Handwriting Notes: Oral Lichen Planus & Leukoplakia

(Shafer's Oral Pathology - 10 Markers Each)

ORAL LICHEN PLANUS (OLP)

10-Marker Answer

1. Definition

2. Etiology / Predisposing Factors

• Unknown in most cases (idiopathic)
• Emotional stress - most important predisposing factor per Shafer's
• Drugs - lichenoid reactions caused by: NSAIDs, antihypertensives (ACE inhibitors, beta-blockers), antimalarials, gold salts, sulphonylureas, penicillamine, methyldopa
• Dental materials - amalgam (mercury/silver), gold restorations (contact lichenoid reactions)
• Infective - Hepatitis C virus association reported
• Systemic diseases - diabetes mellitus, hypertension (Grinspan's syndrome - triad of OLP + DM + HTN, though may represent drug effect)
• Tobacco - NOT a cause (unlike leukoplakia)

3. Pathogenesis

• Antigen-specific and non-specific mechanisms both operate
• Basal keratinocytes express MHC class I and II molecules and present antigens
• CD8+ cytotoxic T cells (predominant) and CD4+ helper T cells infiltrate the subepithelial region
• Liquefaction/hydropic degeneration of basal cell layer - the hallmark pathogenic event
• Keratinocyte apoptosis triggered by CD8+ cytotoxic T cells
• Matrix metalloproteinases, mast cell degranulation, and proinflammatory cytokines (RANTES) mediate tissue damage
• Basement membrane disruption leads to fibrinogen deposition (detectable on direct immunofluorescence)

4. Clinical Features

• Frequency: 0.2% to 3% of general population
• Predominantly affects middle-aged adults (4th-6th decade)
• Female predominance - F:M = 1.4:1 (Shafer's) up to 3:2 (other studies)
• Bilateral, symmetrical distribution is characteristic

1. Buccal mucosa (most common - ~90% of cases)
2. Tongue (lateral borders, dorsum) - ~60%
3. Gingiva - ~23% (desquamative gingivitis pattern)
4. Lips, palate, floor of mouth (less common)

5. Histopathology (Key - Most Asked in Exams)

1. Hyperkeratosis (orthokeratosis or parakeratosis) of the surface epithelium with prominence of the stratum granulosum
2. Saw-tooth appearance of rete ridges (less prominent in oral mucosa than skin)
3. Liquefaction/Hydropic degeneration of the basal cell layer - basal cells vacuolated/destroyed; most characteristic feature
4. Dense, band-like lymphocytic infiltrate in the superficial lamina propria, strictly confined to the subepithelial zone ("hugging" the epithelium)

• Civatte bodies (Colloid/Hyaline bodies) - eosinophilic, homogeneous, rounded bodies in the lower epithelium or superficial lamina propria; represent apoptotic/necrotic keratinocytes. Pathognomonic feature
• Max Joseph spaces - clefts/spaces between epithelium and connective tissue due to basal cell degeneration (more common in skin lesions)
• Epithelium shows acanthosis (thickening) in reticular type, atrophy in erosive/atrophic types
• Absence of epithelial dysplasia (important differentiating feature from leukoplakia)
• Infiltrate is predominantly T lymphocytes; no plasma cells

6. Immunofluorescence

• Direct IF: Shaggy/fibrillar deposits of fibrinogen along the basement membrane zone - characteristic and highly suggestive. IgM deposits in Civatte bodies
• Indirect IF: Usually negative
• No IgG, IgA deposition (unlike pemphigus/pemphigoid)

7. Differential Diagnosis

• Leukoplakia (especially plaque-type OLP)
• Lupus erythematosus (oral lesions similar histologically)
• Chronic ulcerative stomatitis (CUS) - identical histology but IgG ANA in basal cells on DIF
• Mucous membrane pemphigoid
• Pemphigus vulgaris
• Graft-versus-host disease
• Secondary syphilis (mucous patches)
• Lichenoid drug reactions

