Oral Pathology – Exam 1


Primitive plants composed of symbiotic algae and fungi

Grow on tree trunks or rocks

Pathology: any of various skin diseases characterized by patchy eruptions of small, firm papules

Lichen Planus
Chronic immunologically-mediated disease
Oral lesions; +/- lesions on skin, other mucosae
Oral lesions more persistant than skin lesions
Middle age onset
Slight greater predilection in females over males

Lichen Planus – Skin Lesions
Most on flexor surfaces
Plaques or papules
Purple, flat-topped with white (Wickham’s) striae
Wax and wane and often subside in 2 years
Oral Lichen Planus – Types
White adherent
Erosive (e.g. desquamative gingivitis)
White Adherent Lesions
Reticular striae
White Adherent Lesions – Reticular Type
Interlacing white lines
Bilateral and symmetrical
Buccal mucosa > tongue > gingivae, lips, etc.
White Adherent Lesions – Plaques

Tongue and buccal mucosa

*The most common site for plaque is the dorsum of the tongue

Erosive Lichen Planus
E.g. Desquamative gingivitis (slide 120)
Atrophy, erythema around central ulceration
Peripheral radiating white striae
Rare malignant transformation
Thick fibrinous exudate gives an appearance suggesting a bulla
Erosive Lichen Planus – Clinical Differential Diagnosis
Hypersensitivity reactions:
Systemic (e.g. drugs)
Local or contact (e.g. amalgam, cinnamon)Lupus erythematosus

Chronic ulcerative stomatitis

Oral graft-versus-host disease

Lichen Planus – Management
In general, monitor for iatrogenic candidiasis
Reticular Type
No treatment needed after diagnosis
Clinical monitoring
Topical corticosteroids
Systemic immunosuppressive, if necessary
Monitor for potential dysplasia, SCC
Oral Lichen Planus – Histology
Orthokeratosis or parakeratosis
Uneven acanthosis (diffuse epidermal hyperplasia)
Rete ridges prominent, sharp (“saw tooth”), or absent (due to lymphocyte “remodeling” rete ridges)
T-LYMPHOCYTE zone in UPPER LAMINA PROPRIA (immediately below the epithelium)
Loss of basal cells (lymphocytes attack basal cell layer; apoptotic bodies left behind)
Immunofluorescence non-specific: shaggy fibrinogen band along BMZ
Oral Lichen Planus – Histology, cont’d.
Colloid, cytoid or Civette bodies (apoptotic basal cells are eosinophilic degenerating keratinocytes)
Lichen mucositis may have similar features
“Lichen Mucositis”
Lesions with clinical and/or histological resemblance to classical lichen planus
May exhibit some variation from classical features*See slide 24 for picture

Pemphigus – Types
Drug induced*Foliaceus and erythematosus do not affect the oral cavity

Pemphigus Vulgaris – Clinical Features
Autoimmune vesiculobullous mucocutaneous disease
Appears first in mouth in some cases
Childhood to old age, but most occur between 30-50 years old
Pemphix (Greek) = bubble or blister
Skin lesions appear as flaccid blisters*Autoantibody against Desmoglein 3 triggers response and destroys epithelial cells

*See slides 26-28 for pictures

Pemphigus Vulgaris – Clinical Features
Oral mucosa:
Positive Nikolsky signOral lesions:
Vesicles rupture rapidly
Ulcers with irregular outlines
Spread peripherally and coalesce

Positive Nikolsky Sign
Pemphigus vulgaris
Paraneoplastic pemphigus
Pemphigoid (all types)
Bullous lichen planus
Erythema multiforme
Epidermolysis bullosa
Hypersensitivity reactions*May not be demonstrable in all cases

Pemphigus Vulgaris – Histology
Autoantibodies against desmoglein 3
Acantholysis (“acantho” = prickle)
Suprabasilar cleft with tombstone basal cells:
Cleft contains Tzanck cells (float off into space)*Basal cells lose attachment to the cells above them, but remain attached to the basement membrane

Pemphigus Vulgaris – Diagnosis

Exfoliative cytology: acantholytic round epithelial (Tzanck) cells

Histology: suprabasilar cledft with tombstone basal cells (cleft contains Tzanck cells)

DIF: Labelled Igs attached to autoantibodies against desmoglein 3 around epithelial cells in specimen (creates fishnet pattern)

IIF: Labelled CIRCULATING AUTOANTIBODIES to desmoglein 3 create same pattern on animal mucosa

