- Precancerous lesions of the oral cavity include premalignant lesions like leukoplakia, erythroplakia, oral submucous fibrosis, and lichen planus as well as premalignant conditions. - Leukoplakia presents as a white patch that cannot be scraped off. Erythroplakia appears as a bright red patch. Oral submucous fibrosis causes stiffness of the oral mucosa and trismus. - Risk factors include tobacco use, betel nut chewing, and poor oral hygiene. Histopathological examination is needed for diagnosis. Management involves eliminating risk factors, surgical excision of high risk lesions, and close follow up

2. PRECANCEROUS
LESIONS OF ORAL
CAVITY
BY,
BIBINA GEORGE
MDS PERIODONTICS

3. DEFINITION:
Precancerous lesion: A morphologically altered tissue in which cancer is more likely to
occur than in its apparently normal counter part.
[WHO,1978]
Precancerous Condition: A generalized state associated with a significantly increased
risk of cancer
[WHO,1978]

4. Premalignant condition
‘It is a group of disorders of varying etiologies, usually tobacco characterized by mutagen
associated, spontaneous or hereditary alterations or mutations in the genetic material of oral
epithelial cells with or without clinical and histomorphological alterations that may lead to oral
squamous cell carcinoma transformation.’
[WHO, 2005]

5. CLASSIFICATION:
Premalignant Lesions:
Leukoplakia
Proliferative Verrucous Leukoplakia
Intraepithelial carcinoma (Carcinoma in situ)
Erythroplakia
Palatal changes associated with reverse smoking
R.V. Subramanyam

6. Premalignant Conditions:
OSMF
Lichen Planus (erosive type)
Sideropenic dysphagia (Plummer- Vinson Syndrome)
Syphilis – Syphilitic glossitis
Discoid lupus erythematosus
Xeroderma pigmentosum
Epidermolysis Bullosa
R.V. Subramanyam

7. Premalignant / Precancerous / Potentially malignant oral lesions
involve
Skin lining of the mouth (known as the epithelium)
At risk for transforming into an oral cancer
Difficult to predict which lesions will transform and how long it will take
VICTOR BABES, 1875
Introduction

8. Etiopathogenesis
 Salivary thiobarbituric acid reacting
substance & advanced glycation end pdts
 Expression of CK8 & CK18
Expression of Podoplanin & ABCG2
Prevalence of p53 mutations
 Salivary advanced oxidation products
Vascular endothelial growth factor
Sialotransferase and Neuraminidase
 Salivary IL-8 concentration
(Vlková et al)
(Nanda et al)
(Qin et al)
(Puniyani et al)
(Feng et al)
No
Significant
difference

9. Age group ≥ 40
Poor oral hygiene ; Genetic theory (???)
Habits such as :
Tobacco (Smoking, Smokeless or inhaled)
Pan masala, Betel nut quid
Heavy alcohol use
Although such lesions can also be found in younger individuals and/or those without classic risk
factors.
Risk Factors

10. Clinical Features
 Lesion ≥ 14 days require a diagnostic biopsy even after irritant is removed
 Anatomical Location:
Epithelial dysplasia rate: 21.8% - Buccal mucosa
13.7%- Palate
12.3%- Floor of the mouth
Leukoplakia : 25.2% - Mand. Mucosa & Sulcus
21.9% - Buccal mucosa
(Shafer and Waldron)

11.  Age: Mean age for diagnosis: 37 – 59
<5% : < 30 yrs
 Sex: Epithelial dysplasia: Male
Oral SCC : Decrease in M:F rate

12. DYSPLASIA:
Definition: It comprises a loss in the uniformity of individual cells, as well as loss in their
architectural orientation.
It is characteristically associated with protracted chronic irritation or inflammation.

13. Histomorphological changes of dysplasia
Loss of basal cell polarity
Parabasilar hyperplasia
Increased nuclear:cytoplasmic ratio
Drop-shaped rete ridges
Abnormal epithelial maturation
Increased mitotic activity
Mitoses in the superficial half of the surface epithelium
Cellular pleomorphism
Nuclear hyperchromaticity
Enlarged nucleoli
Loss of cellular cohesiveness
Individual cell keratinization in the spinous cell layer.

