Correlation of histopathological diagnosis with habits and clinical findings in oral submucous fibrosis

Background Oral submucous fibrosis is a common oral health problem in India. This study was conducted to correlate the histopathological diagnosis with habits and clinical findings in patients suffering from oral submucous fibrosis (OSF). Methods Patients suffering from oral submucous fibrosis from the Departments of Otorhinolayngology and Pathology, Moti Lal Nehru Medical College, Allahabad, India were studied from 2004–2008. Detailed information was gathered in a pretested proforma. Emphasis was given to the various addictions, clinical findings and histological examination was done. Results Two hundred and thirty nine patients were studied, yielding a male to female ratio of 6.8:1. Maximum patients were in the 21–30 years age group with a marked male predominance. Of these, 197 (82.4%) patients chewed areca nut/dohra, 14 (5.8%) were smokers and 2 (0.8%) patients were habituated to alcohol. 89(37.2%) patients reported difficulty in opening of the mouth (trismus). 51 (57.4%) patients were found to have stage II (2–3 cm) trismus while rest had stage I and III. The buccal mucosa was found to be the most commonly involved site. On the basis of histopathological examination, 52(21.7%) were classified as OSF grade I, 75(31.3%) patients as grade II and 112(46.8%) had grade III disease. Conclusion The widespread habit of chewing dohra/paan masala is a major risk factor of OSF, especially in the younger age group. In this study, an increase in histopathological grading was found with severity and duration of addiction habit. However no significant correlation was found between clinical staging and histopathological grading.


Background
Oral submucous fibrosis (OSF) is a chronic and potentially malignant condition of the oral cavity. It is characterized by a juxtraepithelial inflammatory reaction followed by fibroelastic changes in the lamina propia and associated epithelial atrophy. The disease affects most part of the oral cavity as well as the upper third of the esophagus. [1] The pathogenesis of OSF is not well established, but is believed to be multifactorial. The chewing of betel quid (containing areca nut, tobacco and slaked lime) has been recognized as one of the most important risk factors for OSF. [2][3][4] Over the years, the incidence of OSF has increased manifold in various parts of the Indian subcontinent including Allahabad. [5] In spite of the fact that the habit of areca nut chewing with or without betel quid is rampant, the correlation between the extent and duration of addictions with clinical and histopathological grading has not been attempted so far. Thus, this study was designed investigate to these issues.

Methods
Patients suffering from OSF from the Departments of Otorhinolayngology and Pathology, Moti Lal Nehru Medical College, Allahabad were studied from 2004-2008, after obtaining clearance from the institutional ethical committee. Detailed information of each patient was noted in a pretested proforma. Information regarding the patients' name, age, sex, occupation, background, dietary habits, dental hygiene, personal habits and present complaints was gathered. Emphasis was given to addictions like areca nut, tobacco and alcohol. Detailed clinical examination of each patient was done to assess the site, size and type of lesion. Trismus was classified as stage I (> 3 cm), stage II (2-3 cm) and stage III (<2 cm). For confirmation of the clinical diagnosis, histopathological examination was carried out. The biopsy tissue was processed by paraffin embedding and 2-3 micrometer thick sections were cut and stained by Haematoxylin and eosin (H and E). Histopathological examination was done and results were recorded according to the traditional grading by Pindborg and Sirsat. [6] who had described four consecutive stages (Table 1)

Results
Two hundred and thirty nine OSF patients were studied, of which 204(85.4%) were males and 35(14.6%) females with a male to female ratio of 6.8:1. Maximum number of patients, 109(45.6%) were in the 21-30 years age group followed by 67 (28%) patients in the 31-40 years of age [ Figure 1].
With regard to site distribution, the buccal mucosa was the most common involved site with 66(20.8%) patients being involved. Palate was the second common site and affected 37(17.7%) patients. Both buccal mucosa and the palate were involved in 19(7.9%) patients. Buccal mucosa with the retro molar area involvement was found in 27 (3.1%) patients [ Figure 2].

