oral pathology lec.12

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ORAL PATHOLOGY (2)

Monday >>> 26th Mar.2012

Dr. Rima Safadi

Slides for this lecture are titled Infections of the Oral Mucosa2

Slide (1): Infections of the Oral Mucosa 2.

We have already talked about the viral infections, bacterial infections

and today we will start talking about the fungal infections and also we

will talk about AIDS.

Slide (2): Fungal Infections.

Now the most common fungal organism affecting the oral cavity is the

Candida, and from the Candida we have several species like; C.

glabrata, tropicalis, parapsilosis,

C. krusei and C. albicans.

- Doctor Rima is not sure about the exact terminology of this in

microbiology, so lets consider Candida the most common one as a

family and the types of Candida as species -.

Albicans is the most common type of Candida.

Candida in general is the most common fungal organism presents in

the oral cavity and it causes lesions Fungal infections in the oral

cavity.

From the Candida the type Albicans Albicans species is the most

common causative type in the oral cavity, but other types are alsopathogenic and they may cause diseases and lesions inside the oral

cavity.

The Candida is dimorphic that means it presents in two forms two

morphologic appearances; the bud form which is rounded small or

oval-like appearance and the hyphae or the hyphal form which is

elongated rod-like very long actually it is ribbon-like.

So the long one is the hyphae, and the small rounded or oval is thebud.

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Multiplying of Candida is by budding; it means that this rounded

form will start giving small younger rounds or buds, it is forming small

buds from the oval-shaped type, and the rod-shaped form will give a

small little bud which will separate later on and it will grow, so it

multiplies by budding.

But the pathogenic type is the hyphal form the hyphae, it is

the one that causes diseases and lesions in the oral cavity, and when I

detect it in the oral cavity in a lesion I will say that the patient is having

Candidosis.

And if I found the oval shaped I will say that the patient may be carrier.

So the hyphal form is the pathogenic type and it is the one that gets a

diagnosis of Candidosis.

***There were two questions from students Dose they transform

from one type to the other? And can we see all of the types in just a

single lesion?

The doctors answers were: Yes, it may transform from the buds The

oval-shaped into the hyphae, depending on the situation.

And in a single lesion we can see hyphal and oval-shaped appearance

of the organism.

It is commensal; that means it lives in a commensal manner , so it lives inside the oral cavity and sometimes it lives therewithout causing diseases.

It is living with other types of bacteria in a commensal relationship; so

it gives a good thing to the bacteria and the bacteria does the same

with it, so they live together in a commensal relationship it is a

commensal organism.It is causing opportunistic infections , once the surroundingsituation is in imbalance in favor of the candidal organisms infection

will occur.

So if the imbalance occurred in the favor of the candidal organisms the

Candida will cause infection and that will give us Candidosis it is one

of the several forms of infections and we will talk about them in a

minute.

So those were the candidal characteristics in general:

1) It is dimorphic.

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2) It multiplies by budding.

3) It is commensal; it is living inside our oral cavities in a relationship

with bacteria and with other organisms which is living there without

causing diseases, unless the balance or the homeostasis of the

surrounding environment of the Candida is disturbed disturbance in

the favor of Candida and not in favor of the bacteria, then the Candidawill take the opportunity to cause infection.

Slide (3): Candida albicans.

Now this is a general information about Candida albicans inside our

oral cavity, that presents there without causing diseases, there is a

variable carriage rate; it means if they did counts for all of our oral

cavity Candida the Candida inside our oral cavity, they will find that

at least 40% of us are carrying Candida, but without having the

disease, and some studies says 40% others says 60% and some of

them says 80% of the population are carriers of the Candida.

The main location inside the oral cavity is the tongue, may be

because of its rough surface; so it will collect Candida more than other

locations.

And note that this is the carriage rate and it is not necessarily the

count, and even the count is variable, and some patients with the

disease with Candidosis may have high counts compared with

normal people whom are without the disease.

But there is overlap even between the counts, so we cannot rely on the

presence or the counts, we should rely on the presence of

hyphae, if there are hyphae in the smear then we can diagnose the

patient with Candidosis.

And now recently they say that you should find the hyphae with alesion, which means if I dont have a candidal lesion a Candidosis in

my patients mouth but there were hyphae, in this situation there is a

question mark, because they say that the hyphae alone does not make

infection.

They say that you cannot call the patient with Candidosis unless you

have two things; the hyphae and the lesion, so then the patient will

have Candidosis.

Doctor Rima had just read it in some articles that the hyphae should be

present to diagnose a lesion with Candidosis, so you will have the

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lesion and the hyphae, and the hyphae could be presented in normal

oral cavity, but these results are not that public till now.

BUT YOUR BOOK SAYS: when there are hyphae there is Candidosis.

So lets say that the presence of hyphae the morphologic type is the

indicative of having an active fungal infection, not the count and notthe carriage rate or the presence.

*** There were questions from a student:

The first question was: Do we always have to check the presence of

hyphae?

The doctors answer was: It is not necessarily; it means that we may

find hyphae but not necessarily a lesion, so to call a lesion a fungal

infection or Candidosis, you should find a clinical lesion and hyphae.

The second question was: Is it possible to find a Candidosis lesion

without hyphae?

