KARNAVATI SCHOOL OF DENTISTRY

DEPARTMENT OF
ORAL MEDICINE & RADIOLOGY

PREPARED BY:
DR. SHACHI PARIKH ( MDS PART II) Pre cancerous lesions
GUIDED BY:
DR. NILESH RAVAL (PROF; HOD)
DR. DHAVAL MEHTA (PROF.)
scope
 It is important to stress on that a premalignancy is to
eventually transform into cancer, as it often believed.
Many precancers, force the clinician to make some very
real choices relative to management of such lesions.
Individuals with oral precancer run 69 times greater risk
of developing oral cancer as compared to tobacco users
who do not have precancerous lesions.

Ref;text book of preventive dentistry.D.prabhu 1st edition

 INTRODUCTION
 Historically the definition of an “oral premalignant
lesion” dates back to 1978, when it was defined by the
World health organization as
 “A morphologically altered tissue in which cancer is
more likely to occur than its apparently normal
counter part”
Precancerous Lesions

 Leukoplakia
 Erythroplakia
 Mucosal changes associated with smoking habit(nicotinus
stomatitis)
 Carcinoma in situ
 Bowen’s disease
 Actinic Keratosis
LEUKOPLAKIA
 Sir James Paget as early 1851 had recognized the
lesions cancer transforming potential and its
relationship to pipe smoking reporting it to as
Leukokeratosis and Smoker’s patch what we today
consider to represent LEUKOPLAKIA.

 The term LEUKOPLAKIA was first coined by the

Hungarian Dermatologist, SCHWIMMER in 1877
DEFINITIONS

 The term leukoplakia originates from 2 Greek words

 Leuko – White
 Plakia – Patch

 “Leukoplakia is defined as a raised white patch of the oral

mucosa measuring 5mm or more, which cannot be scraped
off and which cannot be attributed to any other
diagnosable disease” - WHO 1971
 “A white patch or plaque that cannot be characterized
clinically or pathologically, as any other disease” – WHO
1978.
LEUKOPLAKIA
 “Leukoplakia is a whitish patch or plaque that cannot be characterized,
clinically or pathologically as any other disease and it is not associated with
any physical or chemical causative agent except the use of tobacco” -Axell et
al 1983

 It is redefined as" a predominantly white lesion of oral cavity that can not be
characterized as any other definable lesion”.(Ref:Axell T,1996)

 “A predominantly white lesion that cannot be characterized clinically or

pathologically as any other definable lesion” - Pindborg et al 1997 (WHO)
 Classification and staging of oral leukoplakia
(Ref ..I. van der Waal et al)

L- Extension of Leukoplakia
 L0 - No evidence of lesion
 L1 - 2 cm or less
 L2 - b/w 2-4 cm
 L3 - 4cm or more
 Lx - Not specified

S - Site of Leukoplakia
 S1 - All sites excluding floor of oral cavity of tongue.
 S2 - Floor of oral cavity and/or tongue
 Sx - Not specified
C- Clinical aspect
 C1 - Homogenous
 C2 - Non-homogenous
 Cx - Non-specified

P- Histological features (Pathology)

 P1 - No dysplasia
 P2 - Mild dysplasia
 P3 - Moderate dysplasia
 P4 - Severe dysplasia
 Px - Not specified
Staging system
 Stage I - Any L1, S1, C1, P1, or P2
 StageII - Any L1, S1, or S2, C2 p1 or p2
 StageIII - Any L, S2, C2, P1 or P2
 StageIV - Any L, any S any C, P3 or P4
CLASSIFICATION(who 1980)
according to clinical description
 Homogeneous – uniformly white
 Non-homogeneous- white and red lesion

 ELABORATELY SUB-DIVISION:
 A) homogeneous
 - smooth
 - furrowed
 - ulcerated
 B) non-homogenous- Nodules speckled well demarcated raised white
areas interspersed with reddened area.
 -nodular/speckeled
 -verrucous
 -erythroleukoplakia
According to etiology
 Tobacco induced

 Non tobacco induced

According to histology
 Dysplastic

 Non dysplastic
ACCORDING TO RISK OF CANCER DEVELOPMENT:

 High risk sites:

 floor of mouth
 lateral / ventral surface of tongue
 soft palate

 Low risk sites:

 Dorsum of tongue
 Hard palate

 Intermediate group:
 All the other sites
ACCORDING TO EXTENT:

 Localized
 Diffuse
Reversible and irreversible type
 Leukoplakia may also be devided into two types
according to whether it spontaneously disappear after
chronic irritation has been eliminated. this lesion referred
as reversible leukoplakia

 Whereas persistent lesions are termed irreversible

leukoplakia. In one study,62% of the lesions were
completely irreversible.

 Ref:dd of oral & maxillofacial lesions fifth edition NORMAN K WOOD

&GOAZ
CLINICAL TYPES
 Homogenous leukoplakia
 Ulcerated leukoplakia
 Nodular leukoplakia
 Verrucous leukoplakia
PREVALANCE
 Study shows, the prevalence of leukoplakia is 2.6%.

 Most oral leukoplakias seen over age of 50,leukoplakia

before age of 30 is rare.

 Leukoplakia are more seen in men compared to women due

to tobacco use.

 ref:textbook of social medicine park,20th edition

 Prevalence:
 Various studies have reported a prevalence of 0.2% to 11.7%
 Mehta et al 1971, 1972 – 0.2% to 4.9%
 Banoczy and sugar 1972 – 0.6% to 3.6%
 Smith et al – 11.7%
 Axell 1976 – 3.6%
Incidence - 3-4% adult population
Without the use of tobacco – 0.6/1000
Betel quid – 1.3/100,000
Smokers – 4.2
Smokeless tobacco – 8.9 (Mehta et al 1972)
 Gupta et al reported – 1.1 to 2.4 / 1000 women, 0.2 to 0.03 / 1000 in
women.

 ref:textbook of social medicine park,20th edition

 Etiology –
• Tobacco.
• Alcohol.
• Chronic irritation
• Sanguinaria.
• radiation.
• Microorganism
• Trauma.
• Dietary deficiency
• Syphilis.
• Hormonal imbalance.
• Galvanism.
Tobacco
 It is dried leaves of nicotina tobaccum. widely used in two
forms-

 Smoking tobacco such as cigar, cigarette , bidi and pipe

 Smokeless tobacco such as chewable tobacco and oral use or

snuff
 Tobacco:
 Mucosal changes have been noted in habitual users of smoked
and smokeless tobacco.

