Oral pathology sheet # 2 - Zaid 5oury

by **Shadi Jarrar** 8/10/2011, 10:16 pm

There’s an article that we have to read found at http://blackboard.ju.edu.jo

Leukoplakia

Definition : A white plaque of questionable risk having excluded other known diseases or disorders

Epidemiology: approximately less than 1% or maybe less than 0.5% ( 5 per 1000) may have leukoplakia , males have more tendency than females, affects people above 40 years of age (similar to oral cancer), no site is immune but mostly in the tongue, buccal mucosa, and gingiva

Clinically: leukoplakia is variable in size (it may be small or extensive lesion), its color is white or gray

Once you have diagnosed a patient with leukoplakia, clinically it’s divided into two categories; homogenous and non-homogenous. Homogenous leukoplakia is plaque-like , it may not be uniform , criss-crossings and a little roughness can be found on the surface.

Non-homogenous leukoplakia is a potentially malignant oral lesion as some my transform into squamous cell carcinoma, so we have to know the difference between the two types clinically. It may be speckled, meaning that it’s mainly white, but some areas have atrophy and appear clinically red. This is known as speckled leukoplakia or erythroleukoplakia . Another type of non-homogenous leukoplakia is nodular , it’s a white lesion of unknown cause that has elevations (nodularity)on the surface. Another type is ulcerated, it’s a white lesion that has an ulcer.

Erythroplakia: the whole lesion is red in color and usually there’s atrophy , so its not elevated above the surface; it’s flat, therefore it isn’t a correct naming and it is more correct to be called erythroplasia. So it’s a bright-red patch on the oral mucosa which cannot be characterized clinically or pathologically as any other lesion (so it’s a red lesion of unknown cause or disease).

Etiology: by definition it’s unknown or idiopathic (for both leukoplakia and erythroplakia), but it’s thought that the causes are these factors( these are suspected causes):

1. Tobacco; the tendency for the appearance of leukoplakia or other white lesions in smokers is 6 times of non-smokers. You can prove whether smoking is the cause or not by asking the patient to stop smoking and by doing a follow-up ,if the lesion disappeared it will be due to smoking ,if not it’s not due to smoking.

2. Alcohol

3. Candida was found in leukoplakia and some white lesions. But it’s still unproven whether they are its primary cause or not. Most people say it’s secondary because candida like any area with abnormality to reproduce in.

4. Viruses. The most suspected is Human Papilloma Virus type 16.

5. Epithelial atrophy: these lesions may be preceded by epithelial atrophy such as people with sever iron deficiency anemia who have more tendency for white lesions and squamous cell carcinoma in the oral cavity and the pharynx especially in people who suffer from Patterson-Kelly Syndrome or Plummer-Vinson Syndrome. Other causes includes vitamins deficiency especially vitamin A and B, people with oral submucous fibrosis in which the whole oral cavity will have atrophy and fibrosis, the atrophy may damage the epithelium leading to mutations followed by leukoplakia. Tertiary syphilis results in atrophy and then syphilitic leukoplakia on the dorsum of the tongue.

Note: if the cause of the leukoplakia turned out to be due to smoking the lesion will be called smoker ‘s keratosis.

Histopathologically : has no specific histopathologicalfeatures , so the pathologist can’t say if the lesion is leukoplakia or not. So the definition of leukoplakia is by exclusion; if you look for all the diseases and you didn’t find a cause clinically or pathologically related to any disease you’ll reach for the diagnosis of leukoplakia (a white lesion of no known cause).

it appears clinically white either due to orthokeratinization or parakeratinization or a mix of both in the same lesion. There’s hyperplasia in the epithelium or atrophy if it has redness (speckled), there’s chronic inflammatory cells infiltrate in the lamina propria.

The most important question to ask the pathologist if there’s any dysplasia or not, because these are potentially malignant disorders, it’s not necessarily that all the leukoplakias have dysplasia.

Dysplasia has cellular and nuclear features:

-Nuclear and cellular pleomorphism (variation in the size and shape of the nucleus and the cells in the oral epithelium)

-Nuclear hyperchromatism (the amount of DNA is more so darker nucleus)

-Disturbed polarity of basal cells ( instead of being aligned beside each other on the basement membrane)

-Drop-shaped rete ridges (instead of being triangular in shape or rounded)

-Deep cell keratinization (instead of surface maturation and keratenization)

-Increase in the nuclear cytoplasmic ratio because of increased nuclear size

-Increased mitotic figures and abnormal mitosis (cells divide into 3 or more cells instead of 2) and it may occur in abnormal site instead of the basal or parabasal region.

-Basal cell hyperplasia (basal cells found in multiple layers instead of one)

-Disturbed maturation (absence of stratifications and you can’t separate the epithelium into layers( basal cell ,prickle cell..etc))

-Loss of intercellular adherence(the number of desmosomes will decrease and the cells begin to invade the basement membrane)

It’s not necessarily to find all these changes in a dysplasia.