The doctors answer was: Actually the hyphae is the form that causes

the infection, usually if you find the hyphae you will find the lesion, but

I cannot say 100% because I read it somewhere that even thepresence of hyphae should be accompanied by a lesion, by redness or

white lesion or whatever; there should be a change to call the patient

as having an active Candidosis.

May be the patients with hyphae are at higher risks of having

Candidosis, but the hyphae is the thing that tells you that there is a

lesion.

Let us stick to this piece of information; that the hyphal form is the

diagnostic form of a lesion, so as we were saying you cannot rely on

the counts to say that this patient is having the lesion, because normal

people without Candidosis may have high counts of Candida, but

without hyphae may be, and now the researches are going on in this

area.

FOR THE EXAM: You should know that from these three points; the

presence, the count, the form, the form is the most importantfactor.

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Slide (4): Candidosis.

We said that it is an opportunistic pathogen, and it depends on the

disturbance of balance between the host and the organism, actually it

is something called homeostasis balance and not the hemostasis

balance.

Hemostasis balance is a blood related balance, but the homeostasis is

a balance in the surrounding environment.

And now we will talk about what disturbs this balance, which may be

depends on local factors or systemic factors.

Slide (5): Factors predisposing to candidal infection.

When talking about factors predisposing to candidal infection we have:

1) The local factors that favors candidal infections whichincludes:

* Trauma that means rocking or ill-fitting denture which enhances

Candidosis.

* Carbohydrate-rich diet, people who eat food with high

carbohydrate amount are more likely to get Candidosis; because

Candida likes sugar.

2) The age, it is a general factor; meaning when the patient is young

or old, the immune system will not be competent as in the adult, so it

may favor Candidosis.

3) Medications Drugs, broad spectrum antibiotics; because it will

kill the bacteria inside the oral cavity which is living in balance with the

Candida, and if the bacteria is killed Candida will proliferate more and

it may induce the infection.

4) Xerostomia; it means decreased in the salivary flow rate, so that

will caused decreased washing effect of the saliva, it will favors

Candida; because it will allow the adhesion and the adherence of

Candida to the oral mucosa, because there is no washing effect, so

there will be more adherence of Candida to the mucosa.

5) Systemic diseases; it includes any other systemic diseases that

suppress the immunity or require medications that suppress the

immune response.

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Now patients on cortisone are more likely to have oral Candidosis;

because they suppress the immune response and Candida will increase

in number, change in form and cause the infection.

There is a question mark about asthmatic patients there is a debate

about them if they use the cortisone inhaler they said that it should

not necessarily increase the likely-hood of Candidosis; because it is

just inhaler, but sometimes they have Candidosis.

Slide (6): Protection against candidal infection.

When talking about our normal protection against Candida we have:

1) The non specific factors, which are the same for everything; for

the bacteria, for the fungal organisms and for the viruses, it applies for

all, and it is like;

* Shedding of epithelium, we have continuous shedding of the

epithelium in our oral cavity; so suppose that the hyphae started to

adhere to the epithelium and then shedding occurred; so shedding

decreases the likely-hood of Candidosis.

* Salivary flow, we said that the continuous washing effect will

prevent the adhesion and also the adherence of the hyphae to the

epithelium.

* Commensal bacteria is good; because if the bacteria number

decreased by antibiotics the Candida will proliferate more and it will

start causing the infection, so they are living in balance the bacteria

and the Candida, and by the way the bacteria we are talking about

here is the normal flora.

*** There was a question from a student: when the patient is immune-

suppressed doesnt that mean increasing in the bacteria number, so inthis case why does the patient get Candidosis?

The doctors answer was: In fact yes, the bacteria number should be

increased, but may be the type of immuno-suppression plays a role

here, means that the immunity or the neutrophils can attack the

bacteria and kill them for example, and I think it is something related

to the CD4 helper cells, and the type of cells suppressed - and this is

doctor Rimas understanding -; that the type of the immuno-

suppression, and may be the innate immune response can attack thebacteria but not the fungus.

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2) The specific type of protection, it is specific for fungal or for

Candida specifically, like:

* Some serum antibodies; in our serum we have antibodies against

Candida.

* But the more important type of the antibodies is the secretory typeof the antibodies, the type of immunoglobulin secreted in the saliva

and in the gingival fluid, it is more important than the serum

antibodies; because it is more handy.

And in general the importance of antibodies is that when the antibody

binds to the Candida, it decreases or prevents the adherence, and the

adhesion is the first step of infection.

For the Candida to cause infection it should adhere first, and theantibody prevents its adherence.

*** There was a question from a student: How do the antibodies

decrease the adherence of Candida?

The doctors answer was: When a binding happens between the anti-

gene and the antibody, the part of the anti-gene that will adhere will

be covered.

Suppose that the adherence occurs in the edge of the hyphae where

the adherence occurs for example, so if the antibody come and bind

here - in the site of adhesion of the Candida -, the adherence will not

occur.

Suppose that you have several antibodies to several epitops or

locations in the hyphae, and they all bound to the hyphae, how can it

adhere?, there will be a blockage of the epitops that are important to

the adhesion; in other words it will decrease the adhesion, maybethere will be still some adhesion, but it will decrease it.

