IADVL
Indexed with PubMed and Science Citation Index (E) 
 
Users online: 193 
     Home | Feedback | Login 
About Current Issue Archive Ahead of print Search Instructions Online Submission Subscribe What's New Contact  
  Navigate here 
  Search
 
   Next article
   Previous article 
   Table of Contents
  
 Resource links
   Similar in PUBMED
    Search Pubmed for
    Search in Google Scholar for
  Related articles
   Article in PDF (102 KB)
   Citation Manager
   Access Statistics
   Reader Comments
   Email Alert *
   Add to My List *
* Registration required (free)  

 
  In this article
   Abstract
   Introduction
   Methods
   Results
   Discussion
   References
   Article Tables

 Article Access Statistics
    Viewed13441    
    Printed226    
    Emailed16    
    PDF Downloaded877    
    Comments [Add]    
    Cited by others 12    

Recommend this journal

 


 
STUDIES
Year : 2005  |  Volume : 71  |  Issue : 3  |  Page : 161-165

Epidemiological and clinicopathological study of oral leukoplakia


1 Department of Dermatology & Venereology, S.C.B. Medical College, Cuttack, Orissa, India
2 Department of Oncopathology, A. H. Regional Cancer Institute, Cuttack, Orissa, India

Correspondence Address:
Minati Mishra
698, Nayapalli, (Behind Kasturba Women's College), Bhubaneswar - 12, Orissa
India
Login to access the Email id


DOI: 10.4103/0378-6323.16229

PMID: 16394403

Get Permissions

  Abstract 

BACKGROUND: Oral white lesions that cannot be clinically or pathologically characterized by any specific disease are referred to as leukoplakia. Such lesions are well known for their propensity for malignant transformation to the extent of 10-20%.Exfoliative cytology is a simple and useful screening tool for detection of malignant or dysplastic changes in such lesions. AIMS: A clinicoepidemiological and cytological study of oral leukoplakia was undertaken to detect their malignant potential and value of cytology in diagnosis. METHODS: This 2 year duration multicentre study was undertaken on all patients presenting with oral white lesions to the out patient department of the two institutions. Those cases in which a specific cause (infective, systemic disease or specific disease entity) for the white lesions were elicited were excluded from the study. The group with idiopathic white lesions was included in the study and was subjected to periodic exfoliative cytological study at three monthly intervals to detect any malignant change. Patients presenting less than two times for follow up were excluded from the final analysis of the study. RESULTS: Out of total 2920 patients studied, 89.53% showed benign, 9.93% showed dysplastic and, 0.72% showed malignant cells on exfoliative cytological study. All the dysplastic and malignant lesions were subjected to histopathological study by incisional biopsy. Among the dysplastic lesions 13.79% proved benign and the rest true dysplastic. Among the cytologically malignant group 4.76% showed dysplasia and the rest true malignant lesions. CONCLUSION: Persistent leukoplakia has a potential for malignant transformation and exfoliative cytology could be a simple method for early detection of dysplastic and malignant changes.


Keywords: Leukoplakia, Dysplasia


How to cite this article:
Mishra M, Mohanty J, Sengupta S, Tripathy S. Epidemiological and clinicopathological study of oral leukoplakia. Indian J Dermatol Venereol Leprol 2005;71:161-5

How to cite this URL:
Mishra M, Mohanty J, Sengupta S, Tripathy S. Epidemiological and clinicopathological study of oral leukoplakia. Indian J Dermatol Venereol Leprol [serial online] 2005 [cited 2014 Oct 2];71:161-5. Available from: http://www.ijdvl.com/text.asp?2005/71/3/161/16229



  Introduction Top


In 1978 a World Health Organization (WHO) group defined oral leukoplakia as: "A white patch or plaque that cannot be characterized clinically or pathologically as any other disease".[1] It is therefore a diagnosis of exclusion from other oral white lesions such as leukokeratosis, infective lesions (candidiasis, syphilitic oral lesion, oral hairy leukoplakia caused by Epstein Barr virus), lichen planus, lupus erythematosus, dyskeratosis congenita, white sponge nevus, submucosal fibrosis and frank carcinomas.[1],[2],[3] It is common in adults beyond 40 years of age, and affects 1% of the total population.[4]

The present study aims to explore the possible etiological factors responsible for oral leukoplakia and assess the utility of exfoliative cytology in the detection of malignant changes.


