1. LEUKOPLAKIA
PRESENTER:
Dr. Apala Baduni

2. CONTENTS:
• INTRODUCTION
• CLASSIFICATION
• CLINCAL FEATURES
• TREATMENT MODALITIES

3. Introduction
• The oral mucosa is normally semi-translucent, allowing the
color of underlying tissues to show through to a variable
degree.
Lesions most commonly appear white secondary to
• Increased thickness of the epithelium caused by
 Epithelial hypertrophy or hyperplasia,
 Edema

4.  Increased production of surface keratin(hyperkeratosis).
 Thickening specifically in the spinous layer
 Collapsed bullae or ulcerative lesions covered with a surface
layer of fibrin may also appear white.
 Keratin production as a protective response
• Decreased submucosal vascularity

5. • (Wood and Goaz)

6. • Keratotic
Leukoedema
Linea alba
Leukoplakia
Nicotina stomatitis
Migratory glossitis
Lichen Planus
Lichenoid Reaction
Papilloma
Verrucous Vulgaris
Smokers tobacco lesion
Carcinoma
Cigarette smokers lip lesion

7. • Non keratotic
(Wood and Goaz)
Pyogenic Granuloma,
Traumatic ulcer,
Skin Grafts,
Chemical burns,
ANUG,
Candidiasis,
Hairy Leukoplakia,
White Sponge Nevus,
Diffuse gangrenous stomatitis,
White Exophytic Squamous Cell
Carcinoma,
Verrucous Carcinoma,
Necrotic Ulcers of Systemic Diseases,
Rarities

8. • According to Burket’s

9. • Hereditary
• Reactive/ Inflammatory
Burket’s
1.Leukoedema
2.White sponge nevus
3.Heriditary benign
intraepithelial dyskeratosis
• Linea alba [white line]
• Frictional [traumatic] keratosis
• Cheek chewing
• Chemical injuries of the oral
mucosa
• Actinic keratosis [cheilitis]
• Smokeless tobacco –induced
keratosis
• Nicotine stomatitis
• Sanguinaria –induced
leukoplakia

10. • Infectious
• Idiopathic
• Miscellaneous
Burket’s
1.Oral hairy
leukoplakia
2.Candidiasis
3.Mucous patches
4.Parulis
Leukoplakia
• Geographic Tongue
• Hairy Tongue (Black)
• Oral Submucous Fibrosis

11.  Leukoplakia literally means white patch
 Sir James Paget had recognized the lesion's cancer-transforming
potential and its relationship to pipe smoking, reporting on
"leukokeratosis" and "smoker's patch" as early as 1851.
 Schwimmer of Budapest coined the term "leukoplakia“.- As a white
lesion of the tongue which probably represented a syphylitic
glossitis(1877)
 More than any other oral disease, leukoplakia has suffered from an
excess of diagnostic terms and definitions; at least 75 have been
used thus far.
HISTORY

12. Definition
1stdefinition (1961 Shafer) Leukoplakia should be used as a clinical
term. It has no specific histopathological connotation & it should never
be used as a microscopic diagnosis
WHO definition (1978) a white patch or plaque that cannot be
characterized clinically or pathologically as any other disease
Modified Definition (Axell et al 1984): a white patch/plaque that cannot
be characterized clinically or histopathologically as any other disease
& is not associated with any physical/ chemical causative agent
except the use of tobacco

13. Modified Definition (Pindborg 1997):a predominantly white
lesion of the oral mucosa that cannot be characterized as any
other definable lesion
Revised WHO Definition (2007):the term leukoplakia should
be used to recognize white patches of questionable risk
having excluded other known diseases/ disorders that carry
no increased risk of cancer

14. Epidemiology
 More prevalent in Southeast Asia
 Prevalence in India=0.2% to 4.9%
 Tobacco abuse is the most common etiological
factor
 MT –<smokeless leukoplakia

15. Epidemiology
 Malignant transformation rate=3% to 6%
 Age: b/w40-70 years
 Sex: males>>> females
 Site: buccal/vestibular mucosa (habit
related)>>Floor of mouth (least)

16. Etiology & Pathogenesis
Local factors:
 Tobacco abuse
•Commonest
•~ 80% tobacco users develop leukoplakia
•Prevalence: 1.8 % who used; 0.03% who did not use (Mehta, Bhonsle)
•Both smoke & smokeless tobacco
•Dose & duration dependant
•Cause & effect relation confirmed by studies