* Cell mediated type of immunity is also important and not only the

immune-globulins.

You know the CD4 cells, the T helpers type I, the T helpers type II and

the consequences of activation of cells, etc.

And the importance of the cell mediated immunity appears in thepatients who have hereditary cell mediated immunity defects, those

patients will have chronic Candidosis.

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Slide (7): Pathogenesis of candidal infection.

Adherence, now we have said that Candida to start causing a disease,

it should start by the adherence, and most of these factors decrease

the adherence, which is the first step of the pathogenesis of

Candidosis, so adherence is the first step, and the morphologic form of

Candida which is responsible of the adherence is the hyphae.

After the adherence there will be secretion of enzymes like the

proteineases, that will facilitate slight invasion of the hyphae

invasion of epithelium by hyphae; because the hyphae will not

invade the full thickness of the epithelium, it invades only the

superficial layers, and these enzymes may facilitate the products of

Candida to reach the

sub-epithelial area.

It facilitates slight insertion of the hyphae and the passage or the

transport of the products of the hyphae Candida to the sub-

epithelium.

Secretion of nitrosamine compounds; now when looking at the

products of the Candida we will see nitrosamine; which is also presents

in tobacco.

So Candida produces nitrosamine; which is the product that everyoneis pointing at in the chronic hyper-plastic Candidosis as the causative

factor in the premalignant potential.

As we have already taken before; we have candidal leukoplakia, and

we said that it is having a higher risk than the homogenous

leukoplakia, and that is for several reasons and one of these reasons is

that; when the Candida is there, the Candida produces nitrosamine,

which is known to be a carcinogenic agent, so this is something noteasy from the Candida.

There may be type IV hypersensitivity to candidal pathogens;

meaning the cell mediated immunity or reaction to the candidal

products.

Also they said that this is one way of the pathogenesis of Candida,

even if the Candida didnt produce for example nitrosamine, may be

the immune system will attack the products or the pathogens of theCandida, and the net result will be a lesion; because of the immunity

and because of the immune system itself.

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And this is the pathogenesis or how Candida will cause the 4 lesions

that we will talk about then, and as we have just said; adherence,

secretion of enzymes, secretion of nitrosamine and the immune

response, all of these will result in lesions, and these lesions can be

divided into acute and chronic.

Slide (8): PAS stain.

Here we have the PAS stain; this is the Periodic Acid Schiff stain,

and this is a special stain for fungal organisms and for other types of

tissues we wont talk about them -, but for Candida or fungal

organisms, it will stain the sugar-rich carbohydrate-rich wall of the

Candida in a pink or a red color, so I will see Candida as red, so these

red things are the hyphae, the spores and they are causing budding

buds.

So there are the hyphae, the spores and the buds stained with the PAS

stain, and suppose these were taken from a lesion, then for sure we

will say that the patient is having Candidosis.

The problem is not with the lesion itself, for example if we have a

patient and we look at his tongue, you may say that it is normal, but I

may say that it is not normal, so here in this situation what shall we do

to say that this is normal or not normal?

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Hypha

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Spore

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We will do a smear; we will bring a glass slide or a wooden spatula and

scrap the tongue, then spread it over a glass slide and stain it with the

PAS stain, and then we see it.

If we find hyphae then for sure we have a lesion, and if we didnt see

hyphae then we will start thinking about other causes.

Slide (9): Classification of Oral Candidosis.

The acute lesions; we have:

1) The pseudo-membranous.

2) Erythematous (atrophic).

The chronic lesions; we also have:

1) The pseudo-membranous.

2) Erythematous (atrophic).

You can call the erythematous also atrophic, because both of them

indicate red colour, whether you call it atrophic epithelium or

erythematous, and erythematous is referring more to the colour.

So we have a white lesion which is the pseudo-membranous, or a red

lesion which is the erythematous (atrophic) in both the acute and thechronic, and they could happen in a one week or two weeks duration.

And here in the chronic we have another type which is:

3) The hyper-plastic Candidosis (candidal leukoplakia); it is

classified with the chronic; because you cant have leukoplakia in

a one week duration.

And we will talk about all of them in details.

Slide (10): Classification of Oral Candidosis (cont.).

Doctor Rima didnt talk about this slide, but it is a continuation of the

classifications, have a look at it.

Slides (11+12): Acute pseudo-membranous Candidosis

(Thrush).

Now lets start with the first acute lesion which is the pseudo-

membranous Candidosis, here clinically you will see a whitish

membrane on the mucosa.

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It is called pseudo-membranous; because it can be removed by

scraping, so it differs from the leukoplakia - remember that leukoplakia

cant be removed by scraping -, here if you scrap the lesion you can

remove some or most of it, but it is painful to the patient.

And the base under this pseudo-membrane is red, and it may bleed

slightly, and it is annoying to the patient, so this is pseudo-membrane,

it is acute because it starts and heals within days, it is not chronic, thepatient complains of pain or burning in the area, so it is not

asymptomatic, it is painful.

The predisposing factors are the things we have already mentioned;

1) The age; it occurs in newborns infants more than the grown up

children, it occurs in elderly more than the adults.

2) Xerostomia; it is an important factor.