  Methods Top


This prospective study was carried out from November 1999 to October 2001 in joint collaboration between the Department of Dermatology, S.C.B. Medical College Cuttack and Department of Oncopathology, AH Regional Cancer Institute, Cuttack. Both the institutes are tertiary referral centers of the State Orissa. During this period all cases presenting to the dermatology out patient department with white lesions in the oral cavity were subjected to detailed dermatological and systemic examination followed by microbiological study of lesions for yeast, and serology for syphilis. Cases of oral white lesions found to be of any infective etiology or a part of any other systemic disease were excluded from the study. The rest of the cases with no demonstrable cause, except tobacco use, were subjected to histopathological examination to exclude conditions like lichen planus, lupus erythematosus, white sponge nevus, etc. Total number of patients with oral white lesions that we came across during the two year study period numbered 3748. Only the idiopathic cases of white lesions were considered for the study. Such cases of leukoplakia numbered 2920, excluding the cases lost to follow-up. All the cases were subjected to clinical examination and scrape cytology at an interval of three months. Those cases reporting for less than two times for cytology study during the 2-year period (numbering 205) were considered lost to follow-up and they were excluded from the final analysis of the study. At the end of the study period the results were compiled, tabulated and analyzed using suitable statistical tools like percentages and Student's t-test.


  Results Top


During the time span of the study, 2920 cases were diagnosed to have oral leukoplakia, excluding the cases lost to follow up. This constituted 0.78% of all new cases attending the outpatient department of Dermatology. Out of these 1570 (53.76%) were male and 1350 (46.24%) female [Table - 1]. Their ages ranged from 9 years to 84 years with a mean of 40.8 years. The maximum percentage of patients (55.47%) were seen in the 21-30 years age group (3rd decade) followed by the 4th, 5th and 2nd decades. In the younger age groups, males tended to outnumber the females. But above the age of 40 years, females were more in number. The duration of the disease varied from 1 month to 3 years with a mean disease duration of 1 year 5 months.

The sites involved included the lips, tongue, inner side of the cheeks and palate [Table - 1]. In both sexes, the commonest site involved was the buccal mucosa on the inner side of the cheek (52.26%, P <0.05) followed by the tongue in 31.23%. The lips and palate showed lesions in 11.7% and 2.22% cases respectively.

A detailed history was taken to elicit any incriminating factors and in 94.62% patients, a possible causal agent could be elicited. As seen in [Table - 2], in 3.2% males and 7.85% females, no definite incriminating factor was found. Betel leaf ( Paan ) was found to be the commonest associated addiction, seen in 28.2% patients, and the use of snuff (khaini) was seen in 16.26% patients. Both these were found to be more common in females than males. Of the total, 11.7% cases reported cigarette smoking. Tobacco in some form or other was observed as the most common associated factor in development of leukoplakia. So far as the malignant lesion are considered betel quid was the commonest association (35% of all malignant lesions) followed by smoking (20%), guthka, bidi/chutka, khaini and gudakhu (10% each). In one case (5%) of the malignant leukoplakia no incriminating factor was detected.

On scrape cytology [Table - 3] 2609 (89.35%) cases showed evidence of being benign, in the form of non-specific inflammatory changes whereas 290 cases (9.93%) showed dysplasia, and frank malignancy was recorded in 0.72% cases. Histopathology of these cases showed that 40 out of the 290 cases (13.79%) showing dysplasia on scrape cytology were actually benign. Out of the 21 cases reported to be malignant on cytology, 18 (85.7%) proved to be invasive squamous cell carcinoma, 2 (9.5%) in situ carcinoma and 1 (4.8%) dysplastic leukoplakia. Thus there was an agreement between cytology and histopathological diagnosis in 86.2% cases of dysplastic lesions and 95.2% in the malignant lesions. Different morphological types of leukoplakia [Table - 4] was observed, among which thin homogenous leukoplakia was the commonest (58.39%) followed by thick homogeneous leukoplakia (25.95%), granular type (12.56%), verrucous (1.57%) speckled (1.19%), and proliferative verrucous (0.3%). The last mentioned type i.e. proliferative verrucous although least common, had the highest rate of malignant changes (44.4%).


  Discussion Top


Idiopathic leukoplakias are mostly benign lesions occurring in response to chronic irritation. Tobacco in different forms has been described as the most common incriminating factor for such lesions.[5],[6],[7] However, other factors, depending on the socio-cultural habits of the patients that lead to chronic irritation of oral and buccal mucosa may also be contributory. It starts as a thin homogeneous grayish white plaque either well defined or blending with the surrounding tissue. The lesion enlarges to leathery appearance with surface fissures (thick homogeneous leukoplakia). Some lesions develop surface irregularities (granular or nodular leukoplakia), warty papillary surface projections (verrucous leukoplakia), or mixed red and white lesions (speckled leukoplakia or erythroplakia). The uncommon variant viz. proliferative verrucous leukoplakia is characterized by widespread multifocal sites of involvement, often in patients with known risk factors. Patients with idiopathic leukoplakia have the highest risk of developing cancer.[8],[9],[10],[11],[12] The frequency of dysplastic or malignant change varies from 15.6-39.2% in different studies.[9],[11],[12],[13],[14] The risk of developing malignancies at lesion sites is 5 times greater in patients with leukoplakia than in patients without them. Erythroleukoplakia, verrucous leukoplakia, and nodular leukoplakia show an increasing frequency of dysplastic histological changes or aneuploidy. Frequently oral white patches are noted secondary to some identifiable local irritation. For example, thickened hyperkeratotic lesions are frequently seen over edentulous areas of alveolar ridges (ridge keratosis), chronic tongue chewing (morsicatio linguarum) or chronic cheek chewing (morsicatio buccarum). All such lesions are secondary responses to a chronic irritation leading to compensatory hyperkeratosis of the epithelium developing as a protective phenomenon, similar to the development of a callus over skin of hand or feet. Such lesions do not show any dysplasia and are reversible on eliminating the causative factor. These lesions are better termed as leukokeratosis rather than leukoplakia as agreed by most experts.[7] The usage of the term leukoplakia continues to undergo refinement.[7]

A retrospective study of 3,300 biopsies of oral leukoplakia by Waldron and Shafer determined that 19.9% of all leukoplakia showed some degree of epithelial dysplasia. In this group 3.1% were unsuspected squamous cell carcinomas, 4.6% showed severe dysplasia or carcinoma in situ, and 12.2% showed mild to moderate dysplasia.[9] Silverman et al in a clinicopathological study of 57,518 industrial workers over 35 years of age from Gujarat elucidated the natural history and malignant transformation of oral leukoplakia.[15] They followed up this group and showed that leukoplakia was the oral lesion that proved to be precancerous, with a transformation rate of 0.13% in a 2-year interval.[16]

Ramesh et al assessed the efficacy of exfoliative cytology in the detection of oral premalignant and malignant lesions. They concluded that exfoliative cytology is a useful method for detecting oral premalignant and malignant lesions. Anucleated squames in a smear are non-diagnostic.[17] A correlative study of exfoliative cytology and histopathology of oral carcinoma was conducted by Reddy et al and they commented that oral exfoliative cytology should only be used as an adjunctive measure and not as a substitute for biopsy.[18] Exfoliative cytological study of the leukoplakia has shown sensitivity of 77% and specificity of 100% in the detection of dysplastic or malignant changes.[18],[19]

Oral cancer is the commonest malignancy in Indian males.[20] Leukoplakia is the most common precancerous lesion of the oral mucosa.[10],[11],[12],[13],[14],[15],[21] Its implicating factors, like chewing and smoking of tobacco is widely prevalent in our country. However, few Indian studies have been published on this topic. The total number of cases of leukoplakia i.e. 2920 formed 0.78% of the total new attendees at the OPD of the two institutions where the study was conducted. The age range was wide showing that no age was exempted whereas several other studies worldwide[4],[7],[8],[9] have shown preponderance of leukoplakia in a later age group beyond 40 years. The discrepancy could be due to the use of tobacco, lime and betel quite prevalent among the younger population in our country. The male to female ratio was found to be 1.16:1. Even though a study on world leukoplakia prevalence showed[9] a significant male predominance, we found females outnumbering males in the older age group, which could be explained by the widespread use of tobacco in elderly females. As seen in a recent study in Kerala, in India and another study in Gujarat, India, among industrial workers, tobacco chewing in the form of betel nut, " pan" "or " supari" was found to be most important implicating factor.[15],[17],[21],[22] This is in contrast to a study in the US population, where smoking of tobacco was found to be the strongest independent risk factor.[23] Other forms of tobacco, hyperacidity, lipstick, and ill-fitting dentures were found to be a causative factor, which shows that socioeconomic status and lifestyle are involved in causing premalignant lesions.[5]

