Precancerous

Lesions & Conditions

Contents

• Introduction

• Classification of precancerous lesions & conditions

• Leukoplakia

• Erythroplakia

• Carcinoma in Situ

• Oral lichen planus

• Oral submucous fibrosis

Introduction

• Precancerous lesion

• “Morphologically altered tissue in which cancer is more

likely to occur, than in its apparently normal

counterpart”

• Precancerous condition

• “Generalized state of the body, which is associated with a

significantly increased risk of cancer”

PREMALIGNANT LESIONS

• Leukoplakia

• Erythroplakia

• Carcinoma in situ

• Bowens disease

• Actinic keratosis & chelitis

• Dyskeratosis follicularis

PREMALIGNANT CONDITIONS

• Oral submucous fibrosis

• Oral lichen planus

• Syphilitic glossitis

• Sideropenic dysphagia

• Dyskeratosis congenita

Leukoplakia

• The term LEUKOPLAKIA was first coined by a Hungarian

Dermatologist SCHWIMMER in 1877

• Originates from Greek words – “leucos” - white and “plakia” -

patch

• WHO 1978

• “A white patch or plaque in the oral cavity which cannot be

scrapped off or stripped off easily & more over, which cannot be

characterized clinically or pathologically as any other disease”

Epidemiology

1. Prevalence

• Represents 85% of all oral precancers

2. Incidence

3 – 4 % of adult population

3. Age

Usually in the 4th – 6th decades of life

4. Sex

Males have the highest incidence, with the trend changing gradually

Classification of leukoplakia(Axell & Pindborg et al 1983)

• Based on CLINICAL TYPE:

Homogenous

Non homogenous

• Based on ETIOLOGY:

Tobacco associated

Idiopathic

• Based on EXTENT:

Localized

Diffuse

• Based on risk of MALIGNANT TRANSFORMATION

High risk sites

Floor of mouth

Lateral/ventral surface of tongue

Soft palate

Low risk sites

Dorsum of tongue

Hard palate

• Based on HISTOLOGY:

Dysplastic

Non dysplastic

Sharp’s staging of leukoplakia

• Stage I- Earliest lesion-non palpable, faintly translucent,

white discoloration

• Stage II- Localized or diffuse, slightly elevated plaque of

irregular outline. It is opaque white & may have a fine

granular texture

• Stage III- Thickened white lesion showing induration and

fissuring

Etiopathogenesis

• Tobacco – most imp offending agent

• Alcohol

• Chronic irritation

• Syphilis

• Nutritional deficiency

• Actinic radiation

• Galvanism

• Most studies have reported mortality ratios for smokers

versus never smokers of about 5:1, with several reporting

ratios in excess of 10:1. Furthermore, the risk for death

from oral cancer is consumption related

• Male cigarette smokers had a relative risk for oral cancer

27.7 times greater than that of a male never smoker

• These studies have found that after 3 to 5 years of smoking

abstinence, oral cancer risk decreased by about 50%

Clinical presentation

• Any mucosal surface, solitary or multiple,

“White patches”

• Varies from a non-palpable faintly

translucent white area to a thick fissured,

papillomatous or indurated lesion

• Colour varies from white, grey or yellowish

white, sometimes brownish-yellow

• 70% in buccal mucosa, commissural areas, followed by lower lip,

floor of the mouth, palate & gingiva

SYMPTOMS

• Patients may report with a feeling of increased thickness of

mucosa

• Those with ulcerated or nodular type may complain of

burning sensation

• Enlarged cervical lymph nodes may signal occurrence of

metastasis

Clinical variants of leukoplakia

Homogeneous/ Leukoplakia Simplex Speckled/Nodular

Ulcerative

Histopathological features

• Keratinization pattern

• Thickness of epithelium

• Changes in underlying

connective tissue

• Waldron & Shafer (1975)

80% lesions show benign hyperkeratosis with/without acanthosis &

17% represent CIS

Dysplastic changes typically begin in basal & parabasal zones of

epithelium

• Five clinical criteria for high risk of malignant change

– The nodular type

– Erosion or ulceration within lesion

– Presence of a nodule indicates malignant potential

– A lesion that is hard in its periphery

– Lesion of anterior floor of mouth & undersurface of tongue

• In all cases, relative risk of malignant potential is determined

by presence of epithelial dysplasia upon histological

examination

Diferential diagnosis

• Leukoedema

• Lichen planus

• Chemical burn

• Morsicatio buccarum

• Lupus erythematosus

• White sponge nevus

Conservative management

• Elimination of etiological factor

• Restraining from smoking or chewing tobacco

• To remove sharp broken down teeth

• Correction & replacement of overhanging or faulty metal

restorations with a metal bridge

CHEMOPREVENTION

1) Isotrenitoin / 13- cis- retinoic acid –

2) Beta carotene -30mg TID

3) Topical Bleomycin – 0.5-1% solution/2wks

4) 5-Fluorouracil & Cisplatin

• Surgical Excision: entire lesion excised if it is >1cm in size,

following modalities used:

a) Scalpel – surgical stripping

b) Cryosurgery – with liquid nitrogen

c) Electrocautery

d) Laser ablation

Erythroplakia

WHO DEFINITION:

“Any lesion of the oral mucosa that presents as a

bright red velvety patch or plaque, which cannot be

characterized clinically or pathologically as any other

recognizable condition”

Reported by Querat in 1911

CLASSIFICATION

• Clinical variants

1. Homogenous erythroplakia

2. Erythroplakia interspersed with patches of leukoplakia

3. Granular or Speckled erythroplakia

• Etiology : Same as oral leukoplakia

• Age : Mainly middle age, peak 65-74 years

• Gender : Predilection for men

• Location/size

- Soft palate, floor of the mouth & buccal mucosa & tongue

- Typical lesion < 1.5 cm in diameter but >4cm also

observed

- Smooth and granular/nodular, well defined

- May have an irregular, red granular surface interspersed

with white or yellow foci

- Soft on palpation

• Highest risk for malignant transformation - 14-50%

• Based on the fact that on histology 80-90% of cases

present as-

- Carcinoma In Situ

- Severe epithelial dysplasia

- Microinvasive carcinoma

Management

• Biopsy should be performed

• Treatment guided by histopathologic diagnosis

• Recurrence , multifocality common

• Careful long term follow up

Intraepthelial carcinoma (Ca in Situ)

• Arises frequently on the skin, but also on mucous membranes,

including oral cavity

• Most severe stage of epithelial dysplasia

• Striking feature – dysplastic epithelial cells donot invade into

connective tissue

• Common among elderly, with a male prdiliction

• Present as white plaques or ulcerated, & reddened areas

• Site – floor of the mouth, tongue, lips

• Has combined features of leuko & erythroplakia

• Histopathology

• Keratin may or may not be present on the surface, but if present it

is usually parakeratin

• Individual cell keratinization or keratin pearl formation are rare

• Consistent finding – loss of orientation & normal polarity of cells

• Treatment

• No accepted treatment

• Surgical excision, irradiation & cauterization

Precancerous conditions

Oral lichen planus

• Named by E Wilson ( British physician) 1896

Lichen – latin for primitive plants (symbiotic algae & fungi)

Planus – latin for flat

• Definition

• “A common chronic immunologic inflammatory mucocutaneous

disorder that varies in appearance from keratotic (reticular or plaque

like) to erythematous and ulcerative, affecting the stratified squamous

epithelium”

• Affects 0.5% to 1% of world's population

• Approx half patients with cutaneous LP have oral

involvement

• Mucosal involvement, sole manifestation in up to 25%

cases

• Peak incidence - middle age, F:M- 2:1

• Characteristically associated with persistent clinical

course & resistance to most conventional treatments

• On skin-

• Flat-topped purple polygonal & pruritic papular rash

• Koebner phenomenon

Etiology & pathogenesis

• Both antigen-specific & non-specific mechanisms may be involved

in pathogenesis of OLP

• Antigen-specific mechanisms:

– antigen presentation by basal keratinocytes and

– antigen-specific keratinocyte killing by CD8+ cytotoxic T-cells

• Non-specific mechanisms:

– mast cell degranulation and

– matrix metalloproteinase (MMP) activation

• These mechanisms may combine to cause

T-cell accumulation in superficial lamina propria

Basement membrane disruption

Intra-epithelial T-cell migration &

Keratinocyte apoptosis

Clinical features

• Lesions usually symmetrical

• Frequently affects buccal mucosa,

tongue, gingiva, lip and palate

• Extra-oral mucosal involvements -

anogenital area, conjunctivae,

oesophagus/larynx

• Approx 1.2% - 5.3% lesions undergo

malignant changes

• Hence regular follow up mandatory

Clinical variants

Reticular (92%) Atrophic (44%) Plaque (36%)

Erosive (9%) Bullous (1%)

Clinical features

Asymptomatic

• Reticular – Wickham’s striae + discrete erythematous border

• Plaque-like – Resemble leukoplakia, common in smokers

Symptomatic

• Atrophic – Diffuse red patch, peripheral radiating white striae

• Erosive – Irregular erosion covered with a pseudomembrane

• Bullous – Small bullae / vesicles that may rupture easily

Histology

Shklar -3 classic microscopic

features of OLP

• Overlying hyperkeratinization

• A bandlike layer of chronic

inflammatory cells within

underlying connective tissue

• Liquefaction degeneration of basal

cell zone

Diagnosis

• The characteristic clinical aspects of OLP - sufficient for

correct diagnosis

• An oral biopsy - to confirm clinical diagnosis

(exclude dysplasia & malignancy)