3) Antibiotics; it is an important factor too, sometimes you will see

patients having these lesions and you should immediately take the

detailed history, like;

Have you taken antibiotics recently? Lets assume his answer was: yes,

and I have stopped it. Then you should ask him when exactly? And his

answer may be: one week ago for example or five days ago or

whatever the answer was; so there may be a recent history of broad

spectrum antibiotics; because there are other causes.

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*** There was a question from a student: when we talked about white

lesion before we said that we perform a scraping test, and if it is gone

then it is food debris or chemical necrosis or sloughed tissue and now

Candidosis, do they differ from each other in the burning sensation?

The doctors answer was: Not the burning sensation what differs, but

both of them will be slightly painful, the patient with chemical burns for

example; if you remove the tissue it will be painful, but in the chemical

burn usually you have wide sloughed areas wide areas of necrosis,

but here you see a small pieces spread all over, in addition to the

history and in addition to the smear, you should perform the smear, if

you couldnt confirm, you should order a smear perform a smear and

send it.

*** There was another question from a student: Do we have to do thesmear test even if the lesion disappears in the scraping test?

The doctors answer was: If you have a white lesion that can be

removed by scraping, and if you have another white lesion that cannot

be removed by scraping, you should put a list of differential diagnosies.

The lesion that can be removed by scraping, you will include; tissue

necrosis by chemical burns; thermal burns or even mechanical causes

for necrosis trauma - or even if the patient is having habitual cheekbiting; because you may see sloughing of the epithelium - and

Candidosis.

And then you will start considering them one by one, you will need

more information from the patient, and you will need more clinical

information.

And for the burn you have to find a cause, and you have to ask the

patient, and later on your eyes will be trained to see these small pin-pointed white areas, and compare them with whitish bigger areas of

the chemical necrosis.

And the location; this is in the middle of the buccal mucosa; but in the

necrosis usually it will be only in the location of the application of the

aspirin, this Candidosis is wide spread, but that chemical burns is

not wide spread, it is localized.

It was a good question actually; because white lesions that can beremoved by scraping have a different differential diagnosies compared

to the white lesions that cannot be removed by scraping.

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*** There was another question from a student: How do the

antibiotics affect the fungal infection?

The doctors answer was: The antibiotics result in decreasing the

number of bacteria inside the oral cavity, and then the balance

between bacteria and Candida will be impaired, the environment

better for Candida to live, proliferate and induce the infection.

Suppose that the bacteria is producing something that is not good for

Candida, by that if the bacteria is gone Candida will be happy; because

the annoying thing is gone.

So it is about the host and the organism in terms of the immune

system, salivary flow, etc., and since the bacteria is our normal flora,

we can consider it as the host, you can consider balance between

Candida and the bacteria and balance between Candida and the host.

Another logical explanation based on microbiology was given from a

student which is The high number of bacteria in the oral cavity covers

the receptors for the Candida, so it may decrease the adherence of

Candida to the epithelium.

*** There was another question from a student: If you give the patient

antibiotics will the immunity be better, so that the body can defend

itself better?

The doctors answer was: No, it will not be better; because the

pathogenesis of Candida in terms of antibiotics is not that the

immunity will be better, the patient immunity will not be better, and

may be the patient is overwhelmed with another infection.

In the first place the patient takes the antibiotics because he is sick,

and may be his immunity is overwhelmed with infection onsomewhere, so doctor Rima dont think it is related to the immunity,

but it is related to the number of bacteria.

If you want you can search for it, but as doctor Rima understood over

the past years, it is related to the number of bacteria.

Slide (13): Acute Pseudo-membranous Candidosis (Thrush).

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Here is another example of thrush; thrush is the other name for the

acute pseudo-membranous Candidosis, and this is very common in

newborns, you can see it in newborn infants.

Look here at the palate, you can see whitish areas in the palate, these

whitish areas can be removed by scraping leaving a red painful base,

and if you perform the smear you would see the hyphae, and then the

hyphae will confirm your diagnosis of thrush or acute pseudo-

membranous Candidosis.

Slide (14): Acute erythematous (atrophic) Candidosis.

Now the erythematous or atrophic Candidosis the acute form is also

related to the antibiotics, actually this form is called antibiotics sore

tongue, it is commonly related to antibiotics, but not 100% of all of

these patients are having antibiotics history.

It is the same mechanism here; which is decreased in the number of

bacteria inside the oral cavity, so the Candida will have better

environment to adhere either because of the decrease in the products

of the bacteria or because of the openings now of the receptors for the

Candida to adhere.

The patient will have generalized different sensations, doctor Rima

doesnt want to say pain; because some patients dont feel pain,they feel discomfort; so it is a different feeling inside their oral cavity,

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and upon examination you will see depapillated area of the tongue

depapillation of the tongue, and it is relatively erythematous ( ).

Sometimes the patient will have prolonged corticosteroids history, and

corticosteroids will suppress the immunity and enhance the infection

with Candida; so if the patient is on a prolonged corticosteroids, in this

case we will use the suppressed immunity mechanism, but for the

antibiotics let us use the decreased in the bacterial count way of the

pathogenesis, unless approved otherwise; if you bring another

information we will consider it.

