ORAL SUBMUCOUS

FIBROSIS
PRESENTED BY: MODERATED BY:
Sanju Pandit Dr. Harleen Bali
Roll no. 25
BDS 6th batch
Kathmandu University School of
Medical Sciences, Dhulikhel, Kavre
CONTENTS:
 Introduction
 Etiology
 Pathogenesis
 Clinical Features
 Diagnosis
 Histopathological Features
 Management
INTRODUCTION
Oral Submucous fibrosis (OSMF) has traditionally
been described as “a chronic, insidious, scarring
disease of the oral cavity, often with involvement of
the pharynx and the upper esophagus”.

It is potentially malignant disorder which was 1st

described by Schwartz as “atrophica idiopathica
mucosae oris”
Definition: (Jens J. Pindborg in 1966)

It is defined as “an insidious, chronic disease that affects any

part of the oral cavity and sometimes the pharynx, although
occasionally preceded by, or associated with, the formation
of vesicles, it is always associated with a juxtaepithelial
inflammatory reaction followed by fibroelastic change of the
lamina propria and epithelial atrophy that leads to stiffness
of the oral mucosa and causes trismus and an inability to
eat”
Other terms used to describe OSMF includes:
 idiopathic scleroderma of mouth
 Juxta epithelial fibrosis
 idiopathic palatal fibrosis
 diffuse oral submucous fibrosis &
 sclerosing stomatitis
ETIOLOGY
Major etiology
Chewing of areca nut and its
derivatives like Gutka, Pan masala,
Mawa, Betel quid, sweet supari &
other formulations.
Description
Arecoline and Arecaidine
nitrosation causes DNA alkylation
with proliferation of fibroblasts and
elevated collagen synthesis.
Arecoline has capacity to modulate
matrix metalloproteinase, lysyl
oxidases and collagenases, all
affecting the metabolism of
collagen, which leads to increased
fibrosis.
Derivatives of areca nut
Contributary risk factors Description
Chewing smokeless tobacco Dip, snuff, snus & chewing tobacco have
been reported as major contributing factor.
Nutritional deficiency Deficiencies of iron, folate & vitaminB12
mucosal atrophy
Increase susceptibility of oral mucosa

Chilies Hypersensitive reactions to capsaicin may

contribute to fibrosis
Toxic levels of copper Upregulates lysyl oxidase cross linking of
collagen & elastin.
Immunological predisposition high endogenous expression of CD4 and
HLA-DR on lymphocytes and Langerhans
cells dysregulation of immune
inflammatory response
Smokeless tobacco
PATHOGENESIS
The occurrence of OSMF may be due to-
 Disruption of collagen metabolism by components of areca nut.
 High amount of collagen production by stimulation of fibroblast
proliferation (by alkaloids) during long term exposure to areca nut
ingredients.
 Fibrogenic cytokines secreted by activated macrophages & T
lymphocytes.
 Production & stabilization of collagen structure by catechin & tannins
from areca nut.
 Decrease secretion of collagenase- an enzyme that catalyzes collagen
breakdown (by flavonoids) & deficiency in collagen phagocytosis.
 Copper in areca nut upregulates lysyl oxidase (enzyme involved in
collagen cross linking) which makes collagen fibrils resistant to
degradation by collagenase.
 Oral Mucosa

Areca nut consumption + other risk factors(tobacco, nutritional

deficiencies, chilies, etc.)

