ORAL POTENTIALLY MALIGNANT DISORDERS

Histological spectrum of oral potentially malignant lesions and oral cancer

• Hyperkeratosis

• Epithelial dysplasia

• Carcinoma-in-situ

• Invasive Squamous cell carcinoma

• Oral lichen planus

• Oral submucous fibrosis

Leukoplakia and Erythroplakia

Histological premalignant classification:

1) Squamous epithelial dysplasia

2) Squamous cell carcinoma-in-situ

3) Solar keratosis

Histologically Precancerous Lesions

Squamos epithelial dysplasia:

- A precancerous lesions of stratified squamuos epithelium characterized by cellular atypia and loss of
normal maturation and stratification short of carcinoma in situ –

Histological Presentation of OPMD -Squamous cell carcinoma-in-situ, Currently accepted as Severe

Epithelial Dysplasia :

A lesion in which the full thickness, of squamous epithelium shows the cellular features of carcinoma
without stromal invasion

Possible Histological Progression of OPMD

Normal epithelium> Hyperplasia>Dysplasia>Carcinoma in-situ>Invasive carcinoma

Risk Factors

• Idiopathic

• Possible contributing factors: Tobacco, Alcohol, Microorganisms (Candida, viruses, treponema

pallidium),Ultraviolet light

Tobacco

• Smoking & usage of smokeless tobacco (includes betel quid chewing) have been strongly associated
with leukoplakia.
• 80% of patients presenting with leukoplakia has a history of tobacco usage.

Alcohol

• There is no clear evidence that alcohol on its own plays an important role in the aetiology of
leukoplakia.

• Alcohol acts synergistically with tobacco in the development of oral SCC.

Ultraviolet light

• May play a role especially for lip lesions.

• Associated with development actinic cheilosis where there is epithelial atrophy & hyperkeratosis.

• 6-10% of actinic cheilosis becomes carcinoma.

Microorganisms

• Candida often associated with idiopathic leukoplakia or tobacco-associated leukoplakia.

• Candidal leukoplakia often shows dysplasia or hyperplasia.

• It is still not certain if the candida causes the dysplasia or if it is merely a superimpoed infection on
altered epithelium.

• Cancer may develop from candidal leukoplakia

• Contradictory evidence that Human papilloma virus (especially HPV 16 & 18) has been associated with
oral carcinoma.

•Treponema pallidum can cause glossitis & epithelial atrophy.

•Leukoplakia has been shown to have a tendency to develop in atrophic epithelium.

•Cancer may develop from leukoplakia in syphillis patients

Oral epithelial atrophy

• Conditions such as iron deficiency, and possibly some vitamin deficiencies predispose to epithelial
atrophy.ststr

• Tendency for leukoplakia to occur in atrophic epithelium.

• Cancer may develop from leukoplakia

Epidemiology of Oral Potentially Malignant Disorders (OPMDs)

• Leukoplakia most common OPMDs – 85%

• Strong male predilection (4:1) except in Asian region with high usage of betel quid by women

• Age distribution 40-70 years

Clinical Features of OPMD

1) White lesions

2) Red/erythematous lesions

3) Red and white lesions

4) Other features

Diagnostic Spectrum of OPMDs

1) Leukoplakia – white/red & white lesions

2) Erythoplakia – red lesions

3) Oral submucous fibrosis – other features

4) Oral lichen planus – white/red & white

5) Other lesions - white/red & white lesions/other

features eg. Palatal keratosis from reverse smoking

Clinical spectrum of oral potentially malignant disorders

Clinical diagnoses based on alterations of the oral mucosa (swelling, ulcer, red or white flat lesions):

• Leukoplakia

• Erythroplakia

• Palatal lesions in from reverse smokers

• Oral submucous fibrosis

• Actinic keratosis

• Lichen planus

• Discoid lupus erythematosus

• Hereditary disorders with increased risk: Dyskeratosis Congenita, Epidermolysis Bullosa

LEUKOPLAKIA

Definition: A predominantly white lesion of the oral mucosa that cannot be characterized as any other
definable lesion.

Clinical features:

 Homogenous leukoplakia : White/whitish lesion with a surface that maybe

flat,corrugated, cracked, wrinkled or pumice-like.
  Non Homogenous Leukoplakia : Predominantly white lesion
with one or more red or erythematous areas.

 Nodular leukoplakia: Predominantly white lesion with multiple

red/white nodular or granular areas.

 Verrucous leukoplakia: Predominantly white lesion with warty or

irregular blunt / pointed projections.

