Epidemiological and clinicopathological study of oral leukoplakia

Transcription

1 Study Epidemiological and clinicopathological study of oral Minati Mishra, Janardan Mohanty*, Sujata Sengupta, Satyabrata Tripathy Department of Dermatology & Venereology, S.C.B. Medical College, *Department of Oncopathology, A. H. Regional Cancer Institute, Cuttack, Orissa, India Address for correspondence: Dr. Minati Mishra, 698, Nayapalli, (Behind Kasturba Women s College), Bhubaneswar - 12, Orissa, India. minatimishra@yahoo.com ABSTRACT Background: Oral white lesions that cannot be clinically or pathologically characterized by any specific disease are referred to as. 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 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 has a potential for malignant transformation and exfoliative cytology could be a simple method for early detection of dysplastic and malignant changes. KEY WORDS: Leukoplakia, Dysplasia INTRODUCTION In 1978 a World Health Organization (WHO) group defined oral 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 caused by Epstein Barr virus), lichen planus, lupus erythematosus, dyskeratosis congenita, white sponge nevus, submucosal fibrosis and frank carcinomas. [1-3] 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 and assess the utility of exfoliative cytology in the detection How to cite this article: Mishra M, Mohanty J, Sengupta S, Tripathy S. Epidemiological and clinicopathological study of oral. Indian J Dermatol Venereol Leprol 2005;71: Received: April, Accepted: October, Source of Support: Nil. Conflict of interest: None declared. 161

2 of malignant changes. METHODS 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 Only the idiopathic cases of white lesions were considered for the study. Such cases of 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 followup 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 During the time span of the study, 2920 cases were diagnosed to have oral, 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 years age group (3 rd decade) followed by the 4 th, 5 th Table 1: Sites of Involvement Site of lesion Male Female No. of Total no Malignant of lesions lesions Buccal mucosa of Cheek (52.26%)* Tongue Dorsal surface (31.23%) Ventral surface Lateral surface Floor of mouth Lips (11.71%) Palate (2.22%) Total (53.78%) (46.22%) (0.68%) (100%) *P<0.05 and 2 nd 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 Table 2: Incriminating factors for Leukoplakia Causal Agents Male Female Total No. of Malignant Lesions Betel (Paan) (28.21) 7(35) Cigarette (11.71) 4(20) Gutkha (9.34) 2(10) Bidi/Chutka (9.34) 2(10) Khaini snuff (Nasa) (16.26) 2(10) Gudakhu (9.79) 2(10) Hyperacidity with (2.91) 0 smoking Hyperacidity without smoking Denture / infected gum (16.57) 0 Lipstick (0.51) 0 Unknown (5) Total (100) 20(100) All parenthesis are in percentage 162

3 Table 3: Cytological and Histopathological profile of the lesions Character Cytology (%) Histopathology Benign 2609 (89.35) Not done Dysplastic 290 (9.93) Dysplastic Benign Malignant 21 (0.72) Malignant Dysplastic 20 1 Total 2920 (100) 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. 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 no incriminating factor was detected. On scrape cytology [Table 3] 2609 (89.35%) cases showed evidence of being benign, in the form of nonspecific 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. 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 [Table 4] was observed, among which thin homogenous was the commonest (58.39%) followed by thick homogeneous (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 Idiopathic s are mostly benign lesions Table 4: Morphological types of Leukoplakia based on their clinical appearance Morphological Total No. No. of cases No. of cases type of lesion of cases of confirmed of confirmed dysplasia malignancy Thin 1705 (58.39) 3 (0.17) 0 Thick homogeneous 758 (25.95) 96 (12) 0 Granular (nodular) 367 (12.56) 95 (25.8) 2 (0.54) Verrucous 46 (1.57) 26 (56.8) 7 (15.72) Speckled 35 (1.19) 23 (65.7) 7 (20) Proliferative verrucous 9 (0.3) 7 (77.7) 4 (44.4) All parenthesis are in percentage occurring in response to chronic irritation. Tobacco in different forms has been described as the most common incriminating factor for such lesions. [5-7] 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 ). Some lesions develop surface irregularities (granular or nodular ), warty papillary surface projections (verrucous ), or mixed red and white lesions (speckled or erythroplakia). The uncommon variant viz. proliferative verrucous is characterized by widespread multifocal sites of involvement, often in patients with known risk factors. Patients with idiopathic have the highest risk of developing cancer. [8-12] The frequency of dysplastic or malignant change varies from % in different studies. [9,11-14] The risk of developing malignancies at lesion sites is 5 times greater in patients with than in patients without them. Erythro, verrucous, and nodular 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 163