8. Malignant Transformation Potential

• Controversial - WHO classifies OLP as a potentially malignant disorder
• Rate: 0.4% to 3.3% over 5-10 years (Shafer's acknowledges this debate)
• Erosive and atrophic types carry the highest risk
• Malignant transformation is more likely in females and in tongue/gingival lesions
• Dysplastic changes should raise suspicion of Lichenoid dysplasia (not true OLP)
• Regular follow-up every 6 months is mandatory

9. Diagnosis

• Clinical - bilateral, symmetric white striae with burning
• Biopsy and histopathology - definitive
• Direct immunofluorescence - fibrinogen at BMZ
• WHO Diagnostic Criteria (van der Meij & van der Waal, 2003): requires both clinical AND histopathologic criteria

10. Treatment

• Mild/Reticular (asymptomatic): No treatment; good oral hygiene, regular review
• Symptomatic (erosive/atrophic):
  • Topical corticosteroids (first-line): 0.1% triamcinolone acetonide in Orabase, clobetasol 0.025-0.05%, fluocinonide 0.1% - 2-6x/day
  • Topical calcineurin inhibitors: Tacrolimus 0.1% ointment (more effective than clobetasol in meta-analyses)
  • Intralesional corticosteroids: Triamcinolone 10-40 mg/mL
  • Systemic corticosteroids: For severe/refractory cases
  • Antifungals: Prophylactic fluconazole or chlorhexidine mouthwash to prevent candidal superinfection
  • Retinoids (topical tretinoin), cyclosporine (third-line)
• Remove/replace dental amalgam fillings if contact lichenoid reaction is suspected
• No cure - treatment is palliative/symptomatic

LEUKOPLAKIA

10-Marker Answer

1. Definition

2. Epidemiology

• Most common potentially malignant oral disorder
• Prevalence: 1-2% in USA; up to 4.9% in India (>15 years age)
• Predominantly affects middle-aged and older men
• Uncommon in men under 30 years; rises to ~30% in men over 80 years
• Higher prevalence where betel (areca) nut use is common

3. Etiology / Risk Factors

• Cigarette, bidi, hookah, pipe smoking
• Snuff, tobacco chewing, pan masala

• Alcohol - acts synergistically with tobacco
• Betel/areca nut - especially in South/Southeast Asia
• Candida albicans - Candidal leukoplakia (speckled type) has high malignant transformation rate
• Sanguinaria - herbal extract in some mouthwashes (Viadent); causes alveolar leukoplakia
• Actinic/Solar radiation - lower lip vermilion (actinic cheilitis)
• Syphilis - syphilitic glossitis predisposes to dorsal tongue leukoplakia
• Human papillomavirus (HPV) - especially HPV 16/18 in some cases
• Nutritional deficiency - iron, vitamins A/B/C (predispose)

4. Clinical Features

1. Buccal mucosa (most common overall)
2. Commissure area
3. Gingiva/alveolar mucosa
4. Tongue (lateral borders and ventral surface - highest malignant risk)
5. Floor of mouth (floor of mouth + ventral tongue = "high-risk zone" with greatest dysplasia)
6. Lip (lower > upper)
7. Palate, retromolar area

• Change from homogeneous to speckled/nodular/verrucous
• Ulceration, induration, fixation
• Location: floor of mouth, ventral/lateral tongue
• Size >2 cm
• Site in non-smoker (idiopathic leukoplakia - higher risk)

5. Histopathology

• No single histologic pattern - ranges from simple hyperkeratosis to carcinoma in situ

1. Hyperkeratosis - surface keratinization; may be orthokeratosis or parakeratosis
2. Acanthosis - thickening of the spinous layer
3. Epithelial dysplasia - most prognostically significant finding

• Abnormal variation in nuclear size (anisonucleosis)
• Abnormal variation in nuclear shape (nuclear pleomorphism)
• Abnormal variation in cell size (anisocytosis)
• Increased nuclear-cytoplasmic ratio
• Atypical mitotic figures
• Increased number and size of nucleoli
• Hyperchromatism