The dysplasia begins as basal cell hyperplasia then if the other dysplastic features follow only for the lower 1/3 of the epithelium it is classified as mild, if it reached ½ the epithelium it’s moderate, if more it’s sever dysplasia. It may become carcinoma-in-situ in which the whole epithelial thickness is dysplastic which in turn transform into squamous cell carcinoma .

The possibility to find dysplasia in homogenous leukoplakia is 10%, and the possibility to find dysplasia in non-homogenous leukoplakia is 50% or more. 80-90% of erythroplakia have either sever dysplasia or carcinoma-in-situ (pre invasive stage; intact basement membrane) or even carcinoma.

So the redder the lesion is, the more the possibility to transform into cancer.

Prognosis: varies due to it’s many types, but between (0.3-20%) transform into cancer the average around 4%

The risk of developing malignancies at lesion sites is 5 times greater in patients with leukoplakia than in patients without leukoplakia. This is in general, but if it was erythroplakia the risk will be more.

Risk factors:

1. Family history: eg. if the patient’s parents had oral cancer

2. If the lesion was non-homogenous

3. If the size of the lesion increased in diameter and size (particularly when exceeding 200 mm2)

4. If the lesion changed from being homogenous to non-homogenous

5. The site: on buccal mucosa and tongue or the floor of the mouth and the ventral surface of tongue( this region is known as the sublingual region, if you find leukoplakia there this will be known as sublingual keratosis and it’s associated with high risk (about 25% become squamous cell carcinoma))

6. The more the duration of the white lesion, the more the risk

7. DNA content and number of chromosomes, if they increase the risk increases

8. the most important prognostic factor is the presence or absence of dysplasia

-Studies have revealed carcinoma or sever dysplasia in the excisioned specimens of approximately 5% of leukoplakias incised when the diagnostic biopsy specimens have revealed no dysplasia.

Explanation: 5% of biopsies sent to the pathologist revealed no dysplasia but actually the specimen was dysplastic.. but this happened because of a problem in the procedure.. such as taking the biopsy from the white part rather than the red part of a speckled lesion. And this happens in the case of taking an incisional biopsy.

The definitive answer of ‘no dysplasia’ is done after taking an excisional biopsy of the lesion.

-There are molecular markers that indicates the risk of a lesion to become a cancer .

If the biopsy was stained or immunohistochemistry or genetic make up was made and mutations in p53 were found, this is associated with increased risk of cancer .Also mutations in oncogenes (inappropriate expression of oncogenes) such as cyclin D1 or Keratins or blood group antigens or cell surface carbohydrates may be associated with increased risk. The most predictive marker that indicates whether a lesion will become a cancer or not is DNA aneuploidy.

Classification and staging system for oral leukoplakia.. ( refer to the article)

OL-system is used for staging (4 stages); L refers to the size of the lesion and it’s divided into L1, L2 ,L3 depending on the diameter of the lesion. P refers to the pathology if there’s dysplasia or not and if the dysplasia is mild or moderate or sever or carcinoma-in-situ. Some classifications place mild or moderate dysplasia in one category as being associated with low risk and sever dysplasia and carcinoma-in-situ another category as being associated with high risk.

Dermatological white lesions:

Skin lesions that appear in the oral cavity.

Lichen Planus: chronic inflammatory disease of the skin and the mucous membranes including the oral cavity and it’s widespread in Jordan.

Mostly affects females postmenopausal, it may affect the skin alone(35%) or both the skin and the oral cavity(40%) or the oral cavity alone(25%).

Clinically:

The skin lesions appear as papules{/elevated}, purple in color, pruritic (they itch), a thin whitish line may appear on some of them known as Wickham’s Striae.

They are 2-3 mm in diameter, they may persist for two years on the skin and then disappear and another lesions will appear later on. Some patients have nail abnormalities; thinning and vertical ridges in the nails.

It may be confused with psoriasis ( such patients may have geographic tongue and the lesions appear as spots with elevations that may be red or white resembling sea shells ).

The oral lesions appear most frequently on the buccal mucosa or posterior buccal mucosa but it may also appear on the tongue, lip , gingiva , the least frequent site is the floor of the mouth and the hard palate region.

The characteristic features clinically is that it’s distributed in a bilateral symmetrical pattern (the lesions appear as mirror images).

Note: lichen planus is not contagious.

Lichen planus has clinical types:

1.Reticular:

The most common type, it appears as lines like lacework( webbed lines in the buccal mucosa) not homogenous grayish membrane like the leukoedema .

This type is asymptomatic but some people may feel roughness in the buccal mucosa , and few complain of burning sensation

The site is mostly in the buccal mucosa and they are bilateral and symmetrical

2.Plaque-like:

It resembles leukoplakia clinically but differs from it histologically( leukoplakia has no specific histological features, but lichen planus has specific features)

Asymptomatic , the most common site is the tongue on the lateral border or the dorsum of the tongue.

