Download - OSMF (2)
RED & WHITE
LESIONS(PART III)
CONTENTS
• ORAL SUBMUCOUS FIBROSIS• CLASSIFICATION OF RED LESIONS• ERYTHROPLAKIA
ORAL SUBMUCOUS FIBROSIS
• Schwartz In 1952, First described OSMF as a fibrosing condition – ‘Atrophica Idiopathica Tropica Mucosae Oris’
• Joshi In 1953, coined term OSMF, implying to its histological nature
• Sui P In 1954, termed it ‘Idiopathic Scleroderma Of The Mouth’
• Paymaster In 1956 described it as a Precancerous Condition.
• The term derives from: oral (meaning mouth), submucosal (meaning below the mucosa of mouth), and fibrosis (meaning hardening and scarring) (Aziz, 1997)
DEFINITION BY PINDBORG J.J & SIRSAT S.M (1966) STATES-
“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”.
CLINICAL FEATURES
AGE• Range wide & regional; even prevalent among
teenagers in India. Ranges from 11-60 years (Ahmed, 2006; Aziz, 1997)
SEX• From 0.2-2.3% in males to 1.2-4.57% in females in
Indian communities (Aziz, 1997). RACE• Indian subcontinent, in Indian immigrants to other
countries & among Asians & Pacific Islanders (Cox, 1997).
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 , at rate of 7.6% (Aziz, 1997).
PATHOGENESIS
• Areca alkaloids causing fibroblast proliferation and increased collagen synthesis
• Stabilization of collagen structure by tannins - by inhibiting collagenases - more resistant collagen molecules • Copper in nut and fibrosis• Upregulation of cyclo-oxygenase (COX-2)• Fibrogenic cytokines - endothelin & TGF, proinflammatory cytokines
& anti fibrotic IFN gamma.
• Inhibition of collagen phagocytosis• Stabilization of extracellular matrix -disruption of balance of MMP’s & TIMP• Nutritional deficiencies -Iron deficiency -Folic acid deficiency : increased premitotic
phase of cells & delayed cell turnover - Vitamin A & beta carotene -Proteins
• Ingestion of chilies • Genetic - HLA-A10, HLA-B7, HLA-DR3• Immunologic processes - PGE2 induced by areca nut -potent immunosupressor, induces CD4+ helper cells to synthesize immunosuppressive cytokines & inhibit CMI -Decreased CD4:CD8 ratio
OSF AS AN AUTOIMMUNE DISORDER
Reasons for investigating autoimmune basis:- 1) slight female predilection 2) occurrence in middle age 3) the presence of circulating immune complexes, 4) their immunoglobulin contents and 5) detection of various autoantibodies in pt’s sera
ORAL MUCOSA SUSCEPTIBILITY DUE TO DEFICENCY BETEL QUID
CONSTANT IRRITATION
CHRONIC INFLAMMATION
ACTIVATED T-CELL & MACROPHAGES
CYTOKINES – IL-6, TNF, IFN GROWTH FACTOR – TGF-ß
INITIAL EVENTS IN THE DISEASE PROCESS
COLLAGEN PRODUCTION PATHWAY
Three events: 1) Activation of procollagen genes
2) Elevation of procollagen proteinases levels
3) Upregulation of lysyl oxidase (LOX) activity
TGF-ß
PNP Procollagen gene PCP activation ProLOX LOX Increased procollagen
Increased collagen(soluble) LOX Increased collagen(insoluble) INCREASE IN COLLAGEN PRODUCTION
COLLAGEN DEGRADATION PATHWAY
Two main events:-
1) Activation of tissue inhibitor of MMP gene
(TIMP)
2) Activation of plasminogen activator inhibitor
(PAI) gene
TGF-ßActivation of TIMP gene Activation of PAI gene Increased TIMP’s Increase PAI
Inhibits activated Plasminogen Plasmin collagenase Procollagenase Collagenase
Decrease in collagenase activity DECREASE IN COLLAGEN DEGRADATION
OVERALL EFFECT OF ACTIVATED TGF-ß PATHWAY
Increase in collagen Decrease in collagen
production production Increased collagen (cross linking of insoluble collagen) Fibrosis
ORAL SUBMUCOUS FIBROSIS
MALIGNANT TRANSFORMATION
• Malignant transformation rate was found to be 7–13%.
Dense fibrosis & less vascularity of corium +altered cytokine activity unique environment for carcinogens from tobacco & areca nut to act on epithelium.
• PAYMASTER in 1957, first to consider OSF as precancerous condition.