17. Etiology &pathogenesis
•Tobacco Chewing
•Prevalence: 1.8% - betel tobacco chewers
•Risk for leukoplakia - 60 times >>in chewers than in non chewers
•The risk ↑s with-
•↑ in frequency of chewing
• Earlier initiation of habit
• Duration of exposure to quid.
Various chemicals leach out like- nitrosonornicotine, nicotine,
pyridine, picoline and collidin- chemical damage which causes
epithelial hyperplasia

18. Etiology &pathogenesis
Smoking
• Development is dose and duration dependent
• Old age group - higher prevalence
• Site correlation exists
•Heavy cigarette smokers – more palatal lesions
• Majority of lesions - cheeks. (due to heat & combustion products)
(Jean M. Baric et al OOO 1982 -54; 424-429)
Polycyclic hydrocarbons, betanaphthylamine, nitrosamines, carbon
monooxide, nicotine- irritation along with heat.

19. Alcohol:
• Not associated with ↑d risk of leukoplakia development
alone. Acts synergistically with tobacco.
• It facilitates the entry of carcinogen into exposed cells and thus
alters the epithelium and its metabolism.

20. Sanguinaria- maxillary vestibule or on the alveolar mucosa.
The affected epithelium may demonstrate dyslpasia identical to
that seen in other leukoplakia.
Etiology &pathogenesis

21. Candida Infection
Etiology &pathogenesis
•Found frequently in leukoplakic lesions (candidal leukoplakia)
• 60% nodular type, 3% homogenous type
•Can colonize the superficial epithelial layers of the mucosa.
• Longstanding discussion - candida infection is a cause or a
superimposed infection in a pre-existing lesion

22. Viruses
Etiology &pathogenesis
HSV & HPV – HPV 16 & 18 strains
• Role remains questionable BUT evidence exists of association of
HPV 16 strain with ↑d risk of MT
likelihood of detecting HPV
• 2-3 times >r in pre-cancerous lesion
• 4-5 times >r in OSCC
than in normal oral epithelium.
Induce dysplasia like changes.

23. Syphilis –
a higher incidence of leukoplakia seen in
patients with syphilic glossitis- tongue becomes stiff and
frequently has extensive dorsal leukoplakia.
Etiology &pathogenesis

24. Sunlight: UV radiation from sun rays – leukoplakia
development at vermillion border of lower lips and
associated with actinic chelitis.
Etiology &pathogenesis

25. Stages of leukoplakia (Sharp et al)
 Earliest lesion: non palpable, faintly translucent,
white discoloration
 Later: localized/difuse, slightly elevated plaques with
irregular outline, opaque white with fine granular
texture
 Progressive lesion: thick white lesion showing
induration, fissuring & ulcer formation

26. Leukoplakia
14. Clinical Classification
 Scuibba, 1995
• Homogenous
• Focal/ Smooth/ Pumice like
• low risk malignant transformation
• Non Homogenous/ Heterogenous
• Interspersed with red/ atrophic areas
• Speckled, erosive, ulcerative, verrucous
• High risk of dysplasia/ malignant transformation

27. Leukoplakia
14. Clinical Classification
 Scuibba, 1995
 WHO (Pindborg, 1997)
• Homogenous
* Flat, Corrugated, Wrinkled, Pumice like
* Low risk MT
• Non Homogenous
* Verrucous * Nodular
* Ulcerated * Erythroplakic

28. 14. Clinical Classification
 Scuibba, 1995
 WHO (Pindborg, 1997)
 Amagasa et al, 2006
Type 1 - flat, white patch/ plaque without red component
Type 2 - flat, white patch/ plaque with red component
Type 3 - slightly raised/ elevated white patch/ plaque
Type 4 - markedly raised/ elevated white patch/ plaque

29. 14. Clinical Classification
 Scuibba, 1995
 WHO (Pindborg, 1997)
 Amagasa et al, 2006
 Wood & Goaz
* Homogenous * Reversible
* Speckled * Irreversible
* Erythroplakic
* Verrucous

30. Leukoplakia
14. Clinical Classification
 Scuibba, 1995
 WHO (Pindborg, 1997)
 Amagasa et al, 2006
 Wood & Goaz
 WHO 2007
• Homogenous
• Non Homogenous
 Speckled
 Nodular
 Verrucous
 Proliferative Verrucous Leukoplakia (PVL)