4 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 as agreed by most experts. [7] The usage of the term continues to undergo refinement. [7] A retrospective study of 3,300 biopsies of oral by Waldron and Shafer determined that 19.9% of all 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. [15] They followed up this group and showed that 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 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. [10-15,21] 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 i.e 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 [4,7-9] have shown preponderance of 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 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 were confirmed histologically to be malignant lesions. This suggests that certain morphologic types of 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. [10-14] 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 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 164

5 studies were done on exfoliative cytology, DNA cytometric diagnosis, and histopathology on oral 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, 3.2% of verrucous and none in the simplex group. [2,10] Moreover, cytology was highly effective in detecting malignancy in the erosive group. [16,17] However, interobserver reliability in the cytological and histologic diagnosis [24] of 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 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 1. Kramer IR, Lucas RB, Pindborg JJ. Definition of and related lesions: An aid to studies on oral precancer. Oral Surg Oral Med Oral Pathol 1978;46: Shafer WB, Waldron CA. A clinical and histopathologic study of oral. Surg Gynecol Obstet 1961;112: Scully C. The oral cavity. In: Champion RH, Burton JL, Burns DA, Breathnach SM, editors. Rook/Wilkins/Ebling Textbook of Dermatology, 6 th Ed. London: Blackwell Science; p Petit S. Pooled estimate of world prevalence: A systemic review. Oral Oncol 2003;39: 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; International collaborative Group on Oral White Lesions. J Oral Pathol Med 1996;25: 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: Dictrich T, Reichart PA, Scheifele C. Clinical risk factors of oral in representative sample of the U.S. population. Oral Oncol 2004;40: Waldron CA, Shafer WG. Leukoplakia revisited: A clinicopathologic study of 3256 oral s. Cancer 1975;36: Einhorn J, Wersäll J. Incidence of oral carcinoma in patients with of the oral mucosa. Cancer 1967;20: Bánóczy J. Follow-up studies in oral. J Maxillofac Surg 1977;5: Pindborg JJ, Jlst O, Renstrup G, Roed-Peterson B. Studies on oral : A preliminary report on the period prevalence of malignant transformation in based on a followup study of 248 patients. J Am Dent Assoc 1968;76: Roed-Petersen B. Cancer development in oral : Follow-up of 331 patients. J Dent Res 1971;50: Lind PO. Malignant transformation in oral. Scand J Dent Res 1987;95: Silverman S, Bhargava K, Smith LW, Mallowalla AM. Malignant transformation and natural history of oral in 57,518 industrial workers of Gujarat, India. Cancer 1976;38: 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: Ramesh T, Ranatunga N, Mendis BR, Rajapaksa S. Exfoliative Cytology in screening for malignant lesions in the buccal mucosa. Ceylon Med J 1998;43: 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: Banoczy J, Rigo O. Comparative cytologic and histologic studies in oral. Acta Cytol 1976;20: Jayant K. Statistical appraisal of the association of smoking and chewing habits to oral and pharyngeal cancers. Indian J Cancer 1977;14: Silverman S Jr, Dillon WP, Fischbein NJ. Diagnosis In: Silverman S Jr, editor. Oral Cancer. 4 th Ed. Hamilton, Ontario, Canada: BC Decker Inc; p 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: Silverman S Jr. Observations on the clinical characteristics and natural history of oral. J Am Dent Assoc 1968;76: Fischer DJ, Epstein JB, Morton TH, Schwartz SM. Interobserver reliability in histopathologic diagnosis of oral premalignant lesions. J Oral Pathol Med 2004;33: