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 Table of Contents  
CASE REPORT
Year : 2014  |  Volume : 5  |  Issue : 1  |  Page : 55-58

Oral submucous fibrosis associated with malignancy


Department of Oral and Maxillofacial Pathology, Guru Nanak Institute of Dental Sciences and Research, Panihati, Kolkata, West Bengal, India

Date of Web Publication19-Mar-2014

Correspondence Address:
Gargi Chaudhuri
Department of Oral and Maxillofacial Pathology, Guru Nanak Institute of Dental Sciences and Research, Panihati, Kolkata - 700 114, West Bengal
India
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DOI: 10.4103/0976-433X.129075

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  Abstract 

Oral submucous fibrosis (OSF) is a chronic condition of the oral mucosa, first described among five East African women of Indian origin under the term "atrophia idiopathica (tropica) mucosae oris." It is characterized by a generalized submucous fibrosis. The pathogenesis of the disease is not well-established, but epidemiological evidences strongly indicate the association of betel quid habit. It is logical to hypothesize that the increased collagen production or reduced collagen degradation is the possible mechanism in the development of the disease. The malignant potentiality and also the origin of cancers in different intraoral locations in OSF patients is attributable to the generalized epithelial atrophy. Here, a clinical case of OSF in a 36-year-old male patient is being discussed, encompassing the pathogenesis and malignant potentiality of the disease.

Keywords: Arecanut, malignant transformation, oral precancer, oral submucous fibrosis, transforming growth factor beta


How to cite this article:
Chaudhuri G, Das R, Pal M, Kundu S. Oral submucous fibrosis associated with malignancy. SRM J Res Dent Sci 2014;5:55-8

How to cite this URL:
Chaudhuri G, Das R, Pal M, Kundu S. Oral submucous fibrosis associated with malignancy. SRM J Res Dent Sci [serial online] 2014 [cited 2021 Dec 1];5:55-8. Available from: https://www.srmjrds.in/text.asp?2014/5/1/55/129075


  Introduction Top


Oral submucous fibrosis (OSF) is a chronic, progressive, scarring, high-risk precancerous condition of the oral mucosa [1] characterized by changes in the connective tissue fibers of the lamina propria and deeper parts leading to the stiffness of the mucosa and restricted mouth opening. It predominantly occurs in the Indian subcontinent and people of Southeast Asian origin with a reported prevalence ranging up to 0.4% in Indian rural population. The disease was first described by Schwartz in 1952 [2] and its possible pre-cancerous nature was first mentioned by Paymaster in the year 1956. [2] OSMF has a high rate of morbidity because it causes a progressive inability to open the mouth, resulting in eating and consequent nutritional deficiencies. It also has significant mortality rate due to its transformation into oral cancer particularly oral squamous cell carcinoma at a rate of 7.6%. [3]

The pathogenesis of OSF is believed to be multifactorial which has been linked to the chronic placement in the mouth of a betel quid (BQ) or paan consisting of arecanut, slaked lime, tobacco and sometimes with sweeteners and condiments wrapped in a betel leaf. [3] Other factors such as iron and nutritional deficiencies, chronic candidiasis, genetic abnormalities, herpes simplex virus, human papilloma virus, autoimmunity, etc., have been postulated and are known to have either direct effect in causing the disease or an indirect effect by mediating the immune system which is compromised in these precancerous conditions. [4]

The arecanut (betel nut) component of BQ especially an alkaloid called arecoline, lays a major role in the pathogenesis of OSF by causing an abnormal increase in collagen production. [5],[6] The exact mechanism is not known. It has been found that alkaloid exposure of buccal mucosal fibroblasts results in the accumulation of collagen. [5],[7] The synthesis of collagen is influenced by a variety of mediators, of which prominent mediator is transforming growth factor beta which causes the deposition of extra cellular matrix by increasing the synthesis of matrix proteins like collagen and decreasing its degradation by stimulating various inhibitory mechanisms. A decreased degradation of collagen due to increased cross-linking of fibers and reduced collagenase activity implies that OSF may be considered a collagen metabolic disorder resulting from exposure to arecanuts. [5],[8] Overall increased collagen production and decreased collagen breakdown results in increased collagen deposition in the oral tissues, leading to fibrosis. [5]

Normal oral mucosal epithelial cells are continuously subjected to the attack of genotoxic agents present in the BQ which leads to the impairment of cellular defense system. An excessive amount of reactive oxygen species, reactive metabolic intermediates from BQ and tobacco can attack cellular deoxyribonucleic acid (DNA) and induce various kinds of DNA damage. If the DNA-damaged cells are subsequently induced by proliferative agents to replicate, the DNA damage will remain permanently in the cells and thereby leading to the formation of mutated initiated cells. The further promotion and progression of such initiated cells can lead to the occurrence of oral pre-cancerous lesions and clinical tumors. [9] Epithelial atrophy in OSF patients increases the penetration of carcinogenic ingredients of BQ and thereby subsequently increasing the rate of oral cancer. [10]