15. Leukoplakia
DEFINITION: “A white patch or plaque in the oral cavity which cannot be scrapped off or
stripped off easily & more over, which cannot be characterized clinically or pathologically as any
other disease” (WHO 1978)
Originates from Greek words – “leucos” - white and “plakia” – patch
“ A predominantly white lesion of the oral mucosa that cannot be characterised
as any other definable lesion.” (WHO,2012)
SCHWIMMER,1877

16. Classification of leukoplakia
Based on CLINICAL TYPE:
 Homogenous : Smooth,Furrowed, Ulcerative
 Non homogenous : Ulcerative, Verrucous, Speckled
Based on ETIOLOGY:
 Tobacco associated
 Idiopathic
Based on EXTENT:
 Localized
 Diffuse (Axell & Pindborg et al 1983)

17. Based on risk of MALIGNANT TRANSFORMATION
 High risk sites
Floor of mouth
Lateral/ventral surface of tongue
Soft palate
 Low risk sites
Dorsum of tongue
Hard palate
Based on HISTOLOGY:
 Dysplastic
 Non dysplastic (Axell & Pindborg et al 1983)

18. Sharp’s staging of leukoplakia
Stage I - Earliest lesion-non palpable, faintly translucent, white discoloration
Stage II - Localized or diffuse, slightly elevated plaque of irregular outline. It is
opaque white & may have a fine granular texture
Stage III - Thickened white lesion showing induration and fissuring

19. Clinical presentation
Solitary or multiple, “White patches”
Varies from a non-palpable faintly translucent white
area to a thick fissured, papillomatous or indurated
lesion
• 70% in buccal mucosa, commissural areas, followed by lower lip,
floor of the mouth, palate & gingiva

20. SYMPTOMS
Feeling of increased thickness of mucosa
Ulcerated or nodular type: c/o burning sensation
Enlarged cervical lymph nodes (metastasis)
Homogeneous/ Leukoplakia Simplex
Speckled/Nodular Ulcerative

21. Histopathological features
• Keratinization pattern
• Thickness of epithelium
• Changes in underlying connective tissue
• Waldron & Shafer (1975)
 80% lesions show benign hyperkeratosis with/without acanthosis
 Dysplastic changes typically begin in basal & parabasal zones of epithelium

22. Conservative management
Elimination of etiological factor
Restraining from smoking or chewing tobacco
To remove sharp broken down teeth
Correction & replacement of overhanging or faulty metal restorations with a
metal bridge

23. 1) Isoretinoin / 13- cis- retinoic acid
2) Beta carotene -30mg TID
3) Topical Bleomycin – 0.5-1% solution/2wks
4) 5-Fluorouracil & Cisplatin
CHEMOPREVENTION

24. Surgical Excision: entire lesion excised if it is >1cm in size, following modalities used:
a) Scalpel – surgical stripping
b) Cryosurgery – with liquid nitrogen
c) Electrocautery
d) Laser ablation

25. Erythroplakia
DEFINITION: “Any lesion of the oral mucosa that presents as a bright red velvety
patch or plaque, which cannot be characterized clinically or pathologically as any
other recognizable condition”
[WHO]
Reported by Querat in 1911

26. Clinical variants
1. Homogenous erythroplakia
2. Erythroplakia interspersed with patches of leukoplakia
3. Granular or Speckled erythroplakia
CLASSIFICATION

27. - Smooth and granular/nodular, well defined
- May have an irregular, red granular surface interspersed with white or yellow foci
- Soft on palpation

28. Management
 Biopsy should be performed
 Treatment guided by histopathologic diagnosis
 Recurrence , multifocality common
 Careful long term follow up