• PINDBORG in 1972 suggested 5 criteria:1.high occurrence of OSF in cancer patients2.high incidence of cancer in OSF patients3.histological diagnosis of cancer without clinical
suspicion in OSF cases4.high frequency of epithelial dysplasia5.high prevalence of leukoplakia among OSF cases
SYMPTOMS OF OSF (Murti, 1992; Cox, 1996)
• Progressive inability to open the mouth (trismus) due to oral fibrosis and scarring
• Oral pain and a burning sensation upon consumption of spicy foodstuffs
• Increased salivation • Change of gustatory sensation • Hearing loss due to stenosis of eustachian tubes • Dryness of the mouth
• Nasal tonality to the voice • Dysphagia to solids (if the esophagus is
involved) • Impaired mouth movements (eg, eating,
whistling, blowing, sucking)
CHEEK FLEXIBILITY
MULTIPLE PIN POINT PETECHIAE & GENERALISED DEPAPILATION OF TONGUE IN OSMF
Oral submucousfibrosis involving the buccal mucosa with leukoplakia
Oral submucousfibrosis involving the entire anterior tongue with leukoplakia (thick arrows)
CLINICAL DIVISION OF OSF
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. – Early lesions demonstrate blanching of the oral
mucosa.
– Older lesions - vertical & circular palpable fibrous bands in buccal mucosa & around mouth opening or lips, resulting in a mottled, marble like appearance of mucosa because of vertical, thick, fibrous bands running in a blanching mucosa.
– Specific findings include the following: • Reduction of the mouth opening (trismus) • Stiff and small tongue • Blanched and leathery floor of the mouth • Fibrotic and depigmented gingiva • Rubbery soft palate with decreased mobility
• Blanched and atrophic tonsils • Shrunken budlike uvula• Sinking of the cheeks, not commensurate with age or
nutritional status
• Stage 3: Sequelae of OSF are as follows: – Leukoplakia is precancerous and 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.
LAI D R (1995) : Divided population based on interincisal distance
Group A : Mouth opening greater than 35mm Group B : Mouth Opening Between 30-35 mm Group C : Mouth Opening Between 20-30 mm Group D: Mouth opening less than 20 mm
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
DIFFERENTIAL DIAGNOSIS
• Amyloidosis• Generalized fibromatosis• Scleroderma• Oral lichen planus• Anemia
LABORATORY STUDIES
• No specific laboratory tests available. Some OSF studies report following findings: – Decreased hemoglobin levels – Decreased iron levels – Decreased protein levels – Increased erythrocyte sedimentation rate – Decreased vitamin B complex levels
HISTOPATHOLOGY [PINDBORG J J & SIRSAT S M (1996)]
VERY EARLY STAGE – - fine fibrillar collagen dispersed with marked oedema.- many plump, young fibroblast with abundant cytoplasm.- dilated & congested vessels- inflammatory cells- PMN’S, eosinophils EARLY STAGE – - juxta epithelial hyalinization- collagen – thick, separate bundles- moderate, plump young fibroblasts- dilated & congested vessel- inflammatory cells – lymphocytes, eosinophils, plasma cells.
MODERATELY ADVANCED STAGE – - collagen moderately hyalinized- thickened collagen bundles separated by residual edema-fibroblastic response- less- vessels- normal or compressed- inflammatory cells- lymphocytes & plasma cells
ADVANCED STAGE – -collagen completely hyalinized- smooth sheets, no edema- no fibroblasts- vessels- obliterated or narrowed- inflammatory cells- lymphocytes & plasma cells.
MANAGEMENT
1. BEHAVIORAL THERAPY - Patient counseling, stoppage of habit
2. MEDICINAL THERAPY -Supportive treatment -Vitamin supplements -Steroids a) Local b) Systemic
-Placental extracts - Hyaluronidase - Antioxidants
3. SURGICAL THERAPY - Conventional - Laser - Cryosurgery - Diathermy - Physiotherapy
THERAPEUTIC INTERVENTION
CLASSIFICATION OF RED LESIONS
INFLAMMATORY• Red lesion due to
trauma• Red lesion due to
Infection Pharyngitis
Scarlet fever Chronic erythematous
candidiasis
Red lesion due to Immunological reaction Allergic Mucositis Lupus Erythematosus Sjogren Syndrome Erosive Lichen planus Desquamative gingivitis Erythema multiforme
NON INFLAMMATORY– Red lesion due to Vascular defect
1)Purpura due to thrombocytopenia 2)Echymosis due to clotting factor deficiency 3)Hereditary Haemorrhagic Telangiectasia 4)Haematoma
5)Port wine naevus– Red lesion due to Unknown cause
Erythroplakia Geographic tongue– Red lesion due to Nutritional disorder
Vitamin def. Glossitis/Mucositis Iron def. Glossitis/Mucositis
ERYTHROPLAKIA
CLASSIFICATIONA) Clinical variants -Homogenous erythroplakia -Erythroplakia interspersed with patches of leukoplakia -Granular or Speckled leukoplakiaB) Microscopic variations 1) Neoplastic -Squamous carcinoma -Carcinoma in situ
2) Inflammatory -Candida albicans infections -Tuberculosis -Histoplasmosis -Miscellaneous
DEFINITION
WHO DEFINITION: “Any lesion of the oral mucosa that
presents as bright red velvety plaques which cannot be characterized clinically or pathologically as any other recognizable condition”
• Etiology: same as oral SCC & 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.