The hallmark of the disease is trismus or inability to open the mouth often accompanied by mucosal pain while eating spicy food. Females are affected more than the males in the ratio of 3:1. Vesicles, petechiae, melanosis, xerostomia and a generalized oral burning sensation (stomatopyrosis) are usually the first signs and symptoms. The buccal mucosa, retromolar area and soft palate are the most commonly affected sites which develops a blotchy, marble like pallor and a progressive stiffness of underlying connective tissue. When the tongue is involved, it becomes rather immobile, diminished in size with depapillation. Palpable fibrous bands appear on the buccal mucosa, soft palate and labial mucosa of fully developed cases. Involvement may extend beyond the oral cavity to oropharynx and upper esophagus. [1],[9],[10]

Histopathologically it is characterized by atrophic surface epithelium and submucosal deposition of dense and hypo vascular collagenous connective tissue with variable numbers of chronic inflammatory cells. The atrophic epithelium becomes more vulnerable to carcinogens. The epithelium shows first an intercellular edema and later epithelial atypia associated with moderate epithelial hyperplasia. Epithelial dysplasia is found in 10-15% of cases, which may lead to the development of squamous cell carcinoma. [1]

Based on the above clinicopathological and histopathological findings, a case of OSF associated with oral squamous cell carcinoma involving the left side of the mandible was diagnosed and has been discussed herewith.


  Case Report Top


The present case report is about a 36-year-old male patient who reported to the Oral and Maxillofacial Pathology Department of Guru Nanak Institute of Dental Sciences and Research, Panihati, Kolkata with a chief complaint of burning sensation affecting the oral mucosa with limited mouth opening for about 07-08 months. He had a habit of chewing commercialized BQ, 4-5 packets/day for last 10 years. Extraoral features of the patient appeared normal [Figure 1]. Intraoral examination revealed the presence of a non-tendered, non-hemorrhagic ulceroproliferative growth with granular surface and indurated borders involving the buccal mucosa and buccal vestibule in relation to left mandibular premolar and molar region. There was presence of white plaque type areas near the posterior margin of the ulceroproliferative growth, while the anterior margin was covered by a greyish-white pseudomembrane [Figure 2],[Figure 3]. Right buccal mucosa appears blanched and opaque with presence of palpable thick fibrotic bands without any ulceration [Figure 2]. The left submandibular lymph node was palpable and fixed to the underlying tissues. Based on the above clinical findings, two incisional biopsies were performed from two different representative sites, one from the right cheek and another one from the ulceroproliferative growth involving the left buccal vestibule and submitted for histopathological examination.
Figure 1: Extraoral photograph of the patient

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Figure 2: Intraoral photograph showing blanched and opaque appearance of right buccal mucosa

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Figure 3: Intraoral photograph showing an ulceroproliferative growth involving the buccal mucosa and vestibule in relation to left mandibular premolar and molar region

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The light microscopic features involving the right cheek reveals the presence of an atrophic stratified squamous surface epithelium showing dysplastic changes, being supported by the avascular dense connective tissue stroma characterized by the presence of hyalinization and homogenization of the collagen fibers along with perivascular fibrosis [Figure 4]. The light microscopic features involving the left cheek reveals the presence of actively proliferating, neoplastic stratified squamous epithelial cells invading deep into the underlying connective tissue stroma with presence of nuclear and cellular pleomorphism, nuclear hyperchromatism, along with formation of multiple keratin and epithelial pearls [Figure 5],[Figure 6] and [Figure 7].
Figure 4: Low power photomicrograph showing features of submucous fibrosis with epithelial dysplasia (H and E, ×10)

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Figure 5: Low power photomicrograph showing presence of actively proliferating neoplastic epithelial cells within the connective tissue stroma associated with multiple keratin and epithelial pearls (H and E, ×10)

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Figure 6: High power photomicrograph showing active invasion of the neoplastic epithelial cells into the underlying connective tissue stroma (H and E, ×40)

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Figure 7: High power photomicrograph showing pronounced features of cellular and nuclear pleomorphism along with presence of epithelial pearls (H and E, ×40)

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Based on the above clinical and histopathological findings, diagnosis of OSF involving the right cheek and
"Well-differentiated squamous cell carcinoma" involving the left cheek were established and the patient was send to Oral surgery department for further surgical management.


