Leukoplakia is a precancerous white lesion that occurs on mucous membranes in the mouth or other areas. It is caused by thickening of the keratin layer in the epithelium, which makes the tissue appear white. Tobacco use is the most common cause. Leukoplakia may appear as a homogeneous white patch or have mixed white and red areas (erythroleukoplakia), and the most common sites are the inside of the cheeks, gums, and tongue. A biopsy is needed to examine the tissue for signs of dysplasia and rule out other causes. While most cases remain benign, leukoplakia has an increased risk of transforming into oral cancer

1. LEUKOPLAKIA

2. DEFINITION
• Leukoplakia is defined as “white plaques of questionable risk having excluded (other)
known diseases or disorders that carry no increased risk for cancer.” It is considered as
a premalignant lesion and has a malignant transformation rate of around 0.13%–34%.
• The edges of the lesion are typically abrupt and the lesion changes with time.
Advanced forms may develop red patches. There are generally no other symptoms. It
usually occurs within the mouth, although sometimes mucosa in other parts of the
gastrointestinal tract, urinary tract, or genitals may be affected.

3. L E U KO P L A K I A O F
T H E S O F T PA L AT E
The exact appearance of the
lesion is variable. Leukoplakia
may be white, whitish yellow or
grey. The size can range from a
small area to much larger
lesions. The most common
sites affected are the buccal
mucosa, the labial mucosa and
the alveolar mucosa, although
any mucosal surface in the
mouth may be involved. The
clinical appearance, including
the surface texture and color,
may be homogenous or non-
homogenous

4. CAUSES AND CLINICAL VIEW
• The cause of leukoplakia is unknown. Risk factors for formation inside the mouth
include smoking, chewing tobacco, excessive alcohol, and use of betel nuts.
• The cause of leukoplakia is likely multifactorial, with the main factor being the use of
tobacco.The mechanism of the white appearance is thickening of the keratin layer,
called hyperkeratosis.
• The abnormal keratin appears white when it becomes hydrated by saliva, and light
reflects off the surface evenly. This hides the normal pink-red color of mucosae (the
result of underlying vasculature showing through the epithelium).
• Another possible mechanism is thickening of the stratum spinosum, called acanthosis.

5. CAUSES- TABACCO
• Tobacco smoking or chewing is the most common causative factor, with more than
80% of persons with leukoplakia having a positive smoking history. Smokers are much
more likely to suffer from leukoplakia than non-smokers.
• The size and number of leukoplakia lesions in an individual is also correlated with the
level of smoking and how long the habit has lasted for. Cigarette smoking may
produce a diffuse leukoplakia of the buccal mucosa, lips, tongue and rarely the floor of
mouth.
• Tobacco chewing, e.g. betel leaf and areca nut, called paan, tends to produce a
distinctive white patch in a buccal sulcus termed "tobacco pouch keratosis.

6. CAUSES-TRAUMA
• Another very common cause of white patches in the mouth is frictional or irritational
trauma leading to keratosis. Examples include nicotine stomatitis, which is keratosis in
response to heat from tobacco smoking (rather than a response to the carcinogens in
tobacco smoke). The risk of malignant transformation is similar to normal mucosa.
Mechanical trauma, e.g. caused by a sharp edge on a denture, or a broken tooth, may
cause white patches which appear very similar to leukoplakia. However, these white
patches represent a normal hyperkeratotic reaction, similar to a callus on the skin, and
will resolve when the cause is removed.Where there is a demonstrable cause such as
mechanical or thermal trauma, the term idiopathic leukoplakia should not be used.

7. CAUSES- MICRO-ORGANISMS
• Candida in its pathogenic hyphal form is occasionally seen in biopsies of idiopathic
leukoplakia. It is debated whether candida infection is a primary cause of leukoplakia
with or without dysplasia, or a superimposed (secondary) infection that occurs after the
development of the lesion.
• It is known that Candida species thrive in altered tissues. Some leukoplakias with
dysplasia reduce or disappear entirely following use of antifungal medication.
Smoking, which as discussed above can lead to the development of leukoplakia, can
also promote oral candidiasis. Candida in association with leukoplakia should not be
confused with white patches which are primarily caused by candida infection, such as
chronic hyperplastic candidiasis ("candidal leukoplakia").

9. HOW IS ORAL LEUKOPLAKIA
ANALYZED?
• Oral Leukoplakia is normally determined to have an oral test. During an oral test, your
medicinal services supplier can affirm if the patches are leukoplakia. You may confuse the
condition with oral thrush. Thrush is a yeast contamination of the mouth. The patches it
causes are generally milder than leukoplakia patches. They may drain all the more without
any problem. Leukoplakia patches, in contrast to oral thrush, can’t be cleaned away.
• Your human services supplier may need to do different tests to affirm the reason for your
spots. This causes them to recommend a treatment that may keep future patches from
creating.
• In the event that a fix looks dubious, your social insurance supplier will do a biopsy. To do a
biopsy, they expel a little bit of tissue from at least one of your spots.
• They at that point send that tissue test to a pathologist for determination to check for
precancerous or dangerous cells.