Constant irritation of oral mucosa

Chronic inflammation & trauma due to irritation

Activation of T cells & macrophages

Increase in growth factors TGF-β, interleukin 6, IF-α & TNF

CLINICAL FEATURES
The onset is insidious over 2 to 5 years.
1. Prodromal symptoms (Early OSF)
Burning sensations in the mouth while consuming hot & spicy food.
Vascular dilatations manifest clinically as petechiae.
Ulcerations & generalized inflammation of the oral mucosa.
Mucosa appears pale comprising white marbling.
Appearance of vesicles in the cheeks & palate in the periods of
exacerbation, the interval between such exacerbation vary from 3
months to 1 year.
Defective gustatory sensation.
Pain during palpation in the areas where submucosal fibrotic bands
are developing is useful clinical sign.
2. Advanced OSF
 As the disease progresses, oral mucosa becomes blanched,
slight opaque & white fibrous bands occur.
 Oral mucosa is involved symmetrically.
 White fibrous bands in buccal mucosa run in vertical direction.
 Density of fibrous deposits vary:
-slight whitish area on soft palate causing no symptoms/
-dense fibrosis causing fixation, shortening or even deviation
of uvula & soft palate
 The fibrous tissue can accumulate or extend into the faucial
pillars.
 Dense fibrosis around pterygomandibular raphe causes
difficulty in mouth opening.
 On palpation circular fibrous bands can be felt around rima oris.
 There is impairment in tongue movement in the patients with
advanced OSF.
 Significant atrophy of papillae of tongue.
 With the progression of fibrosis stiffness occur in certain areas
of oral mucosa leading to:
- trismus
- inability to whistle
- difficulty in swallowing
 Fibrosis may involve the nasopharynx resulting in referred pain
to the ears and nasal voice as one of the later signs.
 More than 25% of the patients with oral
submucous fibrosis also exhibit oral leukoplakia.