LEUKOPLAKIA AETHIOLOGY

•Idiopathic

•Tobacco: smoking, chewing

•Infection: Candida albicans > candidal leukoplakia, Human papilloma virus, Epstein Barr Virus

HISTOPATHOLOGICAL FEATURES

• Hyperkeratosis without displasia

• Squamous Epithelium displasia

• Ca in situ

• Atypia > keratinocyte

Management for leukoplakia

Generally, first to eliminate any predisposing factors eg. Stop any associated habits.

For persistent lesion:

• Homogenous

 Observe or Biopsy.
 If histopathology do not show dysplasia or carcinoma, then regular follow-up is necessary.
Other leukoplakia types(should be managed by specialists):

• Biopsy or antifungal therapy.

• If becomes homogenous after antifungal therapy, observe or biopsy.

• If biopsy indicates dysplasia, excise lesion.

• If biopsy indicates carcinoma, protocol for carcinoma followed (surgery-chemotherapy-radiotherapy)

• Total excision > laser CO2 or cryosurgery

• Bila luas :

 Retinoic acid 13 cis 1 mg/kg for 2 – 3 months

 Retinoic acid solution or cream in orabase

• Without displasia > heal in 2 – 3 months

Prognosis for leukoplakia

• Non Homogenous Leukoplakia (Speckled leukoplakia) / Nodular Leukoplakia, & Verrucous leukoplakia
has a higher risk of malignancy.

• 26% of nodular leukoplakia turns into carcinoma, whereas only 2% of homogenous leukoplakia
becomes cancerous.

• Epithelial dysplasia seen mostly in nodular leukoplakia.

• Idiopathic leukoplakia has a 8X higher risk of malignant change compared to those associated with use
of tobacco.

ERYTHROPLAKIA

Definition: Fiery red patch that cannot be characterized clinically or pathologically as any other definable
lesion.

Aethiology: Unclear

Predisposing factor: Tobacco > smoking, Alcohol, Human papillomavirus

Clinical features of erythroplakia

Incidence & behaviour :

• Not common.

• No gender preference.

• Usually seen in the 6 – 7 decade.

• Has a high malignant potential.

Site : Mostly on the soft palate, ventral surfaceof the tongue & floor of mouth.
Clinical features of erythroplakia

 Appears as smooth, granular or nodular erythematous lesion. Maybe flat or depressed below
the surroundingmucosa. Fiery, clear border, asymptomatic
 Common location > buccal mucosa, butmight appear in otherarea of mucous membrane

 DD : Erythematous candidosis, Median rhomboid glassitis, Denture stomatitis, TBC (lupus

vulgaris)

Diagnosis : biopsi and histopathological examination

Histopathological features:

 Numerous cell atypia with epithelial atrophy

 Cell atypia sel on whole epithelial layer (Ca in situ)

Treatment for erythroplakia

• As risk of malignant change is high, BIOPSY is MANDATORY.

• If biopsy shows Dysplasia, then lesion need tobe excise.

• If biopsy shows carcinoma, protocol for carcinoma has to be followed (surgery- chemotherapy-
radiotherapy)

Prognosis for Erythroplakia

Malignant Potential:

• High with one of the studies show 91% with severe dysplasia.

• Rate of progression to invasive carcinoma is about 60%.

VARIANCE OF LEUKOPLAKIA OR ERYTHROPLAKIA

• Speckled leukoplakia

• Candidal leukoplakia (chronic hyperplastic candidosis)

• Appearance: white patch on erythematous area or hyperplastic similar

non homogenous leukoplakia

• Histopathological features : Numerous atypic cell and hyphae on

epithellium

MANAGEMENT

• Observation for 1 – 2 weeks & eliminating irritant, persisten lesion > biopsi
• Gargle or swab with toluidine blue 1% > to distinguished with other lesion, repeat this step after
inflammation disappear

• Result z> positive > excision / laser

• Secondary infection: antifungal topical or systemic >2 weeks

• Keratosis : Vitamin A synthetic, topical or systemic

• Stop tobacco usage

• Chemotherapy topical > bleomycine or radiation

Leukoplakia and Erythroplakia

Clinical and Pathologic Implications:

•Leukoplakia and erythoplakia are clinical terms with no implications with regards to histology.

•The histological picture may vary from benign to premalignant / malignant.

Oral Lichen Planus

Definitions: - Lichen planus is an inflammotory disease of skin and mucosa of unknown aetiology, though
alterations in cell-mediated immunity may be important –

•Insidence : 0,1 – 4%, mid-age

• Gender predilection: female

• Aethiology:

 Genetic, environment, drug and lifestyle

 Estimated > affected by cellular immunology
 Common in diabetes mellitus and liver disease

Lichen planus Clinical presentation

•White striae

•Small malignant potential – Controversial

ORAL LICHEN PLANUS

• Occurs only in oral mucosa or simultaneously with cutaneous lesion.

