Dent 355-10Keratoses and Related

Disorders of Oral Mucosa I

IntroductionClassificationDefinition of histopathologic termsHereditary conditionsTraumatic keratosesLeukoplakiaDermatological causes of white patches

Introduction:Normal Oral Mucosa

• Color of normal oral mucosa: vascularity, melanin, epithelial thickness, keratinization.

• Non-keratinized parts.

• Non-keratinized parts.

Introduction: White Patches

• White patches may be due to increased or abnormal production of keratin which appears white in the wet oral environment: they cannot be scraped off.

• Accumulation of debris and desquamated cells on oral mucosa may also result in white areas: can be scraped off.

Etiological Classification of White Oral Lesions

HereditaryOral epithelial nevus

Oral manifestations of other rare

genodermatoses

Leukoedema

TraumaticMechanical (frictional keratosis)

Chemical

Thermal

InfectiveCandidosis:

- acute psuedomembranous

- chronic hyperplastic

- chronic mucocutaneous

Syphilitic leukoplakia

Hairy leukoplakia

IdiopathicLeukoplakia

DermatologicalLichen planus

Lupus erythematosus

NeoplasticCarcinoma in situ

Squamous cell carcinoma

Definition of Histopathological Terms

• Orthokeratosis: superficial keratinized squames are flattened, anucleate, with homogeneous, acidophilic cytoplasm.

• Parakeratosis: superficial keratinized squames are flattened, with homogeneous, acidophilic cytoplasm, but contain pyknotic nuclei.

• Hyperkeratosis: increased thickness of keratin layer.

• Hyperparakeratosis: increased thickness of parakeratin layer.

• Keratosis: keratinization of epithelium that is not normally keratinized.

Definition of Histopathological Terms

• Acanthosis: hyperplasia of prickle cell layer which results in overall increased thickness of epithelium, with broadened, elongated rete ridges.

• Epithelial atrophy: decreased epithelial thickness usually associated with loss of rete ridges.

• Cellular atypia: a group of cellular changes which cytologically characterize dysplasia and which are typically seen in premalignant lesions.

• Epithelial dysplasia: a term describing epithelium when features of cellular atypia are present.

* Atypia refers to cells, while dysplasia refers to the tissue as a whole.

Hereditary Conditions (Genodermatoses): Oral Epithelial Nevus (White Sponge Nevus)

• Autosomal dominant with incomplete penetrance and variable expressivity.

• Mutations in genes coding for keratins 4 & 13.

• Abnormality in desquamation.

• Benign condition with no consequences other than altered appearance of mucosa.

• Any part of oral mucosa may be affected, as well as other mucosal surfaces in the body.

• Edges not well-defined.

• Shaggy or folded appearance.

• May appear in infancy, childhood, or adolescence.

• Histopathology:- Acanthosis.- Hyperparakeratosis.- Intracellular edema of prickle and parakeratinized cell layers.- Pyknotic nuclei impart basketweave appearance.

Hereditary Conditions (Genodermatoses):Leukoedema

• Particularly evident in persons with racial pigmentation of oral mucosa.

• Ethnic and racial clustering suggest hereditary factors.

• Regarded as a variant of normal.

• Presents as a translucent, milky whiteness of the surface of the mucosa with a slightly folded appearance.

• It tends to disappear on stretching.

• Histology:- Acanthosis with broadened rete ridges.- Superficial prickle cells appear vacuolated

and contain glycogen.

Traumatic Keratoses:Mechanical Trauma-Frictional Keratosis

• Acute friction may lead to blistering and ulceration.

• Chronic friction leads to epithelial thickening and hyperkeratinization known as frictional keratosis.

• Frictional keratosis may result from: sharp tooth, chronic cheek biting, prolonged wear of ill-fitting dentures.

• To diagnose frictional keratosis a source of chronic irritation that fits the size and shape of the lesion must be identified. Lesion must resolve upon removal of the source.

• Histopathology: - Hyperkeratosis +/- acanthosis.- There is no dysplasia.

Traumatic Keratoses: Chemical

• Severe chemical insult to oral mucosa produces epithelial necrosis, sloughing & ulceration, e. g. Aspirin burn.

• Low grade, chronic insult is seen in tobacco users, whether it is smoked, chewed, or used as snuff. Also in other chewing habits such as betel nut.

Traumatic Keratoses: Thermal

• Generalized hyperkeratosis is seen is smokers of cigarettes, cigars, and pipes, particularly anterior buccal mucosa, tongue & palate.

• Combination of thermal and chemical factors likely.

• Localized keratosis on lips at site of cigarette may be seen with constant use, also on palate and dorsal tongue in pipe smokers.

Traumatic Keratoses: Thermal-Nicotinic Stomatitis

• A characteristic palatal condition seen in smokers, particularly in pipe smokers.

• Characterized by hyperkeratinized palatal mucosa with a cobblestone appearance, with inflamed orifices of minor salivary gland ducts showing as red dots centrally.

