Precancerous Lesions Oral Cancer Dr Sheetal Rai Asst

Precancerous Lesions & Oral Cancer Dr Sheetal Rai Asst Prof Dept of ENT Yenepoya Medical College

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

Epidemiology 1. Prevalence • Represents 85% of all oral precancers 2. Incidence 3 – 4 % of adult population 3. Age Usually in the 4 th – 6 th 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: Ø Homogenous Ø Non homogenous • Based on ETIOLOGY: Ø Tobacco associated Ø Idiopathic • Based on EXTENT: Ø Localized Ø Diffuse

• Based on risk of MALIGNANT TRANSFORMATION Ø High risk sites Floor of mouth Lateral/ventral surface of tongue Soft palate Ø Low risk sites Dorsum of tongue Hard palate • Based on HISTOLOGY: Ø Dysplastic Ø Non dysplastic

Etiopathogenesis • Tobacco – most imp offending agent • Alcohol • Chronic irritation • Syphilis • Nutritional deficiency • Actinic radiation • Galvanism

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 • 70% in buccal mucosa, commissural areas, followed by lo brownish-yellow 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 Ulcerative Speckled/Nodular

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

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 -30 mg TID 3) Topical Bleomycin – 0. 5 -1% solution/2 wks 4) 5 -Fluorouracil & Cisplatin

• Surgical Excision: entire lesion excised if it is >1 cm 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 >4 cm 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 8090% 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 do not invade into connective tissue • Common among elderly, with a male prediliction • Present as white plaques or ulcerated, & reddened areas • Site – floor of the mouth, tongue, lips

• 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

• 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 – appearance of lesions along a site of injury

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

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

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

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 3 mnths 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 features Age • 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

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

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

Histopathology • Hyperkeratinized, atrophic epithelium with flattening & shortening of rete pegs • Nuclear pleomorphism & severe intercellular 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

Management 1. 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

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