Oral submucous fibrosis

1. CHITWAN MEDICAL COLLEGE AND TEACHING HOSPITAL
DEPARTMENT OF ORAL AND MAXILLOFACIAL
PATHOLOGY,MICROBIOLOGY AND FORENSIC ODONTOLOGY
ORAL SUBMUCOUS FIBROSIS
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Under Guidance of:
Dr. Neha Mishra
Assistant Professor
College Of Dental Sciences,CMC

2. Contents
 INTRODUCTION
 DEFINITION
 HISTORY
 EPIDEMIOLOGY
 ETIOLOGY
 ETIOPATHOGENESIS
 CLASSIFICATION
 HISTOPATHOLOGY
 CLINICAL FEATURES
 INVESTIGATIONS
 DIFFERENTIAL DIAGNOSIS
 TREATMENT
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3. INTRODUCTION
 Oral mucous membrane is a unique area of the body, which is
continuously exposed to various kinds of stresses such as heat,
cold, microorganisms, chemicals and mechanical irritations.
 In response to these stresses, both epithelium and connective
tissue layers of the oral mucosa exhibit acute and chronic reactive
changes
 Oral Submucous Fibrosis(OSMF) is a chronic, progressive,
scarring disease that predominantly affects people of South-East
Asian origin.
 OSMF is characterized by deposition of dense collagen in the
connective tissue
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4. DEFINITION
 (Schwarts 1952)- ‘an insidious chronic disease affecting any
part of the oral cavity and sometimes pharynx , Although
occasionally preceded by / or associated with vesicle
formation, it is always associated with juxtaepithelial
inflammatory reaction followed by fibroblastic change of the
lamina propria with epithelial atrophy leading to stiffness of
the oral mucosa and causing trismus and inability to eat.’
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5. HISTORY
 Sushrutha in 600 B. C described a condition similar to OSMF as
“Vidari”
 First described by Schwartz(1952) while examining five Indian
women from Kenya as ‘atrophia idiopathica mucosae oris’
 In 1953,Joshi from Bombay redesignated condition as “Oral
Submucous Fibrosis”, implying predominantly its histologic
features.
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6. EPIDEMIOLOGY
 Higher in people from certain parts of the world including South-
East Asia, South Africa and the Middle East :India, Bangladesh,
Nepal, Burma, Veitnam, Taiwan, Malaysia, China, Singapore &
South Africa etc. Also found in Indians and Pakistanis living in
UK.
 More prevalent among younger individuals(15-35yrs)
 Prevalence in Indian population is 5% for women & 2% for men.
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7. ETIOLOGY
 Multifactorial
 Local factors
-Habitual Chewing of Arecanut(Pan Masala),Tobacco
-Excessive consumption of Red Chillies
-Oral habits
 Systemic Factors
- Deficiency of iron and vitamin B Complex
- Immunological factors
- Genetic susceptibility
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8. ARECANUT
 Four alkaloids- Arecoline, Arecaidine, Guvacine,
Guvacoline. Arecoline – main agent. (Tilakaratne 2006)
 Flavanoid components- tannins and catechins
 Fibroblastic proliferation and inceased collagen formation
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9. ROLE OF ARECA NUT
Chronic Placement of betel quid(areca nut)
Arecoline
Fibrosis
Rigidity and limited mouth opening
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10. CHILLIES
 Capsaicin, an active principle, mild irritant, which brings
about epithelial and connective tissue changes in OSMF
patients
 Elastic degradation of collagen and ultrastructurally, partial or
complete degeneration of collagen into elastin-like
filaments, sheets or dense amorphous material (Sirsat &
Khanolkar 1960).
 Mutogenic and enhance the tumorigenicity of tobacco in
experimental animals
 Increases the risk of cancers in the upper aero digestive tract
in a dose- dependent manner (Notani 1992)
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11. NUTRITIONAL DEFICIENCIES
 May be secondary
 OSMF patients cannot tolerate spicy food & the opening of
the mouth in OSF patients becomes smaller which may affect
normal food intake and lead to nutritional deficiencies
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12. GENETIC SUSCEPTIBILITY
 Raised frequencies of HLA-A10, -B7 and –DR3 are found in
OSMF patients compared to normal subjects
 Further HLA-typing done by the use of the polymerase
chain reaction (PCR) also demonstrates significantly
increased frequencies of HLA-A24, DRBI-11 and DRB3-
0202/3 antigens in 21 OSMF patients when compared with
the English controls (Saeed et al,1997)
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18. ETIOPATHOGENESIS
Clonal selection of fibroblasts with a high amount of
collagen production during the long term exposure to
areca quid ingredients
Stimulation of fibroblast proliferation and collagen
synthesis by arecanut alkaloids
By fibrogenic cytokines secreted by activated macrophages
and T lymphocytes in the OSMF tissue
By decreased secretion of collagenase
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19.  Deficiency in collagen phagocytosis by OSMF fibroblasts
 By production of collagen with a more stable structure (collagen
type I trimer) by OSMF fibroblast
 By stabilization of collagen by catechin and tannins from the
arecanut
 By an increase in collagen cross-linkage as caused by upregulation
of lysyl oxidase by OSMF fibroblast
 Genetic susceptibility involving the HLA-A10 , -B7 and -DR3
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21. STAGING / GRADING
 Based on Clinical Features
 Pindborg JJ. 1989
 Lai DR et al. 1995
 Ragnathan K et al. 2001
 Rajendra R 2003
 Kumar k. et al. 2007 9/1/2020
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22.  Based on Histopathological classification
 Pindborg JJ. And Sirsat S.M. 1966
 Utsonumiya H. et al. 2005
 Kumar K 2007
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23. Pindborg JJ. 1989
 Stage I / Early OSMF
 Stage II /Moderate OSMF
 Stage III / Severe OSMF
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24.  Stage I / Early OSMF
 Stomatitis and vesiculation:
Erythematous mucosa, vesicles , mucosal ulcers ,
melanotic mucosal pigmentation and mucosal petechiae
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26.  Stage II / Moderate OSMF
 Fibrosis in healing vesicles and ulcers
 Early lesion : blanching
 Palpable bands
 Mottled marble like appearance
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27. SPECIAL FINDINGS
 Trismus
 Stiff small tongue
 Blanch and leathery floor of mouth
 Fibrotic and depigmented gingiva
 Blanched atropic tonsils
 Shrunked bud like Uvula ( Hockey stick appearance)
 Shrinking of cheeks
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32.  Stage III / Severe OSMF
 Sequelae of OSMF
 Leukoplakia and Erythroplakia in 25% cases
 Speech and hearing deficit
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33. Lai DR et al-1995
(On the basis of interincisal distance)
 Group A - Mouth opening >35 mm
 Group B - Mouth opening between 30-35 mm
 Group C - Mouth opening between 20-30 mm
 Group D – Mouth opening <20 mm
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34. Rangnathan K et al. 2001
 Group I - Only symptoms with no demonstrable restricted
opening
 Group II - Limited mouth opening 20 mm or above
 Group III - Mouth opening less than 20 mm
 Group IV - Limited of mouth opening ,Precancerous lesions
seen through the mucosa
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35. Rajendran et al. 2003
 Early
 Advanced
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36.  Early
 Burning sensation
 Blisters especially on palate
 Excessive salivation
 Defective gustatory sensation
 Xerostomia
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37.  Advanced
 Blanced opaque mucosa
 Fibrous band in buccal mucosa running vertically
 Palate and faucial pillars are first involved
 Gradual impairment of tongue movement
 Difficulty in mouth opening
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39. BASED ON HISTOPATHOLOGICAL
FEATURES
 Pindborg J.J and Sirsat SM 1966
 Utsonumiya H. et al.
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40. Pindborg J.J and Sirsat SM 1966
 Very early stage
 Early stage
 Moderately advanced stage
 Advanced stage
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41.  Very early stage
 Fine fibrillar collagen with marked edema , blood vessels
(dilated and congested)
 Large aggregate of plump , young fibroblasts with abundant
cytoplasm
 Inflammatory cells consist of PMNLs with few eosinophils ,
normal epithelium with hyperplastic epithelium
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42.  Early stage
 Juxta epithelial hyalinization
 Thickened bundle of collagen
 Plump young fibroblast
 Dilated and congested blood vessels
 Flattening and shortening of rete pegs
 Inflammatory cells – mononuclear lymphocytes , eosinophils
and occasional plasma cells
 Varrying degree of keratinization
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43.  Moderately advanced stage
 Juxta epithelial hyalinization
 Fairly describable thickened collagen bundle
 Constricted blood vessels and reduced vascularity
 Fibroblast with scanty cytoplasm and elongated spindle
shaped nuclear and atrophic epithelium with total loss of rete
pegs
 Inflammatory exudates with lymphocytes and plasma cells
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44.  Advanced stage
 Completely hyalinized collagen
 Smooth sheet with no separate bundle of collagen
 Edema absent
 Hyalinized area devoid of fibroblast
 Completely obliterated or narrowed blood vessels
 Lymphocytes and plasma cells present
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45. Utsonumiya H. et al.
Divided OSMF based on the concept of Pindborg J.J. and Sirsat
S.M and modified it as:
 Early stage
 Intermediate stage
 Advanced stage
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46. Early Stage
 Large no of lymphocytes in sub epithelial and connective
tissue zones along with myxedemtousnchanges
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47.  Intermediate stage.
 Granulation changes close to muscle layer
 Hyalinization in sub epithelial zone where blood vessels are
compressed by fibrous bundles
 Reduced inflammatory cells in sub epithelial layer
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48.  Advanced Stage
 Inflammatory cells hardly seen
 Less no of blood vessels in sub epithelial zone
 Marked fibrosis areas with hyaline changes extending from
sub epithelial to superficial muscle
 Atrophic and degenerative changes in muscle fibres
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49. Histopathology
 Epithelial changes
 Histological findings in OSMF cases were found to vary
depending on the clinical severity of the cases and the site of
biopsy
 The observed epithelial changes are secondary to changes in
connective tissue
 The findings range from normal to atrophic and hyperplastic
epithelium (Sirsat & Khanolkar, 1957)
 Pindborg and Sirsat (1966) observed marked changes in the
form of atrophy of epithelium with loss of rete pegs in 90% of
the cases as compared to normal oral mucosa
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50.  The atrophic epithelium also exhibits intracellular edema,
signet cells and epithelial atypia (focal dysplasia).
 Epithelial keratinization, especially the tendency of atrophic
and hyperplastic epithelium to show keratinization was higher
when compared to normal.
 Increased mitotic activities were evident in a small number of
cases
 Classical oral submucous fibrosis (OSMF) showing thin
atrophic epithelium
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52.  Connective tissue changes
 Stromal blood vessels are dilated and congested
 Underlying connective tissue stroma in advanced stage shows
homogenization and hyalinization of collagen fibers
 Decreases no of fibroblastic cells and narrowing of blood
vessels due to perivascular fibrois
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53. Early OSMF
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CHRONIC INFLAMMATORY
CELLS
Plump fibroblast

