World Journal of W J C C Clinical Cases Submit a Manuscript: http://www.wjgnet.com/esps/ World J Clin Cases 2014 December 16; 2(12): 866-872 Help Desk: http://www.wjgnet.com/esps/helpdesk.aspx ISSN 2307-8960 (online) DOI: 10.12998/wjcc.v2.i12.866 © 2014 Baishideng Publishing Group Inc. All rights reserved. MINIREVIEWS Precancerous lesions of oral mucosa Gurkan Yardimci, Zekayi Kutlubay, Burhan Engin, Yalcin Tuzun Gurkan Yardimci, Department of Dermatology, Muş State Hos- alternatives such as corticosteroids, calcineurin inhibi- pital, 49100 Muş, Turkey tors, and retinoids are widely used. Zekayi Kutlubay, Burhan Engin, Yalcin Tuzun, Department of Dermatology, Cerrahpaşa Medical Faculty, Istanbul University, © 2014 Baishideng Publishing Group Inc. All rights reserved. 34098 Istanbul, Turkey Author contributions: Kutlubay Z designed research; Yardımci Key words: Oral premalignant lesions; Leukoplakia; G performed research; Tuzun Y contributed new reagents or ana- Erythroplakia; Submucous fibrosis; Lichen planus; Ma- lytic tools; Engin B analyzed data; Yardımci G wrote the paper. Correspondence to: Zekayi Kutlubay, MD, Department of lignant transformation Dermatology, Cerrahpaşa Medical Faculty, Istanbul University, Cerrah Paşa Mh., 34098 Istanbul, Core tip: Precancerous lesions of oral mucosa are the Turkey. [email protected] diseases that have malignant transformation risk at dif- Telephone: +90-212-4143120 Fax: +90-212-4147156 ferent ratios. Clinically, these diseases may sometimes Received: July 22, 2014 Revised: August 28, 2014 resemble each other. Thus, the diagnosis should be Accepted: September 23, 2014 confirmed by biopsy. In early stages, histopathological Published online: December 16, 2014 findings are distinctive, but if malignant transformation occurs, identical histological features with oral carci- noma are seen. If these diseases left untreated, they can cause many problems, which may affect a patient’s Abstract social and daily life. Precancerous lesions of oral mucosa, known as poten- tially malignant disorders in recent years, are consists of a group of diseases, which should be diagnosed Yardimci G, Kutlubay Z, Engin B, Tuzun Y. Precancerous lesions in the early stage. Oral leukoplakia, oral submucous of oral mucosa. World J Clin Cases 2014; 2(12): 866-872 Avail- fibrosis, and oral erythroplakia are the most common able from: URL: http://www.wjgnet.com/2307-8960/full/v2/ oral mucosal diseases that have a very high malignant i12/866.htm DOI: http://dx.doi.org/10.12998/wjcc.v2.i12.866 transformation rate. Oral lichen planus is one of the potentially malignant disorders that may be seen in six different subtypes including papular, reticular, plaque- like, atrophic, erosive, and bullous type, clinically. Atro- INTRODUCTION phic and erosive subtypes have the greater increased In a World Health Organization Workshop, held in 2005, malignant transformation risk compared to another the terminology, definitions and classifications of oral le- subtypes. Although there are various etiological stud- ies, the etiology of almost all these diseases is not fully sions with a predisposition to malignant transformation understood. Geographically, etiologic factors may vary. have been discussed and recommended to use the term “potentially malignant disorders” to eliminate termino- The most frequently reported possible factors are to- [1] bacco use, alcohol drinking, chewing of betel quid con- logical confusion . taining areca nut, and solar rays. Early diagnosis is very The most common oral precancerous lesions are important and can be lifesaving, because in late stages, oral leukoplakia, oral submucous fibrosis (OSMF), and they may be progressed to severe dysplasia and even oral erythroplakia. Actinic cheilitis, some miscellaneous carcinoma in situ and/or squamous cell carcinoma. For inherited diseases such as xeroderma pigmentosum and most diseases, treatment results are not satisfactory in Fanconi’s anemia, and immunodeficiency are another spite of miscellaneous therapies. While at the forefront potentially malignant disorders for oral carcinoma as well of surgical intervention, topical and systemic treatment as these three diseases[1,2]. In a clinicopathological study WJCC|www.wjgnet.com 866 December 16, 2014|Volume 2|Issue 12| Yardimci G et al . Premalignant oral lesions Table 1 Risk factors of malignant transformation Female gender Long duration of leukoplakia Leukoplakia in non-smokers Location on the tongue and/or floor of the mouth Size > 200 mm2 Non-homogenous type Presence of epithelial dysplasia Early detection of premalignant lesions and oral can- cer is very important. Therefore, miscellaneous modalities such as oral cavity examination, supravital staining, oral Figure 1 White and red lesions