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Lets start our lecture , Last time we defined leukoplakia as a white patches that cant be removed by scrubbing and it cant be diagnosed as any clinical disease , it doesnt reflect a true histopathological features and true picture . sometime the appearance of leukoplakia -as homogenous or non homogenous- can tell us if leukoplakia is having a higher tendency for epithelial dysplasia or not ( non is higher), but we cant rely on this clinical appearance to determine if theres high risk or low because some of homogenous leaukoplakia ll have dysplasia . Histopathological appearances of leaukoplakia are epithelial dysplasia , keratosis alone , hyperplasia alone , keratosis and hyperplasia together or karatosis hyperplasia dysplasia , squamous cell carcinoma ( malignant change ) . The factors that ll give us clinical pic of leaukoplakia are : -keratosis, -epithelial thickness, -epithelial dysplasia, -chronic inflammation Now we mention keratosis and as we know it can be parakeratosis (with nuclei ) or orthokeratosis ( without

neuclei). We can see an prominent layer here (the arrow ) and its called granular layer ( its more obvious in orthokeratosis than parakeratosis ) .

Para

ortho

The thickness of epithelium is variable , Some leaukoplakia can give you increased epithelial thickness ( acanthosis ) , or atrophy espesialy if the leakoplakia is speckled . because of atrophy the lesion is red . ( *remember from histology : as we know the epithelium is avascular and its supplied by the vascular connective tissue that lied under it , so when the epithelium is thinner the blood vessels of connective tissue will be more prominent so the red color ll appear .

Acanthosis

atrophy

Epithelial dysplasia may show clear cut (abrupt) junction between dysplastic epithelium and normal one , or may show gradual transition between them. In dysplastic epithelium we can see hyperchromatism like as in the pic .

Dysplastic side

normal side

Features of dysplasia that indicate smoking : 1- chevron peaks(triangular curve) of keratin or epithelium itself

2- increased melanin production in basal keratinocytes ( melanin incontinence ) , its over production of melanin that ll escape to the underlying tissue then itll be engulfed by macrophages , so most of the time we see melanin in the underlying connective tissue inside the cytoplasm of macrophages .

So these two features are highly suggestive of smoking as etiological factor that associated with leaukoplakia . Now epithelial dysplasia isnt present in most leaukoplakias , it depend on geographic location , habits , risk factors . the percents of finding dysplasia is usually 18% ( less than 20%) . The dysplasia is an architecture change in the epithelium that include cellular atypia and the over all morphology of the epithelium . as we know the cellular atypia is the change in the individual cell , but the dysplasia is the change in whole epithelium . we can classify dysplasia according to cellular atypia extension into mild , moderate and severe : -Mild dysplasia when atypia isnt extending beyond the lower(basal) third of the epithelium

-moderate dysplasia when atypia involves the basal two thirds -severe one when atypia involves the superficial third In the pic below we can say its severe because we can see atypical cells ( large and have increased nuclear to cytoplasmic ratio ) in the upper third .

We said that we cant predict the histopatholigical features of leaukoplakia based on the clinical pic alone , however theres indication by homogenous and non homogenous , non homogenous usually have dysplasia ( 50% according to some studies ) more than homogenous(10%) . Speckled leaukoplakia have 100% of presence of dysplasia . Now in the figure below :

First we can see the normal , then the homogenous we can notice increase thickness of keratin in comparison to normal , increase thickness of epithelium and theres some lymphocytic infiltrate but the dysplasia isnt present . Now when we have thick fissured leaukoplakia it still homogenous except some grooves and fissures and here we can see some dysplastic ( mild in the lower third ) features . but the surface of leakoplakia start to be nodular with more fissuring then the dysplasia ll be more present and in higher rate , so here its moderate severe and then there ll be erythroplakia and now we can notice how the epithelium start to be atrophic ( so the epithelium ll be atrophic when there is erythroplakia . if it is erythroplakia and hyperplastic then itll be speckled leaukoplakia .

The dysplastic features ll reflect change in maturation , proliferation and differentiation of the epithelium . features of dysplasia :

1.

Increased and abnormal mitoses , now the normal location of mitoses is in the basal layer , while in dysplasia it ll be higher suprabasal , and in the basal layer there ll be increase in number and this ll give abnormal shape . As we see in the pics its not the normal mitoses that we know ( not two parallel lines of chromosomes in the midline ), here we have X shape or star shape appearance . here we may find normal mitoses but it can be suprabasal .

2.

