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White lesions Premalignant Lesions & Conditions

Oral Pathology

Dr. Sathya

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Scope of the lecture

1. Why a lesion appears white?

2. Classification of white lesions

3. White lesions

4. Premalignant lesions & conditions

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Based on Chapter Nineof Oral Pathology

by J.V. Soames and J.C. SouthamOxford :4th edition

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Why a lesion appears white ?

1. Increased thickness of keratin layer

2. Increased thickness of epithelium eg Acanthosis

3. Pseudomembrane formation eg Candidiasis

“ White patch ” is a term used clinically to describe lesions presenting as white areas on the oral mucosa

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Increased thickness of keratin layer

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Increased thickness of epithelium eg Acanthosis

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Pseudomembrane formation eg Candidiasis

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Causes of oral white lesions

Normal variants : Fordyce’s spots, Leukoedema

Hereditary : White sponge naevus, Oral manifestation of genodermatoses

Traumatic : Mechanical (frictional keratosis) Chemical, Thermal

Infective : Candidosis Syphilitic leukoplakia Hairy leukoplakia

HPV infections

Dermatologic : Lichen planus Lupus erythematosus

Preneoplastic : Leukoplakia& Neoplastic Carcinoma in situ, Squamous cell carcinoma

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Fordyce’s spots – heterotopic collection of sebaceous glands

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epithelium

sebaceous glands

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Leukoedema

Diffuse greyish white lesion on the buccal mucosa

Absence of folding / thickening / loss of flexibility of mucosa

Whiteness disappears on stretching

Predisposing factors:

• Poor oral hygiene

• Tobacco usage

• Intake of spices

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Hyperkeratosis and intracellular edema

“Spongiosis”

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• Hereditary disorder, autosomal dominant

• Mutations in genes coding for keratins 4 & 13 – keratin defects and abnormal desquamation process

C/F

• Affects any part of oral mucosa

• White patch of irregular borders, uneven thickness

• May be present from infancy / early childhood

White sponge naevus

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Histopathology

• Epithelium shows acanthosis, with hyperparakeratosis

• Intra cellular edema of the prickle cell layer & parakeratinized cell layers

• Basket weave appearance

acanthosis

hyperkeratosis

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Traumatic keratoses

Mechanical trauma – frictional keratosis

• Acute trauma leads to ulceration• Chronic frictional irritation leads to epithelial thickening & keratosis

• Chronic irritation – sharp tooth

cheek biting (morsicatio buccarum)

prolonged wearing of ill-fitting dentures

• Frictional keratosis – lesion resolves when source irritation is removed

Frictional keratosis

17Clinical implication………?

Sharp broken / ill-fitting denturesSharp tooth

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Linea alba – Frictional keratosis along the occlusal plane

Morsicatio buccarumMorsicatio labiorum

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Frictional keratosis - Improper tooth brushing

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H/ P : Hyperkeratosis

Acanthosis (increase in thickness of spinous cell layer)

Hyperkeratosis

Acanthosis

Epithelium

Connective tissue

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Chemical trauma

Chemical insult to oral mucosa

1. Topical use of aspirin (aspirin burn)

2. Use of tobacco – smoked or chewed (tobacco pouch keratosis)

3. Chewing betel nut

H/ P : Epithelial thickening and hyperkeratosis

Aspirin burn

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Tobacco pouch keratosis

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Chevron peaks / pattern of hyperkeratosis

Tobacco induced keratosis

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• Regular smokers of cigarettes, cigars & pipes often develop white plaques

• Usually on anterior aspect of buccal mucosa, tongue, palate & lips

• Produced by both thermal and chemical factors

Nicotinic Stomatitis / Stomatitis Nicotina / Pipe smokers palate

• Involves palatal mucosa

• Greyish-white area with scattered red spots

• Red spots are orifices of the minor salivary gland ducts

H/P :

• Hyperkeratosis

• Acanthosis

• Periductal chronic inflammation

Thermal trauma

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Stomatitis Nicotina – early lesion

Stomatitis Nicotina – advanced lesion

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keratosis acanthosis minor salivary gland duct

Minor salivary gland Periductal

chronic inflammatory infiltrate

Histopathology of Nicotinic stomatitis

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Infections – Oral thrush

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Infections – Syphilitic leukoplakia

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Infections – Oral hairy leukoplakia

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Infections – HPV associated Papilloma

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EPITHELIAL DYSPLASIA

Abnormalities in proliferation, maturation and differentiation of

epithelial cells

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Epithelial dysplasia

Abnormalities in proliferation, maturation and differentiation of epithelial cells

1. Increased / abnormal mitosis

2. Altered nuclear / cytoplasmic ratio

3. Abnormal keratinization : Intra epithelial keratin pearls / individual cell

keratinization

4. Irregular epithelial stratification

5. Loss of Polarity of basal cells

6. Loss of intercellular adhesion

7. Basal cell hyperplasia

8. Nuclear hyperchromatism

9. Enlarged and prominent nucleoli

10. Nuclear and cellular pleomorphism

11. Drop shaped retepegs

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Intercellular adhesions - desmosomes

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Altered nuclear cytoplasmic ratio

Loss of epithelial stratification, Loss of polarity of basal cells

Nuclear hyperchromatism, Nuclear and cellular pleomorphism

Drop shaped retepegs

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Basal cell hyperplasia

Nuclear hyperchromatism

Altered nuclear cytoplasmic ratio

36Hyperkeratosis, acanthosis, drop shaped retepegs……???

37Epithelial dysplasia - Drop shaped rete pegs & basal cell hyperplasia

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Epithelial dysplasia involving lower third of the epithelium cellular & nuclear pleomorphism, suprabasal mitosis, loss of ordered

stratification

Mitotic figure

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Moderate epithelial dysplasia – involving lower 2/3rds of the epithelium

Severe epithelial dysplasia – involving the entire epithelium

also called Carcinoma in situ

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Leukoplakia

Definition : “A white patch or plaque that cannot be characterized clinically or histopathologically as any other disease”

Leukoplakia is a clinical diagnosis arrived at by exclusion.

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Prevalence : varies from 1 – 10%

Non Homogenous :

Speckled / Nodular :

• irregular nodular / thickened surface

• areas of redness or ulceration producing speckled appearance

Verrucous : warty appearance

Clinical features :

Homogenous :

• Flat, uniform white plaques

• may show shallow cracks / fissures

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Predisposing factors :

• Tobacco – Smoked / chewed

• Betel Chewing

• Snuff

• Alcohol

• Candida

• Viruses – HPV

• Oral epithelial atrophy - Iron deficeiency, Vitamin deficiency, Tertiary syphilis, Sideropenic dysphagia

• Mutation of tumor suppressor genes

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H/P :

Leukoplakia is a clinical term, diagnosis not based on specific H/P features

• Varying degrees of Keratosis - Hyperkeratosis

• Varying degrees of epithelial thickness - Acanthosis

• Chronic inflammatory infiltration in lamina propria

• Features of epithelial dysplasia

Hyperkeratosis Acanthosis

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Epithelial dysplasia

Abnormalities in proliferation, maturation and differentiation of epithelial cells

1. Increased / abnormal mitosis

2. Altered nuclear / cytoplasmic ratio

3. Abnormal keratinization : Intra epithelial keratin pearls / individual cell

keratinization

4. Irregular epithelial stratification

5. Loss of Polarity of basal cells

6. Loss of intercellular adhesion

7. Basal cell hyperplasia

8. Nuclear hyperchromatism

9. Enlarged and prominent nucleoli

10. Nuclear and cellular pleomorphism

11. Drop shaped retepegs

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Epithelial dysplasia involving lower third of the epithelium cellular & nuclear pleomorphism, suprabasal mitosis, loss of ordered

stratification

Mitotic figure

46Epithelial dysplasia - Drop shaped rete pegs & basal cell hyperplasia

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Moderate epithelial dysplasia – involving lower 2/3rds of the epithelium

Severe epithelial dysplasia – involving the entire epithelium

also called Carcinoma in situ

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Prognosis :

Epithelial dysplasia

• Homogenous leukoplakia – epithelial dysplasia in 10%

• Non homogenous leukoplakia – are more dysplastic 50%

• Speckled leukoplakia – Epithelial dysplasia in 100%

Malignant transformation (Oral squamous cell carcinoma)

• 0.3 – 18%

• Ventral surface of tongue, floor of mouth, lingual aspect of lower alveolar mucosa show higher risk of malignant transformation

• Leukoplakia with epithelial dysplasia are more likely to become malignant

• Speckled & non homogenous leukoplakia – increased rate of malignant transformation

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• Defined as a bright red velvety plaque on the oral mucosa which cannot be categorized clinically or pathologically as any other condition.

