Keratoses and Related Disorders of Oral Mucosa

•Introduction: Normal Oral Mucosa

•The color of normal mucosa is kind of pink, This color result from interplay of factors which are the : vascularity , epithelium and melanin

•

•The epithelium itself depend on the thickness of epithelium , and the keratin layer of the epithelium in that area

•Some time we have white appearing mucosa in those case the problem will be in the epithelium itself ,,, that the epithelium may

be thicker than normal, or the keratin layer is thicker

•Some time we have pale mucosa in that situation the : vascularity is less than normal

•In smokers the melanin pigmentation layer will increase and we will have certain area in oral cavity with brownish appearance this appearance not because the epithelium is altered

Where do we have the melanocytes ? in the basal layer of the epithelium it will produce melanin

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keratin layer

Epithelium

Blood vessels

•Kertinaization of the oral cavity

•We have keratinized, and Non-keratinized mucosa

•Actually all oral mucosa in the oral cavity will have a keratin layer but some area are more keratinized than others so they well known as keratinized and the rest as non keratinized

•Non keratinized areas

lower labial epithelium , the buccal epithelium of mucosa , the soft palate , part of the hard palate ,floor of the mouth ,ventral surface of the tongue

and the lateral lateral border of it are non keratinized .

**although these tissue are not keratinized but we will see keratin layer microscopically but it’s very minimal

•The keratinized areas

the dorsum of the tongue, the gingiva “ the attached gingival because removable gingival will be non keratinized up in the sulcus” , and the hard palate mainly the anterior part “ roughe area” are keratinized areas

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•Introduction: White Patches

white patch , maybe result of either of the increase of the thickness of epithelium itself, or the production of the keratin itself, or having

abnormal keratin

why is that?

increase in keratin will give us white appearance because you will not see the blood vessels in the underlining mucosa the reflection of light over the blood vessels will not be normal you will see it as white and especially that when kertin absorbed saliva or water it will appear whitish we will

not have the normal pink appearance.

When the keratin increase in thickness we cannot remove it be scrapping, if u scrapped it with tongue depressor it will not wiped off.

while if u have debris food debris or necrotic tissue “e.g due to burn” it can be wiped off easily even if it because Candida infection it can be removed be scrapping but increase in keratin thickness it will not whipped

off

Debris , necrotic tissue , infection of Candida “ like the acute candidosis ‘ it can be scraped off

Why some time do we have debris accumulating on the tongue to give this whitish appearance especially in patient who are ill or having

tonsillitis or fever ?

Because there will be lack of mechanical stimulation of the tongue so there will be no movement of the tongue the patient doesn’t have appetite doesn’t eat doesn’t speak like normal , so stimulation will be less than normal and there will be no sloughing of the debris especially when they

silvery flow is low.

•Definition of Histopathological Terms

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•Orthokeratosis: superficial keratinized squames are flattened, anucleate, with homogeneous, acidophilic cytoplasm.

•Parakeratosis: superficial keratinized squames are flattened, with homogeneous, acidophilic cytoplasm, but contain pyknotic nuclei

•Hyperkeratosis: increased thickness of keratin layer “ where it’s normally present ”

•Keratosis: keratinization of epithelium that is not normally keratinized

•Hyperparakeratosis: increased thickness of parakeratin layer

•Hyperorthokeratosis: increased thickness of orthokeratin layer

•Acanthosis is increase in thickness of the epithelium in general {close to hyperplasia in the epithelium} but mainly it’s in the prickle cell layers , and when we say hyperplastic we mean all layer

of the epithelium

- when there is acanthosis there will be elongation of the rete ridges

rete ridges

•Epithelial atrophy: decrease in thickness of epithelium

•Celluler atypia changes affecting certain cells that may mean premalignant lesion. - we said may mean because some time the change is due to

inflammation.

