Dent 355-10 Keratoses and Related Disorders of Oral Mucosa I

Introduction Classification Definition of histopathologic terms Hereditary conditions Traumatic keratoses Leukoplakia Dermatological 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

Hereditary
Oral epithelial nevus Oral manifestations of other rare genodermatoses Leukoedema

Traumatic

Mechanical (frictional keratosis) Chemical Thermal Candidosis: - acute psuedomembranous - chronic hyperplastic - chronic mucocutaneous Syphilitic leukoplakia Hairy leukoplakia Leukoplakia Lichen planus Lupus erythematosus Carcinoma in situ Squamous cell carcinoma

Infective

Idiopathic Dermatological

Neoplastic

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. fixation 3. induration 4. ulceration 5. lymphadenopathy 6. bone destruction if it overlies bone 7. 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.