• Premalignant lesion, may develop in a previously white lesion

Erythroplakia

C/F :

Homogenous red lesion with irregular outline

Erythroleukoplakia : Intermingled with patches of leukoplakia (speckled leukoplakia)

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H/P :

• Epithelial atrophy, severe epithelial dysplasia

• Basement membrane is intact, no connective tissue invasion

• 50% may represent Carcinoma in situ or even invasive carcinoma

Prognosis :

• Nearly 100 % of lesions show malignant transformation

• Ulceration, induration, fixation, lymphadenopathy are clinical features that indicate malignancy

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Prevalence :

0.5 – 2% in general population

Lichen planus

C/F :

• 60% affects women

• Age : 30 – 50 yrs more common

• Skin lesion with oral manifestations in 50% of cases

• Only oral manifestations – Oral lichen planus

• Skin lesions – purple, pruritic, papules

• Distinctive white streaks on the surface – Wickham’s striae

• Skin lesions may be discrete, linear, annular or wide spread

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Oral lesions :

• Buccal mucosa, tongue, gingiva, palate, lips may be affected

• Usually bilateral

• Clinical types : Reticular – lace like striae

Papular – small white raised lesions <5mm

Plaques – white raised lesions >5mm

Atrophic / Erosive – red areas / shallow ulceration

Bullous – subepithelial bullae

• Wickham’s striae evident

• Pain & discomfort (burning sensation) vary from mild to severe

53Bullous Erosive / atrophic

Reticular Papular

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Pathogenesis

• Cell mediated immune response to antigenic changes in epithelial cells

Antigens in epithelial cells

Cytokine release from Langerhans cells & keratinocytes

Activates T cells (CD4, CD8 cells)

T cells migrate to the basal cell region

Cytotoxic CD8 cells damage the basal cells

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Lichenoid Reactions :

• Hypersensitivity to drugs / dental materials produces lichen planus like lesions.

• Lesions usually resolve on withdrawal of offending drug

Lichenoid reaction resulting from hypersensitivity to amalgam restoration

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H/P:

• Ortho / parakeratinization

• Epithelium may be atrophic / acanthotic

• Rete pegs show saw tooth pattern

• Subepithelial band of chronic inflammatory cell infiltrate (T lymphocytes)

• Basal cell degeneration – liquefactive degeneration

• Civatte bodies – degenerating basal cells undergoing apoptosis

appear as hyaline, shrunken / condensed bodies

• Bullous lichen planus - subepithelial bulla

Prognosis :

Premalignant condition, 1 - 4 % malignant transformation

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Saw tooth rete pegs and dense subepithelial inflammatory infiltrate evident

Lichen planus

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Premalignant Lesions and Conditions

Premalignant lesion is defined as a morphologically altered tissue in which cancer is more likely to occur than its normal counterpart. The lesion itself undergoes malignant transformation.

Premalignant condition is a generalized disorder associated with a significantly increased risk of cancer development some where in the mouth.

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Premalignant lesions

1. Leukoplakia – Homogenous, non-homogenous, nodular, speckled,

Verrucous leukoplakia, Candidal Leukoplakia

2. Erythroplakia

3. Carcinoma in Situ

Premalignant conditions

1. Oral submucous fibrosis

2. Lichen planus

3. Actinic keratosis

4. Conditions associated with epithelial atrophy – sideropenic dysphagia

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Oral submucous fibrosis

Chronic disease may affect any part of oral mucosa

Increased stiffening with progressive fibrosis

Etiology

Areca-nut chewing habits

Genetic predisposition

Nutritional factors

C/F

Burning sensation in mouth when consuming spicy food

Reduced mouth opening & tongue protrusion

Mucosa is blanched with marble-like appearance

Palpable bands of fibrous tissue

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blanched appearance of mucosa

fibrosis with resultant atrophy of the papillae

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H/P

1. Atrophic and thin stratified squamous epithelium, absence of rete ridges

2. Hyalinization of subepithelial connective tissue

3. Very few fibroblasts, blood vessels obliterated by dense fibrosis

4. Inflammatory infiltrate (lymphocytes and plasma cells)

Epithelial dysplasia may be seen in 10 – 15 % of cases

Premalignant condition : 5 - 8% malignant transformation

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Actinic keratosis / actinic cheilitis

Exposure to UV component of the sun

Disease of outdoor workers – farmers and fisherman

Risk of developing lip cancer

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Also called as Plummer-Vinson syndrome / Paterson-Brown-Kelly syndrome

Triad of dysphagia (due to esophageal webs) glossitis iron deficiency anemia.

Sideropenic dysphagia

Blood picture Bald tongue, glossitis

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Principles of management of dysplastic lesions

1. Stop any associated habits

2. Treat candidial infection / iron def

3. Biopsy to assess dysplasia

4. Assess risk of malignant change on clinical & H/P findings

5. Consider ablation of individual lesions

6. Regular observation

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Options for management of premalignant lesions

1. Early detection of cancer

2. Surgical excision with grafting

3. Laser excision

4. Topical chemotherapy

5. Retinoids