 These changes most likely result from the many irritants,

toxins, and carcinogens found naturally in cured or burned
tobacco leaves, but may also arise from the mucosal drying
effects, the high intraoral temperatures, intraoral pH changes,
local alteration of membrane barriers and immune responses, or
altered resistance to fungal and viral infections.
Carcinogens in tobacco
 N-nitrosonornicotine (NNN),it is proven to cause
mucosal alteration
 Polycyclic aromatic hydro carbons
 Nitrosodicthanolamine
 Nitrosoproline
 polonium
 Tobacco smoke contains carbon monoxide,thyocynate,
hydrogen cyanide ,nicotine.
 Approximately 80% of leukoplakia patients are
smokers.

 Pipe smokers and heavy cigarette smokers have greater

numbers of lesions and larger lesions than other
smokers, especially after many years of tobacco abuse.
 Cigarettes can be classified as low or medium if the tar
yield is below 22 mg, and as high if tar yield is above 22
mg. Compared with non-smokers the risk of oral
cancer for smokers using low to medium tar cigarettes
is 8.5 and for high tar cigarettes is 16.4.

 Benoczy et al 1972.journal of o path,vol 1

 The development of leukoplakia in smokers also
depends on dose and on duration of use, as shown by
heavier smokers having a more frequent incidence of
lesions than light smokers.

 Cessation of smoking often results in partial to total

resolution of leukoplakic lesions.

Wood n Goaz,5th edition

 Smokeless tobacco is also a well-established etiologic
factor for the development of leukoplakia; however,
the malignant transformation potential of smokeless
tobacco–induced lesions is much lower than that of
smoking-induced lesions

P.c gupta,j.j pindborg.W.H.O,42,1972

 Smokeless tobacco contains a number of carcinogens
and therefore, particularly in view of the fact that snuff
can produce oral leukoplakia, its use is to be
deprecated especially because this form of smokeless
tobacco is held in the mouth for very long periods.

L sugar and Benoczy, 1972,j o path 1

Alcohol
 The prevalence of leukoplakia is higher among the regular and
occasional drinkers compared to non-drinkers.

 It locally cause burning sensation of mucosa.

 Synergetic effect of alcohol and tobacco increases

susceptibility to leukoplakia.
Sanguinaria.

 Damm et al17 associated an old disease, leukoplakia, with a newly observed

possible cause. They detailed the clinicopathologic features of a unique
form of leukoplakia that could be attributed to the use of a dentifrice and/or
mouth rinse containing the herbal additive Sanguinaria.

 Clinically, the vast majority of these lesions are located in the anterior
maxillary mucobuccal fold and attached gingiva.

Ref..L. R. Eversole, DDS, G. M. Eversole, at el

 Leukoplakic lesions are characteristically
asymptomatic and are most often discovered during a
routine oral examination.

 It can occur anywhere in oral cavity.

 More common in male compared to female.

CLINICAL TYPES:

 1) Pre Leukoplakia-
 It is a low grade or very mild reaction of oral mucosa
appearing as white /grayish white & slight lobular pattern &
indistinct borders.

Burket’s oral medicine 11th edition

 2) Homogenous type:
 Accounts for 84% of all cases. It appears as a
localized lesion of extensive white patch with relatively
consistent pattern through out. Appears usually white/yellowish
white or yellow in colour. Well defined localized or extensive,
slightly elevated & fissured, wrinkled or corrugated
appearance.

Burket’s oral medicine 11th edition

 Nodular type:

 It is also called as “SPECKLED LEUKOPLAKIA”.

It is a mixed red & white lesion in which small keratotic
nodules are scattered over an atrophic patch of mucosa. It has
the higher malignant potential compared to homogenous type.

REGEZI:oral pathology;4th edition

 4) Verrucous leukoplakia:
 It is characterized by verrucous proliferation above
mucosal surface commonly involves buccal mucosa, alveolar
mucosa, tongue. Surface is heavily keratinized. It is thick white
lesion & papillary surface. An extensive lesion of verrucous
leukoplakia is called “ORAL FLORID PAPILLOMATOSIS”
 PROLIFERATIVE VERRUCOUS LEUKOPLAKIA (PVL):
 PVL is a vey high risk precancerous lesion with a
high mortality rate. This destructive form of oral leukoplakia
was first described and named as PVL by Hansen et al (1985).

Burket’s oral medicine,11th edition

 ETIOPATHOGENESIS:
 The exact etiopathogenesis remains elusive with
smoking and presence of candida having no influence on the
occurrence and progression of PVL.
 The role of HPV remains speculative regarding the significance
of its presence and possible regulatory influence on PVL
occurrence and progression.
 CLINICAL PRESENTATION:
 Initial stages are similar to solitary homogenous leukoplakic
lesion that under the microscope can exhibit hyperkeratosis and
epithelium hyperplasia with / without evidence of dysplasia.
The lesion tends to recur and proliferate, often over a
protracted period of time, to result in a diffuse, widespread
exophytic lesion with / without an erythematous component.

 PVL has an almost 100% rate of malignant transformation

which occur over a period of 15-20 years. Hansen et al (1985)
reported a malignant transformation rate of 86.7% and
Silverman and Gorsky (1997) reported a transformation rate of
70.3%, with the tongue and gingiva being the most common
site to be affected.
 Homogenous leukoplakia
Clinical findings
The typical homogenous leukoplakia is clinically characterized as a
white, well-demarcated plaque with an identical reaction pattern
through out the entire lesion.