10. Most cases of leukoplakia cause
no symptoms, but infrequently
there may be discomfort or pain

11. Leukoplakia could be classified as mucosal
disease, and also as a premalignant condition.
Although the white color in leukoplakia is a
result of hyperkeratosis (or acanthosis),
similarly appearing white lesions that are
caused by reactive keratosis (smoker's
keratosis or frictional keratoses e.g.
morsicatio buccarum) are not considered to
be leukoplakias.
Leukoplakia could also be considered
according to the affected site, e.g. oral
leukoplakia, leukoplakia of the urinary tract,
including bladder leukoplakia or leukoplakia
of the penis, vulvae, cervix or vagina.
Leukoplakia may also occur in the larynx,
possibly in association with gastro-
esophageal reflux disease. Oropharyngeal
leukoplakia is linked to the development of
esophageal squamous cell carcinoma, and
sometimes this is associated with tylosis,
which is thickening of the skin on the palms
and soles of the feet. Dyskeratosis congenita
may be associated with leukoplakia of the

12. MOUTH LEUKOPLAKIA
• Within the mouth, leukoplakia is sometimes further classified according to the site
involved, e.g. leukoplakia buccalis (leukoplakia of the buccal mucosa) or leukoplakia
lingualis (leukoplakia of the lingual mucosa).
• There are two main clinical variants of oral leukoplakia, namely homogenous
leukoplakia and non-homogenous (heterogenous) leukoplakia, which are described
below.
• The word leukoplakia is also included within the nomenclature of other oral conditions
which present as white patches, however these are specific diagnoses which are
generally considered separate from leukoplakia, with the notable exception of
proliferative verrucous leukoplakia, which is a recognized sub-type of leukoplakia.

15. HAIRY LEUKOPLAKIA
• Hairy leukoplakia is a particular type of leukoplakia that affects people with a weakened immune
system (the body’s natural defence against infection and illness), particularly those who have HIV
disease.
• Hairy leukoplakia does not give rise to any symptoms but, unlike other types of leukoplakia, it almost
always occurs on the side or top of the tongue. It does not cause pain or any change in your sensation
of taste. It usually resolves when the ineffective immune system is corrected.
• Hairy leukoplakia is actually caused by the Epstein-Barr virus, although specific antiviral medicines
rarely improve this disorder. Unlike ‘traditional’ leukoplakia, hairy leukoplakia does not carry a risk of
oral cancer.
• However, it should be taken as an important warning sign that your immune system may be
weakened. Visit your GP or specialist as soon as possible if you develop hairy leukoplakia and you have
HIV or any other condition, or are on medication (such as immunosuppressives) that is known to
weaken the immune system.

17. APPERANCE- HISTOLOGY
• Leukoplakia has a wide range of possible histologic appearances. The degree of
hyperkeratosis, epithelial thickness (acanthosis/atrophy), dysplasia and inflammatory cell
infiltration in the underlying lamina propria are variable. In mucous membranes,
hyperkeratosis can be defined as "an increase in the thickness of the keratin layer of the
epithelium, or the presence of such a layer in a site where none would normally be
expected." In leukoplakia, the hyperkeratosis varies in thickness, and may be either ortho-
or para-keratosis, (depending upon whether cell nuclei are lost or retained in the superficial
layers respectively), or a mixture of both in different areas of the lesion.
• The epithelium may show hypertrophy (e.g. acanthosis) or atrophy. Red areas within
leukoplakia represent atrophic or immature epithelium which has lost the ability to
keratinize. The transition between the lesion and normal surrounding mucosa may be well
demarcated, or poorly defined. Melanin, a pigment naturally produced in oral mucosa, can
leak from cells and give a grey color to some leukoplakia lesions.
• Hyperkeratosis and altered epithelial thickness may be the only histologic features of a
leukoplakia lesion, but some show dysplasia. The word "dysplasia" generally means
"abnormal growth", and specifically in the context of oral red or white lesions refers to
microscopic changes ("cellular atypia") in the mucosa that indicate a risk of malignant
transformation. When dysplasia is present, there is generally an inflammatory cell
infiltration in the lamina propria.