CLINICAL APPEARANCE
ERYTHROLEUKOPLAKIA
Malignant transformation
• Highest risk-14-50%• Based on the fact that on histology 80-90%
of cases present as- -CIS -Severe epithelial dysplasia -Microinvasive carcinoma
DIFFERENTIAL DIAGNOSIS
• Atrophic candidiasis• Atrophic lichen planus• Lupus erythematosus • Nutritional deficiency• Allergic mucosal reaction• Geographic tongue
MANAGEMENT
• Biopsy should be performed• Treatment guided by histopathologic
diagnosis• Recurrence , multifocality common• Careful long term follow up
REFERENCES
• BURKET’S ORAL MEDICINE DIAGNOSIS & TREATMENT – 9TH & 10TH EDITION
• TEXTBOOK OF ORAL PATHOLOGY –SHAFER 5TH EDITION• ORAL SUBMUCOUS FIBROSIS -Critical reviews in oral
medicine and biology, 6(2);147-160,1995.• A MODIFIED CLASSIFICATION & STAGING SYSTEM FOR
ORAL SUBMUCOUS FIBROSIS- Oral oncology Vol36; 264-266,2000.
• ORAL SUBMUCOUS FIBROSIS :A CLINICOPATHOLOGIC REVIEW. Oral oncology vol 33,no.5,291-301
THANK YOU
8. APOPTOSIS & OSMF - AS FIBROSIS INCREASES, MEAN APOPTOTIC BODIES ALSO INCREASE - GENETIC PREDISPOSITION RENDERS MUCOSA SUSCEPTIBLE TO CHRONIC INFLAMMATORY CHANGES
INFLAMMATORY CELLS
CYTOKINES / CHEMICAL MEDIATORS
INDIRECT EFFECTS DIRECT EFFECTS
FIBROBLAST CELL DEATH OF PROLIFERATION SURROUNDING TISSUE
FIBROSIS
ATROPHIC EPITHELIUM ATROPHIC EPITHELIUM
TREATMENT• 1. Reduce / stop habit• 2. i) Local treatment• a) Vitamin A• b) Local corticosteroid ointment• ii) Systemic Therapy• a) Intra lesional injection • b) Placentrix• Corticosteriods• a) Hydrocortisone• b) Dexamethasone• c) Betamethasone1. Collagenases • 7. Diathermy • 1. Hyalorunic acid • Fibrinolytic agent
CLINICAL PRESENTATION
1. GEOGRAPHIC DISTRIBUTION:• ETHNIC BASIS – ASIAN – INDIANS – SOUTHERN STATES• CHINA, MALAYSIA, SRI LANKA, S. AFRICA, UK, CANADA
2. AGE PREDILICTION:• 2nd & 3rd DECADE OF LIFE• AVGERAGE - 53.6yrs IN MEN & 37.7yrs IN WOMEN
3. SEX PREDILICTION:• MALE PREDOMINANCE BUT WOMEN AFFECTED EQUALLY
4. CLINICAL SYMPTOMS:• PRODROMAL SYMPTOMS:
- ONSET INSIDIOUS, 2-5yrs DURATION
- NON SPECIFC SIGNS & SYMPTOMS
- COMMON FEATURES: BURNING SENSATION, BLISTER, ULCERATION, RECURRENT STOMATITIS, EXCESSIVE SALIVATION, DEFECTIVE
GUSTATORY SENSATION
- VESICLES : PAINFUL, RUPTURE – SUPERFICIAL ULCERATION
- FOCAL VASCULAR DILATATIONS MANIFEST CLINICALLY AS PETECHIAE ON TONGUE, LABIAL & BUCCAL MUCOSA
• LATE SYMPTOMS:
- STIFFENING OF CERTAIN AREAS OF THE MUCOSA
- DIFFICULTY IN MOUTH OPENING & SWALLOWING
- INABILITY TO WHISTLE OR BLOW
- REFERRED PAIN IN THE EAR WITH LOSS OF AUDITORY ACUITY - NASAL VOICE