•Epithelial dysplasia a term describing epithelium when features of cellular atypia are present -

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in these term we describe the whole epithelium not a certain cells , because sometime we will have cells without atypia but the whole surface of the whole epithelium is dysplastic but not all the epithiulm are showing the a typical features

So epithelial dysplasia refers to epithelia itself including celluer atypia and architecture changes while

Cellular atypia refers to specific cells …

If we have a white lesion in oral cavity it will be classified according to this table

Hereditary Oral epithelial nevusOral manifestations of other rare genodermatosesLeukoedema

Traumatic Mechanical (frictional keratosis)ChemicalThermal

Infective Candidosis: - acute psuedomembranous

- chronic hyperplastic - chronic mucocutaneous

Syphilitic leukoplakiaHairy leukoplakia

Idiopathic LeukoplakiaDermatological Lichen planus

Lupus erythematosusNeoplastic Carcinoma in situ

Squamous cell carcinoma•

•Heredity conditions

•White sponge nevus

•Featuers

•We have white lesion in oral cavity in different position for example buccal and labial mucosa

•The patient is having a white lesion which can’t be removed be scrapping

•These spot appear in child hold because it’s heredity so it’s genetically determinant “ early stages of life

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•The problem here in keratin genes 13 and 4 - We have 20 genes only two of them are mutated and we will have this net result which is white sponge nevus appearance of the mucosa

•The border of the lesion are usually ill defined there continuation between the lesion and the adjacent normal epithelium

•The other feature not only the oral cavity is involved but the soft palate the esophagus nose , nasal mucosa and other mucosal surfaces are involved with this mutation

•Histologicaly

We have hyper keratosis and we have edematous intra cellularly “ inside the epithelium we have spaces which are edematous and also we have small piknotic nucleus

which is important because it’s is not seen in leuko edema >>>> in which we have intracellular edema we have glycogen accumulation but there is no specific feature of the nuclei

So when u have empty cytoplasm and when u have prominent cell borders and small nucleus it will look like the basket weave“ سله just the” نسيج

cellular border are obvious while the cytoplasm is empty {empty in appearance}

This edema is in the super facial prickle cell layer and also it may extend to the parakertinazed layer

hyper keratosis

acanthosis and edema

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•What is the concern of these white patches is it malignant potential ?

no , It’s just esthetic appearance it does not have any other feature of concern like pre malignant potential While luka plasia is a pre malignant has pre malignant potential

•Lukoedema

It may be familial , it apper as white milky appearance in the buccal mucosa that disappear upon starching it’s appear more in dark people and smokers

Histologicaly

the lukoedema will show intercellular edema and glycogenic accumulation inside the cell in addition to the intra cellular edema there is also increase in the thickness of the prickle cell layer we don’t have hyper keratosis so it should be easy for us to differentiate between white sponge nevus and

lukoedema

-Traumatic

What are the tube of trauma mechanical , thermal and chemical

Some time in mechanical irritation we have ulcer or erosion of surface epithelium and some mechanical irritation will give us white lesion what’s

the difference ?

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It depends on the severity of the trauma ,For example if we had a bite from a sharp cusp acute bite with a considerable force we will have ulcer or erosion ,But if I have a sharp cusp which is chronically irritating the buccal mucosa in low grade force for example while talking .. in this situation the body will have enough time to increase the thickness of epithelium or to form keratin so I will have white lesion of frictional keratosis in low grade friction of the cusp ….while I will have ulcer if I accidently had a bite to my buccal mucosa and this bite was sharp

•In traumatic keratosis | or frictional keratosis I need to identified a cause so I can call it frictional keratossis and this cause should

match the size and the site of the lesion.

