Dent 355 Keratoses and Related Disorders of Oral Mucosa II

Dr. Rima Safadi Modified from Dr. Huda Hammad lectures Reference: Oral pathology book by Soams and Southam

Leukoplakia: Pathology, Epithelial Dysplasia

Wide range in histological appearances reflects varying degrees of: keratosis, epithelial thickness, epithelial dysplasia, chronic inflammation in the lamina propria.

It is important to remember that:

Leukoplakia is a clinical diagnosis arrived at after exclusion of other diseases and is not based on any specific histopathological features, i.e. the term leukoplakia has no histological connotation.

Leukoplakia: Pathology, Epithelial Dysplasia

Hyperkeratosis may be due to orthokeratosis, parakeratosis, or both.

Leukoplakia: Pathology, Epithelial Dysplasia

Epithelium may be hyperplastic or atrophic.

Areas of erythroplakia are often associated with epithelial atrophy.

Leukoplakia: Pathology, Epithelial Dysplasia

The junction between normal and abnormal epithelium may be abrupt or there may be gradual transition.

Leukoplakia: Pathology, Epithelial Dysplasia

2 features are highly suggestive of smoking as an etiological factor: 1. presence of chevron peaks in keratin.

2. increased melanin production in basal keratinocytes and leakage of melanin into the underlying connective tissue (melanin incontinence).

Leukoplakia: Pathology, Epithelial Dysplasia

In some leukoplakias, keratosis and change in thickness are the only abnormal features. Other cases show features of epithelial dysplasia. When dysplasia is present, not all dysplastic features are necessarily seen in any one case.

Leukoplakia: Pathology, Epithelial Dysplasia

The degree of dysplasia is subjectively assessed using terms such as mild, moderate and severe based on the thickness of epithelium involved. Mild (grade I) dysplasia demonstrates proliferation of atypical or immature basal cells above the parabasal region but not extending beyond the lower third of the epithelium.

The term severe (grade III) dysplasia is reserved for abnormal proliferation from the basal layer into the upper third of the epithelium.

Moderate (grade II) dysplasia demonstrates a similar proliferation into the middle onethird of the epithelial crosssection.

Leukoplakia: Pathology, Epithelial Dysplasia

Although it is not possible to predict the presence and severity of dysplasia from clinical appearance lesion, erythroplakias and nonhomogeneous leukoplakias are more likely to be dysplastic (or even malignant) than homogeneous leukoplakias. Several studies showed only about 10% of homogeneous leukoplakias to be dysplastic, as opposed to 50% or more of nonhomogeneous types. Speckled leukoplakias show a very high incidence of dysplasia, which approaches 100% as speckling increases and as the clinical features more closely resemble erythroplakia.

Leukoplakia: Pathology, Epithelial Dysplasia

Leukoplakia: Pathology, Epithelial Dysplasia

The individual cellular changes (cellular atypia) seen in dysplastic epithelium reflect abnormalities in proliferation, maturation, and differentiation of epithelial cells.

Leukoplakia: Pathology, Epithelial DysplasiaFeatures of Epithelial Dysplasia

Increased and abnormal mitoses. 2. Basal cell hyperplasia. 3. Drop-shaped rete ridges. 4. Disturbed polarity of basal cells or loss of cellular orientation. 5. Increase in nuclear/cytoplasmic ratio. 6. Nuclear hyperchromatism. 7. Prominent and enlarged nucleoli. 8. Irregular epithelial stratification or disturbed maturation. 9. Nuclear and cellular pleomorphism. 10. Abnormal keratinization. 11. Loss or reduction of intercellular adhesion. First 7 features represents abnormal proliferation while last 4 represents abnormal maturation/differentiation
1.