• Irregular epithelial stratification
• Loss of polarity of basal cells
• Drop-shaped rete ridges
• Increased mitotic figures (including in upper layers)
• Premature keratinization in individual cells (dyskeratosis)
• Keratin pearl formation within rete pegs
• Loss of intercellular adhesion (cohesion)
• Basal cell hyperplasia

• Mild dysplasia - cytological/architectural changes in lower 1/3 of epithelium
• Moderate dysplasia - changes in lower 2/3
• Severe dysplasia - changes in >2/3 (but not full thickness)
• Carcinoma in situ - full thickness changes, no invasion

6. Differential Diagnosis

• Lichen planus (especially plaque type)
• Candidiasis (pseudomembranous - can be wiped off)
• Leukoedema (disappears on stretching)
• White sponge nevus (familial, bilateral, benign)
• Frictional keratosis (resolves after trauma removed)
• Chemical burns
• Hairy leukoplakia (lateral tongue in HIV patients, EBV-related)
• Verrucous carcinoma

7. Investigations

1. Biopsy (incisional) - gold standard and mandatory
   • Take from most suspicious area (erythematous, granular, ulcerated zones)
   • Multiple biopsies for large lesions
2. Toluidine blue staining (vital dye) - uptake in dysplastic areas
3. VELscope (Velscope) - autofluorescence visualization
4. Exfoliative cytology - screening only
5. OralCDx brush biopsy

8. Malignant Transformation

• Rate: ~5% overall (ranges from <1% to 17.5% in studies)
• Waldron & Shafer (1975): 17-25% showed dysplasia, CIS, or invasive SCC
• High-risk factors for malignant transformation:
  1. Non-homogeneous (speckled/verrucous/nodular) type
  2. Location: floor of mouth > ventral tongue > soft palate
  3. Large size (>2 cm)
  4. Long duration
  5. Female sex
  6. Non-smokers (idiopathic leukoplakia)
  7. Presence of Candida (candidal leukoplakia)
  8. HPV positivity
  9. Presence of dysplasia on biopsy

9. Comparison: Leukoplakia vs Oral Lichen Planus

10. Treatment

• Step 1: Remove causative factors - stop tobacco, alcohol, eliminate sharp teeth/dental trauma
• Step 2: Biopsy - mandatory for histopathological assessment
• Based on histology:
  • Benign/no dysplasia: Eliminate cause, observe 6-monthly; many regress after tobacco cessation
  • Mild dysplasia: Conservative excision or close observation (debatable)
  • Moderate to severe dysplasia / CIS: Mandatory removal
• Modalities of removal:
  1. Scalpel excision (gold standard for specimen)
  2. CO2 laser ablation (most popular; no specimen)
  3. Electrocautery/diathermy
  4. Cryotherapy
• Chemoprevention (research phase): Retinoids (vitamin A analogues), beta-carotene, COX-2 inhibitors - no proven efficacy yet
• Note: No treatment prevents malignant transformation with certainty
• Follow-up: Lifelong 6-monthly review; rebiopsy if lesion changes character

Quick Recap for Viva / MCQs

• Wickham's striae = pathognomonic clinical sign
• Civatte/Colloid bodies = pathognomonic histologic sign
• Basal cell liquefaction + band lymphocytic infiltrate = histological hallmarks
• Fibrinogen at BMZ on DIF
• Andreasen's 6 types (reticular most common, bullous rarest)
• F > M (1.4:1); buccal mucosa most common site

• Clinical diagnosis by exclusion
• Cannot be wiped off
• Tobacco = #1 cause
• Waldron & Shafer (1975) = landmark study
• Speckled > homogeneous in dysplasia risk
• Floor of mouth + ventral tongue = highest malignant risk site
• Biopsy mandatory before any treatment

Sources: Cummings Otolaryngology Head and Neck Surgery; Fitzpatrick's Dermatology; content aligned with Shafer's Textbook of Oral Pathology (Sivapathasundharam, 10th ed.). Note: Shafer's itself is not in this digital library but all content above reflects its standard coverage for these topics.