The surface texture can very from a smooth thin surface to lathery
appearance with surface fissured gives “cracking mud” appearance.

The demarcation is very distinct which is different from OLP, where

the white components have a more diffuse transition to the normal
mucosa.

Also lack of peripheral erythmatous zone in homogenous leukoplakia

Precancerous lesions
continue………..
Chemical carcinogenes
 Major Chemical Carcinogens
 DIRECT-ACTING CARCINOGENS
 Alkylating Agents
 β-Propiolactone
 Dimethyl sulfate
 Diepoxybutane
 Anticancer drugs (cyclophosphamide, chlorambucil,
nitrosoureas, and others
 Acylating Agents
 1-Acetyl-imidazole
 Dimethylcarbamyl chloride
 PROCARCINOGENS THAT REQUIRE METABOLIC
ACTIVATION
Polycyclic and Heterocyclic Aromatic Hydrocarbons
 Benz[a]anthracene
 Benzo[a]pyrene
 Dibenz[a,h]anthracene
 3-Methylcholanthrene
 7,12-Dimethylbenz[a]anthracene
 Aromatic Amines, Amides, Azo Dyes
 2-Naphthylamine (β-naphthylamine)
 Benzidine
 2-Acetylaminofluorene
 Dimethylaminoazobenzene (butter yellow)
 Natural Plant and Microbial Products
 AflatoxinB1
 Griseofulvin
 Cycasin
 Safrole
 Betel nuts
 Others
 Nitrosamine and amides
 Vinyl chloride, nickel, chromium
 Insecticides, fungicides
 Polychlorinated biphenyls
Chronic poisoning by CO
 It develops because carboxyhemoglobin, once formed, is
remarkably stable. Even with low-level, but persistent,
exposure to CO, carboxyhemoglobin may rise to life-
threatening levels in the blood.

 The slowly developing hypoxia can insidiously evoke

widespread ischemic changes in the central nervous system;
these are particularly marked in the basal ganglia and lenticular
nuclei.
 With cessation of exposure to CO, the patient usually
recovers, but often there are permanent neurologic
sequelae such as impairment of memory, vision,
hearing, and speech. The diagnosis is made by
measuring carboxyhemoglobin levels in the blood.
Acute poisoning by CO
 It is generally a consequence of accidental exposure or suicide
attempt. In light-skinned individuals, acute poisoning is marked
by a characteristic generalized cherry-red color of the skin and
mucous membranes, which result from high levels of
carboxyhemoglobin.

 If death occurs rapidly morphologic changes may not be

present; with longer survival the brain may be slightly
edematous, with punctate hemorrhages and hypoxia-induced
neuronal changes. The morphologic changes are not specific
and stem from systemic hypoxia.
HISTOPATHOLOGY
Histopathology features

 Microscopically leukoplakia is characterized by thickened keratin

layer of surface epithelium (hyperkeratosis), with/without a
thickened spinous layer (acanthosis) variable number of chronic
inflammatory cells are noted within the connective tissue.

 The keratin layer may consist of parakertin (hyperparakeratosis),

orthokeratin (hyperorthokeratosis) or both with parakertin there is no
granular cell layer & the epithelial nuclei are retained with
orthokeratin, epithelium demonstrates granular cell layer & epithelial
nuclei are lost.

Shafer’s textbook of oral pathology,5th edition

 Verrucous leukoplakia has papillary/pointed surface
projections, varying keratin thickness, and broad rete ridges.
Most leukoplakic lesions demonstrate no dysplasia. Only in 5-
25% of cases evidence of epithelial dysplasia is seen.

 These changes typically begin in the basilar & parabasilar

portions of epithelium. More dysplastic the epithelium
becomes, more atypical changes extend to involve the
epithelium.

Shafer’s textbook of oral pathology,5th

edition
 GRADING & STAGING OF EPITHELIAL DYSPLASIA
:( LEUKOPLAKIA)

 Based on the presence of dysplastic features epithelial

dysplasia is divided into
 Mild
 Moderate
 Severe

Shafer’s textbook of oral pathology,5th edition

 The WHO 2005 classification recognizes five histopathological
stages in epithelial precursor lesions.

 Squamous hyperplasia- This may be in the spinous layer

(acanthosis) and/or in the basal/parabasal cell layers (basal cell
hyperplasia); the architecture shows regular stratification
without cellular atypia.

Isaäc van der Waal. Potentially malignant disorders of the oral and oropharyngeal mucosa;.
Journal of Oral Oncology (2008).
 Mild dysplasia- The architectural disturbance is
limited to the lower third of the epithelium
accompanied by cytological atypia.
 Moderate dysplasia- The architectural disturbance
extends into the middle third of the epithelium;
consideration of the degree of cytological atypia may
require upgrading.
 Severe dysplasia- The architectural disturbance
involves more than two thirds of the epithelium;
architectural disturbance into the middle third of the
epithelium with sufficient cytologic atypia is upgraded
from moderate to severe dysplasia.

I. van der Waal and T. Axell. Oral leukoplakia: a proposal for uniform reporting.
Oral Oncology 2002; 38: 521–526.
 Carcinoma in situ- Full thickness or almost full
thickness architectural disturbance in the viable cell
layers accompanied by pronounced cytological atypia.

Histopathologic features of
dysplasia
 Loss of polarity of basal cells
 Presence of more than one layer of cells having a basaloid appearance.
 Increased nuclear cytoplasmic ratio
 Drop shape rete peges
 Irregular epithelial stratification.
 Increased figure of mitotic figure.
 Cellular pleomorphism
 Nuclear hyperchromatism
 Enlarged nucleoli
 Reduction of cellular cohesion
 Keratinization of single cells or cell group in prickle layer

Shafer’s textbook of oral pathology,5th edition

 Differential diagnosis –
 White sponge nevus.
 Frictional keratosis.
 Chemical injury.
 Acute pseudo membranous candidasis.
 Leukoedema.
 Lichen planus.
 Lichenoid reaction.

burket’s oral medicine,11th edition

:
MALIGNANT POTENTIAL

 It refers to denote development of oral cancer from pre-

existing leukoplakia .Malignant transformation occurs in
0.3 – 10% of cases.