31. Homogenous Leukoplakia
Clinical features
Homogenous white patch/ plaque
No red component
Fine, white, grainy texture.
Low risk malignant transformation rate
Localized or extensive
“Beach at ebbing tide appearance, cracked mud appearance”
Histopathological features
•Hyperkeratosis
•Acanthosis
•Lymphocytes
•Dysplasia

32. Mottled rough
appearance
Homogenous Leukoplakia
Flat
Corrugated

33. • Wrinkled
• Pumice

34. Nodular Leukoplakia
Clinical features
White lesion with raised, pebbly surface with polypoid
outgrowths (nodules) on an erythematous base
Very fine, pin head sized or larger, rounded, red or white
Associated with high malignant transformation rate showing ED/
carcinoma.
Appearance often similar to Candidiasis
Mild complaints of localized pain/ discomfort
Histopathological features
Irregular hyperkeratosis
Bulbous rete pegs
Lymphocytes
Moderate/Severe dysplasia

35. Verrucous Leukoplakia
Clinical features
White lesion with raised corrugated surface
White component is thicker than red &
protrudes over surface mucosa
The surface exhibits multiple papillary
projections which are heavily keratinized
60 – 80 years
Histopathological features
Irregular hyperkeratosis- verruciform
hyperkeratosis
Bulbous rete pegs
Lymphocytes
Moderate/Severe dysplasia
Congested vessels

36. Non Homogenous/ Heterogenous Leukoplakia/
Speckled leukoplakia
Clinical features
Red and white mixed lesion
White lesions interspersed with red or atrophic
areas
Higher risk of malignant transformation
Histopathological features
Irregular hyperkeratosis
Bulbous and crowded rete pegs
Epithelial atrophy
Lymphocytes
Severe dysplasia

37. Proliferative Verrucous Leukoplakia
Clinical features
1st recognized in 1985 by Hansen
Persistent , extensive verrucoid/ exophytic/
wart like appearance
Begins as simple hyperkeratosis, slow-
growing, persistent & irreversible, but tends to
spread, becomes multifocal with an exophytic
surface.
Most commonly resistant to all forms of
therapy as recurrence is the rule.
Strong female predilection
> 60 years
Highest risk of malignant transformation.
Site- often bilateral & affects mandibular
alveolar &buccal mucosa
Histopathological features
Irregular hyperkeratosis- verruciform
hyperkeratosis
Bulbous rete pegs
Lymphocytes
Moderate/Severe dysplasia
Congested vessels

38. Oral Hairy Leukoplakia
Histopathological features
HPK, acanthosis, koliocytic cells (viral infected
Balloon Cells) in spinous layer
Homogenous viral nuclear inclusions with
residual rim of normal chromatin
Clinical features
Corrugated white lesion on lateral/ ventral tongue
surface in immunodeficient patients
Association with HIV +v adults, AIDS, organ
transplant, prolonged steroid therapy
25% - HIV +v adults; not common in HIV children
80% - AIDS
Lateral/ ventral/ dorsal border of tongue
Corrugated, shaggy/ frayed appearance or plaque
like.
Bilateral

39. Candidal Leukoplakia
Clinical features
Lesion: Firm, white leathery plaques
Site: Cheeks, lips, palate, tongue
Diagnosis: PAS (Periodic Acid Schiff) +.
Histopathological features
Epithelial proliferation (inflammatory/
reactive changes in epithelium)
Epithelial Dysplasia
hyphae in leukoplakic lesions

40. Histopathologically, a distinction can be made between
dysplastic and non-dysplastic leukoplakia

41. Criteria used for diagnosing dysplasia
• Architecture
• Irregular epithelial stratification
• Loss of polarity of basal cells
• Drop-shaped rete ridges
• Increased number of mitotic figures
• Abnormal superficial mitoses
• Premature keratinization in single cells (dyskeratosis)
• Keratin pearls within rete pegs
van der Waal I, Potentially malignant disorders of the oral and oropharyngeal mucosa;
OralOncol(2008),doi:10.1016/j.oraloncology.2008.05.016

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

44. Histopathological stages in epithelial precursor
lesions

46. 46

47. IncisionalBiopsy
 Brush biopsy
Vital staining
Superficial smear
 T pallidum serology
Chemiluminescent Spectroscopy
Molecular Markers
Investigations

48. 48
Investigations
DNA content (ploidy)
The DNA content (DNA ploidy) of a cell gives a rough measurement of
genetic instability & DNA aberration
In cancers, genetically stable diploid cells are replaced by genetically
unstable aneuploid cells
In leukoplakias, aneuploid populations have also been reported
with/out correlation to the grade of dysplasia
DNA aneuploidy is a powerful predictor of malignant development in
oral leukoplakias&erythroplakias
FISH, Karyotyping, PCR