54. Moderately Advanced OSMF
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HYALINIZED COLLAGEN
LOSS OF RETE-RIDGES

55. Advanced OSMF
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Complete Loss of rete-pegs
Signet cell
Hyalinized and
Homogenized collagen
Constricted blood vessels

56. CLINICAL FEATURES
 Fibrotic changes frequently seen in palate , labial and buccal
mucosa , retromolar area , uvula , tongue , ear etc.
 Early OSMF
 Burning sensation
 Blisters
 Ulcerations
 Excessive salivation
 Defective gustatory sensation
 Dryness of mouth
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57.  Advanced OSMF
 Blanched
 Slightly opaque White fibrous bands (vertically)
 Fixation, shortening or deviation of uvula
 Impairment of tongue movement
 Inability to blow or whistle
 Nasal voice
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58. INVESTIGATIONS
 Clinical signs & symptoms
 Biopsy
 Cheek flexibility test
 Laboratory & hematological findings
 Cytogenetics
 Ag NOR
 Immunological studies
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59. INVESTIGATIONS
 SPECIAL STAINS
 Van Gieson's Stain
 Masson's trichrome stain
 Picrosirius red
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60.  IHC MARKERS
 Heat shock proteins 47
 Cystatin c
 Survivin
 Endothelial markers- CD31, CD34, CD105
 Basic fibroblastic growth factor
 P53
 Bcl-2
 Ki-67
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61. DIFFERENTIAL DIAGNOSIS
 Scleroderma
 Fibroma
 Generalized fibromatosis
 Anemia
 Amyloidoisis
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62. TREATMENT
 Restriction of habits
 Corticosteriods
 Hyaluronidase
 Placental extract
 Nutritional support
 Physiotherapy
 Surgical treatment
 Stem cell therapy
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63. REFERENCES
 Neville B W, Damm D D, Allen C M, Bouquot J E. Oral &
maxillofacial pathology; elsevier ,noida,2nd ed.
 Rajendran R & Shivapathasundaram B. Shafer’s textbook of
oral pathology; Elsevier, Noida, 6th ed.
 Dr. Savita JK* Dr. Girish HC** Dr. Sanjay Murgod Dr. Harish
Kumar Oral Submucous Fibrosis - A review [Part 2],, , Journal
of Health Sciences and Research, Volume 1, Number 2,
August – 2010
 Dr. Savita JK* Dr. Girish HC** Dr. Sanjay Murgod Dr. Harish
Kumar Oral Submucous Fibrosis - A review [Part 2],, Journal of
Health Sciences and Research, Volume 2, Number 1, April –
2011 9/1/2020
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64. REFERENCES
 Vikas Berwal et al CLASSIFICATION SYSTEMS FOR ORAL
SUBMUCOUS FIBROSIS- FROM PAST TO PRESENT: A REVIEW,,
International Journal of Dental and Health Sciences Volume
01,Issue 06
 Rasika Priyadharshani Ekanayaka and Wanninayake
Mudiyanselage Tilakaratne Oral Submucous Fibrosis: Review
on Mechanisms of Pathogenesis and Malignant
Transformation,, J Carcinogene Mutagene S5: 002.
doi:10.4172/2157-2518.S5-002.
 R. Rajendran Oral submucous fibrosis: etiology, pathogenesis,
and future research,, Bulletin of the World Health
Organization, 1994, 72 (6): 985-996 9/1/2020
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65. REFERENCES
 Sumathi MK, Narayanan Balaji, Malathi Narasimhan ,A
prospective transmission electron microscopic study of
muscle status in oral submucous fibrosis along with
retrospective analysis of 80 cases of oral submucous fibrosis,,
Journal of Oral and Maxillofacial Pathology Vol. 16 Issue 3 Sep
- Dec 2012
 Surekha Velidandla et al , Histochemical analysis of polarizing
colors of collagen using Picrosirius Red staining in oral
submucous fibrosis,, Journal of International Oral Health 2014;
6(1):33-38
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