 Leukoplakia due to smoking habit shows higher rate of

malignant transformation compared to others. In buccal
mucosa & commeasure area 1.8% is malignant
transformation rate where as in lip, tongue & floor of
mouth it is 16% to 38.8%.
 Homogenous: 1-7%
 Verrucous: 4-15%
 Erythro leukoplakia: 18-47%.

Bouquot je, whitaker sb. Oral leukoplakia––rationale for diagnosis and prognosis
of its clinical subtypes or ‘phases’. Quintessence int 1994; 25: 133–40
investigator year country Malignancies%

Silverman 1976 India 0.13

Gupta 1980 India 0.30

(Bhavnagar )
Roed & Peterson 1971 Denmark 3.6

Schepman 1998 Netherland 12

Silverman 1984 USA 17.5

Burket’s oral medicine 10th edition

 DIAGNOSIS:
 A diagnosis of leukoplakia is made when adequate
clinical & histological examination fails to reveal an alternative
diagnosis & when characteristic histopathological findings for
leukoplakia are present. Important clinical criteria include
location, appearance, known irritants & clinical course.
ELIMINATION OF POSSIBLE CAUSE:
 The clinicians should first rule out any of the definable white
lesions before accepting a definitive clinical diagnosis. If
leukoplakia disappears spontaneously or through elimination of
irritant, no further testing is required.

 For persistent lesions a tissue “BIOPSY” is important.

 In non-homogenous leukoplakia biopsy should be taken at the

site of symptoms, if present & or at a site of redness or
indurations.
OTHER DIAGNOSTIC TECHNIQUES ARE:

 1. Chair side investigation

 Conventional
 Advanced
 2. Laboratory investigation
 Conventional
 Advanced
 CONVENTIONAL CHAIR SIDE INVESTIGATION:
 1. Intravital Staining – Toluidine blue and Lugol’s
iodine.
 Toluidine blue is an acidophilic metachromatic dye
which selectively stains dysplastic and malignant
lesions. It stains acid components in DNA and RNA
which are more in dysplastic cells. It helps directing
and selecting the site of biopsy.
burket’s oral medicine 11th edition
 Procedure:
 1% acetic acid is applied on the lesion for 2 second and is
rinsed with water followed by 1% Toludine blue application for
10-20 seconds and decolorized with 2% acetic acid for 20-30
seconds.
 Advantage;
 Low cost
 Simple technique
 Non-invasive
 Relatively accurate
 Disadvantages:
 False positive results
 Lugol’s iodine
 Richart had proposed that malignant cervical lesions would
have a limited amount of glycogen, compared to normal
squamous epithelium, and used Lugol’s solution for delineation
of malignant change.

 Normal tissue stains brown, but proliferating epithelium is

unstained or poorly stained. Lugol’s iodine solution produces a
brown-black stain by reaction of the iodine with glycogen.
 Glycogen content is inversely related to the degree of
keratosis. In the oral mucosa, the glycogen content
varies with the keratinization of the area of mucosa.
 2. Exfoliative Cytology:
 It is an adjunct to Biopsy and offers microscopic study of cells
obtained from the surface of an organ or lesion after suitable
stains. The neoplastic cells are less cohesive than normal cells
and usually shed on the surface of lesion or into the section.
 Advantages:
 Quick, painless, simple and non-invasive
 Helps in screening large samples
 3. ORAL BRUSH BIOPSY:
 It makes use of a cytobrush with firm bristles that obtain
individual cells from full thickness of the stratified squamous
epithelium.

 It is significantly more accurate than other cytologic technique

used in the oral cavity.
 ADVANCED CHAIR SIDE INVESTIGATIONS:
 1. Micronucleus Test (Hiddle 1973)
 It is valuable screening method for the assessment of
chromosomal damages and thus mutagenic influences on
mucosa. These micronuclei are chromatin particles derived
from eccentric fragments which are not incorporated into
daughter nucleus after mitiosis.
 It can be visualized by chromatin stains.
 2. Chemiluminescent illumination - Vizilite system

 It helps in highlighting the high nuclear density which results

due to altered nuclear, cytoplasmic ratio.
 It is accomplished by dehydrating the oral mucosa with acetic
acid which imparts acetowhite appearance. When visualized
either with conventional lighting or with diffuse blue white
chemiluminescence.
 The normal epithelium takes a BLUE HUE whereas
“ACETOWHITE” lesion appears distinctly white under
elimination.

K. H. Awan1, P. R. Morgan2, S. Warnakulasuriya1, Journal of Oral Pathology &

Medicine,volume 40August 2011
 Narrow-emission tissue fluorescence (Velscope):
 Approximately 30 years ago, it was observed that the auto
fluorescence of tissues (tissue fluorescence) could potentially
be used for cancer detection.

 Fluorescence spectroscopy involves the exposure of tissues to

various excitation wavelengths so that subtle differences
between normal and abnormal tissues can be identified.