Basal cell hyperplasia, its cuboidal and hyperchromatic ( dark color) cells , here we can see these cells more than in the basal third of normal epithelium . so here we can see thick layer of basaloid cells , so this is basal cell hyperplasia and reflect abnormal proliferation . mitotic figures also reflect abnormal proliferation .

3.

Drop-shaped rete ridges that the epithelium ll be elongated and widened like a drop , its constricted above and widened toward the basal layer, and this is because of more and more proliferation in basal area .

4.

Disturbed polarity of basal cells or loss of cellular orientation , you wont see the basal layer normally a lined or side by side next to each other , it ll be poorly oriented and extended suprabasaly to the superficial

layer , this may be by increasing of the proliferation in the basal area .

5.

Increase in nuclear/cytoplasmic ratio , in this case well see nucleus as big and the cytoplasm is less than normal cells . if we go up from the basal layer well see big nucleus and less cytoplasm , so it can be seen in the middle and superficial layers not just in the basal .

6. Nuclear hyperchromatism, well see some nucleis deeply blue because they take stain more than others because they are hyperchromatised . now hyperchromatic cells are restricted to the basal layer , but here we see it in the middle so its abnormal .

7.

Prominent and enlarged nucleoli , as we can see its a nucleus and inside it prominent nucleoli . this feature in many tumors .

8. Irregular epithelial stratification or disturbed maturation , in normal epithelium we have cuboidal basal layer ,above it flattened pickled cell layer ,and at the top will be more flattened and thin. This stratification is lost in dysplasia, everything is looking the same all of them are cuboidal and hyper chromatic. Also maturation will be disturbed, when epithelial cells become mature it starts forming keratin .so we cant see

any granular layer because all layers like each other . this is an architectural feature and thats mean I cant say its atypia because its just in individual cell , but we can say its dysplasia because it involves atypia and archtictural features .

9.Nuclear and cellular pleomorphism , you can see variation in shape and stain of the cells . the nucleus may show slight change in size and shape like to be polyhedral , round several shapes . 10.Abnormal keratinization , keratin as we know ll be in the superficial and top layer (surface) , but sometime we can see it even below the granular layer. So this is abnormal maturation .

11.Loss or reduction of intercellular adhesion , it ll be decreased so we can see a spaces between cells . so this tell us the dysplasia is coming soon .

Now , Sometime the epithelial dysplasia may be seen in a reactive area like candidoses or inflammation , so the dysplasia here ll be considered as reactive because when we give an antifungal or vaccine it can be reversed . In some studies theres a rate up to 14% that leaukoplakia ll transform to carcinoma . this transition depend on the location in the oral cavity , some have high risk like ventral of the tongue, Floor Of the Mouth, lingual aspect

of lower alveolar mucosa. These sight show high malignant transformation even there is any medical treatment or vaccine . these lesions are called sublingual keratosis , it have a high risk of transformation to squamous cell carcinoma even though 25% will transform . If leaukoplasia has a hyperkeratosis alone there ll be no risk to transform . while leaukoplakia that carry dysplastic features ll has high risk . The majority of dysplastic lesions remain unchanged during observation period. We cant leave our patient go home with leaukoplakia without take a biopsy because of high percentage of having transformation . Sometimes we see white areas in the corner of the smokers mouth and it cant be removed by scrubbing , but when we give them antifungal theyll be improved so its a candida infection . in this infection there is 30% to transform . -Dysplastic leukoplakia have higher rate to progress than non neoplastic (10-30%) -More severe dysplasia higher risk -Majority of dysplasia remain unchanged May progress or improve - No clear corelation between histology and clinical:

-Sublingual keratosis even with mild dysplasia is high risk There is a feature that ll indicate transformation its the DNA content . the normal DNA content is diploid , so if the leaukoplakia carry diploid there ll be low risk . but if it carry tetraploid ( double of the normal ) it ll have intermediate risk . and if it carry aneuploid ( abnormal amount of DNA even less than normal or more) it ll have the highest risk to transform . The risk assessment is based on: 1. Size ( bigger have higher risk ) 2. Site 3. Clinical appearance ( speckled vs homogenous vs erythroplakia ) 4. Degree of epithelial dysplasia. **Note : the dr said the percentage is included , so you should know it . We said the causes of white lesions in the oral cavity are :- traumatic causes ( mechanical , chemical and thermal ) - hereditary causes ( sponge nevus ) - idiopathic causes ( leaukoplakia ) - and now terminological causes (Lichen Planus and Lupus Erythematosus)

* Lichen Planus :