 Malignant transformation of the disease has been

estimated in the range of 7% to 13%.
(-Burket’s Oral Medicine, 12th ed.)
A B C

D E F
CLINICAL GRADING OF OSF – Kerr et al.(2011)
1. Grade 1 (Mild):
Any features of the disease triad for OSF (burning
sensation, depapillation, blanching or leathery mucosa)
may be reported & inter-incisal opening >35 mm
2. Grade 2 (Moderate):
Above features of OSMF + inter-incisal limitation of
opening 20–35 mm
3. Grade 3 (Severe):
Above features of OSMF + inter-incisal opening <20
mm
4. Grade 4A:
OSMF + other potentially malignant disorder on
clinical examination
5. Grade 4B:
OSMF with any grade of oral epithelial dysplasia on
biopsy
6. Grade 5:
OSMF + oral squamous cell carcinoma (SCC)
DIAGNOSIS
The diagnosis of OSF is based on clinical examination and
patient history of betel nut chewing habit.
At least one of the following criteria should be present in
the patient to be diagnosed with OSF-
 Palpable fibrous bands
 Mucosal texture feels rough and leathery
 Blanching of the mucosa together with histopathologic features
consistent with oral submucous fibrosis (atrophic epithelium
with loss of rete ridges and juxta- epithelial hyalinization of
lamina propria).
HISTOPATHOLOGICAL FEATURES
1. Epithelial Changes:
 Epithelial hyperplasia (early) & atrophy (advanced).
 Increased tendency for keratinizing metaplasia.
 Lesions involving palate showed- orthokeratosis, those
involving buccal mucosa- parakeratosis.
 High mitotic count in parakeratotic epithelium + atrophic
epithelial changes predispose OSF to malignancy.
2. Subepithelial Changes:
On the basis of histopathological appearance of H and E
stained sections, OSF can be grouped into four clearly
definable stages:
I. very early
II. early
III. moderately advanced, and
IV. advanced
These stages are based on the following criteria taken
together:
 Amount & nature of subepithelial collagen
 Presence or absence of edema
 Physical state of mucosal collagen
 Overall fibroblastic response (number of cells and age
of individual cells)
 State of blood vessels
 Predominant cell type in inflammatory exudate
 I. Very Early
 Fine fibrillar collagen network interspersed with
marked edema
 blood vessels dilated and congested
 large aggregate of plump young fibroblasts present
with abundant cytoplasm
 inflammatory cells mainly consist of
polymorphonuclear leukocytes with few eosinophils.
 The epithelium is normal.
II. Early
 Juxta-epithelial hyalinizalion present
 collagen present as thickened but separate bundles
 blood vessels dilated and congested
 young fibroblasts seen in moderate number
 inflammatory cells mainly consist of
polymorphonuclear leukocytes with few eosinophils
and occasional plasma cells
 flattening or shortening of epithelial rete-pegs evident
with varying degree of keratinization.
III. Moderately Advanced
 Juxta-epithelial hyalinization present
 thickened collagen bundles
 residual edema
 constricted blood vessels
 mature fibroblasts with scanty cytoplasm and spindle-
shaped nuclei
 inflammatory exudates which consists of lymphocytes
and plasma cells
 muscle fibers seen with thickened and dense collagen
fibers.
IV. Advanced
 Collagen hyalinized smooth sheet
 extensive fibrosis
 obliterated the mucosal blood vessels
 absent fibroblasts within the hyalinized zones
 presence of mild to moderate atypia and extensive
degeneration of muscle fibers.
 total loss of epithelial rete pegs
MANAGEMENT
1. Prevention:
The reduction or even elimination of the habit of
areca nut chewing is an important preventive
measure.
2. Treatment:
There are different treatment strategies for OSF &
main focus should be on cessation of chewing habits.
If this is successfully implemented, early lesions may
regress and have good prognosis.
TREATMENT REGIMEN
1. Nutritional support:
Mainly for high proteins and calories, vitamin B
complex and other vitamin(A, beta carotene, C, E) &
minerals.
2. Immunomodulatory drugs:
local and systemic application of glucocorticoids
and placental extracts are commonly used.
These also prevent or suppress inflammatory
reaction, thus preventing fibrosis by decreasing
fibroblastic proliferation and deposition of collagen.
3. Physiotherapy:
This includes measures like forceful mouth opening
or heat therapy. Heat has been commonly used
and results have been described as satisfactory.
4. Local drug delivery:
Local injections of corticosteroids and placental
extracts have been tried in addition to hyaluronidase,
collagenase and similar substances.
5. Combined therapy:
With combination of peripheral vasodilators (nylidrin
hydrochloride), vitamin A, E and B complex, iodine,
placental extract, local and systemic corticosteroids
and physiotherapy claim a high success rate in OSF
management.
6. Surgical management:
i) Submucosal resection of fibrotic bands and replacement
with partial thickness skin or mucosal grafts have also been
attempted.
ii) Procedures such as bilateral temporalis myotomy.
iii) Measures such as forcing the mouth to open and cutting
fibrotic bands have resulted in more fibrosis and disability.
iv) At a retrospective glance, surgery seems to be poor option
in overall management of the disease.
CONCLUSION
 The treatment of patients with oral submucous fibrosis
depends on the degree of clinical involvement. 
  If the disease is detected at a very early stage, cessation
of the habit is sufficient.
 Most patients with oral submucous fibrosis present with
moderate-to-severe disease.
 Severe oral submucous fibrosis is irreversible.
 Moderate oral submucous fibrosis is reversible with
cessation of habit, mouth opening exercise & proper
medical treatments.
REFERENCES
 Michael, Glick. (2015). Burket's Oral Medicine, Twelfth Edition (12th.Ed). USA:
PMPH -USA
 Rajendran R & Sivapathasundaram B. Shafer’s textbook of oral pathology;
Elsevier, Noida, 7th ed.
 Rao, Naman R et al. “Oral submucous fibrosis: a contemporary narrative review
with a proposed inter-professional approach for an early diagnosis and clinical
management.” Journal of otolaryngology - head & neck surgery = Le Journal
d'oto-rhino-laryngologie et de chirurgie cervico-faciale vol. 49,1 3. 8 Jan. 2020,
doi:10.1186/s40463-020-0399-7
 R, Sheshaprasad et al. “Habit History in Oral Submucous Fibrosis: Have We Over
Emphasized?.” Asian Pacific journal of cancer prevention : APJCP vol. 20,2 451-
455. 26 Feb. 2019, doi:10.31557/APJCP.2019.20.2.451