Male
Female results from Chennai. [ Areca nut, incriminated in the causation of OSF is often wrapped in the leaf of a tropical creeper, Piper betle L. commonly known as the betel leaf or paan [ Figure 6]. The usage of paan is widespread in the Indian subcontinent, mostly in the Hindi speaking heartland of North and Central India.
In the Allahabad region, consumption of a unique preparation called dohra is widespread. [11] It is popular in the district as well as neighbouring regions of Jaunpur and Pratapgarh. It is a mixture of tobacco, slaked lime, areca nut and other ingredients like catechu (katha), peppermint and cardomom (illayachi)etc.It is a wet preparation and marketed without any brand name. About 200 mg product is kept in plastic bag and a rubber band is applied.
One packet is sold for as less as one rupee (approx two US cents). Users consume tobacco (Surti/Zarda) with dohra according to their level of addiction. In this study, 110 (46%) patients, chewed paan masala/dohra. On the other hand, Kumar et al reported from Chennai that 81% of their patient's had the habit of chewing raw areca nut/ commercial areca nut/paan masala. [8] Hazarey et al reported in their study from Nagpur in Western India that areca nut in its pure form was more commonly consumed by women while Khara/Mawa, the common name of gutka (combination of areca nut, paan masala and tobacco) in that region, was usually consumed by men.
[9] Babu et al reported that habitual chewing of pan masala/gutkha is associated with earlier presentation of oral submucous fibrosis than betel quid use. [12] Thomas et al from South India suggested tobacco chewing was the most important risk factor for multiple oral premalignant lesions and may be a major etiological factor for cancers on the oral epithelium in the Indian population. [13] In this study, 38 (15.8%) patients were addicted to betel quid with areca nut and tobacco.14 (5.9%) males were addicted to smoking alone. Only 2 (0.8%) males were habituated to alcohol, but no consistent correlation was found between the OSF and smoking/alcohol consump- Buccal mucosa was found the most commonly involved site in 66(20.8%) patients followed by palate 37(17.7%) and the retromolar area 22(14.7%). Previous reports also corroborated these findings. [9,14,15] Bhugari et al from Pakistan also reported that mucosa of the cheek (55.9%) was the most common site followed by the tongue (28.4%) [16] While Reichart and Way reported the tongue was the most common site, in their study. [17] In this series, none of the patients were reported with involvement of the larynx, pharynx or the esophagus. On the correlation of addiction habit and histopathological findings, maximum patients had histopathological grade III OSF and took tobacco products for 8-10 years or more with high frequency (7-10 times per day) followed by histopathological grade II and I. Kumar et al suggested the patients who used paan masala with a greater frequency/day developed OSF with a shorter duration of the habit. [8] Maher et al from Pakistan reported that the daily consumption rate appears to be much more significant with respect to risk than the lifelong duration of the habit. [19] Some reports suggested that both the duration and daily frequency of areca nut use increase the risk of cancer, suggesting a dose-response relationship. [20] Similarly, Shah et al reported that the total duration of the chewing habit was not significantly correlated to OSF. They hypothesized that the exposure to the total burden of various harmful substances in a given period, i.e., daily consumption was more significant that the total duration of the habit. [21] No correlation was found between clinical grading and histopathological grading in this study akin to Kumar et al who did not find any correlation between clinical symptoms and degree of fibrosis. [8] 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. Medical treatment is symptomatic and predominantly aimed at improving mouth movements. Treatment strategies include the following: Steroids, Placental extracts [22], Hyaluronidase, Pentoxifylline [23], IFN-gamma [24] and Lycopene [25].

Gender wise distribution of patients with their clinical symptoms
Surgical treatment is indicated in patients with severe trismus and/or biopsy results revealing dysplastic or neoplastic changes. Surgical modalities that have been used include simple excision of the fibrous bands, Split-thickness skin grafting, Nasolabial flaps and lingual pedicle flaps. Use of a KTP-532 laser release procedure was recently found to increase mouth opening range in 9 Oral mucosa showing OSF grade II demonstrating fibroblasts in the juxta-epithelial area with dilated blood vessels (H and E ×100) Figure 4 Oral mucosa showing OSF grade II demonstrating fibroblasts in the juxta-epithelial area with dilated blood vessels (H and E ×100).  patients over a 12-month follow-up period in one study [26].
Physical therapy using muscle-stretching exercises for the mouth may be helpful in preventing further limitation of mouth movements. This is often combined with medical and surgical therapy.
Surveillance for OSF is being carried out routinely in the department of Otorhinolaryngology out-patients department at the S.R.N. Hospital associated with the Medical School. As a small percentage of patients with OSF go on to develop malignancy, correlation of histopathological findings and clinical findings is important.

Conclusion
This study concluded that the widespread habits of chewing dohra and paan masala are the major risk factors of OSF, especially affecting the younger generation. An increase is found in histopathological grading and addiction habit and to the best of our knowledge, this correlation has not been attempted before. However no significant correlation was found between trismus and histopathological grading.
Oral Mucosa showing OSF grade III showing thinning of the epidermis, hyalinized collagen and lymphocytic infiltration  Paan quids being served at a wedding reception Figure 6 Paan quids being served at a wedding reception.
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