Pemphigus Vulgaris – Management
Diagnosis ASAP
Prescriptions by experienced physician
Systemic corticosteroids
Other immunosuppressive agents
Monitor for iatrogenic candidiasis
Monitor disease by indirect immunofluorescence: circulating Igs correlate with disease activity
Serious drug side effects
10% fatal due to treatment
Systemic Corticosteroid Side Effects
Diabetes mellitus
Adrenal suppression
Weight gain
Peptic ulcers
Severe mood swings
Increased susceptibility to infections
Perilesional Biopsy – Chronic Blisters, Erosions and Ulcers

Perilesion = tissue around the lesion

Diagnosis of immunologically-mediated ulcerative conditions (e.g. PV, MMP, BP, LP, LE)

Biopsy specimen should include perilesional (clinically normal) tissue

One-half in 10% formalin for routine H & E stain
Other half in Michel’s (preservative) solution

Incubated with FLUORESCIN-LABELED KNOWN PREPARED ANTIBODY against tissue-bound autoantibody or tissue antigen (C3, fibrinogen)

Bound fluorescin emits bright yellow-green light when tissue is exposed to UV light

Direct Immunofluorescence

Identifies factors in fresh (or preserved) patient tissue

Patient tissue incubated with F-LABELED KNOWN, PREPARED ANTIBODY against:
Tissue bound autoantibody (in PV, MMP, BP, LE)
PV: autoantibody to desmoglein 3
Tissue antigen (C3, fibrinogen)
Foreign (e.g. viral) antigen

Bound fluorescein emits bright yellow-green light when tissue is exposed to UV light

Indirect Immunofluorescence

Identifies circulating autoantibody in patient’s serum

Monkey mucosa is incubated with patient’s serum

Autoantibody in serum attaches to corresponding structure in the mucosa

F-LABELED KNOWN PREPARED ANTIBODY against the antibody is incubated with tissue section

Bound fluorescein emits bright yellow-green light when tissue is exposed to UV light

Pemphigus Vegetans
Variant of pemphigus vulgaris (less serious form)
Oral involvement in a few cases
Acantholytic bullae followed by epithelial hyperplasia and intraepithelial abscess
Pustular vegetations may look verrucous
Many eosinophils present
Vegetans type may occur in lull in pemphigus vulgaris
Can spontaneously remit
Paraneoplastic Pemphigus
Mucocutaneous disease associated with lymphoma (or benign lymphoprolifierative disease)
May appear before lymphoma diagnosis
Sudden onset of multiple vesiculobullous lesions on skin and mucosae
Also seen in erythema multiforme
Paraneoplastic Pemphigus, cont’d.
Cicatricial conjunctivitis in some cases
Skin lesions papular and pruritic (like lichen planus)
Lips resemble erythema multiforme (crusting)
Corticosteroids controls this disease but make malignancy worse
Paraneoplastic Pemphigus – Pathogenesis
Tumor causes host lymphocytes to release IL-6
IL-6 stimulates Igs against basement membrane antigens
Cytotoxic T lymphocytes presentThis multifaceted immunologic attack produces a variety of clinical, histologic and immunologic changes

Paraneoplastic Pemphigus – Histology

Lichenoid mucositis with subepithelial cleft or intraepithelial cleft

Some cases are only lichenoid

DIF: Weak deposition of immunoreactions (IgG and C); between epithelial cells and/or linear deposits at the basement membrane zone

IIF (using patient serum and epithelium from rat bladder): Igs between epithelial cells against desmogleins 1 and 3; Igs in BMZ against desmoplakin I and II, BPAG-1, etc.

Mucous Membrane Pemphigoid – Clinical Features
Chronic vesiculobullous disease
Most often affects females greater than 40 years old
Vesicles rupture: painful ulcers may persist for months
Positive Nikolsky sign
Usually exclusive to the mucous membrane of the oral mucosa; much lesser extent in the skin
Causes desquamative gingivitis
Desquamative Gingivitis
Gingivae red, edematous and glazed
Superficial ulceration or desquamation/peeling
Occurs more on the buccal gingiva than the lingual
Vesiculobullous conditions: MMP, ELP, PV, CUS, EBA, SLE, drug reactions, LIgA, paraneoplastic pemphigus
Mucous Membrane Pemphigoid – Clinical Features, cont’d.