49. 49
Investigations
Loss of Heterozygosity (LOH)
Loss of genomic material in 1 pair of chromosomes is = loss of
heterozygosity (LOH)
LOH at chromosomal regions containing tumor suppressor
genes might be related to the process of malignant
development
LOH, particularly at chromosome arms 3 & 9, has been
associated with a possibility of malignant development of
premalignant lesions
Microsatellite analysis, RFLP

50. 50
Investigations
p 53
Prevents accumulation of genetic damage in cells by allowing
repair of damage or by causing cell death
Half-life & quantity in normal cells - extremely small
P53 over expression in oral precancers – 47% - very high
Clear expression of p53 above the basal cell layer - indicator
of a developing carcinoma, even in the absence of obvious
dysplasia

51. 51
Investigations
Keratins
Proteins that constitute intermediate filament cytoskeleton of
epithelial cells
K5/K14 is present in basal cells; K4/K13, K1/K10 in spinouscells
in non-cornified&cornified epithelium respectively
In dysplastic epithelia - K5/K14 keratins are also expressed in
parabasal&spinous cell layers
In Severe dysplasia - K4/K13 & K1/K10 - completely lost

52. • Prevention
• Treatment
– Surgical
– Medical
• Studies/ Trials
Management

53. The term leukoplakia can be used at different levels of certainty
(C-factor) as a clinical term only (C1 or C2) or as a clinicopathological
term (C3 or C4).
van der Waal I, Potentially malignant disorders of the oral and oropharyngeal mucosa; ...,
Oral Oncol(2008), doi:10.1016/j.oraloncology.2008.05.016

55. objective of treatment
↓
detect and prevent malignant change.
• Choice of treatment – based on
– known natural history
– careful evaluation of possible a/e of & expected levels of
compliance with, any treatment modality
55
Treatment

56. Treatment
• Spontaneous disappearance after removal of irritant – NO
FURTHER TREATMENT required
• Anti-inflammatory & Anti-mycotic agents
• Elimination of habits
• Lesion persists
– Biopsy
– Adjunctive methods (toluidine blue staining, cyto brush
technique)
Management

57. Systemic Approaches
• Antioxidants, Vitamins
• Antioxidants local application & photodynamic therapy
• Indication-
– recurrence after surgical excision
– Pts with widespread leukoplakia involving larger area
– Pts with extensive surgical risks
57

58. Mechanism of action of free radical
Free radicals are formed by dissociation of neutral molecule
generating two free radicals or loss or addition of single
electron to neutral molecule

59. • Classification of free radicals
First classification
• Examples of free radicals include sigma, pi-delocalized, carbon-
centered, oxygen-centered, sulfur-centered, nitrogen-centered,
reducing radicals, oxidizing radicals.
Second classification
Hydroperoxyl (per hydroxyl) radical
• Superoxide radical
• Hydrogen peroxide
• Singlet oxygen and triplet oxygen.

60. • Antioxidants
Antioxidants may be regarded as those substances which will
significantly delay or inhibit the oxidation of a substance and
protect the body against oxidative damage.
• Mode of action
The antioxidants act by breakage of chain reaction, reducing
concentration of reactive oxygen species, scavenging initiating
radicals or chelation of transition metal catalyst

61. • Classification of antioxidants
Enzymatic antioxidants
• include superoxide dismutase, malondialdehyde, glutathione
peroxides, catalase, glutathione reductase, glutathione
transferase.
Non-enzymatic antioxidants
• Nutrient-alpha tocopherol, beta carotene, vitamin A, vitamin
E, acorbate, glutathione, selenium
Non-nutrient
• ceruloplasmin, transferrin, uric acid, peptides camosine.

62. Antioxidants (AO)
• Choice is usually complex as there is no combination proved
superior
• Combinations:
– Single & combination dosages of vitamins A, C & E
– Beta carotene (BC)
– Analogues of vitamin A
– Diets high in AO & cell growth suppressor proteins (fruits,
vegetables)
• Disadvantage:
– Use not been reproducibly effective in management
– Patterns of response & relapse - quite similar (showing
partial & complete remission in 40/60% cases)
62

