premalignant lesions & conditions of oral cavity

1. POTENTIALLY
MALIGNANT DISORDERS
OF THE ORAL CAVITY

2. DYSPLASIA
 Dysplasia is a term that literally means "disordered growth’’
 It is encountered principally in epithelia.
 It comprises a loss in the uniformity of the individual cells, as well as a loss in their architectural
orientation.
 The nuclear: cytoplasmic ratio increases from 1:4 to 1:1,at the expense of cytoplasmic volume.
 Dysplasia is characteristically associated with protracted chronic irritation or inflammation.
 Dysplasia is a reversible and therefore a controlled cellular alteration.
 When the underlying inciting stimulus is removed, the dysplastic alterations reverts to normal.

4. INTRODUCTION
• Precancerous lesion
• “Morphologicallyaltered tissueinwhichcancerismorelikelytooccur,thaninitsapparently
normal counterpart”.
• Precancerous condition
• “Generalized stateofthebody,whichisassociatedwitha significantlyincreasedrisk ofcancer”.

5. PREMALIGNANT LESIONS
• Leukoplakia
• Erythroplakia
• Carcinomainsitu
• Bowensdisease
• Palatalchangesassociatedwithreverse
smoking
• Candidalleukoplakia

6. PREMALIGNANT CONDITIONS
• Oralsubmucousfibrosis
• Orallichenplanus
• Syphilitic glossitis
• Sideropenicdysphagia
• Dyskeratosis congenita
• Actinicchelitis
• Discoidlupusertythematosis

7. LEUKOPLAKIA
(LEUKOKERATOSIS)
• ThetermLEUKOPLAKIA wasfirstcoinedbyaHungarian Dermatologist
SCHWIMMER in1877
• OriginatesfromGreekwords– “leucos”-whiteand“plakia”- patch
WHO 1978
• Definition:-“A whitepatchorplaqueintheoralcavitywhichcannotbescrappedoffor
strippedoffeasily& moreover
,whichcannotbecharacterizedclinicallyorpathologicallyas
anyother disease”.

8. EPIDEMIOLOGY
1. Prevalence
• Represents85%ofalloralprecancers
2. Incidence
3 – 4 %ofadultpopulation
3. Age
Usuallyinthe4th – 6thdecadesoflife
4. Gender
Maleshavethehighestincidencerate

9. CLASSIFICATION OF
LEUKOPLAKIA
(Axell & Pindborg et al 1983)
• BasedonCLINICAL TYPE:
 Homogenous
 Non homogenous
• BasedonETIOLOGY:
 T
obaccoassociated
 Idiopathic
• BasedonEXTENT:
 Localized
 Diffuse

11. BASED ON CLINICAL TYPE
 Homogeneous type which appears as a flat white lesion and non-homogeneous type which
includes speckled, nodular and verrucous leukoplakia.
 The homogeneous leukoplakia is a uniform, thin white area .
 The speckled type is a white and red lesion, with a predominantly white surface .
 Verrucous leukoplakia has an elevated, proliferative or corrugated surface appearance.
 The nodular type has small polypoid outgrowths, rounded predominantly white excrescence.
Proliferative verrucous leukoplakia-variant of verrucous leukoplakia
 First described by Hansen et al 1985.
 Proliferative verrrucous leukoplakia is characterized by an aggressive evolution, a multifocal appearance, resistance to
treatment, higher degree of recurrence and a high rate of malignant transformation

12. FORMS OF
LEUKOPLAKIA
Homogeneous

14. SPECKLED LEUKOPLAKIA

15. VERRUCOUS LEUKOPLAKIA

16. NODULAR LEUKOPLAKIA

17. PROLIFERATIVE VERRUCOUS
LEUKOPLAKIA

18. SHARP’S STAGING OF
LEUKOPLAKIA
• Stage I- Earliestlesion-faintlytranslucent, white discoloration.
• Stage II- Localizedordiffuse,slightlyelevated plaqueof irregular
outline.It isopaquewhite&mayhavea fine granulartexture
• Stage III- Thickenedwhitelesionshowingindurationand fissuring

19. MODIFIED CLASSIFICATION AND
STAGING SYSTEM FOR ORAL
LEUKOPLAKIA
Presented by VAN DER WAAL ET AL 2000.
IN WHICH THE SIZE OF LEUKOPLAKIA AND PRESENCE OR ABSENCE OF
EPITHELIAL DYSPLASIA ARE CONSIDERED.
L1: SIZE OF LEUKOPLAKIA <2CM
L2:SIZE OF LEUKOPLAKIA 2-4CM
L3:SIZE OF LEUKOPLAKIA >4CM
Lx: SIZE NOT SPECIFIED

