Drg.

Rina Kartika Sari

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 INTRODUCTION

PRE CANCEROUS
POTENTIALLY LESION
MALIGNANT
DISORDER PRE CANCEROUS
CONDITION

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 INTRODUCTION
• Pre cancerous lesion  defined as a benign lesion with
morphologically altered clinical or histopathological
tissue which has greater than normal risk of containing
microscopic focus of cancer or of transforming into
malignant lesion after diagnosis at a later date
• Pre cancerous condition  defined as a disease or
patient habit which does not necessarily alter the
clinical appearance of local tissue but is known to have
a greater than normal risk of precancerous lesion or
cancer development
• Potentially Malignant Disorders (WHO 2005)  the risk
of malignancy being present in a lesion or condition
either at time of initial diagnosis or at a future date. 3
ORAL CANCER EPIDEMIOLOGY
PREVALENCE
• Cancer is the 2nd most common cause of death
• Cancer in oral cavity is 3% of all malignancies
• 270.000 patients annually worlwide

AGE & RACE

• Middle age > About 50 – 60 of life
• Young and children rarely affected
• Black males have higher incidence

GENDER
• 4-8,1% of females
• 8-8,5% of males
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Extrinsic Intrinsic
• Tobacco (smoke/smokeless) • Genetic
• Alcohol /phenol • Malnutrition
• Infection (viral,bacterial,candidal) • Immunosuppresion
• Radiation

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 Predilection site
• Premalignant disor-ders are usually found on
the buccal mucosa, fol-lowed by gingivae,
tongue and floor of the mouth.

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 CLASSIFICATION

Pre Cancer Lesion Pre Cancer Condition

• Erythroplakia • Oral Lichen Planus

• Leukoplakia • Oral Submucous
• Mucosal changes Fibrosis
associated with • Syphilis
smoking habits • Dyskeratosis
• Actinic keratosis, congenita
cheilitis and elastosis. • Lupus erythematosus

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 EARLY DETECTION
CLINICAL

TISSUE ALTERATION PREDISPOSING FACTORS?

DIRECT FLUORESCENCE / STAINING

TOLUIDINE BLUE VELSCOPE

BIOPSY

INCISIONAL EXCISIONAL 10
 APLIKASI TOLUIDINE BLUE 1%
• Kumur rongga mulut dengan air selama 20 detik
• Kumur dengan larutan asam asetat 1% selama 20 detik
• Keringkan dengan seksama area mukosa dengan
menggunakan gauze, jangan sampai melukai atau
mengabrasi jaringan
• Aplikasikan toluidine blue 1% pada lesi dan seluruh
rongga mulut dengan cotton swab
• Kumur lagi dengan asam asetat (kira – kira 150ml untuk
1 menit)
• Kumur lagi dengan air

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 TREATMENT
• Early cancers of the oral cavity and lip (stage I,
stage II) have a better prognosis; therefore,
surgery or radiation are the treatments of
choice.
• Chemotherapy is added to surgery and/or
radiation in stage III and higher.

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ORAL LEUKOPLAKIA

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 DEFINITION
• WHO (1978) as a white lesion that cannot not
clinically or pathologically be characterized as
any other disease.
• It is the mouth's reaction to chronic irritation
of the mucous membranes of the mouth

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 EPIDEMIOLOGY

• 2% estimation worldwide
Prevalence • Global study 2,6%

• Most common occur in 50

Age • Rarely occur under 30

• Men > Women

Gender • Women slightly more in another study
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 ETIOLOGY
• Etiology is unknown
• Tobacco are most common cause
• About 70–90% of oral leukoplakias are related to
smoking and areca nut use, either alone or in
combination, and direct relationship between the
frequency and the duration of cigarette, pipe, or
cigar smoking and the prevalence of oral
leukoplakia
• little evidence of a causal relationship with HPV
infection and alcohol
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ETIOPATOGENESIS
NORMAL CELLS
Predisposing factors
Ex:
Tobacco,Alcohol,Virus
DNA DAMAGE
,Nutrition,etc

Tumor Gene
Protooncogene/ DNA repair
suppresor regulates
oncogene gene
gene apoptosis