29. Intraepithelial carcinoma (Ca in Situ)
Most severe stage of epithelial dysplasia
Striking feature – dysplastic epithelial cells do not invade into connective tissue
Common among elderly, with a male prediliction
Present as white plaques or ulcerated, & reddened areas
Site – floor of the mouth, tongue, lips
Has combined features of leuko & erythroplakia

30. • No accepted treatment
• Surgical excision, irradiation & cauterization
Treatment

31. Oral lichen planus
•Named by E Wilson ( British physician) 1869
Lichen – latin for primitive plants (symbiotic algae & fungi)
Planus – latin for flat
Definition : “A common chronic immunologic inflammatory mucocutaneous
disorder that varies in appearance from keratotic (reticular or plaque like) to
erythematous and ulcerative, affecting the stratified squamous epithelium”

32. Etiology & pathogenesis
•Both antigen-specific & non-specific mechanisms may be involved in pathogenesis of OLP
• Antigen-specific mechanisms:
–antigen presentation by basal keratinocytes and
– antigen-specific keratinocyte killing by CD8 + cytotoxic T-cells
•Non-specific mechanisms:
– mast cell degranulation and matrix metalloproteinase (MMP) activation

33. These mechanisms may combine to cause
 T-cell accumulation in superficial lamina propria
 Basement membrane disruption
 Intra-epithelial T-cell migration &
 Keratinocyte apoptosis

34. Clinical features
Lesions usually symmetrical
Frequently affects buccal mucosa, tongue, gingiva, lip and
palate
Extra-oral mucosal involvements - anogenital area,
conjunctivae, oesophagus/larynx
Approx 1.2% - 5.3% lesions undergo malignant changes
Hence regular follow up mandatory

35. On skin-
Flat-topped purple polygonal & pruritic papular rash
Oral Cavity-
Asymptomatic
Reticular – Wickham’s striae + discrete erythematous border
Plaque-like – Resemble leukoplakia, common in smokers

36. Clinical features
Symptomatic
Atrophic – Diffuse red patch, peripheral radiating white striae
Erosive – Irregular erosion covered with a pseudomembrane
Bullous – Small bullae / vesicles that may rupture easily

37. Histology
 Shklar -3 classic microscopic features of OLP
 Overlying hyperkeratinization
 A bandlike layer of chronic inflammatory cells
within underlying connective tissue
 Liquefaction degeneration of basal cell zone

38. Diagnosis
• Oral biopsy
• Direct Immunofluorescence

39. Management
 Reticular type is asymptomatic & treatment often unnecessary
 Erosive type presents significant management problems
 All patients should optimize oral hygiene
 Oral candidiasis should be excluded/treated
 Cortico steroids, is the treatment of choice eg: Fluocinonide or Clobetasol gel for 2
weeks, with 3months follow-up

40.  In symptomatic patients with apparent contact dental factor, patch test with
replacement of amalgam
 In those with no apparent contact factor, topical or intralesional steroid - first
line treatment. A short course of systemic steroid for more rapid control

41. Oral submucous fibrosis
DEFINITION: “It is an insidious chronic disease affecting any part of the oral cavity and sometimes the
pharynx. Although occasionally preceded by or associated with vesicle formation ,it is always associated
with juxta-epithelial inflammatory reaction followed by a fibro-elastic changes of the lamina propria
with epithelial atrophy leading to stiffness of the oral mucosa and causing trismus and inability to eat.”
(J.J Pindborg and Sirsat 1966)
First described by Joshi (1952) and by Schwatz among East Indian Women.
“

42. Clinical presentation
 Common site – buccal mucosa, retromolar area, uvula, palate, etc
 Initially, pain and a burning sensation upon consumption of hot & spicy foods
 Vesicle & ulcers
 Excessive or reduced salivation & defective gustation
 Hearing loss

43. Depapillation & atrophy of tongue and uvula
Depigmented & loss of stippling over gingiva
Nasal tone in the voice
Difficulty in deglutition
Impaired mouth movements (eg, eating, whistling, blowing, sucking)