In our study, 0.54% of granular or nodular, 15.2% of verrucous, 20% of speckled and 44.4% of proliferative verrucous leukoplakia were confirmed histologically to be malignant lesions. This suggests that certain morphologic types of leukoplakia are particularly prone for malignancy and need to be closely followed up. Also, lesions at the buccal mucosa were of more malignant potential, accounting for 50% of the total malignant lesions detected in the study. In contrast, Western studies have shown lesions of lateral tongue and floor of mouth to be at greatest risk.[10],[11],[12],[13],[14] This discrepancy may be due to the typical habit of betel quid chewing in our population.

In our study, premalignant changes were seen in 9.93% cases which is similar to other studies done before.[5],[8] Frank malignancy was seen in 0.72% of our leukoplakia cases. We found that of the 21 cases reported to be malignant on scrape cytology 18 (85.7%) proved to be invasive squamous cell carcinoma on histopathological study. Hence cytology is an important diagnostic tool for detecting in situ anaplastic changes and further confirmation (by conventional biopsy) will substantiate the dysplasia and the type of malignancy. Different studies were done on exfoliative cytology, DNA cytometric diagnosis, and histopathology on oral leukoplakia and there was an agreement between the cytological and histological results in 76.6% of all cases.[2],[10],[16],[17] Frank carcinoma was encountered in 32.9% of erosive leukoplakia, 3.2% of verrucous leukoplakia and none in the leukoplakia simplex group.[2],[10] Moreover, cytology was highly effective in detecting malignancy in the erosive leukoplakia group.[16],[17]

However, interobserver reliability in the cytological and histologic diagnosis[24] of leukoplakia is a matter of concern and, at the slightest clinical suspicion, particularly in elderly patients with longstanding lesions and multiple risk factors, conventional biopsy followed by histopathological study at a specialist referral institute dealing with oral cancer is a must. We recommend that all white plaques that are idiopathic and persist for 3-4 weeks after elimination of any existing implicating factor should be examined cytologically followed, if required, by histological examination. However, during the 2 years of clinical and cytological follow-up of our leukoplakia cases, none of the benign cases transformed into malignancy, although the potential for such change always exists and mere finding of a benign cytology at one time should not reduce the importance of a periodic follow up cytological study along with avoidance of tobacco or other irritants.