Conjunctival involvement may lead to scarring


Adhesions between bulbar and palpebral conjunctivae
Adhesion of ciliary edges of eyelids to each other
Scarring may cause eyelids to turn inward
Mucous Membrane Pemphigoid – Histology
Subepithelial cleft
Entire epithelium lifts off the surface; looks like “unzipping”
Separation of epithelium from connective tissue at the BMZ results in vesicle formation
Subepithelial Vesicles in Oral Vesiculo-Ulcers
Pemphigoid (all types)
Epidermolysis bullosa (some types)
Linear IgA disease
Angina bullosa hemorrhagica
Dermatitis herpetiformis
Mucous Membrane Pemphigoid – Immunofluorescence
Homogeneous linear fluorescence at BMZ on DIF (IgG, C3, etc.)
See a definite line along the basement membrane zoneCIRCULATING IGs IN ONLY 5-30% OF CASES (this is IIF)

Mucous Membrane Pemphigoid – Pathogenesis and Histology
Hemidesmosome: BPAG (230kd) in plaque (in BP and MMP); BPAG2 (180kd) TRANSMEMBRANE PROTEIN (in MMP); Integrin alpha-6, beta-4 (in MMP)
Lamina lucida: LAMININ (EPILIGRIN) IN ANCHORING FILAMENTS (in MMP)Binding of IgG triggers reaction involving C and PMNs

Weakens basement membrane

Homogenous linear fluorescence at BMZ in DIF

Circulating Igs in only 5-30% of cases

Mucous Membrane Pemphigoid – Management

Removal of drug-induced disease

Ophthalmic consult

Topical corticosteroids:
Increase potency as necessary

Steroid sparing immunosuppressives
Tetracycline or minocycline

Bullous Pemphigoid – Clinical Features
Most common autoimmune blistering disease
Occurs in older people (60-80)
Starts with pruritus
Multiple tense bullae on normal or erythematous skin
Bullous Pemphigoid – Clinical Features, cont’d.
Bullae rupture, producing crust
Heal without scars
Oral lesions uncommon
Clinical course shorter than MMP
Bullous Pemphigoid – Histology
Subepithelial cleavage
Antigens: BP180 and BP230
Eosinophils within bullae
DIF positive in 90-100% of cases
IIF positive in 50-90% of cases
Titers don’t correlate with disease activity
Bullous Pemphigoid – Management
Removal of drug-induced disease
Systemic immunosuppresive agents
Lower doses of prednisone than for pemphigus
Better prognosis
Spontaneous remission in 2 to 5 years in some
Mortality due to treatment in older patients
Systemic Lupus Erythematosus – Pathogenesis
Antibodies against host cell antigens:
Nuclear (seem to do the most damage)
Cell surfaceGenetic, environmental and hormonal factors trigger:
Increased B cell function
Abnormal T cell activity

*Patients most often die from renal failure

Discoid Lupus Erythematosus
Organs Involved
Skin and oral only
Basal cell loss
Lymphocytes at interface and perivascular
Granular/linear basement membrane deposits of IgG and C3
Systemic Lupus Erythematosus
Organs Involved
Skin, oral, heart, kidneys, joints
Fever, malaise, weight loss
Positive ANA
Anti-DNA antibodies
Similar to discoid
Similar to discoid
Systemic Lupus Erythematosus – Clinical Features
Young adult females
Erythematous cutaneous rash (“butterfly” pattern on face)
Fever, weight loss, malaise
Damage to: joints, heart, lungs
Oral Lesions – LE
White plaques +/- ulceration
Desquamative gingivitis*Classical lesion: central red area or ulcer with white spots and peripheral radiating white lines

*Oral lesions may occur in SLE and CCLE

Systemic Lupus Erythematosus – Laboratory Abnormalities
Hematologic changes:
ThrombocytopeniaReduced serum complement concentration


SLE – Antinuclear Antibodies

IIF is the most common technique to detect ANAs

Pattern of nuclear fluorescence suggests type of antibody

Homogenous/diffuse: antibodies to chromatin, histones and ds-DNA

Rim: antibodies to ds-DNA

Speckled: antibodies to non-DNA antigens (histones and RNP):
SS-A (Ro)
SS-B (La)

Nucleolar: antibodies to nucleolar RNP

Lupus Erythematosus – Histology
Follicle keratin plugging in skin in CCLE, but nor in SLEAlternating epithelial atrophy/acanthosis

Basal cell degeneration (apoptotic bodies)

Subepithelial edema (+/- vesicles)

Thick PAS + BMZ

Lupus Erythematosis – Histology, cont’d.