• Gingival LP more difficult to diagnose, direct

immunofluorescence of perilesional mucosa for diagnosis

IMMUNOFLUORESCENCE

• Direct immunofluorescence – shaggy band of fibrinogen

in the basement membrane, IgM stained cytoid bodies

are also seen in dermal papilla or peribasilar area

Management

• Reticular type is asymptomatic & treatment often

unnecessary

• Erosive type presents significant management problems

• All patients should optimize oral hygiene

• Oral candidiasis should be excluded/treated

• Cortico steroids, is the treatment of choice eg – Fluocinonide

or Clobetasol gel for 2 weeks, with 3mnths follow-up

• In symptomatic patients with apparent contact dental

factor, patch test with replacement of amalgam

• In those with no apparent contact factor, topical or

intralesional steroid - first line treatment. A short course

of systemic steroid for more rapid control

Lichenoid reaction

• The oral lichenoid eruption is a less specific entity compared with

LP of the skin.

• Best considered as a reaction pattern of oral mucosa to a variety of

insults, including

– OLP itself

– Contact allergy

– Trauma and

– Other inflammatory dermatoses (e.g. oral lupus erythematosus

may look very lichenoid)

Oral submucous fibrosis

DEFINITION -

“It is a slowly progressing chronic fibrotic disease of the

oral cavity & oropharynx, characterized by fibroelastic

change and inflammation leading to a progressive

inability to open the mouth, swallow or speak”

Clinical featuresAge

• Range wide & regional; even prevalent among teenagers in India

Ranges from 11-60 years

Sex

• From 0.2 - 2.3% in males to 1.2 - 4.5% in females in Indian

communities

Race

• South-East Asian countries, in Indian immigrants to other

countries

Mortality/morbidity

• High rate of morbidity - progressive

inability to open mouth, resulting in

difficulty eating & consequent

nutritional deficiencies

• Significant mortality rate - can

transform into oral cancer, particularly

Squamous cell carcinoma 7.6%

Etiology

• Initially classified as idiopathic, now

• Betel quid & it’s components (Arecoline, an active

alkaloid found in betel nuts, stimulates fibroblasts to

increase production of collagen by 150%)

• Capsaicin – Chillies (hypersensitivity reaction)

• Nutritional factors

• Immunological factors

Clinical presentation

• Common site – buccal mucosa, retromolar area, uvula,

palate, etc

• Initially, pain and a burning sensation upon

consumption of hot & spicy foods

• Vesicle & ulcers

• Excessive or reduced salivation & defective gustation

• Hearing loss

• Depapillation & atrophy of tongue and uvula

• Depigmented & loss of stippling over gingiva

• Nasal tone in the voice

• Difficulty in deglutition

• Impaired mouth movements (eg, eating, whistling,

blowing, sucking)

Clinical stages

Three stages (Pindborg, 1989) based on physical findings:

• Stage 1: Stomatitis includes erythematous mucosa, vesicles,

mucosal ulcers, melanotic mucosal pigmentation & mucosal

petechiae

• Stage 2: Fibrosis occurs in ruptured vesicles & ulcers when

they heal, hallmark of this stage

• Stage 3: Sequelae of OSF

– Leukoplakia is found in more than 25% of

individuals with OSF

– Speech and hearing deficits may occur because of

involvement of the tongue and the eustachian tubes

RANGANATHAN K (2001)

• Group I : Only Symptoms, No mouth opening

• Group II : Mouth opening > 20mm

• Group III : Mouth opening < 20mm

• Group IV: Limited mouth opening, precancerous

& cancerous changes throughout mucosa

Histopathology

• Hyperkeratinized, atrophic epithelium with flattening

& shortening of rete pegs

• Nuclear pleomorphism & severe inter-cellular edema

• Finely fibrilar collagen & increased fibroblastic activity

in early stage showing dilated & congested blood vessels

with areas of hemorrhage

• Advanced stage shows “homogenization” and

“hyalinization” of collagen fibers (important feature)

• Degeneration of muscle fibers and chronic inflammatory

cell infiltration in the connective tissue

Management1. Behavioral therapy

- Patient counseling, stoppage of habit

2. Medicinal therapy

-Hyaluronidase: Topically, shown to improve symptoms more

quickly than steroids alone

- Mild cases – intralesional inj Dexamethasone 4 mg to reduce

symptoms & surgical splitting / excision of fibrous bands

- Recent study – intralesional inj of gamma interferon 3 times a

week, improves mouth opening significantly

References

1. Burket’s oral medicine diagnosis & treatment – 10th edition

2. Textbook of oral pathology –shafer 5th edition

3. Neville’s Oral and Maxillofacial Pathology - 2nd edition

4. Emedicine – Diseases of oral mucosa, Oral submucous fibrosis,

Jan 26, 2007

5. Oral leukoplakia related to malignant transformation, Oral

Science International 2006;45-55

Thank You