known as erythroleukoplakia are seen. cytology and optical technologies including spectroscopy, fluorescence spectroscopy, elastic scattering (reflectance) [3] spectroscopy, Raman spectroscopy, fluorescence imaging, designed by Phookan et al , different oral premalignant optical coherence tomography, narrow-band imaging, and lesions were observed in 70 of 320 patients with lower or [10] multimodal optical imaging may be used . middle socioeconomic group. Leukoplakia was the most We think that the following criteria should be taken common premalignant disorder (20.65% of patients), into consideration in terms of the importance of early while percentages of lichen planus and OSMF were re- [3] diagnosis: (1) symptomatic and/or non-symptomatic non- ported equally (0.62% of patients) . healing lesions of oral mucosa; (2) history of smoking, The etiology of precancerous lesions of oral mucosa chewing tobacco, alcohol consumption, oral HPV infec- is not well-known[4]. Some risk factors such as tobacco tion, drug use, long-term exposure to sunlight; (3) ad- chewing, tobacco smoking, and alcohol play an impor- vanced age; (4) the presence of immunodeficiency; (5) the tant role in development of potentially malignant oral presence of genetic disease; and (6) poor oral hygiene. conditions. While tobacco chewing is a major risk factor for oral leukoplakia, OSMF, and erythroplakia, tobacco smoking may be a risk factor for oral leukoplakia. Alco- ORAL LEUKOPLAKIA hol drinking may increase the risk by 1.5-fold for oral Leukoplaki is defined as “A white plaque of questionable leukoplakia, by 2-fold for OSMF, and 3-fold for erythro- [2] risk having excluded (other) known diseases or disorders plakia. According to Thomas et al , while alcohol drink- that carry no increased risk for cancer”[1]. In studies re- ing and tobacco chewing may possibly be risk factors for ported in recent years, the prevalence of oral leukoplakia multiple oral premalignant lesions, smoking was not asso- varies between 1.1% and 11.7%, with a mean value of ciated with the risk of multiple oral premalignant lesions. 2.9%[11]. Although leukoplakia can occur at any age, it Various studies reported about etiopathogenesis of pre- [12] [4] often occurs in individuals under the age of 40 . Leuko- cancerous lesions of oral mucosa. Vlková et al analyzed plakia is seen six times more among smokers than among saliva markers of oxidative stress and reported that salivary non-smokers[1]. thiobarbituric acid reacting substances and advanced glyca- Clinically, leukoplakia may be affect any part of the tion endproducts were significantly higher in patients than oral and oropharyngeal cavity and can be divided into in control. They also reported that no significant differenc- two subtypes including homogeneous and non-homo- es were found in salivary advanced oxidation protein prod- geneous types[1]. Homogenous lesions are characterized ucts, vascular endothelial growth factor, sialotransferase, by uniformly flat, thin, uniformly white in colour and and neuraminidase. Total antioxidant capacity and expres- shows shallow cracks of the surface keratin[1,13]. Non- sion of superoxide dismutase were lower in patients than homogenous lesions have been defined as a white and [5] in age-matched controls. Nanda et al investigated expres- red lesion (known as erythroleukoplakia) that may be either sion of CK8 and CK18 in potentially malignant disorders irregularly flat (speckled) or nodular (Figure 1). Verrucous such as oral leukoplakia, OSMF, and oral squamous cell leukoplakia is yet another type of non-homogenous leu- carcinoma and they reported that expression of CK8 and koplakia[14]. CK18 were statistically significant higher than controls. Proliferative verrucous leukoplakia, which is a form [6] Feng et al reported that expression of podoplanin and of verrucous leukoplakia, was first described by Hansen ABCG2 in oral erythroplakia correlate with oral cancer et al[14,15] in 1985 and characterized by multifocal presenta- [7] development. Qin et al reported a high prevalence of tion. It has a strong potential for malignant transforma- p53 mutations in premalignant oral erythroplakia. Human tion and is resistance to treatment. papilloma virus (HPV) has been suggested to play a role Histopathologically, two distinct appearances may be in the etiopathogenesis of precancerous lesions of oral seen as dysplastic or non-dysplastic leukoplakia. Risk fac- mucosa[8]. Punyani et al[9] reported that there was no sta- tors of malignant transformation are shown in Table 1[14]. tistically significant in salivary IL-8 concentrations among Oral leukoplakia should be distinguished from miscel- the precancer group and controls. laneous benign and/or potentially malignant disorders WJCC|www.wjgnet.com