The lesion is red and painful, and usually you should search; you

should ask your patient several questions to find the cause, and if you

couldnt then perform a smear, now if you do not find hyphae, then

dont call it antibiotic sore tongue, and try or find another cause; maybe thermal burn, may be the patient is anaemic, but if he is anaemic

he will have generalized atrophy of all of the mucosa, and not a

rounded area on the tongue.

Slides (15+16): Clinical photos.

Here is the lesion; the atrophic area is relatively erythematous area onthe tongue.Actually doctor Rima is not really sure that this is an antibiotic sore

tongue or acute erythematous Candidosis; because all of the tongue is

atrophic, and doctor Rima thinks that the patients is having something

like other systemic problem or condition, so dont consider this.

There are some white spots in the tongue; because of the filiform

papillae, they are still there, and not all of them are gone.

Remember that the thrush is the acute pseudo membranous

which is white in colour.

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And now we are talking about the acute erythematous which is

red in colour.

And both of them are annoying and painful to the patient, but

we have different clinical presentations for both of them.

*** There was a question from a student: How Candida makes the

papilla atrophied?

The doctors answer was: It is red; because the papillas are atrophic,

and why it is atrophic? That is from Allah!!!

Actually it is a clever question, and doctor Rima didnt think about it

before.

Why the body response in this type is by causing atrophic

epithelium?

Doctor Rima thinks that the immune response is related to the

appearance, but she is not sure why, and it may be related to the

nitrosamine as a Colleague suggested.

Now if we ask doctor Rima why the colour is white in the thrush? She

might say that the infection of Candida and its products and enzymes

will cause lysis of the cells may be, or it will have a necrotic debris in

addition to the inflammation.

But here why the epithelium will appear atrophic? Doctor Rima doesnot know.

*** There was a question from a student: Dose it appear atrophic or it

is really atrophic meaning there is a true loss in the tissue thickness?

The doctors answer was: I have never seen a biopsy from atrophic

Candidosis; there is no histological picture of Candidosis in the slides, it

may be truly atrophic, but usually we look for the hyphae invading the

epithelium.

Doctor Rima has many things to do, so probably she will forget to

search for these things, so there were some homework assignments

for some Colleagues which were:

1) The cells where the EB virus and the cytomegalovirus get latent?

>>> Nada.

2) What is the mechanism of antibiotics when associated with

Candidosis? >>> Lana.3) Why Candida sometimes induce atrophic areas? >>> Abu Baker.

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And if you couldnt find an explanation then you will say that it is from

Allah.

And by this we have finished the two acute lesions; the acute

erythematous and the acute pseudo-membranous, and their cause is

usually short term antibiotics, and the lesion is usually short term, it

can be treated and it will go quickly (in 10 days for example).

Slide (17): Chronic atrophic Candidosis (Candida-associated

denture stomatitis).

Now here we have an atrophic appearance of the epithelium, actually

it is not atrophic in this case, it is the inflammation; there is a lot of

inflammation in the epithelium here.

This is another type of lesion, and it is called chronic atrophic

Candidosis or chronic erythematous Candidosis.

And here we have a chronic erythematous Candidosis because of a

denture, there is a prolonged use of a denture that is may be ill-fitting

denture or rocking denture or with poor oral hygiene it is not cleaned,

so the Candida will colonize the fitting surface, but it will induce

inflammation in the mucosa.

So it is red because of the inflammation, due to the direct contact

between the Candida on the denture surface and the epithelium, and

then there will be an inflammation may be due to the products of the

Candida or its enzymes.

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So we have inflammatory reaction in the mucosa to the Candida which

is on the denture, so if I perform a biopsy from this lesion I may not see

Candida invading the superficial layers of the epithelium.

But I will find them on the denture; so I will do a smear for the fitting

surface of the denture to find the Candida.

You have to know that here we have minimal or no candidal invasion of

the mucosa.

Slide (18):Chronic atrophic Candidosis (Candida-associated

denture stomatitis) (Cont.).

We have three patterns of the inflammation according to Newtons

classification of chronic erythematous Candidosis;

1) We may find only pinpointed erythema; just pinpointed redspots on the mucosa.

2)The inflammation may be diffuse erythema; all over the area

which is covered by the denture.

3) Or it may be granular and multi-nodular; the lesion that we

took before in the first chapter we took this semester in the soft

tissue lesions inflammatory papillary palatal hyperplasia or

inflammatory papillary hyperplasia of the palate, andremember when you study it we said that it is strongly associated

with Candida candidal colonization on the fitting surface of the

denture.

It is not the inflammatory fibrous hyperplasia; which is the epulis

fissuratum denture irritation which is related to the edges of the

dentures.

But this one occurs only on the palate, and only under the ill fittingdentures or dentures with poor oral hygiene, but we have papillary

nodular projections of the epithelium, and it is called papillary palatal

hyperplasia.

Slides (19+20): Chronic hyper-plastic Candidosis (Candidal

leukoplakia).

Chronic hyper-plastic Candidosis is the candidal leukoplakia, it is a

white lesion that cannot be removed by scraping, there are questionmarks regarding the association with Candida.

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Some prefers to consider Candida as secondary organism present in

the lesion; meaning that some will consider this as a leukoplakia which

is secondarily colonized by Candida which doesnt have a causative

role in the lesion.