• Lesion on buccal mucosa, tongue, lip and gingiva usually > symmetrical

• Gingiva similar to desquamative gingivitis

• Asymptomatic > but pain persist on erosive, atrophic, bulosa, gingival type

• Cutaneous lichen planus : papula “erythematous” to “violaceous”

  Itchy on flexor surface of the lower arm, wrist, back, nail with symmetric pattern

 Diagnosis :
 Based on clinical features
 Histopathological examination and direct immunofluorescene (difficult case)

Lichenoid lesion – Reaction tom Drugs/Medications

• Clinically similar to OLP

• Patient has a drug history

• Lesion dissappear with elimination of drug (may not be possible to eliminate drugs for chronic medical
problems)

Lichenoid lesion – Reaction to Drugs/Medications

• Antihypertensives (methyldopa; Aldomet)

• Diuretics (furosemide; Lasix)

• Nonsteroidal anti-inflammatory drugs (ibuprofen; Advil)

Lichenoid lesion – Reaction to Dental materials

• Clinically similar to OLP

 Located in areas in contact with filling or denture materials

 Amalgam
 Acrylic dentures

Betel quid lichenoid lesions

• In betel-quid chewers

• Clinically characteristics similar to OLP

• Affects mucosa where there is long contact with the quid

Lichen planus/Lichenoid lesion Histopathology:

• Hyperortho or parakeratosis acanthosis / epithelial atrophy

• may/may not have rete ridges or ‘saw-toothed’ appearance

• Basal cell liquefaction degeneration

• Subepithelial band of lymphocytes

Lichen planus/Lichenoid lesion Histopathology:

• Hyperortho or parakeratosis acanthosis / epithelial atrophy

• May/may not have rete ridges or ‘saw-toothed’ appearance

• Basal cell liquefaction degeneration

• Subepithelial band of lymphocyte

DD :

• Discoid lupus erythematosis (erythematous)

• Median rhomboid glossitis (atrophic)

• Desquamative gingivitis (bulosa)

• Pseudomembranous candidosis

TREATMENT OF OLP

• No specific treatment available other than symptomatic with topical (sometimes systemic)
corticosteroids or other drugs

• Eliminating restoration surrounding lesion which suspected to cause lichenoid reaction

• Cessation of tobaco and alcohol consumption.

• Corticosteroid 20-40 mg/day. After 2-3 weels then tappering 5 mg each week for 4-6 weeks

Oral Lichen Planus

• Is oral lichen planus a potentially malignant disorder?

Malignant Transformation of Oral Lichen Planus

REVIEW OF THE LITERATURE:

• Rate of malignant transformation – 0 to 5.3%

• When strict criteria applied, rate is < 2 %

Oral Submucous Fibrosis

Definition: Oral submucous fibrosis is characterized by epithelial atrophy and fibrosis of the subepithelial
connective tissue, resulting in stiffness of the oral mucosa

Insidence : common in di South East Asia > affected by Indian culture, Africa and Fiji

•Aethiology: unclear ; suspect:

• Combination between genetic factor and respon to betel quid & areca nut chewing habit

• Autoimmune

• Nutrition deficiency (Vitamin B)

• Hypersensitivity to chili and pepper

• Tobacco, alcohol and coffee consumption

Clinical features:

 Oral submucous fibrosis (early phase)

- Vesicle and small ulcer,burning sensation, erosion, hypersaliva, hypermelanosis
 Oral submucous fibrosis (late phase)
- Inelastic oral mucosa, difficulty tongue movement, shrinkage of uvula, dry mouth, dysphagia
- Areas of blanching (b) in buccal mucosa
 Vertical fibrous band (fb) in commisure region which can be palpated

•Characterized by fibrosis of oral submucosa.

•Caused by chewing areca nut

•Mucosa smooth, thin and atrophic with underlying fibrosis & ischaemia.

•Limitation of mouth opening

•Atrophy of tongue papillae

Histology :

•Epithelial atrophy, epithelial dysplasia (13 - 14% )

•Dense aggregation of collagen in (dc) subepithelial

region

•Dense collagen (dc) aggregation extend into underlying fat(f)

•Loss of rete ridge

DD : non homogenous leukoplakia, lichen planus atrophic type, pernicious anemia, plummer-vinson
syndrome

Management:

• Eliminating predisposing factor

• No satisfactory treatment

• Early detection

• Supplements > iron, topical vit A

• Palliative/symptomatic > steroid injection, hyaluronidase in submucosa or topical corticosteroid in

localized lesion.

• Surgical > improve mouth opening & prevent malignant transformation

Prognosis: •Poor due to progression to cancer (one- third progress to cancer)