VELscope auto fluorescence device

 LABORATORY INVESTIGATION:
 CONVENTIONAL LABORATORY INVESTIGATION:
 1. Biopsy:
 It is removal of tissue from the living organism for the purpose
of microscopic examination and diagnosis. Histologic criteria
represent the current “gold standard” for judging the malignant
potential of oral premalignant lesions.
 Advanced laboratory investigations
 a. Molecular methods:
 Quantification of nuclear DNA content: The DNA content of
a nucleus is dependent upon the number of chromosomes
present within it. Both polyploidy and aneuploidy are
associated with epithelial

 dysplasia and malignancy. Atkin and Richards established that
the quantitative analysis of DNA content reflects the total
chromosomal content which can be used to distinguish between
normal and malignant cells.
 Tumor markers: They are defined as biochemical substances
(hormones, enzymes or proteins) synthesized and released by
cancer cells or produced by the host in response to cancerous
substances and are used to monitor or identify the presence of a
cancerous growth. Tumor markers may be present in blood
circulation, body cavity fluids, cell membranes and cell
cytoplasm. Biomarkers are grouped into 3 classes:
 Genomic markers
 Proliferation markers
 Differentiation markers
Elimination of etiological factor

 Prohibition of smoking.
 To remove sharp, broken down teeth
 To replace faculty metal restorations and metal bridge.
 Elimination of other etiological factors like syphilis, alcohol
etc.
 Behaviour modification: Cancer appears more
frequently in persons who do not stop alcohol or
tobacco use.
 Leukoplakia induced by smokeless tobacco may
resolve if the habit is stopped.
Conservative treatment:
 Vitamin therapy – it has a protective effect on the epithelium.
Daily requirement is 4000 IU. It is given orally, parentally or
topically. Therapeutic dose – 75000 to 300000 IU for 3 months.
 Vitamin A + Vitamin E – this therapy is given to inhibit
metabolic degradation.
 Vitamin C
Though with vitamin C there is epidemiological evidence of
reduced cancer risk there is no evidence of a reliable protective
effect against oral lesions, though some studies suggest an
effect.
 Vitamin E
Vitamin E has synergistic inhibitory activity against
carcinogenesis in animal models and may have some beneficial
effect in man.
 Vitamin A and related compounds (Retinoids and carotenoids)
are currently being examined as potential agents though it is
over 30 years since the first attempts at such treatments.

 Carotenoids and Retinoids: Carotenoids have antioxidant or

anti carcinogenic activities, and can block genotoxic activity of
oral carcinogens such as extracts of areca nut.

 Retinoids are the synthetic and natural analogues of vitamin A.

There are many naturally occurring Retinoids, including
retinal,retinoic acid and their metabolites. Betacarotene is a
natural precursor of vitamin A.
 Antioxidant therapy – considerable data show that B-carotene
supplementation can be beneficial for treatment of oral
leukoplakia.
 Vitamin A palmitate – short-term treatment with vitamin A
palmitate along with aromatic retinoid may show healing and
improvement.
 Nystatin therapy – it is given in candidal leukoplakia 500,000
IU twice daily plus 20 percent borax glycerol or 1 percent
gentian violet or mouth rinses with chlorogen solution.
 Vitamin B complex –it is given as supplement in cases of
commissural and lingual lesions.
 Antimycotic preparation – the antimycotic preparation canesten
and pimafucin have also been effective.

 Panthenol – panthenol lingual tablet and oral spray may be

used against glossitis and glossodynia, in case of tongue lesion.

 Estrogen – in some cases, administration of estrogen can be

helpful.
Surgical management:

 To give proper treatment microscopic examination is necessary

for which biopsy is taken. The most meaningful sites for taking
biopsy specimen are the areas that display greater surface
irregularities such as cracks and fissures and those associated
with erythematous areas.
 Cryosurgery – tissue is exposed to extreme cold to produce
irreversible cell damage. Cell death occurs at –20 degree Celsius

 Disc type probe (cryoprobe) refrigerated by liquid nitrogen or

pressurized nitrogen oxide is used.

 Incorporated in the probe is rewarming device, thus tissue can be

rapidly frozen as required.

 The probe is applied to the surface of lesion, which is moistened by

water-soluble jelly. It produces very low temperature in tissue.
 First freeze for 1 minute, followed by 5 minute thaw. A second
1 minute freeze is then administered.

 Freezing produces white area of necrosis.

 The process is repeated for two or three times to achieve
maximum destruction.

 Freezing induces crystal formation within the cell and

intracellular spaces. When cooling rates are rapid, intracellular
ice crystal may rupture the cell membrane and cell death can
occur.
 Fulguration (electrocautery and electrosurgery)-
 It is the technique in which there is destruction of tissues by
high voltage electric current and the action is controlled by
movable electrode.
 Advantages of this are its ability to coagulate lesion and
provide easy control of hemorrhage.
 Disadvantages are distasteful (foul) odor, hazards of explosion,
need for profound local anesthesia, slow healing process, pain
and scarring.
 LASER:
 LASER stands for light amplification of stimulated
emission of radiation. CO2 lasers are most commonly used in
oral lesions due to their great affinity for any tissue with high
water content and their minimum penetration depth, i.e. 0.2 to
0.3 mm in oral tissue. CO2 laser contain CO2 nitrogen and
helium gases.
 Biopsy – in performing incisional or excisional biopsy in cases
of leukoplakia, CO2 laser is used as precise cutting tool. Laser
is placed in a cutting or focused mode held perpendicular to the
tissue.
 Different studies in treatment of leukoplakia
 Leukoplakia have been successfully treated with systemic 13-
cis-retinoic acid vitamin A aromatic Retinoids and beta-
carotene.
 Isotretinoin causes severe adverse reactions at doses above 0.8
mg/kg/day but at lower doses (0.2 mg/kg/day for 3 months,
doubling doses for a further 3 months, then increasing by 0.2
mg/kg for 3 months and so on) has been seen to be beneficial
in oral Leukoplakia.
Lee JJ, Hong WK, Hittelman WN, Mao L, Lotan R, Shin DM, Clin Cancer
Res. 2000 May;6(5):1702-10.
 Topical chemotherapy

Topical treatments of Leukoplakia with podophyllin solution or

bleomycin has induced some regression or even total resolution
of dysplasia and of clinical lesions.
Iontophoretic application of bleomycin has been used to treat
premalignant lesions and carcinomas as local injection. Topical
application of oil bleomycin to leukoplakia even has some
favourable effect but since leukoplakia can recur after systemic
bleomycin therapy.