63. CAROTENOIDS
• The carotenoids are a group of extremely hydrophobic molecules with
little or no solubility in water.
Beta carotene
Betacarotene is a vitamin
A precursor
The potential benefits and
protective effects against cancer are
possibly related to its antioxidizing
action.
This function is accomplished through a
ligation between beta-carotene and
oxygen, which is an unstable reactive
molecule, thus diminishing the damaging
effects of free radicals
.
Liede et al 1998, Sankaranarayanan et al.
1997, Garewal et al. 1990, K. Malaker 1991
Lycopene
Lycopene is a carotenoid
without provitamin A
action.
In addition to its antioxidizing property,
lycopene also has the capacity to modify
intercellular exchange junctions, and this
is considered to be an anticancer
mechanism
Lycopene has the uncommon feature of
becoming bound to chemical species that
react to oxygen, thus being the most
efficient biological antioxidizing agent.
Singh et al 2004., Hoppe et al. 2003,
Nagao et al.2000,

65. Vitamins
L-Ascorbic Acid
(Vitamin C).
L-AA has antioxidizing properties and
reacts with superoxide produced as a
result of the cells’ normal metabolic
processes;
This inactivation of superoxide inhibits
the formation of nitrosamines during
protein digestion and helps avoid
damage to DNA and cellular proteins.
T. J. Barth- 1997
.
α-Tocoferol
(Vitamin E).
Benner et al 1993. Erhardt et al 2002. G.
E. Kaugars 1994,
Α- Tocoferol is an effective
antioxidant at high levels of
oxygen, protecting cellular
membranes from lipidic
peroxidation.

67. Retinoic Acid
(Vitamin A).
The current definition of retinoid
includes all the natural and
synthetic compounds with an
activity similar to that of Vitamin A.
13-cRA was used for the first time against
acne, in 1969.
.
S. M. Lippman, 2006
At the cellular-level, retinoids interact with
surface receptors and penetrate the cell.
They are subsequently metabolized and
transported to the nucleus by various
proteins. Retinoids affect diverse
processes, such as keratin production
immunologiaccal and inflammatory
response.
Kaugars et al., Toma et al., Gorsky and
Epstein, Scardina et al.,
Fenretinide. Fenretinide
(4-HPR) or N-(4-
hydroxyphenyl)
vitamin A analogue .
A characteristic feature of 4-HPR is its
ability to inhibit cell growth through the
induction of apoptosis with mechanisms
that may be both receptor-dependent and
receptor-independent.

68. Topical applications- Bleomycin for dysplastic oral leukoplakia
• Bleomycin, a cytotoxic antibiotic, was first used for the treatment of
neoplasms of the penis and scrotum, but has also been employed for
squamous cell carcinoma of the head and neck region, oesophagus,
and skin
• Epstein in 1998 used topical 1% bleomycin in dimethylsulfoxide for
treating dysplastic oral lesions – once/day X 14 days in 19 patients
• 75% - resolution of dysplasia at follow-up biopsy
• 94% - partial responses
• 2 patients – MT – after 1.75 years of treatment.
• After a follow-up period of 3.4 years:
– 31.6% - no clinically visible lesions
– 47.4% - clinically benign lesions

71. Topical applications - Calcipotriol
• Femiano et al in 2001 compared clinical efficacy of 50mg/g topical
calcipotriol & topical tretinoin in oral leukoplakia for 5 weeks
• Calcipotriol – Vit D3 analogue - forms a molecule receptor
complex with keratinocyte& T-lymphocyte specific cytoplasmic
receptor - inhibits cellular proliferation by an apoptotic
mechanism
• Results: 2 weeks - lesions regressed, with leveling of
hyperkeratotic surfaces, softening & an attenuation of whiteness.
• Conclusion: topical Calcipotriol is effective for treating oral
leukplakia topically 71

72. Green tea
• Green tea contains four major polyphenols:
 Epicatechin (EC)
 Epigallocatechin (EGC)
 Epicatechin-3-gallate (ECG)
 Epigallocatechin-3-gallate (EGCG)
• Inhibit a variety of processes associated with cancer cell growth,
survival as well as metastasis.

73. Molecular pathways altered by green tea extract.
• Epigallocatechin-3-gallate (EGCG) modulates the mitogen-
activated protein kinase (MAPK) pathway bringing about growth
inhibition.
• Cell cycle arrest =EGCG.
• Promotion of apoptosis by inhibition of bcl2 and bcl-xl
Ramshankar V, Krishnamurthy A. Chemopreventionof oral cancer: Green tea experience. J Nat Sc Biol Med 2014;5:3-7
• GT suppressing oral premalignant lesions by blocking
angiogenesis stimuli.
Leong H, Mathur PS, Greene GL. Green tea catechins inhibits angiogenesis through suppression of STAT3 activation. Breast Cancer Res Treat
2009;117:505-15.