Abnormal cell
proliferation

POTENTIAL MALIGNANT
DISORDER
 ETIOIMMUNOPATHOGENESIS
Activate NFk-B

Tiocyanate
TSNA Inhibit ions & free
(NNN,NAT,NNK,NAB) antioxidant Fragile radical
+free radicals enzyme epithel
(GST,GR,SOD,ca
talase,GTP)

Ethanol --
asetyldehid
MNPA,MNPN,
Alkaloids
NGC,NGL

chewing
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 CLINICAL FEATURES

Homogenous Erythroleukoplakia

Proliferative
Nodular
Verucous

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HOMOGENOUS (Glick,2015)

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 ERYTHROLEUKOPLAKIA
(SPECKLED LEUKOPLAKIA)

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PROLIFERATIVE VERUCOUS
LEUKOPLAKIA

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NODULAR LEUKOPLAKIA

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omogeneous leukoplakia in a 57-year-old man
). A biopsy showed hyperkeratosis without
pithelial dysplasia. The patient was unable to
op smoking and refused any type of
eatment. He was lost to follow-up and
howed up 12 years later with a large squamous
ell carcinoma
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A 63-year-old man with verrucous
leukoplakia of the buccal mucosa A).
The leukoplakia recurred within three
weeks after surgical removal B).

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LX  ukuran tidak
spesifik
L1  < 2 cm, single atau
multiple STAGE PATHOLOG KLINIS
L2  2-4 cm, single / IS
multiple
Stage 1 L1P0 L1C1
L3  >4 cm, single /
multiple
C1  homogenous Stage 2 L2P0 L2C2
C2  Non homogenous
PX  tidak spesifik Stage 3 L3P0 L3C1
P0  tidak ada dysplasia
epitel
P1  ditemukan Stage 4 L3P1 L3C2
dysplasia epitel
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 HISTOLOGICAL APPEARANCE
• Epithelial keratinization (Hyperortokeratinization or
hyperparakeratinization)
• Acanthosis
• Thinned basal membranes
• Inflammatory cells in connective tissue
• Alteration in cell layer increased ratio
nucleus:cytoplasm, hyperchromatism nucleus, nucleus
hyperplasia, abnormal mitotic figures, increasing
mitosis, nucleus pleomorphism, basal cell hyperplasi,
drop shaped rete peg, loss of polarity. (Liu et al, 2010)
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 DIFFERENTIAL DIAGNOSIS
• Oral Lichen Planus :
• Chemical Burn
• Leukoedema
• White Sponge Nevus
• Cheek Bite

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TREATMENT

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 PROGNOSIS
• Malignant transformation prevalence
betwenn 1%-20% in 1– 30 years.
• Europe, insidence no more than 1%.
• Homogenous leukoplakia < non homogenous
leukoplakia & eritroplakia
• Lesion <200mm2 have better prognosis (Glick,
2015).

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• thin leukoplakia often becomes malignant
without clinical changes. Thick leukoplakia
undergoes malignant transformation in 1–7%
of cases. The frequency of malignant changes
in verruciform and speckled leukoplakia
ranges from 4% to 15% and 18% to 47%,
respectively

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 DEFINITION
• Another term : Erytroplasia of Queyrat
• WHO 1983 defined as Any lesions of oral mucosa
that presents as bright red velvety plaques which
cannot be characterized clinically or pathologically
as any other recognizable condition.
• WHO 1994 ‘‘The term erythroplakia is used
analogously to leukoplakia to designate lesions of
the oral mucosa that present as red areas and
cannot be diagnosed as any other definable lesion’’
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 EPIDEMIOLOGY
• Not as common as oral leukoplakia
• Prevalence (estimated): 0,02 – 0,1%
• Middle aged and elderly >>
• Male = Female.

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 ETIOLOGY
• Unknown
• Tobacco use and heavy alcohol consumption
are most predisposing factor
• Most common area:floor of the mouth,
palatum, retromolar area, ventral of the
tongue and tonsilar.

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CLINICAL FEATURES

Erythroplakia in
alveolar ridge. Well-
demarcated
erythematous
macule, slight
depressed, soft,
velvety texture,
intersperssed with
white area, later
diagnosed as SCC
Homogenous red patch, smooth, soft, well defined,
straight margin, extended area in palatum and
alveolar ridge (Glick,2015)

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HISTOLOGICAL FEATURES
• Shows some degree of dysplasia even carcinoma in situ or invasive
carcinoma
• Atrophic lesions characterized by epithelial atrophy and/or absence
of keratin production, which means that the underlying vascular
lamina propria appears red clinically.