20. P - PATHOLOGY
P0: NO EPITHELIAL DYSPLASIA
P1:DISTINCT EPITHEIAL DYSPLASIA
Px:DYSPLASIA NOT SPECIFIED IN PATHOLOGY REPORT

21. ETIOLOGY
• T
obacco– mostimpoffendingagent
• Alcohol
• Chronic irritation
• Syphilis
• Nutritional deficiency
• Actinic radiation
• Galvanism

22. PATHOGENESIS

23. CLINICAL
PRESENTATION
• Any mucosalsurface,solitaryormultiple, “White
patches”
• Variesfromanon-palpablefaintly translucentwhite
areatoathickfissured,papillomatousorindurated
lesion.
• Colourvariesfromwhite,greyoryellowish white,
sometimesbrownish-yellow.
• 70% inbuccalmucosa,commissuralareas,followedbylowerlip, floorof
themouth,palate& gingiva

24. SYMPTOMS
• Patientsmayreportwithafeelingofincreasedthicknessof mucosa
• Thosewithulceratedornodulartype maycomplainof burningsensation.
• Enlargedcervicallymphnodesmaysignaloccurrenceof metastasis.

25. • Fiveclinicalcriteriaforhighrisk ofmalignantchange
– Thenodulartype
– Erosionorulceration within lesion
– Presenceofanoduleindicatesmalignantpotential
– A lesionthatishardinitsperiphery
– Lesion of anteriorfloorofmouth& undersurfaceoftongue
• In allcases,relativerisk ofmalignantpotentialisdetermined bypresenceofepithelialdysplasia
uponhistological examination

26. HISTOPATHOLOGICAL
FEATURES

29. THE WHO (2017) MAINTAINS A 3-
TIERED GRADING SYSTEM FOR
ORAL EPITHELIAL DYSPLASIA
 Mild
 Moderate
 Severe dysplasia
1. Mild dysplasia is confined to the lower one-third of the epithelium (basal and parabasal layers)
exhibiting cytologic and/or architectural alterations.
2. Moderate dysplasia exhibits disordered maturation from the basal layer extending to the midportion
of the spinous layer (middle third).
3. Severe dysplasia/carcinoma in situ reveals abnormal maturation extending from the basal cells to a
level above the midpoint of the epithelium (upper third) to the entire thickness of the epithelium

36. DIFFERENTIAL
DIAGNOSIS
• Leukoedema
• Lichenplanus
• Chemicalburn
• Lupus erythematosus
• Whitespongenevus

37. CONSERVATIVE
MANAGEMENT
• Eliminationofetiological factor
• Restraining fromsmokingorchewingtobacco
• Toremovesharpbrokendownteeth
• Correction&replacementofoverhangingorfaultymetal restorationswithametal
bridge

38. CHEMOPREVENTION
1) Isotrenitoin/ 13- cis-retinoicacid–
2) Betacarotene-30mgTID
3) TopicalBleomycin– 0.5-1%solution/2wks
4) 5-Fluorouracil& Cisplatin

39. • SurgicalExcision:entirelesionexcisedifit is>1cminsize,
followingmodalitiesused:
a) Scalpel– surgicalstripping
b) Cryosurgery– withliquidnitrogen
c)Electrocautery
d) Laser ablation

40. ERYTHROPLAKIA
WHO DEFINITION:
“Any lesionoftheoralmucosathatpresentsasa bright red velvetypatch
orplaque,whichcannotbecharacterizedclinicallyorpathologicallyasanyother
recognizable condition”

41. CLASSIFICATION
• Clinical variants
1. Homogenouserythroplakia
2. Erythroplakiainterspersedwithpatchesofleukoplakia
3. GranularorSpecklederythroplakia

42. • Etiology:Sameasoralleukoplakia
• Age:Mainlymiddleage,peak65-74years
• Gender:Predilectionformen
• Location/size
- Softpalate,floorofthemouth&buccalmucosa& tongue
- Typicallesion< 1.5 cmindiameterbut>4cmalso observed

43. - Smoothandgranular/nodular,welldefined
- Mayhaveanirregular,red granularsurfaceinterspersed withwhite
oryellowfoci
- Softonpalpation

44. HISTOPATHOLOGICAL FEATURES
Epithelium shows lack of keratin production and is often atrophic but it may be hyperplastic .
This lack of keratinization , especially when combined with epithelial thinness , allows the
underlying microvasculature to show through , thereby causing the red colour.
The underlying connective tissue often demonstrates chronic inflammation.