•for example if I have a sharp cusp this sharp cusp should be on the site of the lesion if the lesion in the left buccal mucosa and the cusp is in the right buccal mucosa it’s not the cause both should be in the left side in addition if I have for example 5 cm lesion and the is only 3cm so it’s not the cause

•

•Another feature that when I remove the cause or when I correct it , the lesion should show a sign of healing within 2 weeks and reevaluate the patient if the lesion shows a sign of healing so it’s the cause

friction keratosis and epithiluim this is the granular cell layer which show granuolsis “which is the top layer before the keratinized layer” usually we have this granular layer in orthokeratosis

In epithiluim We have basal layer – prickle cell layer- granular cell layer then keratin layer the keratin will be flattened cells whith piknotic nucli or without nucli, and then we will have keratin production by the surface epithiluim and ussally we this granular cell layer when we have orthokerstosis

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In this histopathological picture I have thick layer of keratin production …. But usually we don’t have dysplasia no cellular atypia no dysplasia except increase in keratin thickness and some time increase in the thickness of

prickle cell layer or the whole epithelium “ acanthoses “

I may have acanthosis and hyperkeratosis or hyper keratosis alone for frictional keratosis

Done by mohammad elwir

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Chemical truma

In sever chemical trauma( high concentrated of chemicals), it will have necrosis of mucosa and sloughing , and the mucosa will be like depress in

the surface .

But if we have low grade infection like apatient who using for example medications immediately on the mucosa , he feels that if I put panadol next of the tooth , the pain will be relifed, sometimes this chemical irritation of low grade make increase of the thickness of surface epithelium or high production of keratin but if we have severe insult we will have a sloughing of the epithelium , sometimes some patient will place tobacco in the labial surface , which is smokers tobacco or sometimes they use it as snuff. , with time the body will react by having:

1 -increasing in keratin

2 -increasing in thickness of epithelium and sometimes other changes .

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In certain areas like al yemen , they use topical application of certain materials in the oral cavity and that will end up with changes which

sometimes will be malignant , other times affecting traumatic keratosis .

So we talked about hyperkeratosis in association with smookers tobacco and other types like betel nutt which is a topical application .

In the tobacco it self which is smoke tobacco > we have compination of effects which is:

1 -chemical insult to the mucosa .

2 -Thermal insult to the mucosa .

So we have dual irritation in smoking cigarate.

Sometimes we have keratosis in the lip itself but In a certain location which will be in the area where the patient will hold cigar or cigarette , due to frictional trauma and thermal especially in the pipe smokers we may

have these white areas in :

1 -dorsum of the tongue 2- palate .

Where the smoke will go to the palate and the tongue .

So the method of the smoking or the method of using smokeless tobacco , the area which is place will influence the manifestation of traumatic

keratosis .

Sometimes in severe smokers > as the students from the last year said : that they hold cigarette in the opposite way so in this case the soft palate

and the palate will be affecting .

The palatal changes with smokers :

There is white areas because the body is trying to deposite keratin and increase in the thickness of the epithelium to resist the thermal

stimulation by pipe smokers.

•*Characterized by hyperkeratinized palatal mucosa with a cobblestone appearance, with inflamed orifices of minor salivary

gland ducts showing as red dots .entrally.

You see red points and these are inflamed dilated orifices of the minor salivary gland are traumatized and also in the cigarette smokers when we do diagnosis sometimes we see glandular appearance in the lower lip due

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to hyperplastic reactive of the minor salivary gland due to smoking thermal injury and mechanical injury of the cigarate .

28 biopsies from the tongue and lateral border of the tongue, from the floor of the mouth with cell carcinoma and these are smoker not will be smoke , these are heavier smokers so the age of having squamous cell carcinoma of the oral cavity is decreasing , males and females are affected , young age are not protective and some of them are doctors.

In the nicotinic stomatitis we have hyper keratinized palatal mucosa with cobblestone appearance, with inflamed orifices of minor salivary gland ducts showing as red dots centrally.

They appeared white and we will have chronic inflammation surrounding the orifice of the minor salivary gland in addition to hyperkeratosis.So the whitish area is due to increase thickness epithelium and keratin and the red areas where due to inflammation of the ducts and minor salivary glands.

Leukoplakia:It is a white patch that cant be removed by snapping and cant be

attributed to a specific cause. •WHO original definition :definition that it cant be characterized as

any other definable lesion , firstly there is no any characterized clinically or histological as any other disease , and now Definition slightly modified in 1994 to: "a predominantly white lesion of the oral

mucosa that cannot be characterized as any other definable lesion ."