CRITERIA USED FOR DIAGNOSIS OF EPITHELIAL
DYSPLASIA
•Loss of polarity of basal cells
•Increased nuclear-cytoplasmic ratio
•Drop-shaped rete ridges
•Irregular epithelial stratification
•Increased number of mitotic figures
•Mitotic figures that are abnormal in
form
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•The presence of mitotic figures in
the superficial half of the epithelium
•Cellular and nuclear pleomorphism
•Nuclear hyperchromatism
•Enlarged nuclei
•Loss of intercellular adherence
•Keratinization of single cells or cell
groups in the prickle cell layer
 DIFFERENTIAL DIAGNOSIS
• ORAL LICHEN PLANUS – ERYTEMATOUS TYPE
• VASCULAR LESIONS
• ALLERGIC REACTION
• ERYTEMATOUS CANDIDIASIS

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 TREATMENT
• Definitive treatment  controversial. Basically,
same with leukoplakia
• Surgical incision/excision by knife or laser
depend on size.
• May followed with topical or systemic
chemoprevention  vitamin A,C,E, carotene or
lycopene
• No symptomatic treatment
• Patient education : evaluation in 1 month, 3
months, 6 months,12 months, every year.
• Avoid predisposing factors

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 PROGNOSIS
• Long term monitoring (Scully,2010).
• High risk potential premalignant.
Transformation rate including invasion, may
varies from 14-50% (Ali et al, 2015)

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• Moreover, acetaldehyde impairs the process through
which naturally occurring damage to the DNA is
repaired by inhibiting an enzyme that is important for
the repair of a certain type of DNA damage.
• In addition to these mechanisms, acetaldehyde can
interact with DNA building blocks to form new
molecules (i.e., DNA adducts). These adducts may
trigger replication errors and/or mutations in cancer-
causing genes (i.e., oncogenes) or in genes that
normally prevent cancer development (i.e., tumor
suppressor genes).

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 DEFINITION
• Oral lichen planus (OLP) is a chronic
inflammatory mucocutaneus disease mediated
by T cells.
• 75% of the patients with cutaneous lichen
planus also experience oral lesions
• First described clinically by Wilson in 1869 as a
chronic mucocutaneous disorder

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 EPIDEMIOLOGY
PREVALENCE
• 0,5% - 2,2%

AGE
• Middle age > About 50 – 60 of life
• Young and children rarely affected

GENDER
• Woman > Men 1,4:1
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 ETIOLOGY
• Unknown
• May result from an abnormal T-cell-mediated
immune response in which basal epithelial
cells are recognized as foreign because of
changes in the antigenicity of their cell surface
• Associated with multiple causes,disease and
agents

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Initiated by the endogenous or exogenous factors with a
genetic predisposition
1. Genetics
2. Psychological factors
3. Dental materials
4. Habits
5. Drugs
6. Trauma
7. Infectious agents
8. Diabetes & hypertension
9. Immunology
10. Miscellaneous
11. Immunodeficiencies
12. Food allergies
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ETIOIMMUNOPATHOGENESIS

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CLINICAL FEATURES
EXTRAORALLY
• purple,
polygonal,plaque
-like,Pruritic
• Usually in flexor
surface
• (Edward&Kelsch,
2002)

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 CLINICAL FEATURES
INTRAORALLY

RETICULAR PAPULAR PLAQUE-LIKE

EROSIVE ULCERATIVVE BULLOSA 60

Reticuler type OLP (Glick,2015)

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Papular type OLP (Glick,2015)

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Plaque-like type OLP (Glick,2015)

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Erosive type OLP in gingiva
(Glick,2015)
• Gingivitis
desquamative

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Ulcerative type OLP (Glick,2015)

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BULLOSA TYPE OF OLP (Ghom,2010)

