Oral precancerous lesions

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1. Precancerous Lesions & Conditions

2. Contents Introduction Classification of precancerous lesions & conditions Leukoplakia Erythroplakia Carcinoma in Situ Oral lichen planus Oral submucous fibrosis

3. Introduction Precancerous lesion “Morphologically altered tissue in which cancer is more likely to occur, than in its apparently normal counterpart” Precancerous condition “Generalized state of the body, which is associated with a significantly increased risk of cancer”

4. PREMALIGNANT LESIONS Leukoplakia Erythroplakia Carcinoma in situ Bowens disease Actinic keratosis & chelitis Dyskeratosis follicularis

5. PREMALIGNANT CONDITIONS Oral submucous fibrosis Oral lichen planus Syphilitic glossitis Sideropenic dysphagia Dyskeratosis congenita

6. Leukoplakia The term LEUKOPLAKIA was first coined by a Hungarian Dermatologist SCHWIMMER in 1877 Originates from Greek words – “ leucos ” - white and “ plakia ” - patch WHO 1978 “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”

7. Epidemiology 1. Prevalence Represents 85% of all oral precancers 2. Incidence 3 – 4 % of adult population 3. Age Usually in the 4 th – 6 th decades of life 4. Sex Males have the highest incidence, with the trend changing gradually

8. Classification of leukoplakia ( Axell & Pindborg et al 1983) Based on CLINICAL TYPE: Homogenous Non homogenous Based on ETIOLOGY: Tobacco associated Idiopathic Based on EXTENT: Localized Diffuse

9. 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

10. 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

11. Etiopathogenesis Tobacco – most imp offending agent Alcohol Chronic irritation Syphilis Nutritional deficiency Actinic radiation Galvanism

12. Most studies have reported mortality ratios for smokers versus never smokers of about 5:1, with several reporting ratios in excess of 10:1. Furthermore, the risk for death from oral cancer is consumption related Male cigarette smokers had a relative risk for oral cancer 27.7 times greater than that of a male never smoker These studies have found that after 3 to 5 years of smoking abstinence, oral cancer risk decreased by about 50%

13. Clinical presentation Any mucosal surface, solitary or multiple, “White patches” Varies from a non-palpable faintly translucent white area to a thick fissured, papillomatous or indurated lesion Colour varies from white, grey or yellowish white, sometimes brownish-yellow 70% in buccal mucosa, commissural areas, followed by lower lip, floor of the mouth, palate & gingiva

14. SYMPTOMS Patients may report with a feeling of increased thickness of mucosa Those with ulcerated or nodular type may complain of burning sensation Enlarged cervical lymph nodes may signal occurrence of metastasis

15. Clinical variants of leukoplakia Homogeneous/ Leukoplakia Simplex Speckled/Nodular Ulcerative

16. Histopathological features Keratinization pattern Thickness of epithelium Changes in underlying connective tissue Waldron & Shafer (1975) 80% lesions show benign hyperkeratosis with/without acanthosis & 17% represent CIS Dysplastic changes typically begin in basal & parabasal zones of epithelium

17. Five clinical criteria for high risk of malignant change The nodular type Erosion or ulceration within lesion Presence of a nodule indicates malignant potential A lesion that is hard in its periphery Lesion of anterior floor of mouth & undersurface of tongue In all cases, relative risk of malignant potential is determined by presence of epithelial dysplasia upon histological examination

18. Diferential diagnosis Leukoedema Lichen planus Chemical burn Morsicatio buccarum Lupus erythematosus White sponge nevus

19. 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

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

21. 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

22. Erythroplakia WHO 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” Reported by Querat in 1911

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

24. Etiology : Same as oral leukoplakia Age : Mainly middle age, peak 65-74 years Gender : Predilection for men Location/size - Soft palate, floor of the mouth & buccal mucosa & tongue - Typical lesion < 1.5 cm in diameter but >4cm also observed

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

26. Highest risk for malignant transformation - 14-50% Based on the fact that on histology 80-90% of cases present as- - Carcinoma In Situ - Severe epithelial dysplasia - Microinvasive carcinoma