3.Papular:

Rare, appears as small whitish multiple papules they may coalesce to look like the plaque type

Asymptomatic .

4.Atrophic:

There’s atrophy in the epithelium, appearing red clinically, most commonly affecting the gingiva

White lines ( Wickham’s Striae) surround the red areas, so whenever you see white lines remember lichen planus.

The clinical diagnosis of this lesion if you didn’t see white lines will be desquamative gingivitis. Lichen planus is one of the lesions that may result in desquamative gingivitis. some autoimmune diseases such as pemphigus and pemphigoid also have the clinical diagnosis of desquamative gingivitis. But after you take a biopsy you can determine the type of the lesion.

This type is symptomatic; the patient complains of pain and burning sensation

5.Bullous:

Rare, is seen in the skin more, appear as bullae filled with fluid in the oral mucosa, may rupture to form an ulcer in its place maybe associated with atrophic areas, mostly found in the posterior buccal mucosa .

It appears for a short period and may rupture within the same day or the next.

6.Erosive:

The most dangerous type, there’s no epithelium and the connective tissue is exposed

Shallow irregular areas, erosions are present but it doesn’t appear red due to fibrin deposition so it looks like yellowish membranes surrounded by red areas, and some areas have white lines (striations) which helps in diagnosis

Can be very persistent (remaining for years) if not treated… so they may be chronic lesions

Symptomatic, painful and interferes with feeding and results in poor oral hygiene and candidal infections.

Histologically: has specific histological features

Focal acanthosis with hyperparakeratosis or hyperorthokeratosis in the areas of white lines

The most important character that it has a well defined band of T-lymphocytes in the superficial lamina propria underneath the epithelium

The inflammation isn’t limited to the lamina propria but it extends to the overlying epithelium (basal and parabasal layers )damaging it resulting in atrophy and erosions clinically.

There’s no normal basal cells in lichen planus, as liquefactive degeneration occurs( because of the inflammation the basal cells will degenerate).

There’s dying cells (apoptotic figures) known as Civatte bodies found in the basal cell region

Prognosis: 0.5-2.5% of patients with lichen planus my develop squamous cell carcinoma especially the erosive type, but even the plaque-like type may develop to cancer.

Etiology: unknown, may be related to infective agents such as bacteria and viruses in the oral cavity or systemic diseases such as diabetes mellitus, hypertension, ulcerative colitis, liver disease, and graft versus host disease( individuals with such disease have lesions that look like lichen planus), also stress ,anxiety ,depression (or the personality factors)may play a role.

Pathogenesis: it is thought that some abnormality ( such as viruses or other factors)made changes in the antigens found on the surface of the epithelial cells, therefore the inflammatory cells thought that these epithelial cells are abnormal so they came from the lamina propria upwards causing damage to the epithelial cells. The damage was caused by cytotoxic T-cells.

Lichenoid reactions are lesions that resemble lichen planus clinically but with a known etiology

You’ll find a lesion that looks like lichen planus but the patient will be taking drugs, such as antimalarial drugs taken by patients with rheumatoid arthritis or other inflammatory disease , or methyldopa , NSAIDs , or amalgam .

A white lesion may be found adjacent to an old amalgam restoration especially if it was large and in contact with the mucosa, this is due to hypersensitivity for amalgam, in such case you should replace the amalgam until healing takes place. Or you should stop the drug use until the lesion resolves.

Lichenoid reactions are unilateral in contrast to lichen planus which is bilateral and symmetrical, and they occur in areas rarely affected by lichen planus.

Lupus Erythromatosus:

A connective tissue disease (autoimmune disease) of two types:

1. Chronic discoidlupus erythromatosus which is limited not systemic and usually affects the face or scalp or the ears or the hair.

Butterfly rash on the cheeks and nose may appear

The lesions have red areas with erosion or ulceration surrounded by white lines that look like sun rays radiating out of the border.

50% of patients with discoidlupus may have oral white lesions like lichenoid reactions or lichen planus especially on the buccal mucosa or vermilion border (the lips).

Histologically: the inflammation here is deep -not in the form of a band- and it’s perivascular (around the blood vessels)

By direct immunofluorescence linear depositions of IGg and C3 and fibrinogen in the basement membrane region appear which is diagnostic of lupus.

2. Systemic lupus erythromatosus affects the whole body, so many organs whether internal or external would be affected( inflammations).

Most patients die from kidney failure or renal failure. They also suffer from arthritis , inflammations in the heart and lung, anemia , malaise and fever.

Females are affected more than males.

Oral lesions: sever red patches are associated with the disease mostly in buccal mucosa , these are found in 1/5 of patients

Oral Pathology

Lecture date,, 26-9-2011

Written By: zaid khoury

The secret to success is to start from scratch and keep on scratching