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• skin lesions present typically as flat-topped
violaceous papules affecting the wrists,
ankles, and genitalia.
• Nail involvement results in pitting, pterygium
formation, and permanent nail loss.
• Scalp involvement results in scarring alopecia
(Sugerman et al., 2000a).
• Rarely, there is laryngeal, esophageal, and
conjunctival involvement
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 HISTOLOGICAL FEATURES
• Hyperparakeratosis or hyperortokeratosis,thickness
granulosum layer and saw-tooth appearance of
rete peg (atropi epitel dimana rete peg memendek
dan menjulur)
• Degenerasi liquefaksi or necrosis of basal cell layer
with apoptosis keratinoscyte
• Eosinophilic band (eosinophillic colloid bodies/
civatte bodies)  degenerasi keratinocyte in basal
membrane contain fibrin that covers lamina
propria. Subepitel infiltrated with lymphocyte and
macrophag. Deposit antibody and complemen may
found but not patognomonic OLP.
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 DIFFERENTIAL DIAGNOSIS
• Oral Lichenoid reaction
• Oral Graft-Versus-Host Disease:
• Discoid Lupus Eritematus
• Homogenous Oral Leukoplakia
• Mucous Membrane Pemphigoid

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 TREATMENT
CORTICOSTEROID

• 0.05% clobetasol propionate gel,

• 0.1% or 0.05% betamethasone valerate gel,
• 0.05% fluocinonide gel,
• 0.05% clobetasol butyrate ointment or cream,
• 0.1% triamcinolone acetonide ointment.

OTHER APPROACH
• Retinoids
• PUVA
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• Surgery
 PROGNOSIS
• Malignant potential transformation  very low,
still debatable  evaluation annually
• Potential malignanat for some type of OLP  ???
Some studies, plaque-like type more risk but
other study shows ulcerative one. (Glick, 2015)
• Squamous cell carcinoma (SCC) may arise at the
site of a pre-existing OLP lesion in less than 5%
cases, most frequently in atrophic, erosive, and
plaque lesions
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ORAL SUB MUCOUS
FIBROSIS

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 DEFINITION
• Oral submucous fibrosis is a chronic disease
affecting the oral mucosa, as well as the
pharynx and the upper two-thirds of the
esophagus
• premalignant disorder associated with the
chewing of areca nut (betel nut).

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 EPIDEMIOLOGY
• Insidence worldwide 2,5million
Prevalence • India 0,2-0,5%

• Under 30 y.o
Age • Restriction for young people

• Female 5% : Male 2%
Gender • Female 1,2-4,57% : Male 0,2-2,3%

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 ETIOLOGY
• Areca nuts is primary
etiologic factor
• Tobacco
• Slake lime
• Sirih
• Other ingredients (flavor
etc)

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• Capsaicin
• Nutritional deficiencies
• Ineffective iron metabolism
• Collagen destruction
• Changing of Saliva composition
• Genetic factor

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ETIOIMMUNOPATHOGENESIS

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 CLINICAL FEATURES
Subjective Extraoral Intraoral

• Difficult in • Limitation in • Erythematous

eating,speaking, mouth opening • Ptechiae
• Burning • Vesicle
sensation • Mucosa paler
• Xerostomia • Marble
• Change of taste appearance
• Dysphagia • Fibrous band
• Hearing
impairement
• History of areca
nut chewing 81
• Mucosa paler
• Erytematous area
• Pigmentation
• (Glick,2015)

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• Mucosal
paler
• (Wollina et
al, 2015)

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Limitation in mouth opening (Wollina
et al, 2015)

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 OSMF STADIUM
• Stadium 1: Stomatitis, mucosal
erythema, vesikel , ulcer,
Pigmentasi Melanotic ,petechiae
in mucosa
• Stadium 2: fibrosis, vesicle
rupture and ulcer healed is
characteristic in this stadium.
Early lesion shows mucosal paler,
fibrous band vertical or circular,
palpable in buccal mucosa,
mouth or lips. Marble
appearance in mucosa. Mouth
opening limitations, lidah kaku
dan mengecil , gingival fibrotik,
depigmentation , penyusutan
• Group I: early stadium, no limitation
in mouth opening. Interincisal space
maxilla n mandibula >35 mm.
•Group II: . Interincisal space maxilla n
mandibula 26-35 mm.
•Group III: Moderate stadium. .
Interincisal space maxilla n mandibula
15-26 mm. Fibrotic band in palatum
molle & pterygomandibular raphe &
pilar anterior tonsillar.
•Group IVA: Severe trismus ,
nterincisal space maxilla n mandibula
<15 mm , fibrosis in whole mucosa
• Group IVB: Late stadium with
premalignant and malignant
condition in oral mucosa.
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HISTOPATHOLOGIC CLASSIFICATION
(Wollina et al, 2015)