It is diagnose of exclusion , you have to exclude all lesions in the oral cavity , if you know that friction will give you a white lesion you should

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exclude friction , if you know that a chemical and thermal injuries give you white lesions , you should exclude thermal and chemical injuries before arrive to the diagnoses of leukoplakia.

The difference in definition is not dangerous here , they said logically and clinically , and here they said definable lesion and this definition may also change later when they study leukoplakia more and more.

Leukoplakia is a clinical diagnose , when I say leukoplakia I will have white patch , and it is clinical lesion , you should find a white patch that doesn’t show attributed or any other case or lesion , but at the same time leukoplakia you cant say that this leukoplakia is premalignant and this one

is not.

So it is clinical diagnosis arrived by exclusion and it is implies that there are no particular change or behavior , this is in general.

Certain clinical features of leukoplakia may indicate for premalignant changes , but it cant give you if the premalignant is mild or sever.

The incidence of leukoplakia is different to geographic location, because it is more in India for example and a certain geographic area while it is less in others, so it may range from 1- 10% of population or even more according to geographic areas. When we Compares between geographic areas it is difficult because of the etiological factors and diagnostic criteria .

Etiological factor is not a correct word to use here because in leukoplakia the smoking is the correlated cause but even though smoking should not be direct etiological cause.

There is a sentence in the book that if smoking was stopped and the white patches

Which is called leukoplakia decreased or even relived I should not called leukoplakia , this should be just reactive keratosis even smoking or tobacco is not major factor of leukoplakia but the lesion is decrease.

Then it is not leukoplakia it is only reactive leukoplakia can occur any where in the oral cavity.

*What are the most common location for leukoplakia? 1-floor of the mouth.

2-Buccal mucosa.

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*What are the areas that carry increased in potential for malignant or pramalignant change?

1-floor of the mouth. 2-ventral surface of the tongue.

3-Lateral surface of the tongue ( some times because most of the time due to frictional keratosis from the teeth unless we have leukoplakia without finding any cause).

Leukoplakia: Incidence: -Previous studies in Western Europe & North America:-predominance in

males- generally described as affect in older people- FOM & buccal mucosa mostly affected.

-Recent studies in the same areas indicate that:-M:F ratio is becoming almost equal- incidence in younger adults is increasing- this possibly reflects changes in smoking habits. Clinical features of leukoplakia:

We have homogenous types > you may see white patch in the ventral surface of the tongue and also the lateral border of the tongue , this white patch is having homogenous surface.

We have fissures and grooves , even though it is still considered homogenous , it will be not homogenous when there is lobularity of the

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lesion , when red areas are mixed with white areas . so this is called non homogenous leukoplakia which is more dangerous and carry higher

premalignant potential.. If homogenous leukoplakia started to show lobularity , this is an alarm

that there maybe increase in risk to have premalignant changes

Erythroplakia

leukoplakia is a white patch.

Erythroplakia: "a bright red velvety plaque on the oral mucosa which cannot be categorized clinically or pathologically as being

due to any other condition."

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Erythroplakia is a red patch on the oral mucosa that cant be categorized clinically or pathologically as being due to any other condition , sometimes burn ( thermal burn) will give us patch.

In the thermal burn we have pus , it can be diagnose as clinical or pathological cause but the erythroplakia this red patch in the floor of the mouth I cant find the cause by that. And this is even more dangerous than leukoplakia .and in general have higher risk of having premalignant.

Histopathologically, erythroplakia may represent carcinoma-in-situ or invasive carcinoma.

-its development in a previously uniform white lesion is an important clinical sign which may indicate sinister change.

Why we have red appearance in erythroplakia while leukoplakia have white appearance?

Because of something related to thickness of epithelium: -Leukoplakia > hyperkeratosis , increase thickness of epithelium.

-Erythroplakia > atrophic epithelium , decrease thickness of epithelium and this may be associated with inflammation too.

So there is increase in the redness of epithelium.