74. • The first clinical trial using green tea for oral premalignant
lesions was a double-blind, placebo-controlled randomized trial
in patients with oral leukoplakia
• 760 mg of mixed tea capsules along with mixed tea ointment
topically vs placebo with topical glycerin.
• The treatment groups showed 37.9% response rate after 6
months vs the control arm.

75. • The dose limiting toxicities reported were tremors, cough,
constipation, and headache; attributed to the caffeine
components of GTE.
• Oral GTE dose of 1 gm/m2 thrice daily for at least 6 months
was recommended.
• This study showed that applying tea extracts directly to the
lesions may help in improving the local concentrations of the
active constituents.
Tsao AS, Liu D, Martin J, Tang XM, Lee JJ, El-Naggar AK, et al.Phase II randomized, placebo-controlled trial of green tea extractin patients with high-risk oral
premalignant lesions. Cancer PrevRes (Phila) 2009;2:931-41.

76. Possible action mechanism for curcumin in pre-cancerous lesions based on serum and
salivary markers of oxidative stress
Journal of Oral Science
Vol. 52 (2010) No. 2 June P 251-256
• Patients with oral leukoplakia, oral submucous fibrosis or lichen
planus, and healthy individuals (n = 25 for each group)
• 17-50 years were selected.
• Salivary and serum oxidative markers such as malonaldehyde (MDA),
8-hydroxydeoxyguanosine (8-OHdG), vitamins C and E were
measured just prior to the intake of curcumin
• After one week of curcumin intake and following clinical cure of
precancerous lesions.

77. • Serum and salivary vitamins C and E showed increase
• MDA and 8-OHdG levels showed decreases in patients with
oral leukoplakia, submucous fibrosis and lichen planus after
intake of curcumin for all categories of precancerous lesions
• The changes in these values were observed to be statistically
significant after clinical cure of the disease (P < 0.05).
• The five-point rating scale for pain, as well as lesion size in
oral leukoplakia, submucous fibrosis and lichen planus,
improved significantly (P < 0.05).

78. • Values for serum and salivary vitamins C and E showed a
significant decrease in oral leukoplakia, submucous fibrosis
and lichen planus, in contrast to healthy individuals, but
increased significantly in all groups subsequent to curcumin
administration after clinical cure of lesions
• Conclusion: curcumin mediates its anti-pre-cancer activities
by increasing levels of vitamins C and E, and preventing lipid
peroxidation and DNA damage.

79. Curcuma species contains
turmerin,
turmerons,
atlantones
zingiberene and
curcumin regarded as most active constituent
Curcumin also affect carcinogenesis process associated with the
growth and dissemination of established malignancy. Angionesis
is a now regarded as critical to the transition of premalignant
lesion in a hyperproliferative state to malignant phenotype
this facilitating tumour growth and metastasis
Singh V, Pal M, Gupta S, Tiwari SK, Malkunje L,Das S. Turmeric - A new treatment option for lichen planus: A pilot study.
Natl J Maxillofac Surg 2013;4:198-201.

80. • Treatment
– Homogenous:
1. Patient education and motivation to discontinue tobacco
habit.
2. Identification and removal of any predisposing factors.
3. Anti-fungal agents for 2 weeks may reduce lesion size.
4. Periodic observation.
5. Increase in lesion size or change in appearance indicates
need for histological examination.
6. Dysplastic changes indicate surgical removal&long term
follow-up.
Management

81. • Treatment
– Non Homogenous
1. Patient education and motivation to discontinue tobacco
habit
2. Identification and removal of any predisposing factors
3. Histological examination
4. Dysplastic changes indicate surgical removal&long term
follow-up
5. Non-dysplastic lesions may be treated similar to
homogenous variety
Management

82. • Surgical removal of the lesion, including surgical excision,
laser surgery, cryotherapy.
• Topical medical treatment, including anti-inflammatory
agents, antimycotic agents, carotenoids and retinoids, cytotoxic
agents, etc.
• Systemic medical treatment.
• Removal of predisposing habits (e.g. tobacco, alcohol, etc.).
• Other treatment (e.g. photodynamic therapy).
• Combined treatment.