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 HISTOPATHOLOGIC APPEARANCE
• Early OSMF fine smooth fibril from collagen,
edema, hypertrophy fibroblast, dilatated &
blocking blood, infiltration of neutrophil dan
eosinophil granulocyte.
• Advance OSMF  defect fibroblast, epithelial
atrophy, loss of rete peg, early sign
hyalinization with inflammatory cell
infiltration.
• Epithel Dysplasia  7%-26%

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 Late stadium OSMF A. HE staining
100x..B. HE staining 400x (Wollina et al.
2015)
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 DIFFERENTIAL DIAGNOSIS
• Amyloidosis
• Generalized fibromatosis
• Oral manifestation of Scleroderma
• Oral lichen planus
• Anemia

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 TREATMENT

Avoid Medication Surgery

Carsinogenic • Topical/Systemic steroids • Simple excision
• Areca nut • Hyaluronidase • Grafting
• Tobacco • IFN Gamma • Flap
• Lycopene • Laser
• Pentoxyfilline • Physical exercise
• Vitamin supplement
• Nutrition improvement

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 PROGNOSIS
• Malignant transformation approximately 7%-
13%
• Insidence >10 years  8%.
• OSMF complication  Oral dysplasias &
squamous cell carcinomas
• Stenosis tuba eustachian hearing
impairement

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 DEFINITION
• Actinic cheilitis (actinic cheilosis) is a
pre malignant lesions on vermilion
border of lower lip, caused by
exposure to solar radiation

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 EPIDEMIOLOGY
PREVALENCE
• Prevalence rate : 0,45% - 2,4% of population
• In group engaged in outdoor activities : 4,2 % - 43, 2
%

AGE & SEX

• Sex predilection Male : female = 1,5:1 to 4:1
• Age predilection 50,6 -64,3 years old,
• >37 years old more risk to 1,9 times

RACE
• Ethnicity  European ethnic : 26 %
• Others : 9%
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 ETIOLOGY
 Chronic ultraviolet
radiation exposure
Predisposing factors :
1. Skin phenotype
2. Age
3. Male sex
4. Outdoor occupation,
rural living
5. Tobacco habits
6. oral hygiene
7. Host immunological
status

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 Initial sun-induced
damage:
 Short term and acute
 Sunburn, blistering, or
Solar peeling
radiation
(UV-A,
UV-B) Repeat exposure:
 Long term and chronic
changes
 Freckling, loss of
elasticity
Telangiectasia, actinic
cheilosis

3/20/2019 96
 Solar Radiation
Change in protein & DNA
(UV-B, UV-A)

Transition mutations Impaired tumor

(p53) suppressor activity

Epidermal dysplasia

PATHOGENESIS
3/20/2019 97
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mottling of the lip with atrophic areas or
shallow erosions and rough, scaly, flaky
keratotic patches on some parts, white to
gray, sometimes with small wrinkles,
delineated of vermilion border..
 The keratotic patches progress to palpable
thickening and induration.
(Scully,2011)

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Actinic cheilosis. Crusted and
ulcerated lesions of the lower
lip vermilion. (Neville, 2003)

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The possibility of malignant change must
always be considered when there are suspect
features such as:
 ulceration
 a red and white blotchy appearance with
an indistinct vermilion border
 generalized atrophy with focal areas of
whitish thickening
 persistent flaking and crusting
 Induration

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Hyperorthokeratosis and epithelial
atrophy.
Note the striking underlying solar
elastosis.
(Neville, 2003)

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 PREVENTION :
SUNSCREEN
LIP BALM
Topical Chemoexfoliants
Surgery
Laser Ablation
Vermillionectomy

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The prognosis is good.

Long-term exposure can progress and develop

into invasive squamous cell carcinomas.
Approximately 10% of carcinomas whose origin
is in the lip metastasize.
Presence of bleeding, indurations, disease
recurrence and persistent pain should be
considered as markers of AC transformation
into SCC.
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