44. Mortality/morbidity
 High rate of morbidity - progressive
inability to open mouth, resulting in
difficulty eating & consequent nutritional
deficiencies
 Significant mortality rate - can transform
into oral cancer, particularly SCC (7.6%)
Prodromal symptoms

45. Clinical stages
Three stages based on physical findings:
Stage 1: Stomatitis includes erythematous mucosa, vesicles, mucosal ulcers,
melanotic mucosal pigmentation & mucosal petechiae
Stage 2: Fibrosis occurs in ruptured vesicles & ulcers when they heal, hallmark
of this stage
(Pindborg,1989)

46. Stage 3: Sequelae of OSMF
◦ Leukoplakia is found in more than 25% of individuals with OSMF
◦ Speech and hearing deficits may occur because of involvement of the tongue and
the eustachian tubes
(Pindborg,1989)

47. Group I : Only Symptoms, No mouth opening
Group II : Mouth opening > 20mm
Group III : Mouth opening < 20mm
Group IV: Limited mouth opening, precancerous & cancerous changes
throughout mucosa
RANGANATHAN K (2001)

48. Histopathology
 Hyperkeratinized, atrophic epithelium with flattening & shortening of rete pegs
 Nuclear pleomorphism & severe inter-cellular edema
 Finely fibrilar collagen & increased fibroblastic activity in early stage showing
dilated & congested blood vessels with areas of hemorrhage

49.  Advanced stage shows “homogenization” and “hyalinization” of collagen fibers
(important feature)
 Degeneration of muscle fibers and chronic inflammatory cell infiltration in the
connective tissue

50. Management
1. Behavioral therapy
- Patient counseling, Stoppage of habit
2. Medicinal therapy
-Hyaluronidase: Topically, shown to improve symptoms more quickly than steroids alone
- Mild cases – intralesional inj. Dexamethasone 4 mg to reduce symptoms & surgical splitting /
excision of fibrous bands
- Recent study – intralesional inj. of gamma interferon 3 times a week, improves mouth opening
significantly

51. Emerging Trends
HPV 16 and 18 : Cervical Carcinoma (90%)
Oncogenes
E6 and E7 (Tumor Supressor Proteins)
Degradation
(-) Apoptotic pathway in these cells
Overproliferation

52. OPPORTUNITIES & BARRIERS TO PROGRESS
 Validating Histopathological criteria/ biomarkers
 Identifying C/F of premalignancy that predict higher probability of malignant change
 Clarifying premalignant risk of lichen planus
 Comparing efficacy of conventional scalpel excision with laser excision for control of
oral leukoplakias
 Identifying an accurate biomarker for premalignant state would aid in diagnosis

53. CONCLUSION
Patient presenting with Potentially malignant disorders should undergo a careful examination to
identify any causative factors, which are best eliminated at the first stage of the treatment.
However, many patients may not have any obvious causative factor. A biopsy of the lesion is
necessary to demonstrate the histological features of the lesion and detect any existing invasive
carcinoma. Frequent monitoring of histopathological changes is essential to obtain an accurate
assessment of histological activity of the lesion and to try to predict its future behavior. The
subsequent management of the patient depends on how “high risk” the lesion is.

54. REFERENCES:
 Textbook of Oral Pathology, Shafers, 1st edition.
Dr. R.V. Subramanyam. Classification of oral lesions.
 Neville BW et al. Oral cancer and Precancerous lesions. CA Cancer J Clin 2002;52:195-
215.
 Carnelio S, Rodrigues GS et al. A Brief Review of Common Oral Premalignant Lesions
with Emphasis on Their Management and Cancer Prevention. Indian J Surg (July–August
2011); 73(4):256–261.
 Yardimci G, Kutlubay Z et al. Precancerous lesions of oral mucosa. World J Clin Cases
2014 December 16; 2(12): 866-872.
 Nourelahi M, Roshannia B et al. The relation between periodontal diseases and
Neoplasms of the oral cavity: A Review article. Middle East J Rehabil Health. 2016
October; 3(4):e39234.