Subepithelial, perivascular and adnexal lymphocytes

Intense inflammation in superficial lamina propria; inflammatory cells in deeper connective tissue (perivascular tissue)

See bulging of rete ridges due to attacking lymphocytes

*See zone of lymphocytes attacking the basal cells
*Looks like lichen planus, until you see deeper perivascular inflammation

Lupus Erythematosus – Histology, cont’d.
IF shows shaggy, granular-linear deposits in BAND along mucocutaneous BMZ:
IgG (IgM and IgA), C3 and fibrinogen
Positive in clinically normal skin in SLE (not CCLE)*In patients with CCLE, will only see the bands in the lesions; in SLE patients, will see the bands even in normal skin

Systemic Sclerosis
Probable autoimmune pathogenesis
Occurs much more in females than males
Insidious onset
INCREASED COLLAGEN (produces a mask-like facies)
Sclerodactyly (fingers with tightly bound skin)
Systemic Sclerosis – Scleroderma
Fibrosis of lungs, heart, kidneys, GI tract
Fibrosis also causes atrophy of the ramus, coronoid process or condyle; PDL space around mandibular molar is widened (with intact lamina dura)
Interstitial pulmonary disease, which leads to pulmonary hypertension and heart failure
Localized Scleroderma


The cutaneous alteration (from a limited form of scleroderma) called en coup de sabre because the lesion resembles a scar that might result from a cut with a sword

Raynaud’s Phenomenon

Arterial insufficiency of acral parts SECONDARY to another disorder that causes arterial narrowing (e.g. SLE, systemic sclerosis, etc.)

Claudication (limping), color and temperature changes

Chronic ulcerations and eventual gangrene

See breakdown and resorption of digits (fingers may be fixed in a claw-like position; shortening may occur from acro-osteolysis; ulcerated fingertips)

Raynaud’s Disease
Vasospasm and its consequences are primary (increased response to stimuli has no known cause
Systemic Sclerosis – Diagnosis


Rheumatoid factor (antibody against Fc fragment of human IgG)

ANAs (including Anto-Scl-70; Scl-70 is a centromere antigen)

Systemic Sclerosis – Management

D-penicillamine inhibits collagen formation

Surgery (esophageal dilation)

Calcium channel blockers (increase peripheral blood flow and reduce Raynaud’s)

ACE inhibitors (reduce hypertension if kidneys severely affected)

Oral hygiene instruction

Poor long-term prognosis


Mild form of systemic sclerosis

C: calcinosis cutis
R: Raynaud’s phenomenon
E: esophageal dysfunction
S: sclerodactyly
T: telangiectasia

Mostly affects 50-70 year old females

Erythema Multiforme
Vesiculo-ulcerative mucocutaneous disease
Mostly affects the lips
Occurs in young adults
Occurs in males more than females
Prodrome: fever, malaise, headache
Abrupt onset; usually resolves in four weeks
Recurrence linked to HSV
Erythema Multiforme – Pathogenesis
Self-limiting hypersensitivity reaction
Precise mechanism unknown
Possible involvement of both cell-mediated and humoral immune systems
Ag-Ab complexes target small mucocutaneous vessels
Some drugs may cause EM: Sulfas, Penicillin, Dilantin, Barbiturates, Iodines, Salicylates
Erythema Multiforme – Clinical
Usually acute, self-limited
Some cases chronic or recurring acute
Headache, fever, lymphadenopathy
Target skin lesions (concentric erythematous rings)
Skin macules, papules, vesicles, bullae, etc
Oral ulcers
Erythema Multiforme – Oral Lesions
Aphthous-type ulcers
Multiple superficial extensive ulcers
Bullae soon rupture*Destruction of epithelium that is superficial, but deeper than pemphigus vulgaris

Erythema Multiforme – Types
Stevens Johnson syndrome (oral, eye and genital lesions)
*These three may overlapToxic epidermal necrolysis (usually caused by drugs; patients look like they have extensive burns)

Erythema Multiforme – Histology
Necrotic keratinocytes
Vesicles in epithelium may extend to the subepithelium
Necrosis of vesicle roof
Interface infiltrate lymphohistiocytic
Perivascular inflammation
IF nonspecific*Histology is characteristic but not pathognomonic

Erythema Multiforme – Management
Eliminate triggers (antiviral agents in cases triggered by HSV)
Early corticosteroids (topical, systemic)
TEN (toxic epidermal necrolysis): burn unit, avoid corticosteroids, pooled IgGs (blocks Fas ligand, which caused epithelial destruction)
Reactive Arthritis (Reiter’s Syndrome)
Abnormal immune reaction to microbial antigen (STD or dysentery)
See 1-4 weeks after exposure
Acute onset of triad: non-specific urethritis, conjunctivitis, arthritis
Skin lesions in some (histology is psoriasiform)
Reactive Arthritis (Reiter’s Syndrome), cont’d.
Oral in less than 20% of cases:
Ulcers (RAU)
Erythema migrans?Most affects young adult males

HLA-B27 phenotype

Lasts weeks to months with recurrences

NSAIDS for arthritis

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