83. In the absence of histologically demonstrable
dysplastic changes
↓
careful routine follow up with elimination of
risk associated habits
(alcohol, tobacco, irritation, trauma
is a mandatory 1st step)
83

84. Surgery
• Recommended treatment (traditionally), with/out
epithelial dysplasia
• Surgical modalities -
– Scalpel
– Cryosurgery
– Laser surgeries
• Recurrence:
– Rate - 20 to 35%.
– Site - adjacent to previous excised lesion
84

85. Surgery
• Advantages:
– Most effective
– Safe means of removing pathological tissue
• Disadvantage:
– Difficulty in determining proper margin of lesion
– dysplastic epithelium extending into salivary ducts
(possible explanations for the comparatively high
recurrence rate )
85

86. Surgery
• M. Pandey et al in 2001 - cold knife surgical excision of 59 cases of
non-homogeneous leukoplakia of the oral cavity in Kerala.
• After a 12 month follow-up - 44 (74.8%) became disease free with no
evidence of recurrent/new lesions
• During follow-up - 3 (5%) developed new & 6 (10.1%) - recurrent
lesions
• No event of malignant change during follow-up
• Conclusion:long-term follow-up of large number of surgically treated
cases may provide valuable leads to management of oral leukoplakia
86

87. Surgery
• Saito et al in 2001 studied 142 patients with oral leukoplakia
–
– 75 - surgical excision
– 12 - cryosurgery
– 4 - cryosurgery, followed by surgical excision
– 51 – no surgical treatments
• MTR – Surgical group < non surgical group (4 – 16 yr follow
up)
• Results: surgical excision may ↓ risk of carcinoma
development
87

88. Surgery
• P. Holmstrup in 2006 studied 269 lesions in 236 patients to learn
the long term outcome of leukoplakia&erythroplakia, with/out
surgical intervention & to relate the outcome to factors supposed
to be significant for malignant development (clinical type,
demarcation, size, site, presence of ED, smoking & surgery)
• Without surgical intervention 16% lesions disappeared, 4%
developed Carcinoma (mean follow up - 6.6 yrs)
• No other examined variables including presence of any degree of
epithelial dysplasia, site, demarcation, smoking and surgical
intervention were statistically significant factors for malignant
development
88

89. CO2- laser surgery
• Causes excision of lesion & part of underlying tissue or
evaporation of surface epithelium
• Entire lesion can be sent for h/p examination
• Advantages:
– magnification & precise beam control by microscope
– healing by secondary intention & epithelial
regeneration
– ↓s wound contraction & impairment of functions due
to scar formation
– ↓d morbidity
89

90. Photodynamic Therapy
• Photochemical reactions are mediated via interaction of
photosensitizing agents, light & oxygen
• Indication: treatment of malignant & benign diseases
• Advantages:
– potentially curative procedures
– minimal host toxicity.
• Procedure:
– Photosensitizer administration by 1 of several routes (topical, oral,
iv) - taken up by target cells
– photosensitizer activation in presence of O2 with a specific
wavelength of light - direct damage to cytoplasmic structures
90

91. • The principle of PDT is a nonthermal photochemical reaction,
• Which requires the simultaneous presence of a photosensitising
drug (photosensitiser), oxygen, and visible light.
• After a period to allow the photosensitiser to collect in the target
tissue
• The photosensitiser is activated by exposure to low-power visible
light of a drug-specificwavelength.
• The light source consists of a portable diode laser and the light is
transmitted via laser fibres to or into the tumour

92. • Illumination of the tumour by light at the activating wavelength
results in the destruction of cells by a nonfree radical oxidative
process.
• These reactive oxygen species may damage crucial cell components,
such as structural proteins, enzymes, DNA, and phospholipids.
• PDT is a cold photochemical reaction, and the photosensitising
agents are of inherently low systemic toxicity. PDT damage heals
mainly by regeneration rather than scarring.

93. Topical application of 5-aminolevulinic acid& Photodynamic
Therapy
• 5 ALA - a precursor in the biosynthesis of haeme - induces the
production of the endogenous photosensitizer protoporphyrin IX
which can be used for PDT
• ALA - used as a topical photosensitizer (20% ALA cream applied
for 2 hours - light activated)
• complete response – 45%
• partial response – 33%
• Unsuccessful – 22%
93

94. Cryosurgery
• Deliberate destruction of tissue by application of extreme cold
• Advantages:
– as an easily applicable outpatient technique
– very low incidence of infection
– can be repeated without permanent side effects
• Disadvantages –
– Lack of visual control over extent in depth of treatment
– Unavailability of intact specimen for h/p examination
– pain & edematous swelling – 1st 2 postoperative weeks