• Condition is reversible upon cessation of smoking and is not considered premalignant.

• However, in smokers, the presence of these conditions indicates the potential for abnormal changes that may be premalignant, therefore the whole mouth should be examined carefully for other lesions.

• Histopathologic Features:- Hyperkaratinized and acanthotic squamous

epithelium.- Mild chronic inflammation of subepithelial

connective tissue and mucous glands.

Leukoplakia

•Leukoplakia = white patch.

•WHO original definition: "a white patch which cannot be characterized clinically

or histopathologically as any other disease."

•Definition slightly modified in 1994 to: "a predominantly white lesion of the oral

mucosa that cannot be characterized as any other definable lesion ."

Leukoplakia

• Leukoplakia is a clinical diagnosis arrived at by exclusion of other white lesions.

• It implies no particular histopathologic change or behavior.

• However, a small percentage are premalignant and some may be invasive carcinomas at presentation.

• It is impossible to predict which lesions are likely to become malignant, but certain clinical and histopathological features are recognized as being associated with an increased risk.

Leukoplakia: Incidence• Worldwide variation from <1%->10%.

• Problems in comparison due to difficulties in standardization of diagnostic criteria.

• Marked variation in incidence, sex, site, and age groups affected between different cultural and ethnic groups, reflecting variations in possible etiological factors.

• Leukoplakias involving ventral tongue and/or FOM (sublingual keratosis) have a higher risk of malignant transformation.

• Previous studies in Western Europe & North America: - predominance in males - generally described as affecting older people- FOM & buccal mucosa mostly affected.

• Recent studies in the same areas indicate that:- M:F ratio is becoming almost equal- incidence in younger adults is increasing- this possibly reflects changes in smoking habits.

Leukoplakia: Clinical Features

• Homogeneous- flat, uniform, predominantly white

plaques- may show shallow cracks/fissures

• Non-homogeneous (including speckled)

- irregular nodular/thickened, sometimes verrucous surface.

- often speckled with areas of erythroplakia.

• Non homogeneous lesions have a worse prognosis.

Leukoplakia: Clinical Features

• Erythroplakia: "a bright red velvety plaque on the oral mucosa which cannot be categorized clinically or pathologically as being due to any other condition".

• Erythroplakia: - may be homogeneous with a well-defined

but irregular outline- or may be intermingled with patches of

leukoplakia (speckled leukoplakia)- histopathologically, erythroplakia may

represent carcinoma-in-situ or invasive carcinoma.

- its development in a previously uniform white lesion is an important clinical sign which may indicate sinister change.

Leukoplakia: Clinical Features

• Clinical features that may indicate malignant change in leukoplakia/erythroplakia:

1. development of erythroplakia in a previously uniform white lesion

2. fixation3. induration4. ulceration5. lymphadenopathy6. bone destruction if it overlies bone7. other clinical features of

malignancy.

Leukoplakia: Etiological Factors

• Leukoplakia is by definition idiopathic, but in some patients, predisposing factors can be identified.

• Etiology is likely to be multifactorial

• Tobacco use is a major factor.

Leukoplakia: Etiological Factors

1. Tobacco

• The most common factor in patients with leukoplakia.

• Higher prevalence of leukoplakia among smokers.

• Prevalence increases with amount of tobacco.

• Distribution of lesions may vary with particular type of habit: cigarettes, bidis, reverse smoking, tobacco chewing, pans, snuff dipping.

• In those patients whose tobacco-associated keratosis regresses on cessation of the habit the lesion should not be classified as leukoplakia.

• Smoked tobacco.

• Smokeless tobacco: areca nut (betel nut), chewing tobacco and snuff.

Leukoplakia: Etiological Factors

2. Alcohol:

No clear evidence for importance as a factor.

Many heavy smokers however are also heavy drinkers.

3. Candida:

• Candidal leukoplakia (chronic hyperplastic candidosis).

• May be associated with idiopathic leukoplakia.

Leukoplakia: Etiological Factors

4. Viruses: • HPV: type 16 & 18, uncertain role.

• EBV: hairy leukoplakia, completely different lesion, no premalignant potential.

5. Oral Epithelial Atrophy:

• Iron deficiency.

• Submucous fibrosis.

• Tertiary syphilis.

• Some vitamin deficiencies.

• Sideropenic dysphagia (Plummer-Vinson syndrome).

Leukoplakia: Etiological Factors

6. Tumor-Suppressor Genes: • Mutations in tumor suppressor genes, mainly p53.

7. Sanguinaria canadensis:

• The common bloodroot plant Sanguinaria canadensis has been used since 1982 and found to be effective against plaque build up and gingivitis.

• Sanguinaria-associated leukoplakia is a unique form of oral leukoplakia attributed to the chronic use of oral rinses and toothpastes containing the extract of the plant.

• It is usually located on the attached gingiva and the alveolar mucosa of the maxillary vestibule.

• Preparations containing Sanguinaria should be avoided until the risk for malignant transformation is determined.