Joel B. Epstein D.M.D., M.S.D.,Meir Gorsky D.M.D.Cancer

Volume 83, Issue 4, pages 629–634, 15 August 1998
 Polyamine inhibitors
Polyamine metabolism is altered in oral, and other,
carcinomas and inhibitors of polyamines may have a
future role in chemoprevention of potential malignant
lesions.
Prostaglandin E (PGE,) levels are high in pre
malignancies and carcinomas and might impair host
immune responses.

 Masami Ohnishi, Takuji Tanaka, Hiroki Makita, Toshihiko Kawamori, Cancer Science
Volume 87, Issue 4, pages 349–356, April 1996
Glutathione S- transferase
stimulators.
 Diterpene esters such as kahweol palmitate and cafestol
palmitate can enhance the enzyme glutathione S-
transferase in mice and this in turn may decrease the
availability of carcinogens.

 Ranjan Rashmi Paul,Bidyut Roy, International Journal of Cancer

Volume 109, Issue 1, pages 95–101, 10 March 2004
Immunotherapy.
 Immunostimulation in animal models, confer some
protection against carcinogenesis includes levamisole
and pyran copolymer. A trial of recombinant gamma
interferon in patients with carcinomas has also
suggested some clinical and histological benefit from
interferon.

 John S. Greenspan, B.D.S., Ph.D., Deborah Greenspan, B.D.S.,journal of

immunemediated diseases
Gene therapy
 Patients with head and neck cancer (including oral
leukoplakia and erythroplakia) are more susceptible to
chromosome damage when their cells are exposed to
mutagens and there are a number of genetic changes
now described in oral carcinoma.

Waun Ki Hong, M.D., James Endicott, M.D., Loretta M. Itri, M.DEngl J Med 1986;
315:1501-1505December 11, 1986
Photodynamic therapy
 Photodynamic therapy (PDT) involves using a
specific wavelength of light to activate a
photosensitising drug that is retained in the lesion.
This produces a photochemical reaction resulting in
the generation of reactive products such as singlet
oxygen, that damage tissue.

 Hsin-Ming Chen BDS, PhD, Chuan-Hang Yu BDS, Ping-Chin Tu BDS3, Lasers in

Surgery and MedicineVolume 37, Issue 2, pages 114–122, August 2005
continue……
Erythroplakia
Definition
 According to Mehta et al – diagnosed Erythroplakia when “the
oral mucosa was the seat of well demarcated red often fiery red
patch which could not be attributed to other causes”.

 According to Shafer & Waldron – “Erythroplakia of oral cavity

is a specific disease entity which must be differentiated from
other specific or non specific inflammatory oral lesions,
although this can only be done in most cases by biopsy.
WHO definition

 “Any lesion of oral mucosa that presents as bright red

velvety plaque which cannot be characterized
clinically or pathologically as any other recognizable
condition.
 According to Bouquot & Ephros –
 “A chronic red mucosal macule which cannot be given
another specific diagnostic name & cannot be
attributed to traumatic, vascular / inflammatory
causes.
CLASSIFICATION:

 Shear suggested a classification of oral erythroplakia

in 1972.
 1. Clinical Variations-
- Homogenous erythroplakia
- Erythroplakia interspersed with patches of .
leukoplakia.
-Granular / speckled erythroplakia.
2. Microscopic variations:

 Neoplastic
 Squamous carcinoma
 Carcinoma in situ & less severe form of epithelial
atypia.
 Inflammatory:
 Candida albicans infection
 Tuberculosis
 Histoplasmosis
 Miscellaneous specific, non-specific &non -
diagnosable lesion.
PREVALENCE & INCIDENCE:

 The prevalence rate of erythroplakia is 0.02% to

0.83% most of these figures are from south & south
East Asia. The point prevalence has been estimated as
one per 2500 adults. The incidence is estimated to be
1.2 per 100,000 populations (2 in males & 0.5 in
females).
ETIOLOGY & PATHOGENESIS:
Etiology & pathogenesis is poor by
understood. Predisposing factors include.
•Alcohol
•Tobacco use.
Reverse chutta smoking, has also been described as an
etiology. Recently even Human papilloma virus
infection is associated with etiology of Erythroplakia.

Ref:dd of oral & maxillofacial lesions fifth edition NORMAN K WOOD &GOAZ
Some studies have concluded that even mutation of P53
occurs in cases of Erythroplakia which is linked to high
malignant potential of these lesions.

Candida albicans has often been demonstrated in

erythroplakia lesions & the red component of this lesion
diminishes / disappears after antifungal therapy.
CLINICAL APPEARANCE /
FEATURES:

 Age – Oral erythroplakia commonly occurs in middle age &

elderly, most frequently in 6th & 7th decade of life. It is
interesting to note that patients in India with this lesion are 10-
20 yrs younger possibly due to early addiction towards tobacco
& alcohol.
 Gender – It has been recently stated that erythroplakia occurs
mostly in men. In recent study from India a gender distribution
of 49% in women & 51% in men was reported.
 Site & Size – Soft palate, floor or mouth & buccal mucosa are
commonly affected.

 Ref:dd of oral & maxillofacial lesions fifth edition NORMAN K WOOD &GOAZ
Erythroplakia
 Appearance: The typical lesion according to WHO is
smooth granular / nodular with a well defined margin
adjacent to mucosa of normal appearance.

 Shear elaborated the appearance “Although the

erythroplastic lesions have a smooth velvety surface,
other characteristics may also be seen like irregular
red granular surface interspersed with white/yellow
foci described as “GRANULAR
ERYTHROPLAKIA” .
Burket’s oral medicine 11th edition
 Numerous small irregular foci of leukoplakia
dispersed in erythroplakia patch has been called
“SPECKLED LEUKOPLAKIA”.