95. • Monitoring
Follow up
• Regular follow ups
• Careful examination every 4 6 months
• Re-biopsy: any evidence of cliniical
change
• Screening: brush/ conventional biopsy
at selected sites & visits

96. • Monitoring
• Patient instructions
Follow up
• Self examination of area in question
• Elimination of risk behaviour

97. • Monitoring
• Patient instructions
• Complications
Follow up
• Squamous Cell Carcinoma
• Verrucous Carcinoma
(malignant transformation into carcinoma
depends upon clinical form, duration &
site)

98. • SPECKLED LEUKOPLAKIA carries the highest average
transformation potential followed by verrucous
leukoplakia
• HOMOGENOUS LEUKOPLAKIA carries the lowest risk.
• The greater degree of dysplasia, the greater the degree of
malignant change.
Prognosis

99. DIFFERENTIAL DIAGNOSIS OF HOMOGENOUS LEUKOPLAKIA
• Lichen Planus(Wickham’s striae, skin lesions, feather margins, >
women)
• Leukoedema (milky opalescense, extent, elimination on stretching)
• Cheek-biting lesion (history & clinical examination, jagged tooth)
• Smokeless tobacco lesion (h/o smokeless tobacco use, lesion in
vestibule)
• Hyperplastic/ Hypertrophic Candidiasis(clinical & h/p examination)

100. • Hairy leukoplakia (tongue, immunosuppresed patient, HIV tests)
• Electrogalvanic/ mercury contact allergy (metal filling)
• White Sponge Nevus (least common, < 15 years, familial
pattern, clinical appearance,bilateral mostly)

101. DIFFERENTIAL DIAGNOSIS OF SPECKELED LEUKOPLAKIA
•MIGRATORY GLOSSITIS (identified by its classicfeatures: location on
the tongue, red patches with raised whitish rims, the changing patterns
CHRONIC MECHANICAL TRAUMA (close inspection reveals rough
tissue tags that surround red areas. These tissue tags are not
characteristic of speckled leukoplakia)

102. NICOTINE STOMATITIS
Characteristically occurs on the hard palate of smokers, usually
pipe smokers.
The white keratotic component may have a cobblestone
appearance speckled with red dots that may be the size of
pinpoints.
Occasionally the soft palate also has an appearance similar to the
reticular pattern of lichen planus with reddened mucosa between
the striae.
A cobblestone appearance with dots in any area of the lesion,
most commonly near the junction of the hard palate, permits the
diagnosis.
A definitive diagnosis be made if the lesion disappears on
discontinuation of smoking.

103. EROSIVE LICHEN PLANUS Erosive lichen planus bilateral or generalized
distribution in the mouth are usually readily identifiable
SQUAMOUS CELL CARCINOMA The classic ulcerative squamous cell
carcinoma is described as a crater like lesion having a velvety red base
and a rolled, indurated border
•HYPERTROPHIC AND HYPERPLASTIC CANDIDIASIS Hypertrophic and
hyperplastic candidiasis are conditions in which leukoplakial lesions are
associated with or caused by low-grade candidiasis. A red component
is frequently part of the clinical picture. Hyperplastic candidiasis is
most commonly seen at the oral commissures as angular cheilosis or
mucocutaneous candidiasis

104. LUPUS ERYTHEMATOSUS
Lupus erythematosus produces variable red and white lesions, which
may be similar to those of lichen planus but usually adopt a broader,
less linear pattern with feathered borders .
the lesions in lichen planus. these lesions have a wide distribution in
the oral cavity and lips and may involve the skin. Systemic workup and
biopsy are usually necessary to establish the diagnosis

105. Differential diagnosis of verrucous leukoplakia
• Verrucavulgaris(uncommon orally, small, raised)
• VERRUCOUS CARCINOMA vs Verrucous hyperplasia
• In 1980, Shear and Pindborg introduced the concept of verrucous
hyperplasia, describing how this differed from verrucous
carcinoma. They described hyperplasia as a proliferative epithelial
lesion with the epithelial hyperplastic folds extending above the
margins of the surrounding mucosa, whereas in carcinoma the
folds invade down into the connective tissue and below the
surrounding normal mucosal margins.

106. CONCLUSION
• Several clinical trials have investigated the treatment of OL with use of
supplements.
• At this time, randomized controlled trials for nonsurgical treatment of OL
demonstrate no evidence of effective treatment in preventing malignant
transformation and recurrence.
• It reinforces that after clinical resolution, OL should be regularly followed.

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