 
  References Top

1.Kramer IR, Lucas RB, Pindborg JJ. Definition of leukoplakia and related lesions: An aid to studies on oral precancer. Oral Surg Oral Med Oral Pathol 1978;46:518-39.   Back to cited text no. 1      
2.Shafer WB, Waldron CA. A clinical and histopathologic study of oral leukoplakia. Surg Gynecol Obstet 1961;112:411-20.   Back to cited text no. 2      
3.Scully C. The oral cavity. In : Champion RH, Burton JL, Burns DA, Breathnach SM, editors. Rook/Wilkins/Ebling Textbook of Dermatology, 6th Ed. London: Blackwell Science; 1998. p. 3097-9.  Back to cited text no. 3      
4.Petit S. Pooled estimate of world leukoplakia prevalence: A systemic review. Oral Oncol 2003;39:770-80.  Back to cited text no. 4      
5.Axell T, Pindborg JJ, Smith CJ, van der Waal I. Oral white lesions with special reference to precancerous and tobacco-related lesions: Conclusions of an international symposium held in Uppsala. Sweden; 1994.  Back to cited text no. 5      
6.International collaborative Group on Oral White Lesions. J Oral Pathol Med 1996;25:49-54.  Back to cited text no. 6  [PUBMED]    
7.Bouquot JE, Gorlin RJ. Leukoplakia, lichen planus, and other oral keratoses in 23,616 white Americans over the age of 35 years. Oral Surg Oral Med Oral Pathol 1986;61:373-81.  Back to cited text no. 7      
8.Dictrich T, Reichart PA, Scheifele C. Clinical risk factors of oral leukoplakia in representative sample of the U.S. population. Oral Oncol 2004;40:158-63.  Back to cited text no. 8      
9.Waldron CA, Shafer WG. Leukoplakia revisited: A clinicopathologic study of 3256 oral leukoplakias. Cancer 1975;36:1386-92.  Back to cited text no. 9  [PUBMED]    
10.Einhorn J, Wersδll J. Incidence of oral carcinoma in patients with leukoplakia of the oral mucosa. Cancer 1967;20:2189-93.  Back to cited text no. 10      
11.Bαnóczy J. Follow-up studies in oral leukoplakia. J Maxillofac Surg 1977;5:69-75.  Back to cited text no. 11      
12.Pindborg JJ, Jlst O, Renstrup G, Roed-Peterson B. Studies on oral leukoplakia: A preliminary report on the period prevalence of malignant transformation in leukoplakia based on a follow-up study of 248 patients. J Am Dent Assoc 1968;76:767-71.  Back to cited text no. 12      
13.Roed-Petersen B. Cancer development in oral leukoplakia: Follow-up of 331 patients. J Dent Res 1971;50:711.   Back to cited text no. 13      
14. Lind PO. Malignant transformation in oral leukoplakia. Scand J Dent Res 1987;95:449-55.  Back to cited text no. 14      
15.Silverman S, Bhargava K, Smith LW, Mallowalla AM. Malignant transformation and natural history of oral leukoplakia in 57,518 industrial workers of Gujarat, India. Cancer 1976;38:1790-5.  Back to cited text no. 15      
16.Silverman S, Bilimoria KF, Bhargava K, Mani NJ, Shah RA. Cytologic, histologic and clinical correlations of precancerous and cancerous oral lesions in 57,518 industrial workers of Gujarat, India. Acta Cytol 1977;21:196-8.  Back to cited text no. 16      
17.Ramesh T, Ranatunga N, Mendis BR, Rajapaksa S. Exfoliative Cytology in screening for malignant lesions in the buccal mucosa. Ceylon Med J 1998;43:206-9.  Back to cited text no. 17      
18.Reddy CR, Kameswari VR, Prahlad D, Ramulu C, Reddy PG. Correlative study of exfoliative cytology and histopathology of oral carcinomas. J Oral Surg 1975;33:435-8.  Back to cited text no. 18  [PUBMED]    
19.Banoczy J, Rigo O. Comparative cytologic and histologic studies in oral leukoplakia. Acta Cytol 1976;20:308-12.  Back to cited text no. 19  [PUBMED]    
20.Jayant K. Statistical appraisal of the association of smoking and chewing habits to oral and pharyngeal cancers. Indian J Cancer 1977;14:293-9.  Back to cited text no. 20      
21.Silverman S Jr, Dillon WP, Fischbein NJ. Diagnosis In: Silverman S Jr, editor. Oral Cancer. 4th Ed. Hamilton, Ontario, Canada: BC Decker Inc; 1998. p. 41-66.  Back to cited text no. 21      
22.Pindborg JJ, Mehta FS, Gupta PC, Daftary DK, Smith CJ. Reverse smoking in Andhra Pradesh, India: A study of palatal lesions among 10,169 villagers. Br J Cancer 1971;25:10-20.  Back to cited text no. 22  [PUBMED]    
23.Silverman S Jr. Observations on the clinical characteristics and natural history of oral leukoplakia. J Am Dent Assoc 1968;76:772-7.  Back to cited text no. 23  [PUBMED]    
24.Fischer DJ, Epstein JB, Morton TH, Schwartz SM. Interobserver reliability in histopathologic diagnosis of oral premalignant lesions. J Oral Pathol Med 2004;33:65-70.  Back to cited text no. 24  [PUBMED]  [FULLTEXT]  



 
 
    Tables

  [Table - 1], [Table - 2], [Table - 3], [Table - 4]