- ADVANCED CASES: JAWS INSEPARABLE : Bu MUCOSA ULCERATED SECONDARY TO ISCHEMIA & CONSTANT IRRITATION VIA TEETH
5. CLINICAL SIGNS:
• ORAL MUCOSA:
- BLANCHED, OPAQUE, FIBROUS BANDS, EXTENT VARIES FROM SMALL FOCAL PALE STREAKED OR PUCKERED AREAS TO EXTENSIVE DIFFUSE
WHITE INDURATED AREAS
• PALATE & FAUCIAL PILLARS:
- OPAQUE, SCAR LIKE FORMATION IN LATERAL PART OF PALATE
- FIBROUS BANDS RADIATE FROM PTERYGOMANDIBULAR RAPHAE - SEAR LIKE APPEARANCE
- LATER, UVULA SHRINKS, APPEARS AS FIBROUS BUD
- ENTIRE ISTHMUS FAUCIUM & MOBILITY OF PALATE REDUCED
- FAUCIAL PILLARS - THICK, SHORT, HARD
- FIBROSIS SPREADS TO PHARYNX & PYRIFORM FOSSA
• BUCCAL MUCOSA & LIPS:
- MUCOSA: PALE & FIRMLY ATTACHED TO UNDERLYING STRUCTURES. VERTICAL FIBROUS BANDS SEEN
- LIPS: CIRCULAR BANDS AROUND RIMA ORIS- ATROPHY OF VERMILION BORDER- DARK BROWN BILATERAL HYPERPIGMENTATION AROUND COMISSURES
• TONGUE:
- IMPAIRED MOVEMENT & DIFFUSE PAPILLARY ATROPHY
• TGF – KEY REGULATOR OF ECM ASSEMBLY & REMODELLING.
• ITS ACTION ON GENES TAKES PLACE AT TRANSCRIPTIONAL LEVEL THROUGH ILL DEFINED INTRACELLULAR PATHWAYS
• MOLECULAR EVENTS THAT FOLLOW – COLLAGEN PRODUCTION PATHWAY & COLLAGEN DEGRADATION PATHWAY.
2. COLLAGEN PRODUCTION PATHWAY
• 3 EVENTS: ACTIVATION OF PROCOLLAGEN GENES
ELEVATION OF PROCOLLAGEN PROTEINASES LEVELS
UPREGULATION OF LYSYL OXIDASE (LOX) ACTIVITY
3. COLLAGEN DEGRADATION PATHWAY • TWO MAIN EVENTS - ACTIVATION OF TISSUE INHIBITOR OF MMP GENE - ACTIVATION OF PLASMINOGEN ACTIVATOR INHIBITOR GENE
ROLE OF OXIDATIVE STRESS
• CELLULAR OXIDATIVE STRESS - IRREVERSIBLE CELL DAMAGE - INFLAMMATION - FIBROSIS - CELL MODULATION
• BODY COUNTERACTS THESE STRESSES BY ANTIOXIDANTS LIKE ENZYMES AND VITAMINS
• THE ANTIOXIDANTS & FREE RADICAL SCAVENGERS DOWN REGULATE FIBROGENIC CYTOKINE GENE EXPRESSION
• IN OSF, SUPEROXIDE DISMUTASE & GLUTATHIONE PEROXIDASE LEVELS ARE REDUCED
• INFLAMMATION ---- CYTOKINES----OXYGEN REACTIVE SPECIES--- DAMAGE TISSUE ARCHITECTURE, MUTAGENIC CHANGES
In 1995 Khanna & Andrade - group classification system for surgical management of trismus:
Group I: This is earliest stage & is not associated with
mouth opening limitations. Interincisal distance >35 mm.
Group II: Patients with an interincisal distance of 26-35 mm
Group III: Moderately advanced cases. interincisal distance of 15-26 mm. Fibrotic bands are visible at soft palate & pterygomandibular raphe & anterior pillars of fauces are present.
Group IVA: Trismus is severe, with an interincisal distance < 15 mm & extensive fibrosis of all the oral mucosa.
Group IVB: Disease is most advanced, with premalignant and malignant changes throughout mucosa.