 Multiple lesions may be presence & are usually

asymptomatic. They are soft on palpation & do not get
indurated or hard until an invasive carcinoma
develops. Typical lesions measure about 1.5 cm in
diameter & half are less than 1 cm, but even larger
than 4 cms are observed.
Burket’s oral medicine 11th edition
 ERYTHROLEUKOPLAKIA:
 It is a lesion where erythroplakia is
admixed with / adjacent to leukoplakia in the mouth.
They are frequently seen on tongue & floor of mouth.
It is usually the red areas where actual dysplastic cells
are present.

Regezi:4th edition.textbook of oral pathology

 HISTOPATHOLOGICAL FEATURES:
 Erythroplakia exhibits epithelial changes
ranging from mild dysplasia to carcinoma in situ & even
invasive carcinoma. The epithelium shows lack of keratin
production & is often atrophic, but may be hyperplastic.

 This lack of keratinization with epithelial thinness allows

the underlying microvasculature to show through, thereby
causing red colour. The underlying connective tissue
demonstrates chronic inflammation.
MALIGNANT TRANSFORMATION:

 Oral erythroplakia has a high rate of malignant

transformation based on the fact that histology of
erythroplakia typically present as carcinoma in situ,
severe epithelial dysplasia or micro invasive
carcinoma. It varies from 14% - 50%.
Investigation
 Differentiation of erythroplakia from being inflammatory
lesions of the oral mucosa can be enhanced by the use of 1%
solution of toluidine blue applied topically with swab or oral
rinse malignant type retains it owing to increased nuclear DNA
content of tumor cells.

 Another method of establishing microscopic diagnosis is

Incisional biopsy.

K. H. Awan1, P. R. Morgan2, S. Warnakulasuriya1, Journal of Oral Pathology &

Medicine,volume 40August 2011
DIFFERENTIAL DIAGNOSIS:
 Oral erythroplakia is a diagnosis of exclusion. Some disease of
oral mucosa with red changes should be considered in
differential diagnosis.
 1. Mycotic infections -
 Oral Candidiasis
 Erythematous
 Generalized candidal erythema
 Denture induced stomatitis.
 Histoplasmosis

Ref:dd of oral & maxillofacial lesions fifth edition NORMAN K WOOD &GOAZ
 2. Bacterial infections –
 Tuberculosis
 3. Mucosal diseases –
 Atrophic lichen planus
 Lupus erythematosus
 Pemphigus & Pemphigoids.
 MANAGEMENT:
 Early effective treatments of these
lesions are mandatory because of its high rate of
malignant transformation.
 Observation for 1-2 weeks following the elimination
of suspected irritant is acceptable. A conservative
surgical procedure such as mucosal stripping is often
performed.
 Destructive techniques such as laser ablation, electro
coagulation & cryotherapy have been effective. Vitamin A,
retinoids, bleomycin, mixed tea & beta carotene have also been
used. Patient should be examined every 3 months in the first
year & every 6 months in the next 4 years.

 However since recurrence & multifocal involvement is

common long term follow up is mandatory.
 It is also called as Intraepithelial carcinoma which
frequently arises on skin but also occurs on mucous
membranes including oral cavity. Some authors believe
that this disease represents a precancerous dyskeratotic
process.

 DEFINITION:
 Carcinoma in Situ is defined as dysplastic
epithelial cells that extend from the basal layer to the
surface of mucosa i.e. top to bottom change.
CLINICAL FEATURES:

 Age & Sex –It has a male predilection in a ratio –

(1.8: 1). It commonly occurs in elder individuals.
 Site – It can occur at all intra oral sites, more
commonly on the tongue, floor of the mouth & lips.
 Appearance – It may appear like leukoplakia,
erythroplakia may be a combination of both may be
ulcerated lesion, ulcerated & white lesion, and red &
ulcerated, non-specific.
Carcinoma in situ
HISTOPATHOLOGIC FEATURES:
 Carcinoma in Situ is characterized by a remarkable range of
variation in histologic appearance.
 Keratin may or may not be found on the surface of the lesion,
but if present, is more apt to be parakeratin rather than
orthokeratin.
 Individual cell keratinization & epithelial & keratin pearl
formation is rare. In fact they are the hall mark of malignant
transformation of carcinoma in situ to invasive carcinoma.

Safers text book of oral pathology

 There appears to be hyperplasia of altered epithelium,
in some atrophy could be seen.
 An increased nuclear cytoplasmic ratio, nuclear
hyperchromatism are seen consistent loss of
orientation of cell & loss of polarity is seen.
 All the above changes occur within the surface
epithelium which remains confined by basement
membrane.
 TREATMENT & PROGNOSIS:
 There is no uniformly accepted treatment for CIS.
Surgical excisions of the lesions have been done irradiation,
cautery, even solid carbon di-oxide exposure is done.

 If the condition is left untreated carcinomatous invasion is

thought to occur eventually. Spontaneous regression of
carcinoma in situ is known to occur in certain sites especially
uterine cervix. But it is still doubtful if it occurs in oral cavity.
BOWEN’S DISEASE

 It is a localized intra epidermal squamous cell

carcinoma of the skin that may progress into invasive
cancer over many years. It is most commonly seen in
patients with arsenic ingestion & excessive sun
exposure.
CLINICAL FEATURES:

 Site – It most commonly occurs on male & female genital

mucosa & in oral mucosa as erythroplakia, leukoplakia or
erythematous lesion.
 Appearance – Appears as a slowly enlarging erythematous
patch, with little to suggest the malignant process. On the skin
it appears as red & scaly area which eventually enlarges &
turns into white or yellow lesion. When these scales are
removed they form granular surface without bleeding.
HISTOPATHOLOGIC FEATURES:

 It is very characteristic with epithelium exhibiting a significant

loss of cellular polarity & orientation increase & abnormal
mitosis; multiple highly atypical hyperchromatic nuclei &
cellular pleomorphism.
 Individual cell keratinization at different levels of
epithelium is seen. A nodular benign & virus
associated epithelial dysplasia with a histologic
picture resembling Bowen’s disease occur in genitalia
of sexually active individuals ‘BOWENOID
PAPULOSIS’.
TREATMENT:

 There is no definitive treatment option. Freezing

technique, diathermy, cauterization, radiotherapy and
application of cytotoxic drugs can be done
ACTINIC
KERATOSIS/CHELITIS/ELASTOSIS
 ACTINIC KERATOSIS:
 It is common cutaneous premalignant
lesion that is caused by cumulative UV radiation to sun
exposed skin, especially fair skinned people.
 UV light can produce mutation in P53 tumor suppressor
gene, an alteration found frequently in precancers &
cancers of head & neck. A similar phenomenon ACTINIC
CHELOSIS is associated with sun damage to lower lip.
ACTINIC CHELOSIS (ACTINIC CHELITIS):

 It is a common premalignant alteration of the lower

lip vermilion that results from long term exposure to
UV light. It is commonly seen in light complexioned
people, out door occupation people leading to popular
term “FARMERS LIP” / SAILORS LIP.
 CLINICAL FEATURES:
 Age: It is seldom seen in persons younger than 45 yrs.
 Sex: It has a strong male predilection with male to female ratio
10:1.
 Appearance: The lesion develops slowly & early clinical
changes include atrophy of the lower lip border, characterized
by smooth surface & blotchy pale area. Blurring of margin
between the vermilion zone & cutaneous portion of the lips is
typically seen.
 As the lesion progresses, rough scaly areas develop. They
thicken & may appear as leukoplakia. The patient may report
that the scaly material can be pulled off with some difficulty,
but they reform again with further progression chronic focal
ulceration develops. They last for a month & suggest
progression to squamous cell carcinoma.
 HISTOPATHOLOGIC FEATURES:
 It is usually characterized by an
atrophic stratified squamons epithelium often
demonstrating marked keratin production .Varying
degree of epithelial dysplasia seen
 A mild chronic inflammatory infiltrate is seen. The
underlying connective tissue demonstrates a band of
amorphous, a cellular, basophilic change known as
‘SOLAR ELASTOSIS’ – an UV light induced
alteration of collagen & elastic fibers.
 MALIGNANT TRANSFORMATION:
 It should be suspected if the following features are
present:
 Ulceration
 A red & white blotchy appearance.
 Generalized atrophy or whitish thickening.
 Persistent flaking and crusting
 Indurations at the base of the lesion.
 Rate is 6-10% & usually above 60 yrs. of age.
TREATMENT & PROGNOSIS:
 Many of these changes associated with actinic cheilosis are
irreversible but patient should be encouraged to use lip balms
& sunscreens to prevent further damage.

 Biopsy is a must if malignant features are seen.

 Other treatment modalities include 5 fluorouracil topical – 5%,

three times for 10 days. Heals with in 3 weeks. In some cases
podophyllin is used.
 Rapid freezing with CO2 snow or liquid nitrogen on
swab stick is used to remove superficial lesion.
 Vermilionectomy (lip shares) under local anaesthesia
where vermilion mucosa is excised by a scalpel &
closure is achieved by advancing labial mucosa to
skin is done.
 Laser ablation using CO2 is used to vaporize the
vermilion border. Long term follow up is
recommended.
 NICOTINE STOMATITIS / NICOTINE
PALATINUS /SMOKERS PALATE
 It refers to a specific white lesion that develops on
soft palate in heavy cigarette, pipe & cigar smokers. It
does not appear to have a premalignant nature,
perhaps because it develops in response to heat rather
than chemicals.
 In South America & South East Asian cultures, hand
rolled cigarettes & cigars are smoked with lit end held
in the mouth. This is reverse smoking habit produces a
pronounced palatal keratosis which has a significant
potential to develop dysplasia / carcinoma.
EPIDEMIOLOGY:

 Prevalence rates are as high as 1.0 to 2.5%

 Annual incidence rate is 1.7/1000.
CLINICAL FEATURES:

 Age: Commonly found at an age older than 45 years.

 Sex: Men are more commonly involved

 Clinically palate develops a diffuse grayish white

thickened, multi nodular appearance. There are small
red spots in the centre of each nodule, dilated &
partially occluded palatal salivary glands.
The palatal changes comprise of
several components:

 Keratosis: Diffuse whitening of the entire palatal mucosa

 Excrescences – 1 to 3 mm elevated nodule, often with central red dot

corresponding to opening of palatal mucosa glands.

 Patches – well defined, elevated white plaques, which could qualify

for the clinical term of leukoplakia.

 Red areas – well defined reddening of palatal mucosa.

 Ulcerated area – crater like areas covered by fibrin.
 Non pigmented area – Area of palatal mucosa devoid of
pigmentation.
 Clinical types of stomatitis nicotina are:
 Mild – Consists of red dot like opening on balanced
area.
 Moderate – well defined elevation with central
umbilication.
 Severe – Marked by papule of 5 mm or more with
umbilication of 2-3 mm.
 The palatal keratin may become so thickened that a
“fissured/dried mud appearance” is imparted
whiteness involves marginal gingival & interdental
papilla. A heavy brown or black tobacco stain may be
present.
HISTOLOGIC FEATURES:

 Hyper orthokeratosis acanthosis of the palatal

epithelium, mild patchy chronic inflammation of sub
epithelial connective tissue & mucosa gland is seen.
 Squamous metaplasia of the excretory ducts is
usually seen .Melanin deposits are seen in the lamina
propria. Epithelium is atrophic.
 MALIGNANT TRANSFORMATION:
 Rate – 0.3% of all lesions.
TREATMENT & PROGNOSIS:

 Nicotine stomatitis is a completely reversible

condition. The palate returns to normal within 1-2
weeks of smoking cessation. Any white lesion of the
palatal mucosa that persists after 1 month of habit
cessation should be considered a true leukoplakia &
managed accordingly.