It may present in the skin and oral cavity . usually if the patient has Lichen Planus in the skin , 50% there ll be in the oral cavity . if the patient has it in the oral cavity, 10% there ll be in the skin . Now Skin lesions: -Violaceous, itchy papules, may have white streaks on surface that we call it Wickhams striae. Usually appear along the scratch -Variable patterns for papules: discrete, linear, annular, bullous, or widespread rash -Predilection to flexor surface of wrist. 10% with nail involvement in the form of vertical ridges. -Lesions develop slowly and 85% resolve within 18 months, sometimes with recurrence. Now oral lesions : it ll show a white striations on the buccal mucosa and mostly affect it , oral lesions show a

much more chronic course sometimes extending over many years. -may also affect tongue, gingiva , palate and lips. -Bilateral (most of the time bilateral) and wide spectrum of presentations, alone or in combination. **Non-erosive type: - reticular or annular, papular, plaque-like. - usually asymptomatic.

**Erosive/atrophic types: - red glazed appearance with areas of superficial ulceration which may take several weeks to heal. - occasionally, ulcers are preceded by bullae (bullous type). - often associated with typical areas of non-erosive lichen planus. - pain and discomfort may be severe.

Why the atrophic type ll take the higher risk ? Because the epithelium ll be thin and the barrier is impaired ( we concern about epithelium as a barrier also , so when the epithelium is atrophic the insult ll be more effective and the barrier is less . When the Lichen planus involve the gingiva often presents as a desquamative gingivitis. But its not the marginal gingiva ( the gingiva at the margin of the tooth and gingiva that lies above it attached gingiva attach to the bone .** I think we took about these two concepts briefly in a figure in oral histo course ** . What are the Histopathologic Features? : - hyper keratosis para or ortho ( white areas) -Epithelial atrophy especially in red areas (so epithelium thickness and keratosis ll reflect the color ) or acanthosis (sawtooth pattern of rete ridges).

the most important well-defined band of subepithelial mononuclear infiltrate immediately below the epithelium , its component is lymphocyte mainly CD8+ type that is cytotoxic T-cells. These cells ll attack the epithelium and ll cause Liquefactive degeneration of basal layer so we cant see the basement membrane . may be the attack occure because of high activity or infection ( we can say like the antigen of epithelium like the virus antigen so itll be attacked ). Sometime by this the fluid ll accumulate and sometime bullae ll be there or not .

we may see Civatte bodies , its hyaline shrunken bodies representing apoptotic cells. And by this the basal layer wont appear .

the causes of the Lichen planus : not fully understood but it can be due to : -Widely accepted that cell-mediated immune responses to an external antigen, or internal antigenic changes in epithelial cells, are involved.

-Response resembles type IV hypersensitivity. -Cytotoxic lymphocytes damage basal epithelium -In most cases the precipitating factors are unknown and when the cause is removed it ll be better. -May be hypersensitivity to drugs and dental materials -Association with systemic conditions: Hepatitis C -Graft versus host reaction that present when the patient has transplant and the body reject it so this rejection ll affect the skin and the oral cavity , so the body ll reject the organ and also ll attack the oral mucosa and others and its fatal sometimes . -In some patients, lesions are triggered by hypersensitivity to drugs or dental materials. -In such cases the condition resolves upon withdrawal of the offending agent. -Such lesions are referred to as lichenoid reactions to distinguish them from idiopathic lichen planus. **** Slide 56 so important and the dr just read it We forgot to say females are affected more than males with lichen planus. The last disease for today :

Lupus erythmatosus Two types : 1. Chronic discoid :more localized, rounded area on the face ll show white and purple scaly like keratosis.intra orally we may have areas that is white but with some atrophic red parts and some striations that are more prominent than systemic(sle) ( so by this we can differentiate between them and by biopsy also , or even examining the patient for antinuclear antibody may help). These areas wont go away by any topical cream Most common is a discoid area of erythema or ulceration surrounded by white keratotis border sometimes with radiating striae --butterfly appearance : more common in sle ( sys lopus eryth) not in discoid because the most common in discoid is round . 2. Systemic LE: disseminated. A variety of autoantibodies are present in SLE, e.g. antinuclear antibodies (ANA)

Females are affected more than males.

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*** important note : after you read this script I advice you to refer to the slides because the dr didnt mention all the things in the slide , the record wasnt good enough to give me support to cover all the lecs information and the drs voice sometimes was too low . so I hope that the record ll be better for you for the next lec script. Forgive me if theres any mistake Best wishes for all ^_^ Done by : Yahya al Omary