Leukoplakia: Pathology, Epithelial DysplasiaFeatures of Epithelial Dysplasia

1. Increased and abnormal mitoses.

Leukoplakia: Pathology, Epithelial DysplasiaFeatures of Epithelial Dysplasia

2. Basal cell hyperplasia.

Leukoplakia: Pathology, Epithelial DysplasiaFeatures of Epithelial Dysplasia

3. Drop-shaped rete ridges.

Leukoplakia: Pathology, Epithelial DysplasiaFeatures of Epithelial Dysplasia

4. Disturbed polarity of basal cells or loss of cellular orientation.

Leukoplakia: Pathology, Epithelial DysplasiaFeatures of Epithelial Dysplasia

5. Increase in nuclear/ cytoplasmic ratio.

Leukoplakia: Pathology, Epithelial DysplasiaFeatures of Epithelial Dysplasia

6. Nuclear hyperchromatism.

Leukoplakia: Pathology, Epithelial DysplasiaFeatures of Epithelial Dysplasia

7. Prominent and enlarged nucleoli.

Leukoplakia: Pathology, Epithelial DysplasiaFeatures of Epithelial Dysplasia

8. Irregular epithelial stratification or disturbed maturation.

Leukoplakia: Pathology, Epithelial DysplasiaFeatures of Epithelial Dysplasia

9. Nuclear and cellular pleomorphism.

Leukoplakia: Pathology, Epithelial DysplasiaFeatures of Epithelial Dysplasia

10. Abnormal keratinization (dyskeratosis).

Leukoplakia: Pathology, Epithelial DysplasiaFeatures of Epithelial Dysplasia

11. Loss or reduction of intercellular adhesion.

Epithelial Dysplasia

Cellular atypia of minor degree may be seen in reaction to inflammation in conditions such as lichen planus and candidosis (reactive cellular atypia)

Leukoplakia: Prognosis

Unpredictable tendency to undergo malignant transformation.

Marked variation in reported rates from different countries. Differences in diagnostic criteria and etiological factors. Transformation times vary from one to several years. Combining results from several studies, a rate of ~14% over a period of up to 20 years has been reported.

Leukoplakia: Prognosis

Potential for malignant transformation is greater in high risk sites (ventral tongue, FOM, lingual aspect of lower alveolar mucosa).
Lesions in these areas are designated as sublingual keratosis to draw attention to these sites.

25% showed invasive SCC in some studies

Leukoplakia: Prognosis

Dysplastic lesions carry an increased risk of malignant transformation (<10%->30%).

The more severe the dysplastic features, the greater the risk, but no clear correlation. The majority of dysplastic lesions remain unchanged during observation period.

A proportion of these will improve or regress.

Leukoplakia: Prognosis

Speckled and other nonhomogeneous types have an increased rate of malignant transformation. Erythroplakia alone or as part of speckled leukoplakia shows invasive carcinoma or carcinoma in situ on ~ 50% of initial biopsies, and most of the remaining show severe dysplasia.

Leukoplakia: Prognosis

Candidal leukoplakia has a high incidence of dysplasia or malignant transformation (~30%).

Epithelial dysplasia

Dysplastic leukoplakia- higher rate to progress than non neoplastic (10-30%) More severe dysplasia higher risk Majority of dysplasia remain unchanged

May progress or improve

No clear corelation between histology and clinical:

Sublingual keratosis even with mild dysplasia is high risk

Leukoplakia: Prognosis

Malignant transformation likely to be due to progressive accumulation of genetic changes over time.
Recent studies show that leukoplakias with abnormal DNA content of epithelial cells are more likely to undergo malignant transformation. This may become an important prognostic indicator in the future.

Leukoplakia Prognosis

DNA content is related to number of chromosomes: Malignant cells have abonormal number of chromosomes (deletions replications etc..) Variation in number of chromosomes: aneuoploidy Duplication of chromosomes: tetraploidy Normal cells with 2 copies: diploidy

Leukoplakia: Diploid low risk Aneuploid high risk Tetraploidintermediate risk

Leukoplakia: Prognosis

1. 2. 3. 4.

At present, risk assessment is based on: Size Site Clinical appearance Degree of epithelial dysplasia.

Dermatological Causes of White Patches

Lichen Planus
Lupus Erythematosus

Lichen Planus
Name provided by Erasmus Wilson in 1869. He probably thought the skin lesions looked like lichens growing on rocks. Lichens are primitive plants composed of symbiotic algae and fungi.

Lichen Planus

Relatively common disease (0.5-2% population). Worldwide distribution. Involves skin and mucous membranes.

Peaks between ages 30-50.

60% females. Oral lesions detected in ~50% of patients with initial skin lesions. Skin lesions in 10-50% of patients with initial oral lesions. Oral lesions may occur before, at the same time as, or after skin lesions.

Lichen Planus: Clinical Features

Skin lesions:

Violaceous, itchy papules, may have white streaks on surface (Wickhams striae). Variable patterns for papules: discrete, linear, annular, bullous, or widespread rash.

Lichen Planus: Clinical Features

Skin Lesions:

Lichen Planus: Clinical Features

Skin Lesions:

Predilection to flexor surface of wrist.

10% with nail involvement in the form of vertical ridges.

Lesions develop slowly and 85% resolve within 18 months, sometimes with recurrence.

Lichen Planus: Clinical Features

Oral Lesions:

In contrast to skin lesions, oral lesions pursue a much more chronic course, sometimes extending over many years. Mostly affect buccal mucosa, may also affect tongue, gingiva, palate, and lips. Bilateral and wide spectrum of presentations, alone or in combination.

Lichen Planus: Clinical Features

Oral Lesions:
Non-erosive type: - reticular or annular, papular, plaque-like. - usually asymptomatic.