18. A: Hematoxylin and eosin stain shows
hyperparakeratinized stratified squamous epithelium with
surface corrugation, acanthosis and clearing of cells
(“balloon cells,” arrowhead) in the upper stratum
spinosum.
B: Control tissue shows hyperkeratosis and acanthosis, but
no significant ballooning of cells, nuclear margination or
beading of chromatin.
C: In OHL patient, in-situ hybridization for Epstein-Barr
virus (EBV) is positive in the nuclei of epithelial cells.
D: Control tissue is negative for EBV RNA.
E: OHL is negative for CD1a in this section; no Langerhans
cells are present.
F: In control tissue, dark brown immunohistochemical
staining for CD1a reveals more numerous Langerhans cells
than in OHL cases.

19. ERYTHROLEUKOPLAKIA
• Erythroleukoplakia (also termed speckled leukoplakia, erythroleukoplasia or
leukoerythroplasia) is a non-homogenous lesion of mixed white (keratotic) and red
(atrophic) color.
• Erythroplakia (erythroplasia) is an entirely red patch that cannot be attributed to any
other cause. Erythroleukoplakia can therefore be considered a variant of either
leukoplakia or erythroplakia since its appearance is midway between.
• Erythroleukoplakia frequently occurs on the buccal mucosa in the commisural area
(just inside the cheek at the corners of the mouth) as a mixed lesion of white nodular
patches on an erythematous background, although any part of the mouth may be
affected. Erythroleukoplakia and erythroplakia have a higher risk of cancerous changes
than homogeneous leukoplakia
Erythroleukoplakia ("speckled leukoplakia"), left
commissure. Biopsy showed mild epithelial dysplasia and
candida infection. Antifungal medication may turn this
type of lesion into a homogenous leukoplakia (i.e. the red
areas would disappear)

20. DIAGNOSIS- BIOPSY
• Tissue biopsy is usually indicated to rule out other causes of white patches and also to
enable a detailed histologic examination to grade the presence of any epithelial dysplasia.
This is an indicator of malignant potential and usually determines the management and
recall interval. The sites of a leukoplakia lesion that are preferentially biopsied are the areas
that show induration (hardening) and erythroplasia (redness), and erosive or ulcerated
areas. These areas are more likely to show any dysplasia than homogenous white areas.
• Brush biopsy/exfoliative cytology is an alternative to incisional biopsy, where a stiff brush is
scraped against the lining of the mouth to remove a sample of cells. This is then made into
a smear which can be examined microscopically. Sometimes the biopsy site can be selected
with adjunct methods which aim to highlight areas of dysplasia. Toluidine blue staining,
where the dye is preferentially retained by dysplastic tissue, is sometimes used, but there is
high false positive rate. Other methods involve the use of illuminescence, relying on either
the property of normal autoflorescent molecules in mucosa such as collagen and keratin
which is lost from areas of dysplasia or carcinoma under blue light, or by initially staining of
the mucosa with toluidine blue or dilute acetic acid and examination under white light.

21. FEATURES OF EPITHELIAL DYSPLASIA
IN LEUKOPLAKIA SPECIMENS
• Cellular pleomorphism, in which cells are of abnormal and different shapes.
• Nuclear atypia, in which the nuclei of cells varies in size, any may be increased in size relative to the
cytoplasm, shape, and may stain more intensely. There may also be more prominent nucleoli.
• Increased number of cells seen undergoing mitosis, including both normal and abnormal mitoses.
Abnormal mitosis may be abnormally located, e.g. occurring in suprabasal cells (cell layers more
superficial to the basal cell layer) or of abnormal form, e.g. "tri-radiate mitoses" (a cell splitting into 3
daughter cells rather than only 2)
• Loss the normal organization of the epithelial layers. The distinction between the epithelial layers may
be lost. Normally stratified squamous epithelium shows progressive changes in the form of cells from
the basal to the superficial layers, with cells becoming more flat ("squames") towards the surface as a
continuous maturation process. In dysplastic epithelium, cells may become vertically orientated rather
than becoming flat towards the surface.
• There may be abnormal keratinization, where keratin is formed below the normal keratin layer. This
can occur in individual cells or groups of cells, forming an intraepithelial keratin pearl. There may be an
increase in number of basal cells, and they may lose their cellular orientation (losing their polarity and
long axis).
• Alteration of the normal epithelial-connective tissue architecture - the rete pegs may become "drop
shaped". wider at their base than more superficially.

22. Microscopic examination of
keratinocytes scraped from the
buccal mucosa

23. SOURCES
• https://jcda.ca/i8
• https://www.hse.ie/eng/health/az/l/leukoplakia/
• https://sabkadentist.com/oral-leukoplakia-symptoms-causes-treatments/
• https://en.wikipedia.org/wiki/Leukoplakia#Causes
• https://www.healthline.com/health/leukoplakia

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