And some will consider that the Candida has a causative role in this

lesion; because once the antifungal is given this lesion will disappear

or it will improve dramatically.

So we have two opinions in this lesion.

The best location for Chronic hyper-plastic Candidosis is the corners of

the mouth or the buccal commissures, the lesion is usually triangular,

the base of the triangle is anteriorly and the apex tip of the triangle is

pointing posteriorly.

The white lesion is usually non-homogenous; it is usually nodular or

mixed red and white lesions, for this reason cause it has a higher

percentage or a higher potential to have dysplasia and also higher

potential to progress may be to carcinoma; because of its higher

potential of dysplasia.

And there is another statement that you should understand which is

not written in the slides; that these lesions which are associated

with Candida may have a higher potential for the dysplasia tostay for a long time.

As we have already took before; sometimes the dysplasia may change,

so sometimes the moderate dysplasia will go back to mild, or sever will

go back to moderate, or they may progress, or it may go.

But in this case the Candida with the leukoplakia will have a higher

potential for the dysplasia to stay there.

*** There was a question from a student: Does that mean that all

leukoplakia or Candida can be dysplastic?

The doctors answer was: No, not all of them, but a high percentage of

Candidal leukoplakia will be dysplastic.

*** There was another question from a student: Does it start as

leukoplakia then the candidal colonization happens or what?

The doctors answer was: In the leukoplakia chapter it is said that we

can consider it as a leukoplakia colonized secondarily by Candida, and

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in the Candida chapter it is considered as one form of the Candida

associated lesions or Candida induced lesions.

So there are two teams; the first team says that it is a type of

Candidosis, and the other team says that it is may be leukoplakia but it

is secondarily colonized by Candida; because Candida prefers or likes

to colonize the rough surfaces, and the leukoplakia is a rough surface,

so it may get secondarily colonized.

By the way, the lichen planus also is having white striations, and it has

a rough surface, and it is of a higher potential to have Candidosis in

association with the lichen planus, also because it has a rough surface.

*** There was another question from a student: Does the chronic start

as chronic or it starts as acute then change into chronic?

The doctors answer was: The chronic starts as chronic, and the acute

starts as acute.

In AIDS patients the HIV infected patients the acute forms may be

changed into chronic; meaning that it will start as acute but it will not

heal, it will be chronic later on.

There is no relationship that indicates when the acute will be changed

into chronic, but they say that the atrophic type is more likely to be

associated with antibiotics, but also the antibiotics may cause thrush.

And now we have finished the pseudo-membranous Candidosis and the

chronic erythematous Candidosis.

About the chronic hyper-plastic Candidosis we have said that it is

triangular in shape, and it may occur bilaterally, or even it may occur

multi-focally; meaning in the buccal mucosa and in the alveolar

mucosa for example in the same patient, so it may occur multi-focal,and it may be associated with angular cheilities, and we will talk about

what is angular cheilities in a minute.

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Slide (21): Candidal leukoplakia clinical photo.

This is candidal leukoplakia, it is hyper-plastic just like the nodular

leukoplakia, it is located on the alveolar mucosa.

Slide (22): Candidal leukoplakia biopsy.

Look at the biopsy and this photo is from you text-book, but you may

find other better pictures; here we see elongated or hyper-plastic

epithelium; it is chronic hyper-plastic Candidosis.

Here there is a hyper-plastic epithelium, also here we have Candidosis;

because this is a PAS stain; because we have hyphal invasion of the

superficial layer of the epithelium.

We can find spores too, but they will be in the surface and they will be

minimal in number, you can see the hyphae invading the superficial

layers, and now we can confirm the diagnosis of hyper-plastic

Candidosis which is chronic; it needs time for the hyperplasia to occur,

it is chronic hyper-plastic Candidosis.

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Slide (23): Candidal leukoplakia PAS Stain.

Now the body response is by inflammatory cells; here all of these black

dots you can see here in the sub-epithelial area are inflammatory cells,

and this is the body response.

Now these inflammatory cells specifically the neutrophils will causesomething called exocytosis, they will start going up and up and up to

the area of the hyphal invasion; meaning that the neutrophils will try to

reach the hyphae, so we can see focal collections of the neutrophils.

And here we have a few or a small collections of neutrophils, and these

are called micro-abscess; because you know the abscess is a collection

of white blood cells, and here we have a collection of neutrophils, but

they are in a small sizes compared to the abscesses that we know; so

this is called micro-abscess.

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Hyper-plastic

epithelium.

Neutrophil

s.

Immunesystemproducts aregoing up to

theepithelium.

Neutrophils Micro-


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So once I have a biopsy, and I see these collections of inflammatory

cells in the superficial layers of the epithelium, even if I couldnt see

the hyphae, I should order a PAS stain, and with the PAS stain, I can

confirm the hyphae.

Two days ago, a similar case came to the hospital, the patient had a

hyper-plastic epithelium, also the patient had inflammatory cells and

micro-abscess, but we couldnt see the hyphae, but after the PAS stain,

we confirm the diagnosis of candidal leukoplakia, and we advised the

clinician to give the patient antifungal, and follow the patient up.

After two weeks if the lesion starts to improve, then this is good. But if

it didnt start to improve then another biopsy should be taken, or the

patient should be followed up regularly.