Lichen Planus: Clinical Features

Oral Lesions:

Erosive/atrophic types: red glazed appearance with areas of superficial ulceration which may take several weeks to heal. occasionally, ulcers are preceded by bullae (bullous type). often associated with typical areas of non-erosive lichen planus. pain and discomfort may be severe.

Lichen Planus: Clinical Features

Oral Lesions:

Lichen planus involving the gingiva often presents as a desquamative gingivitis. More typical areas can usually be seen elsewhere on the oral mucosa.

Regezi

Lichen Planus: Pathology

Histopathologic Features:

Ortho- or parakeratosis. Epithelial atrophy or acanthosis (sawtooth pattern of rete ridges). Dense, well-defined band of subepithelial mononuclear infiltrate, mainly T-cells.

Lichen Planus: Pathology

Histopathologic Features:

Lichen Planus: Pathology

Histopathologic Features:

Liquefactive degeneration of basal cell layer associated with edema and lymphocytic infiltration. Civatte bodies: hyaline shrunken bodies representing apoptotic cells.

Lichen Planus: Pathology

Histopathologic Features:

Basal cell degeneration may result in subepithelial bullae formation and ulceration.

Lichen Planus: Pathology

Almost all cases run a benign course.

Malignant transformation has been described in a very small proportion (0.5%-2.5% over 5 years). Some studies suggest that atrophic/erosive forms are more likely for such transformation. Other studies found it more likely with plaque lesions.

Lichen Planus: Etiology & Pathogenesis

Not fully understood. Widely accepted that cell-mediated immune responses to an external antigen, or internal antigenic changes in epithelial cells, are involved. Response resembles type IV hypersensitivity. Cytotoxic lymphocytes damage basal epithelium. In most cases the precipitating factors are unknown. May be hypersensitivity to drugs and dental materials Association with systemic conditions: Hep C Graft versus host reaction presents with LP like lesions

Lichen Planus: Etiology & Pathogenesis

In some patients, lesions are triggered by hypersensitivity to drugs or dental materials.

In such cases the condition resolves upon withdrawal of the offending agent. Such lesions are referred to as lichenoid reactions to distinguish them from idiopathic lichen planus.

Lichenoid reaction to dental amalgam

Lichen Planus: Pathogenesis

External antigen challenge and/or modified antigenic structure of epithelial cells Antigen challenge Langerhans cells Keratinocytes

Expression of ICAM-1 Cytokine release

Expression of class II MHC

Antigen presentation to CD4 cells

Activation of CD8 cytotoxic cells Damage to basal cells

Lymphocyte infiltration

Lichen Planus: Pathogenesis

Lichen planus has been associated with some systemic diseases. In many of these, a cause-and-effect relationship has not been established. The systemic condition may merely exacerbate a preexisting lesion. Strong evidence of association of chronic liver disease associated with hepatitis C virus infection. Oral and cutaneous lesions resembling lichen planus occur in graft vs. host disease

Transplanted T cells react to antigens on host epithelial cells.

GVH

Lupus Erythematosus

1. 2.

Two main forms: Chronic discoid LE: localized. Systemic LE: disseminated.
A variety of autoantibodies are present in SLE, e.g. antinuclear antibodies (ANAs).

Females > males.

Lupus Erythematosus: Clinical Features

Chronic Discoid Lupus Erythematosus (DLE):

Lesions often restricted to skin and usually occur on the face.

Scaly red patches which heal with scarring.

Sometimes facial lesions in both forms have a symmetric distribution (butterfly rash).

Lupus Erythematosus: Clinical Features

Chronic Discoid Lupus Erythematosus (DLE):

Oral lesions in up to 50% of cases.

Buccal mucosa most frequently affected.

Considerable variation in oral lesions. Most common is a discoid area of erythema or ulceration surrounded by white keratotis border sometimes with radiating striae. Main D/D lichen planus.

Lupus Erythematosus: Clinical Features

Systemic Lupus Erythematosus (SLE):

Disseminated disease almost involving every organ. Skin rashes: maculopapular, photosensitive especially on face (butterfly rash). Oral lesions variable. May be fatal.

Lupus erythematosus histopathology

Deep perivascular Lymphocytic infiltrate

Lupus Erythematosus: Histopathologic Features

Subepithelial and deep perivascular lymphocytic infiltrates.

Liquefactive degenerartion of basal cells.

Lupus erythematosus

Immunofluorescence studies show abundant deposits of IgG and complement- Lupus Band

Revision slides

White Sponge nevus

Leukoplakia

Submucous fibrosis (epithelial atrophy)

SCC

Plummer Vinson syndrome (epithelial atrophy)