45. MANAGEMENT
• Biopsyshouldbeperformed
• Treatmentguidedbyhistopathologicdiagnosis
• Recurrence, multifocality common
• Carefullongtermfollowup
• Highestrisk formalignanttransformation-14-50%

46. INTRAEPTHELIALCARCINOMA (CAIN SITU)
• Arisesfrequentlyontheskin, butalsoonmucousmembranes, includingoralcavity
• Mostseverestageofepithelial dysplasia
• Strikingfeature– dysplasticepithelialcellsdonotinvadeinto connectivetissue.
• Commonamongelderly,witha maleprediliction
• Presentaswhiteplaques,ulcerated,& reddenedareas
• Site– floorofthemouth,tongue,lips
• Has combinedfeaturesofleuko& erythroplakia

47. BOWEN DISEASE
Bowen disease is a special form of intraepithelial carcinoma occurring with some frequency
on the skin , particularly in patients who have had arsenic therapy , and is often associated
with the development of internal or extra cutaneous cancer. Bowen disease may occur in the
oral cavity.

48. • Histopathology
• Keratinmayormaynotbepresentonthesurface,butifpresentit is
usuallyparakeratin.
• Individualcell keratinizationor keratinpearl formation are rare
• Consistentfinding– loss of orientation& normalpolarityof cells
• Treatment
• No acceptedtreatment
• Surgicalexcision,irradiation& cauterization

49. NICOTINE STOMATITIS (SMOKER’S
PALATE,LEUKOKERATOSIS NICOTINA
PALATI)
 Develops in response to heat rather than the chemicals.
 “reverse smoking” habit produces a pronounced palatal keratosis.
 With long-term exposure to heat, the palatal mucosa becomes
diffusely gray or white; numerous slightly elevated papules are noted,
usually with punctate red centers. Such papules represent inflamed
minor salivary glands and their ductal orifices.

50. PALATAL CHANGES
ASSOCIATED WITH REVERSE
SMOKING
Keratosis-diffuse whitening of the entire palatal
mucosa
Excrescences-1-3 mm elevated nodules,often
with central red spots
Patches-well defined elevated white plaque
Red areas-well defined reddening of the palatal
mucosa
Ulcerated areas-crater like areas covered by
fibrin
Non-pigmented areas-areas of palatal mucosa
that are devoid of pigmentation

52. HISTOLOGY
Connective tissue showing hyperorthokeratosis,epithelial dysplasia and
inflammatory cell infiltration
Melanin deposits were notictied in the lamina propria of most of them.

53. CANDIDAL LEUKOPLAKIA

60. PALATAL ERYTHEMA
 This lesion is marked by a diffused erythematous hard palate,occasionally
extending to the soft palate
 About 90% of the cases occurs among smokers,especially bidi smokers.
 About 10% of the lesions were associated with palatal papillary hyperplasia and
25% associated with central papillary atrophy of tongue,and bilateral
commissural leukoplakias.

61. NATURAL HISTORY
Palatal erythema is caused by smoking,especially bidi smoking.
No evidence of malignant transformation

62. CENTRAL PAPILLARY
ATROPHY OF THE TONGUE
 This lesion has also been described in the literature as Median rhomboid glossitis
and localized atrophy of the tongue papillae.
 It consists of a well defined , oval , pink area in the centre of the dorsum of the
tongue devoid of lingual papillae.
 The prevalence of this lesion in general population was 1% , it was present among
2.2% bidi smokers, 1.6% cigarette smokers and 0.3% of non smokers of tobacco.
ETIOLOGY
1.CANDIDA INFECTION
2.SMOKING

64. HISTOPATHOLOGY
Presence of slight parakeratinization of the epithelial surface , long slender rete
ridges and occasional pseudo epitheliomatous hyperplasia .
Chronic inflammatory cells are seen.
Candidal hypae were observed in the superficial layers of the epithelium in
majority of cases.

65. LESIONS ASSOCIATED WITH
BETEL QUID CHEWING(PAAN
CHEWER’S LESION)
 This lesion consists of a thick brownish black encrustation on the buccal or
labial mucosa at the site of placement of betel quid.
 It is often seen among heavily addicted betel quid chewers.
 It regresses spontaneously , more frequently when the habit is discontinued.

67. PRECANCEROUS
CONDITIONS

68. ORAL SUBMUCOUS FIBROSIS
DEFINITION -
“Itisaslowlyprogressingchronicfibroticdiseaseofthe oralcavity& oropharynx,
characterizedbyfibroelastic changeandinflammationleadingtoaprogressive
inabilitytoopenthemouth,swalloworspeak”

69. CLINICAL FEATURES
Age
• Rangewide& regional;evenprevalentamongteenagersinIndia
Rangesfrom11-60years
Sex
• From0.2 -2.3% inmalesto1.2 -4.5% infemalesinIndian
communities
Race
• South-EastAsian countries

70. MORTALITY/MORBIDITY
• Highrateofmorbidity-progressive inabilitytoopenmouth,resultingin
difficultyeating& consequent nutritional deficiencies
• Significantmortalityrate-can transformintooralcancer
,particularly
Squamouscellcarcinoma7.6%