*Clinical features that may indicate malignant change in leukoplakia/erythroplakia:

1.development of erythroplakia in a previously uniform white lesion (erythroplakia transforms to malignant tumors or lesions more than leukoplakia ).

2.fixation ( if I started to get a fix lesion , this is an alarming because you know malignant lesion will invade the underlining structures sand result in fixation , so we don’t know that erythroplakia or leukoplakia is started to have malignant tumor which is invading the

underlining structures. 3.indurations ( is the response of the surrounding structures to the

lesion due to invasion and intense inflammation)4.Ulceration (we see it in squamous cell carcinoma, so this ulcertic

changes in leukoplakia or erythroplakia is alarming ).5.lymphoadenopathy ( which means that in tumor we have

lymphoadenopathy because of spread of malignant cells to the lymph nodes ).

6.bone destruction if it overlies bone (suppose we have this lesion here and when you look to the radiograph you find that the bone destruction in the underlining alveolar process, then start to investigate this mass or this lesion , take a biopsy and follow up the patient because it may have squamous cell carcinoma ).

7.other clinical features of malignancy ( loss of appetite , loosing weight ……ETC. ).

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Etiological factors of leukoplakia: *Leukoplakia is by definition idiopathic ( doesn’t have specific cause

but you have attributed factors or predispose factor that can be identified which is tobacco. (but they are nor causative)

*Etiology is likely to be multifactorial

*Tobacco use is a major factor. which is most commonly factors that associated with leukoplakia and the association depends on the:

1 -duration2 -on the amount of smoke tobacco

3 -the method of smoking and the area in the oral cavity which is mainly with contact with smoking.

Distribution of lesions may vary with particular type of habbit: cigarettes, bidis are for certain areas where they use leafs and they put certain nuts (betel nuts) in it then they rap it and they smoke it, or it maybe topically in the oral cavity so there are several methods like reverse smoking, tobacco chewing, pans, snuff dipping, or they may use sucking like tea bags , they put it in the buccal sulcus , they use it specially in areas where smoking is forbidden.

In those patients whose tobacco-associated keratosis regresses on cessation of the habit the lesion should not be classified as leukoplakia.

Alcohol

No clear evidence . but usually drinkers are also smokers .. we have synergistic effect between alcohol and smoking ( alcohol may dissolve the toxic material that are in smoking or alcohol may affect indirectly the appetite and not having good vitamins so the patient will have iron deficiency and this will lead to atrophic epithelium and this will be more

easy to the toxins to act in the epithelium and get lesions and cancer .

Candida

infection with candida will result in white lesion ( leukoplakia ) or the white lesions will be secondary infected by candida .. when we talk about infection we talk about premalignant potential of candida that is

inserted in affected mucosa.

But IS the candida cause white lesions which is colonized by candida or the white lesions is secondary colonized by candida ??

**until now it is not well known

But it is known that leukoplakia infected with candida have higher malignant potential than leokoplakia without candida

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Viruses

HIV viruses : type 16 and 18 but have uncertain role. EBV : uncertain role . the lesion that will ebv cause Is intraorally and is called hairy lekoplakia and it is not premalignant

etiological factors is epithelial atrophy : when epithelium is atrophic it will be easier for other chemicals to act and atrophic epithelium is associated with syndrome (plummer Vinson syndrome ) which has iron deficiency and esophageal features , also epithelial atrophy may be associated with iron deficiency ( anemic patient ) , with certain vitamin

deficiencies like b12 and folic acid.

Some times when we have red mucosa the indication will be that we have iron deficiency , when the epithelium is atrophic it will appear red because it will decrease in thickness and blood vessel will appear from the

epithelium.

mutation in p53 gene : tumor suppressor gene

there is a plant called sanguinaria Canadensis was used in tooth pastes and mouth washes and it was found that people who use this plant will have white lesions and will have premalignant potential so it not used any more

preparations containing sanguinaria should be avoided until the risk for malignant transformation is determined .

Done By:

We'am Rahamneh (:

9 يوجد , منك أشقى هو من دائمًا :(فًابتسم

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