1) Premalignant lesions of the oral mucosa occur in 1.5-4.5% of the global population and account for 17-35% of new oral cancer cases, with an annual malignant transformation rate of 0.7-2.9%. 2) Common premalignant lesions include leukoplakia, erythroplakia, submucous fibrosis, and lichen planus. Leukoplakia may transform to cancer in 0.13-34% of cases depending on population. 3) Risk factors for oral premalignant lesions include smoking, smokeless tobacco, alcohol, HPV infection, and nutritional deficiencies. Early diagnosis and treatment can prevent malignant transformation

1. Pre-malignant
Lesions of Oral
Mucosa
Dr Safika Zaman
Dept of ENT and HNS
RKMSP, VIMS

2. Contents
Epidemiology
Histology of oral mucosa
Molecular basis
Pathophysiology
Aetiology
Leukoplakia
Erythroplakia
Lichen planus
Sumucosal fibrosis
Summary

3. Epidemiology
• Premalignant lesions occur in roughly between 1.5% and 4.5% of the
world's population
• Pre-malignant lesions account for 17% to 35% of all new cases of oral cavity
cancer
• Undergo malignant transformation between 0.7% and 2.9% annually.
• Premalignant Conditions of the Oral Cavity edited by Peter A. Brennan, Tom Aldridge, Raghav C. Dwivedi

4. WHO Definition
Pre-cancerous lesions
A precancerous lesion is a
morphologically altered tissue in
which oral cancer is more likely to
occur than in apparently normal
counterpart.
Leukoplakia
Erythroplakia
Submucous fibrosis
Lichen planus

5. Histology of oral mucosa
• Contains a complex
variety of tissues from the
hardest enamel to delicate
salivary gland
parenchyma.

6. Histology
• Oral surface of the lips, cheeks,
floor of the mouth and ventral
tongue are covered by a stratified
non-keratinised epithelium.
• Deep to the epithelium lies the
lamina propria where minor salivary
glands are located.
• Masticatory mucosa requires a
harder-wearing surface hence the
need for keratinised epithelium,
gingivae and palate
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7. The molecular basis of carcinogenesis
• Mutation / genetic variation
• Genetic instability
• Oncogenes and proto-oncogenes-
positively regulates a cell cycle
• Tumour suppressor genes are
negative regulators of the cell cycle
• Evasion of apoptosis
Actinic keratosis,lower lip

9. Gene Mutations
The Cancer Genome Atlas Network. Comprehensive genomic characterization of head
and neck squamous cell carcinomas. Nature. 2015;517:576–82.

10. Premalignant Conditions of the Oral Cavity
edited by Peter A. Brennan, Tom Aldridge, Raghav C. Dwivedi

11. Premalignant Conditions of the Oral Cavity
edited by Peter A. Brennan, Tom Aldridge, Raghav C. Dwivedi

12. Field Cancerization in Oral Epithelium
• Slaughter proposed in 1953 the
field cancerization process in
oral stratified squamous
epithelium, showing that
clinically normal tissue
surrounding oral squamous cell
carcinoma already harboured
histopathological changes.
• The field cancerization in oral
mucosa can be as large as 7
cm

14. Pathophysiology

15. Histopathology

16. Aetiological factors

17. High and low risk factors
Premalignant Conditions of the Oral Cavity
edited by Peter A. Brennan, Tom Aldridge, Raghav C. Dwivedi

18. Smoking
• Tobacco products may also cause
methylation of tumour suppressor
genes,
• Induction of oxidative stress, and
inflammatory reactions.
• Oral cancer cells in smokers
contain more hypomethylated and
hypermethylated genes than non-
smokers, indicating a change in the
normal methylation pattern.

19. Betel Quid
• Betel quid has two basic
carcinogenic actions in the oral
mucosa.
• First is the cytotoxic and mutagenic
effect of its components
(arecoline,alkaloids and
polyphenols) on epithelial cells.
• Second is associated with induced
fibrosis, which reduces the oxygen
supply to the epithelial cells.
Premalignant Conditions of the Oral Cavity
edited by Peter A. Brennan, Tom Aldridge, Raghav C. Dwivedi

20. Alcohol
• In chronic alcohol consumption, the CYP2E1
enzyme is utilized and results in
acetaldehyde formation in peroxisomes.
• Acetaldehydes are very toxic and affect DNA
synthesis and repair.
• Acetaldehyde can bind and form Products
with proteins, lipids, and DNA, which impairs
their functions
• Increased oxidative stress, release of
inflammatory cytokines,
• Impairment of retinoid metabolism, and
inhibition of DNA methylation.

21. HPV
• E6 and E7 HPV proteins function as the
dominant onco-proteins of high-risk
HPVs, and they inactivate the tumour
suppressor proteins p53 and pRB,
• TP53 is the “guardian of the genome”,
and its malfunction in most cancers is
the result of DNA mutation. In HPV-
associated cancers, the E6 onco-protein
degrades the wild-type p53 protein and
leads to chromosomal instability

23. Oral leukoplakia
• World Health Organization (WHO) first
defined oral leukoplakia as
• “a white patch or plaque that cannot be
characterized clinically or pathologically
as any other disease”.
• The term leukoplakia be used in a
descriptive clinical sense only with no
histologic association.

