2 copies:Normal cells with 2 copies: diploidydiploidy

LeukoplakiaLeukoplakia::

DiploidDiploid low risklow risk

AneuploidAneuploid high riskhigh risk

TetraploidTetraploidintermediateintermediate riskrisk


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At present, risk assessment is based on:At present, risk assessment is based on:1.1. SizeSize

2.2. SiteSite3.3. Clinical appearanceClinical appearance4.4. Degree of epithelial dysplasia.Degree of epithelial dysplasia.


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Dermatological Causes of White PatchesDermatological Causes of White Patches

Lichen PlanusLichen Planus

Lupus ErythematosusLupus Erythematosus


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Name provided by ErasmusName provided by ErasmusWilson in 1869.Wilson in 1869.

He probably thought the skinHe probably thought the skinlesions looked like lichenslesions looked like lichensgrowing on rocks.growing on rocks.

Lichens are primitive plantsLichens are primitive plantscomposed of symbiotic algaecomposed of symbiotic algae

and fungi.and fungi.


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Relatively common disease (0.5Relatively common disease (0.5--2% population).2% population).

Worldwide distribution.Worldwide distribution.

Involves skin and mucous membranes.Involves skin and mucous membranes.

Peaks between ages 30Peaks between ages 30--50.50.

60% females.60% females.

Oral lesions detected in ~50% of patients with initial skin lesions.Oral lesions detected in ~50% of patients with initial skin lesions.

Skin lesions in 10Skin lesions in 10--50% of patients with initial oral lesions.50% of patients with initial oral lesions.

Oral lesions may occur before, at the same time as, or after skinOral lesions may occur before, at the same time as, or after skinlesions.lesions.


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Lichen Planus: Clinical FeaturesLichen Planus: Clinical Features

Skin lesions:Skin lesions:

Violaceous, itchy papules, mayViolaceous, itchy papules, mayhave white streaks on surfacehave white streaks on surface

(Wickhams striae).(Wickhams striae).

Variable patterns for papules:Variable patterns for papules:discrete, linear, annular,discrete, linear, annular,bullous, or widespread rash.bullous, or widespread rash.


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Skin Lesions:Skin Lesions:


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Skin Lesions:Skin Lesions:

Predilection to flexor surface ofPredilection to flexor surface of

wrist.wrist.

10% with nail involvement in10% with nail involvement inthe form of vertical ridges.the form of vertical ridges.

L

esions develop slowly andL

esions develop slowly and85% resolve within 18 months,85% resolve within 18 months,sometimes with recurrence.sometimes with recurrence.


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Oral Lesions:Oral Lesions:

In contrast to skin lesions, oral lesions pursue a much more chronic course,In contrast to skin lesions, oral lesions pursue a much more chronic course,sometimes extending over many years.sometimes extending over many years.

Mostly affect buccal mucosa, may also affect tongue, gingiva, palate, and lips.Mostly affect buccal mucosa, may also affect tongue, gingiva, palate, and lips.

Bilateral and wide spectrum of presentations, alone or in combination.Bilateral and wide spectrum of presentations, alone or in combination.


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NonNon--erosive typeerosive type::

-- reticular or annular,reticular or annular,papularpapular, plaque, plaque--like.like.

-- usually asymptomatic.usually asymptomatic.


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Erosive/atrophic types:Erosive/atrophic types:

-- red glazed appearance withred glazed appearance with

areas of superficial ulcerationareas of superficial ulcerationwhich may take several weekswhich may take several weeksto heal.to heal.

-- occasionally, ulcers areoccasionally, ulcers arepreceded bypreceded by bullaebullae ((bullousbullous

type).type).-- often associated with typicaloften associated with typical

areas of nonareas of non--erosive lichenerosive lichenplanusplanus..

-- pain and discomfort may bepain and discomfort may be

severe.severe.


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Lichen planus involving theLichen planus involving the

gingiva often presents as agingiva often presents as adesquamative gingivitis.desquamative gingivitis.