71. ETIOLOGY
• Initiallyclassifiedasidiopathic,now
• Betelquid& it’
scomponents(Arecoline,anactive alkaloidfoundinbetelnuts,stimulates
fibroblaststo increaseproductionofcollagen)
• Capsaicin– Chillies(hypersensitivityreaction)
• Nutritional factors
• Immunologicalfactors

72. PATHOGENETIC STUDIES FOR
OCCURRENCE
 Clonal selection of fibroblasts
 Stimulation of fibroblast proliferation and collagen synthesis
 Fibrogenic cytokines
 Decreased synthesis of collagenase
 Deficiency in collagen phagocytosis
 By production of collagen with a more stable structure
 By stabilization of structure by catechin and tannins.
 Increase in collagen cross linkage caused by upregulation of lysyl oxidase by
OSF fibroblasts

74. PATHOGENESIS

75. CLINICALPRESENTATION
• Commonsite– buccalmucosa,retromolararea,uvula, palate, etc
• Initially,painandaburningsensationupon consumptionofhot&spicyfoods
• Vesicle& ulcers
• Excessiveorreducedsalivation& defectivegustation
• Hearing loss

76. • Depapillation&atrophyoftongueanduvula
• Depigmented&lossofstipplingovergingiva
• Nasaltoneinthe voice
• Difficultyindeglutition
• Impairedmouthmovements(eg,eating,whistling, blowing,sucking)

77. CLINICALSTAGES
Threestages(Pindborg,1989) basedonphysicalfindings:
• Stage 1:Stomatitisincludeserythematousmucosa,vesicles, mucosalulcers,
melanoticmucosalpigmentation& mucosal petechiae
• Stage 2: Fibrosis occurs in ruptured vesicles & ulcers when they heal,
hallmarkofthisstage

78. • Stage 3:SequelaeofOSMF
– Leukoplakiaisfoundinmorethan25%of individualswithOSF
– Speechandhearingdeficitsmayoccurbecauseof involvementofthetongueandthe
eustachiantubes

79. RANGANATHAN K (2001)
• Group I :
• Group II :
• Group III:
• Group IV:
OnlySymptoms,No mouthopening
Mouthopening>20mm
Mouthopening<20mm
Limitedmouthopening,precancerous
& cancerouschangesthroughoutmucosa

80. HISTOPATHOLOGY
• Hyperkeratinized, atrophic epithelium with flattening &
shorteningofretepegs
• Finely fibrilar collagen & increased fibroblastic activity in early
stage,alsoshowingdilated& congestedbloodvessels withareasof
hemorrhage

81. • Advancedstageshows“homogenization”and
“hyalinization”ofcollagenfibers(importantfeature)
• Degenerationofmuscle fibersandchronicinflammatory cell
infiltrationintheconnectivetissue

84. BIOLOGICAL STUDIES ON INDIVIDUAL AND
TISSUES FROM OSMF
 Blood chemistry and hematological variations
o Increased ESR
o Anemia
o Eosinophilia
o Increased gammaglobulin
o Decrease in serum iron
o Increased total iron binding capacity.
 AgNOR
 Immunological studies-(HLA)A10,B7and DR3
 Cell kinetic studies-
o Proliferation rate is increased when fibroblasts exposed to alkaloids
o Role of lysyl oxidase
o Decreased collagenase activity
o Reduced phagocytosis by osf fibroblasts

85. MANAGEMENT
1.Behavioral therapy
-Patientcounseling,stoppageofhabit
2. Medicinal therapy
-Hyaluronidase:Topically,showntoimprovesymptomsmore
quicklythansteroidsalone
- Mildcases– intralesionalinjDexamethasone4 mgto reduce
symptoms& surgicalsplitting/ excisionoffibrousbands
- Recentstudy– intralesionalinjofgammainterferon3 timesa
week,improvesmouthopeningsignificantly

86. LICHEN PLANUS

87. SYPHILITIC GLOSSITIS

89. ACTINIC CHELITIS
 Actinic cheilitis is a pathological condition that
most frequently affects the vermilion border of the
lower lip.
 Histopathological changes in actinic cheilitis range
from atrophy to hyperplasia of the squamous cell
epithelium of the vermilion border, with varying
degrees of keratinisation, disordered maturation,
increased mitotic activity and cytological atypia.
 Drop-shaped epithelial pegs are often present, but
the basement membrane is intact.
 The underlying connective tissue shows basophilic
degeneration (solar elastosis).

90. DISCOID LUPUS
ERYTHEMATOSUS

91. Dyskeratosis congenita (DC) is a rare hereditary disorder characterized by bone
marrow failure

92. THANK YOU