This article has been cited by
1 Cytopathology: A useful technique for diagnosing oral lesions?: A systematic literature review
Eder da Silva Dolens,Fabrícia Venâncio Dolens Nakai,José Luiz Santos Parizi,Gisele Alborghetti Nai
Diagnostic Cytopathology. 2013; 41(6): 505
[Pubmed]
2 Evaluation of serum and salivary total sialic acid and a-l-fucosidase in patients with oral precancerous conditions and oral cancer
Bhairavi N. Vajaria,Kinjal R. Patel,Rasheedunnisa Begum,Franky D. Shah,Jayendra B. Patel,Shilin N. Shukla,Prabhudas S. Patel
Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology. 2013; 115(6): 764
[Pubmed]
3 A histopathological and immunohistochemical study of oral leukoplakia
Kayo KUYAMA,Takashi MATSUMOTO,Yan SUN,Miyuki MORIKAWA,Taku KATO,Hirotsugu YAMAMOTO
The Journal of the Japanese Society of Clinical Cytology. 2013; 52(3): 181
[Pubmed]
4 A Brief Review of Common Oral Premalignant Lesions with Emphasis on Their Management and Cancer Prevention
Sunitha Carnelio, Gabriel Sunil Rodrigues, Rajgopal Shenoy, Donald Fernandes
Indian Journal of Surgery. 2011;
[VIEW]
5 A Review on Salivary Genomics and Proteomics Biomarkers in Oral Cancer
Franky D. Shah, Rasheedunnisa Begum, Bhairavi N. Vajaria, Kinjal R. Patel, Jayendra B. Patel, Shilin N. Shukla, Prabhudas S. Patel
Indian Journal of Clinical Biochemistry. 2011;
[VIEW]
6 Correlation between clinical and pathologic diagnosis in oral leukoplakia in 54 patients
Vázquez-Álvarez, R., Fernández-González, F., Gándara-Vila, P., Reboiras-López, D., García-García, A., Gándara-Rey, J.-M.
Medicina Oral, Patologia Oral y Cirugia Bucal. 2010; 15(6): e832-e838
[Pubmed]
7 Polymorphisms at p53, p73, and MDM2 loci modulate the risk of tobacco associated leukoplakia and oral cancer
Misra, C., Majumder, M., Bajaj, S., Ghosh, S., Roy, B., Roychoudhury, S.
Molecular Carcinogenesis. 2009; 48(9): 790-800
[Pubmed]
8 Three-year follow-up of oral leukoplakia after neodymium:yttrium aluminum garnet (Nd:YAG) laser surgery
Vivek, V., Jayasree, R.S., Balan, A., Sreelatha, K.T., Gupta, A.K.
Lasers in Medical Science. 2008; 23(4): 375-379
[Pubmed]
9 Contribution of cytopathology to the diagnosis of oral squamous cells carcinoma | [Contribuição da citopatologia para o diagnóstico de carcinoma de células escamosas oral]
Fontes, K.B.F.D.C., Milagres, A., Piragibe, M.M.M., Da Silva, L.E., Dias, E.P.
Jornal Brasileiro de Patologia e Medicina Laboratorial. 2008; 44(1): 17-24
[Pubmed]
10 Lab-on-a-chip for oral cancer screening and diagnosis
Ziober, B.L., Mauk, M.G., Falls, E.M., Chen, Z., Ziober, A.F., Bau, H.H.
Head and Neck. 2008; 30(1): 111-121
[Pubmed]
11 Lab-on-a-chip for oral cancer screening and diagnosis
Barry L. Ziober,Michael G. Mauk,Erica M. Falls,Zongyuan Chen,Amy F. Ziober,Haim H. Bau
Head & Neck. 2008; 30(1): 111
[Pubmed]
12 Three-year follow-up of oral leukoplakia after neodymium:yttrium aluminum garnet (Nd:YAG) laser surgery
V. Vivek,R. S. Jayasree,Anita Balan,K. T. Sreelatha,A. K. Gupta
Lasers in Medical Science. 2008; 23(4): 375
[Pubmed]



 

Top
Print this article  Email this article
Previous article Next article

    

Online since 15th March '04
Published by Medknow