More typical areas can usuallyMore typical areas can usuallybe seen elsewhere on the oralbe seen elsewhere on the oral

mucosa.mucosa.


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Regezi


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Lichen Planus: PathologyLichen Planus: Pathology

Histopathologic Features:Histopathologic Features:

OrthoOrtho-- or parakeratosis.or parakeratosis.

Epithelial atrophy or acanthosisEpithelial atrophy or acanthosis(sawtooth pattern of rete(sawtooth pattern of reteridges).ridges).

Dense, wellDense, well--defined band ofdefined band ofsubepithelial mononuclearsubepithelial mononuclearinfiltrate, mainly Tinfiltrate, mainly T--cells.cells.


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LiquefactiveLiquefactivedegeneration of basal celldegeneration of basal cell

layer associated withlayer associated withedema and lymphocyticedema and lymphocyticinfiltration.infiltration.

Civatte bodies: hyalineCivatte bodies: hyaline

shrunken bodiesshrunken bodiesrepresenting apoptoticrepresenting apoptoticcells.cells.


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Basal cell degenerationBasal cell degenerationmay result inmay result insubepithelial bullaesubepithelial bullaeformation and ulceration.formation and ulceration.


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Almost all cases run a benignAlmost all cases run a benigncourse.course.

Malignant transformation hasMalignant transformation has

been described in a very smallbeen described in a very smallproportion (0.5%proportion (0.5%--2.5% over 52.5% over 5years).years).

Some studies suggest thatSome studies suggest thatatrophic/erosive forms are moreatrophic/erosive forms are more

likely for such transformation.likely for such transformation.

Other studies found it more likelyOther studies found it more likelywith plaque lesions.with plaque lesions.


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Lichen Planus: Etiology & PathogenesisLichen Planus: Etiology & Pathogenesis

Not fully understood.Not fully understood.

Widely accepted thatWidely accepted thatcellcell--mediated immune responsesmediated immune responses totoan external antigen, or internal antigenic changes inan external antigen, or internal antigenic changes in

epithelial cells, are involved.epithelial cells, are involved.

Response resembles type IV hypersensitivity.Response resembles type IV hypersensitivity.

CytotoxicCytotoxic lymphocytes damage basal epithelium.lymphocytes damage basal epithelium.

In most cases the precipitating factors are unknown.In most cases the precipitating factors are unknown. May be hypersensitivity to drugs and dental materialsMay be hypersensitivity to drugs and dental materials Association with systemic conditions:Association with systemic conditions: HepHep CC Graft versus host reaction presents with LP like lesionsGraft versus host reaction presents with LP like lesions


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Lichen Planus: Etiology & PathogenesisLichen Planus: Etiology & Pathogenesis

In some patients, lesions areIn some patients, lesions aretriggered by hypersensitivity totriggered by hypersensitivity todrugs or dental materials.drugs or dental materials.

In such cases the conditionIn such cases the conditionresolves upon withdrawal ofresolves upon withdrawal ofthe offending agent.the offending agent.

Such lesions are referred to asSuch lesions are referred to as

lichenoidlichenoid reactionsreactions to todistinguish them fromdistinguish them fromidiopathic lichenidiopathic lichen planusplanus.. Lichenoid reaction to dental amalgamLichenoid reaction to dental amalgam


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External antigen challenge and/or modified antigenic structure of epithelial cellsExternal antigen challenge and/or modified antigenic structure of epithelial cells

Antigen challengeAntigen challenge

Langerhans cells KeratinocytesLangerhans cells KeratinocytesExpression of ICAMExpression of ICAM--11

Expression of class II MHC Cytokine releaseExpression of class II MHC Cytokine release

Antigen presentation LymphocyteAntigen presentation Lymphocyteto CD4 cells infiltto CD4 cells infiltratrationion

Activation of CD8 Damage to basal cells Activation of CD8 Damage to basal cellscytotoxic cellscytotoxic cells

Lichen Planus: PathogenesisLichen Planus: Pathogenesis


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LichenLichen PlanusPlanus: Pathogenesis: Pathogenesis LichenLichen planusplanus has been associated with somehas been associated with some systemicsystemic

diseases.diseases.