  Discussion Top


OSF is a chronic, insidious pre-malignant condition that affects the oral mucosa as well as the pharynx and the upper two-third of the esophagus. Besides being regarded as a precancerous condition, it is a seriously debilitating and progressive disease. The strongest risk factor for OSF is the chewing of BQ containing arecanut. The amount of arecanut in BQ along with the frequency and duration of chewing this quid are clearly related to the development of OSF. [9]

When a BQ is placed in a buccal vestibule for about 15 min to an hour with a frequency of 5-6 times a day, it leads to continuous contact between the quid and the oral mucosa resulting in absorption and metabolism of alkaloids in the quid. Further micro trauma produced by the friction of coarse fibers of arecanut also facilitates the diffusion of the alkaloids into the subepithelial connective tissue resulting in juxta-epithelial inflammatory cell infiltration and fibrosis. [3] Epithelial atrophy in OSF patients also increases the penetration of carcinogenic ingredients of BQ and thereby subsequently increasing the risk of developing malignancy. [10]

Here the patient under discussion was a 36-year-old male, having a history of burning sensation affecting both buccal mucosa along with limited mouth opening. He had a habit of chewing pan and commercialized BQ for the last 10 years. Intraorally there was an ulceroproliferative growth with indurations and surface granularity involving the left lower buccal mucosa in the premolar and molar region along with blanching and thick palpable fibrotic bands involving the buccal mucosa on both sides. Extraorally there was no obvious facial swelling. Left submandibular lymph node was tender on palpation. These clinical findings are consistent with the observations reported by various authors. [1],[9],[10] Clinical history also revealed that the patient had not received any treatment for the condition and gradually developed an ulceroproliferative growth involving the left cheek. Accordingly, it was provisionally diagnosed as OSF involving the right cheek and malignancy involving the left cheek which was finally confirmed by histopathology as well-differentiated invasive squamous cell carcinoma. These were in accordance to the studies conducted by various authors. [1],[2],[3],[4],[9],[10]


  Conclusion Top


OSF is regarded as a disease of collagen metabolic disorder and is mainly due to the placement of arecanut with or without tobacco over the oral mucosa for a prolonged period of time which may culminate into malignancy, i.e., oral squamous cell carcinoma. Hence, to prevent the risk of malignant transformation, much stress has to be laid on the stoppage of the usage of arecanut in all forms-irrespective of age, community and socio-economic status.

 
  References Top

1.Neville BW, Damm DD, Allen CM, Bouquot JE. Oral and Maxillofacial Pathology. 3 rd ed. India: Elsevier Publishers; 2009. p. 401, 402.  Back to cited text no. 1
    
2.Rajendran R. Oral submucous fibrosis: Etiology, pathogenesis, and future research. Bull World Health Organ 1994;72:985-96.  Back to cited text no. 2
[PUBMED]    
3.Dyavanagardar SN. Oral submucous fibrosis; review on etiopathogenesis. J Cancer Ther 2009;1:072-7.  Back to cited text no. 3
    
4.Sudarshan R, Annigeri RG, Vijayabala GS. Pathogenesis of oral submucous fibrosis: The past and current concepts. Int J Oral Maxillofac Pathol 2012;3:27-36.  Back to cited text no. 4
    
5.Rajalalitha P, Vali S. Molecular pathogenesis of oral submucous fibrosis - A collagen metabolic disorder. J Oral Pathol Med 2005;34:321-8.  Back to cited text no. 5
    
6.Canniff JP, Harvey W. The aetiology of oral submucous fibrosis: The stimulation of collagen synthesis by extracts of areca nut. Int J Oral Surg 1981;10:163-7.  Back to cited text no. 6
[PUBMED]    
7.Harvey W, Scutt A, Meghji S, Canniff JP. Stimulation of human buccal mucosa fibroblasts in vitro by betel-nut alkaloids. Arch Oral Biol 1986;31:45-9.  Back to cited text no. 7
[PUBMED]    
8.Shieh TY, Yang JF. Collagenase activity in oral submucous fibrosis. Proc Natl Sci Counc Repub China B 1992;16:106-10.  Back to cited text no. 8
    
9.Kumar SP, Shenai P, Chatra L, Rao PK, Veena KM. Oral submucous fibrosis as a forerunner of malignancy - A case report. Biol Biomed Rep 2012;2:119-22.  Back to cited text no. 9
    
10.Pundir S, Saxena S, Aggarwal P. Oral submucous fibrosis a disease with malignant potential - Report of two cases. J Clin Exp Dent 2012;2:e215-8.  Back to cited text no. 10
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7]


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