For the Candida specifically, the neutrophils are the preferred cells to

attack, either if it was acute or chronic, but in this case it was chronic

hyper-plastic Candidosis it is a chronic case; because of the

hyperplasia, and because of the prognosis or the clinical outcome, it

was chronic based on the duration.

So the features were hyper-plastic epithelium, neutrophils micro-

abscess and hyphal invasion.

Slides (24+25): Chronic hyper-plastic Candidosis (pre-

malignancy).

We also said that it is questionably premalignant, and in 50% it is

associated with dysplasia, and about 15% progressed to true

dysplasia; so it may stay there.

And most of the candidal leukoplakias are non-homogenous as we

have mentioned previously, and may be this is another clinical feature

that increases the premalignant potential being non-homogenous.

And Candida can generate a carcinogen called nitrosamine; so this

may be another cause for its increased potential to have dysplasia or

even transformation.

Slide (26): Angular cheilities.

Angular cheilities is a Candida associated lesion; because bacteria may

be the cause of these lesions.

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Cheilities means an inflammation of the lip, and angular means at the

angles, so angular cheilities is an inflammation of the corners of the

mouth.

In the previous 2 or 3 slides there was a statement that chronic hyper-

plastic Candidosis may be associated with angular cheilities; because

the fungal organisms or the Candida may go to the corner and cause

the infection.

But in the angular cheilities we usually have a cause; a predisposing

factor which is something like; decreased in the vertical dimension,

there will be an approximation between the nose and the chin by the

way, we have taken this in prosthodontics.

So there will be a fissure at the corner of the mouth, and in the fissure

there will be pooling of saliva; if there is pooling of saliva then this

environment somehow will facilitate the infection by Candida.

And if you want you can find what does this somehow mean, or why

the continuous wetting of the corners of the mouth makes the

environment better for the Candida to colonize and to induce the

infection, what is the mechanism and how does that affect the

epithelium?, why the continuous wetting by saliva increases the

likely-hood of Candidosis?, now this is a homework for Ali.

Ali tries to answer the question saying: may be the accumulation of

the bacteria, when there is folding in the angles of the lip, so they will

be in a direct contact with the saliva all the time, and Candida will be

inside the saliva as well, but doctor Rima read it somewhere that it is

related to the continuous wetting with saliva or something else.

Slides (27+28): Angular cheilities.

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Look at this patient, she has decreased in the vertical dimension it

happens when the patient loses his teeth an edentulous patient- ;

which makes folds on the skin in the corners of the mouth, and when

there are folds there will be pooling of saliva there, inside the fold

there will be accumulation of the saliva.

This is an old patient, maybe she is not having teeth and the denture is

old with a low vertical dimension, so there will be horizontal folds, with

pooling of saliva which is a better environment for the infection.

The decrease in the vertical dimension will cause these folds in the

skin to occur.

And the patient has fissures, cracks, redness and sometimes crustingof some areas at the corners of the mouth.

It is annoying to the patient, the patient is given antifungal and

antibiotics together most of the time; because most of the time it is a

combined infection, but it may be either candidal alone or bacterial

alone or both of them together.

The bacteria causing angular cheilities may be either Strep. or Staph..

And these patients also have nutritional deficiencies, so these patients

may have other predisposing factors like; iron deficiency, vitamin B12

deficiency and folic acid deficiency, that will predispose more to the

Candidal or bacterial infection in these locations.

Slide (29): PAS stain modified for fungi.

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Hypha

e

Bud

Spore

s


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This here is the normal coated tongue, you can

stand in front of the mirror and check the colorof your tongue, you will find it slightly whitish,

when the tongue is red and glazed that doesnt

mean it is clean, it means there is a problem

there; either it is burned due to hot drinks, may

be the patient may be anemic, or the patient is

having vitamin B12 deficiency, folic acid

deficiency, the patient may be having atrophic

Candidosis for example, and there are other

causes, the red glazed tongue is not a healthy

appearance, these areas of the tongue are

normally coated.

Here is the abnormal appearance in the middle

which is the median rhomboid glossitis.

At the tip of the tongue may be from the hot

drinks sometimes it looks slightly red in color.

Now again you should understand this picture, it is the PAS stain

modified for fungi, it is modified from the PAS stain, you should realize

that this is hyphae, and this is a spore, and you may find budding, look

at the bud here; there is a constriction here in the neck; because it is

budding a new spore, and this spore at a point of time may transform

to be like the hyphae.

So there is a genetic switching in Candida; it may be in either form

according to the surrounding conditions.

*** There was a question from a student: What form does the

budding? Dose the hyphae give the buds or what?

The doctors answer was: The morphologic form which gives the buds

is the spore or the rounded form, and the hyphae dont cause budding;

meaning that the hyphae dont reproduce itself, the one that

reproduce is the spore.

But there will be a genetic switching between them; either form of

them can be switched to the other form.

Slide (30): Median rhomboid glossitis.

Median rhomboid glossitis is a lesion that was considered as a

developmental change, they thought that the area in the middle of the

tongue at the junction between the anterior two thirds with the

posterior one third doesnt develop well, and doesnt develop filiform

papillae well; so it is a developmental change.

But later on they found that there is candidal hyphae colonizing most

of these lesions, so later on it turned to be a Candida associated lesion,

and the patient should be given antifungal for this lesion.