In many of these, aIn many of these, a causecause--andand--effect relationship has noteffect relationship has not

been established.been established.

The systemic condition may merelyThe systemic condition may merely exacerbateexacerbate a prea pre--existing lesion.existing lesion.

Strong evidence of association of chronic liver diseaseStrong evidence of association of chronic liver diseaseassociated withassociated with hepatitis C virus infection.hepatitis C virus infection.

Oral andOral and cutaneouscutaneous lesions resembling lichenlesions resembling lichen planusplanus occuroccurin graft vs. host diseasein graft vs. host disease

Transplanted T cellsTransplanted T cells react to antigens on host epithelial cells.react to antigens on host epithelial cells.


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GVHGVH


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Lupus ErythematosusLupus Erythematosus

Two main forms:Two main forms:

1.1. Chronic discoid LE: localized.Chronic discoid LE: localized.

2.2. Systemic LE: disseminated.Systemic LE: disseminated. A variety ofA variety of autoantibodiesautoantibodies are present in SLE, e.g.are present in SLE, e.g.

antinuclear antibodies (ANAs).antinuclear antibodies (ANAs).

Females > males.Females > males.


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Lupus Erythematosus: Clinical FeaturesLupus Erythematosus: Clinical Features

Chronic Discoid LupusChronic Discoid LupusErythematosusErythematosus (DLE):(DLE):

Lesions often restricted to skinLesions often restricted to skinand usually occur on the face.and usually occur on the face.

Scaly red patches which heal withScaly red patches which heal withscarring.scarring.

Sometimes facial lesions inSometimes facial lesions inboth formsboth forms have a symmetrichave a symmetricdistributiondistribution (butterfly rash).(butterfly rash).


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Chronic Discoid LupusChronic Discoid Lupus ErythematosusErythematosus(DLE):(DLE):

Oral lesions in up to 50% ofOral lesions in up to 50% of

cases.cases.

BuccalBuccal mucosa most frequentlymucosa most frequentlyaffected.affected.

Considerable variation in oralConsiderable variation in orallesions.lesions.

Most common is a discoid area ofMost common is a discoid area oferythemaerythema or ulcerationor ulceration surroundedsurroundedby whiteby white keratotiskeratotis borderbordersometimes withsometimes with radiatingradiating striaestriae..

Main D/D lichenMain D/D lichen planusplanus..


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Systemic Lupus ErythematosusSystemic Lupus Erythematosus(SLE):(SLE):

Disseminated disease almostDisseminated disease almostinvolving every organ.involving every organ.

Skin rashes: maculopapular,Skin rashes: maculopapular,photosensitive especially onphotosensitive especially onface (butterfly rash).face (butterfly rash).

Oral lesions variable.Oral lesions variable.

May be fatal.May be fatal.


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LupusLupus erythematosuserythematosus

histopathologyhistopathology

Deep perivascularLymphocytic infiltrat


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Lupus Erythematosus: Histopathologic FeaturesLupus Erythematosus: Histopathologic Features

Subepithelial and deepSubepithelial and deepperivascular lymphocyticperivascular lymphocyticinfiltrates.infiltrates.

LiquefactiveLiquefactivedegenerartion of basaldegenerartion of basalcells.cells.


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LupusLupus erythematosuserythematosus

ImmunofluorescenceImmunofluorescence studies showstudies showabundant deposits ofabundant deposits of IgGIgG andand

complementcomplement-- Lupus BandLupus Band


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Revision slidesRevision slides


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White Sponge nevusWhite Sponge nevus


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LeukoplakiaLeukoplakia


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SubmucousSubmucous fibrosisfibrosis

(epithelial atrophy)(epithelial atrophy)


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SCCSCC


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Plummer Vinson syndromePlummer Vinson syndrome

(epithelial atrophy)(epithelial atrophy)


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keratoses and related disorders of oral mucosa ii (slide 4 + 5 + 6)

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