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

28. Intraepthelial carcinoma (Ca in Situ) Arises frequently on the skin, but also on mucous membranes, including oral cavity Most severe stage of epithelial dysplasia Striking feature – dysplastic epithelial cells donot invade into connective tissue Common among elderly, with a male prdiliction Present as white plaques or ulcerated, & reddened areas Site – floor of the mouth, tongue, lips Has combined features of leuko & erythroplakia

29. Histopathology Keratin may or may not be present on the surface, but if present it is usually parakeratin Individual cell keratinization or keratin pearl formation are rare Consistent finding – loss of orientation & normal polarity of cells Treatment No accepted treatment Surgical excision, irradiation & cauterization

30. Precancerous conditions

31. Oral lichen planus Named by E Wilson ( British physician) 1896 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. Affects 0.5% to 1% of world's population Approx half patients with cutaneous LP have oral involvement Mucosal involvement, sole manifestation in up to 25% cases Peak incidence - middle age, F:M- 2:1 Characteristically associated with persistent clinical course & resistance to most conventional treatments

33. On skin- F lat-topped purple polygonal & pruritic papular rash Koebner phenomenon

34. 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

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

36. 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

37. Clinical variants Reticular (92%) Atrophic (44%) Plaque (36%) Erosive (9%) Bullous (1%)

38. Clinical features Asymptomatic Reticular – Wickham’s striae + discrete erythematous border Plaque-like – Resemble leukoplakia , common in smokers Symptomatic Atrophic – Diffuse red patch, peripheral radiating white striae Erosive – Irregular erosion covered with a pseudomembrane Bullous – Small bullae / vesicles that may rupture easily

39. 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

40. Diagnosis The characteristic clinical aspects of OLP - sufficient for correct diagnosis An oral biopsy - to confirm clinical diagnosis (exclude dysplasia & malignancy) Gingival LP more difficult to diagnose, direct immunofluorescence of perilesional mucosa for diagnosis

41. IMMUNOFLUORESCENCE Direct immunofluorescence – shaggy band of fibrinogen in the basement membrane, IgM stained cytoid bodies are also seen in dermal papilla or peribasilar area

42. 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 3mnths follow-up

43. 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

44. Lichenoid reaction The oral lichenoid eruption is a less specific entity compared with LP of the skin. Best considered as a reaction pattern of oral mucosa to a variety of insults, including OLP itself Contact allergy Trauma and Other inflammatory dermatoses (e.g. oral lupus erythematosus may look very lichenoid )

45. Oral submucous fibrosis DEFINITION - “It is a slowly progressing chronic fibrotic disease of the oral cavity & oropharynx , characterized by fibroelastic change and inflammation leading to a progressive inability to open the mouth, swallow or speak”

46. Clinical features Age Range wide & regional; even prevalent among teenagers in India Ranges from 11-60 years Sex From 0.2 - 2.3% in males to 1.2 - 4.5% in females in Indian communities Race South-East Asian countries, in Indian immigrants to other countries

47. 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 Squamous cell carcinoma 7.6%

48. Etiology Initially classified as idiopathic, now Betel quid & it’s components ( Arecoline , an active alkaloid found in betel nuts, stimulates fibroblasts to increase production of collagen by 150%) Capsaicin – Chillies ( hypersensitivity reaction) Nutritional factors Immunological factors

49. 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

50. 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)

51. Clinical stages Three stages ( Pindborg , 1989) 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  

52. Stage 3: Sequelae of OSF   Leukoplakia is found in more than 25% of individuals with OSF Speech and hearing deficits may occur because of involvement of the tongue and the eustachian tubes 

53. RANGANATHAN K (2001) 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

54. 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

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

56. 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

57. References Burket’s oral medicine diagnosis & treatment – 10 th edition Textbook of oral pathology – shafer 5 th edition Neville’s Oral and Maxillofacial Pathology - 2 nd edition Emedicine – Diseases of oral mucosa, Oral submucous fibrosis, Jan 26, 2007 Oral leukoplakia related to malignant transformation, Oral Science International 2006;45-55

58. Thank You