24. Differentials of leukoplakia

25. Premalignant Conditions of the Oral Cavity
edited by Peter A. Brennan, Tom Aldridge, Raghav C. Dwivedi

26. Oral leukoplakia staging system(van der
wall et all)

27. Malignant transformation of leukoplakia
• Malignant transformation of oral leukoplakia
varies from 0.13% to 34% in different
populations and geographic areas.
• Dysplastic lesions are about 15 times more
likely to undergo a malignant transformation
than non-dysplastic ones
Warnakulasuriya S, Ariyawardana A. Malignant transformation of oral leukoplakia: a systematic
review of observational studies. J Oral Pathol Med. 2016;45:155–66.

28. Diagnosis of leukoplakia
Elimination of
possible
causes
Biopsy Adjunctive
techniques
Wait for 2-4
weeks
Single deep
biopsy from
edge
Brush biopsy
Toluidine blue

30. Treatment
Preventive Conservative Surgical
Cessation of tobacco ,
alcohol,
Public education
Good oral hygiene,
Balanced diet
vitamin A and retinoids,
systemic
beta carotene,
lycopene, ketorolac
Complete excision
LASER ablation
Life time follow up

31. Erythroplakia and Erythroleucoplakia
• Bouquot in 1994 updated the definition for erythroplakia as “a chronic
red mucosal macule which cannot be given another specific diagnostic
name and cannot be attributed to traumatic, vascular, or inflammatory
causes.
• Erythroplakia should not display histopathologic features of any other
recognizable condition and is a diagnosis of exclusion.

32. Variations

34. Differential diagnosis of a red oral mucosal
lesion

36. Management principle
• Reducing risk/exposure factors.
• Visual examination by trained health care workers
• Biopsy/complete removal of the suspicious lesion.
• Follow-up by continuous monitoring may be lifetime.
• Chemo-prevention : Retinoids, COX inhibitors, green tea polyphenols,
p-53-targeted agents like ONYX-015, thiazolidinediones ,EFGR
inhibitors, blue-green microalgae spirulina, vitamin E, etc. – limited
success

37. Oral Lichen Planus and the Lichenoid
Group of Diseases
• Chronic auto-immunologic and inflammatory muco-cutaneous disorder
that may involve the skin, nails, hair, and mucosa, including the oral
cavity, genital, ocular, otic, esophageal, and, less commonly, bladder,
nasal, laryngeal, and anal mucosa.
• Affect approximately 0.5–2% of the general population.
• Antigenic challenges in the skin and mucosa in a genetically
predisposed patient may represent the initial event to the development
of the disease
• OLP is typically characterized by episodes of remission and
recurrence.

38. Clinical presentation
Premalignant Conditions of the Oral Cavity
edited by Peter A. Brennan, Tom Aldridge, Raghav C. Dwivedi

39. Microscopic features
Epithelium demonstrate areas of hyperkeratosis and atrophy.
Elongated epithelial projections (saw-tooth ridges).
Superficial band-like inflammatory infiltrate predominantly composed of T
lymphocytes and the liquefactive destruction of the epithelial basal layer.
Mucositis and the presence of degenerated keratinocytes (Civatte
bodies).
A narrow, eosinophilic, and PAS-positive zone in the basal membrane.

40. Cont..
Epithelium with a band-like inflammatory infiltrate

41. Associated systemic disease with LP
• Hypertension
• Diabetes,
• Gastrointestinal peptic disease,
• Hepatic diseases,

42. Management
Therapeutic management of this disease is based on the use of
immunomodulatory drugs

43. Management
Lavanya, Nagarajan &
Palani, Jayanthi & Rao,
Umadevi &
Ranganathan, Kannan.
(2011). Oral lichen
planus: An update on
pathogenesis and
treatment. Journal of oral
and maxillofacial
pathology : JOMFP. 15.
127-32. 10.4103/0973-
029X.84474.

44. Oral Submucous Fibrosis
• Chronic, insidious, progressive
oral mucosal disease affecting
the oral cavity, pharynx, and
upper digestive tract, causing
stiffness of the oral mucosa,
restricted mouth opening, and
impaired ability to eat, speak,
or care for oral hygiene.

45. Geographical distribution
Oral Submucous Fibrosis
Saman Warnakulasuriya, W. M. Tilakaratne & Alexander Kerr
Chapter
First Online: 09 December 2016

46. Distribution in Indian population
• Oral submucous fibrosis: A
contemporary narrative review with a
proposed inter-professional approach
for an early diagnosis and clinical
managementJanuary 2020Journal of
otolaryngology - head & neck surgery =
Le Journal d'oto-rhino-laryngologie et
de chirurgie cervico-faciale

47. Pathogenesis
Rai A, Siddiqui M, Parveen
S, Parveen S, Rasheed A,
Ali S. Molecular
Pathogenesis of Oral
Submucous Fibrosis: A
Critical Appraisal. Biomed
Pharmacol J 2019;12(4).

48. Classification ( Passi D et al,2017)

49. Management
• Preventive: discontinuation of habit and counselling
• Medical treatment
• Nutritional supplementation
• Surgical management
• Physiotherapy

50. Surgical options for OSMF
• Local flaps – Intraoral flap –
• - extra oral flap – nasolaial , temporalis
• Distant flaps – Radial fore arm free flaps / Thigh flap
• Grafts – split skin graft , collagen membrane , artificial dermis, human
placenta grafts
• Other – coronoidectomies , myomectomies
• Surgical Interventions in Oral Submucous Fibrosis: A Systematic Analysis of the Literature Venkatesh V. Kamath

52. Management
algorithm

54. Thank you