It is called median; because it is in the middle, rhomboid; because ofits appearance rhomboid means in Arabic, so this is arhomboid appearing lesion, and it is glossitis meaning that it looks like

inflammation of the tongue.

Now somebody may ask could this be atrophic Candidosis?

The location at the foramen cecum, and the history of related factors in

the patient should be taken to differentiate between median rhomboid

glossitis and atrophic Candidosis; but not the smear; because both of

them will be positive in the smear.

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So as we have already said there is an etiologic debate, and another

thing to know here that you may have opposing lesion on the palate;

because we have a contact between the dorsum of the tongue and the

palate, so you may have an opposing palatal lesion.

But the palatal lesion should not be necessarily red, it may be thrush it

may be pseudo-membranous , and the same applies to the antibiotic

sore tongue; so the patient may have antibiotic sore tongue and also

he may have another lesion on the palate; because of the contact

between the palate and the tongue.

Slide (31): Chronic muco-cutaneous Candidosis.

There is a muco-cutaneous Candidosis; which is associated with

impaired immunity, usually there is a defect in the immune system,

and the patients will have persistent or chronic superficial infections ofthe skin; so there will be candidal infections on the skin, but there will

be lesions which are scaly with redness, etc..

The patient will have skin lesions, nail lesions, infection of the nail bed

- here it is slightly whitish and swollen - and intra-oral Candidosis which

looks like the chronic hyper-plastic Candidosis.

In the book they mention associated factors with chronic

muco-cutaneous Candidosis it is written in box 11.2 in page

166.

We have sub-groups of the chronic muco-cutaneous Candidosis; it may

be familial which will be autosomal recessive, it may be diffuse which

is also autosomal recessive, it may be associated with

endocrinopathies, it may be associated with a primary immuno-

deficiency early onset, etc..

So it is inherited or acquired and associated with endocrine

abnormalities.

*** There was a question from a student: Does the Candida infections

transform from the patient to other people?

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The doctors answer was: No, I dont think so; because it also needs

predisposing factors as those in the same host.

So intra-orally the type will look like the candidal leukoplakia, and it

will be multi-focal.

Slides (32+33+34): Deep fungal infections.First of all you should understand that the Candida causes only

superficial infections; the Candida doesnt cause deep infections.

Now the deep fungal infections, these are other types of fungi they

are not Candida, we have other types like; blastomycosis,

histoplasmosis, zycomycosis, and there are other types like; oxido-

iodo-mycosis and other sub-types of the deep fungal infections.

The deep fungal infections dont cause thrush or atrophic areas; theymay cause non-specific ulceration or granulomatous areas.

Do you remember the TB ulcer? When we talked about the TB ulcer

which is a chronic ulcer, we said that when you have a chronic ulcer

you should think of a differential diagnosies list.

We have a one chronic non-healing ulcer, presents for 4 weeks, so you

should think of

a deferential diagnosis list like;

1)Squamous cell carcinoma.

2) Deep fungal infections; because they will cause chronic non-

healing ulcers, like those in the slides.

You should complete the list with other types of lesions and ulcers that

can be single non-healing for 4 or 5 weeks.

Note that here we cant say gonorrhoea; because usually it is not

single, nonspecific and non-healing ulcer.

They are chronic non-healing ulcers, so if you take a biopsy you will

see that - the details are not required-, but here you see that this is a

macrophage all of this is a single cell, it is the macrophage; a big cell

with abundant plenty of cytoplasm, but inside the cytoplasm, you see

dots, and these are the histoplasmosis organisms.

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So the biopsy is important for the chronic non-healing ulcer; because it

will show you either the TB organism or the deferential list we are

supposed to write it down, doctor Rima said we have mentioned them

in the previous lecture, so go back and see them.

Now about the deep fungal infections we have said that they maycause non-specific ulcerations and granulomatous areas, and you know

that the granulomatous areas are usually exophitic, and you should

know what are the lesions that have a granulomatous type of

inflammation.

You should add the deep fungal infections to the diagnostic list of

granulomatous inflammation, remember that the granulomatous

inflammation is usually exophitic.

Do not pass quickly on these pieces of information; because they are

important,

a statement from them may come in the exam and makes you

confused, so take enough time studying these things, take your time in

collecting information from other points in the chapter.

If doctor Rima were studying the material, once she see

granulomatous she will write it aside, in any infection; whether it wasviral, bacterial, fungal, or even if it was in other chapters, just write it

all in one page and then leave it to the exam day.

And in the exam day you will be overwhelmed with studying all of the

information and you will not have time to do this, so just collect the

important information, the ulceration, the deferential diagnosis lists,

and what lesions appears white but cannot be removed by scraping,

and what lesions appears white and can be removed by scraping, etc..

We have mentioned that the granulomatous is clinically exophitic, it is

not always but most of the time they are exophitic.

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Now see here these are hyphae, but they are not candidal hyphae;

they are very long, they branches and they have a specific

microbiologic picture, so these are zycomycosis.

And now we will leave the AIDS the HIV infection to the next lecture,with the lab.

The end.

Done by: Raja Amin Elhaddad.

Sorry for being late, I wish you all good marks in your final

exams.

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