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There is a wide variety of lesions that can present intraorally as macules, papules, or a combination thereof. Lesions with such patterns include geographic tongue, candidiasis, lichen planus/lichenoid lesions, leukoplakia, erythroplakia, and squamous cell carcinoma.
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Geographic Tongue (Migratory Glossitis and Migratory Stomatitis)
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Geographic tongue8 is a common inflammatory disorder of primarily the tongue occurring in approximately 1% to 3% of the population. Some studies have shown increased prevalence in women. There is apparently a genetic predisposition and in some patients there is a family history. Lesions of geographic tongue may be encountered in patients with psoriasis and, according to studies, patients with psoriasis are up to four times more frequently affected than otherwise healthy patients.9 However, this association is not confirmed but other investigators.10 Other conditions that have shown an increased prevalence of geographic tongue include diabetes mellitus, reactive arthritis (Reiter's syndrome), and Down syndrome. Allergies, hormonal disturbances, and stress have also been associated with an increased prevalence of geographic tongue.
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Clinical Presentation
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Clinically, geographic tongue is characterized by a single or frequently several erythematous lesions occasionally surrounded by a white or yellow line representing epithelial hyperplasia (Figure 38-19). They vary in size and change shape and size, sometimes within hours. Lesions typically occur on the dorsum and ventral surfaces of the tongue, extending occasionally to the lateral aspects. When the dorsum of the tongue is affected, there is loss of lingual papillae. Symptomatic depapillation of the tongue may also be seen in anemia (eg, iron deficiency, pernicious), candidiasis, or diabetes mellitus. Thus, such conditions should be excluded in symptomatic cases that have clinically the appearance of geographic tongue.
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In rare occasions lesions can be found in other parts of the mouth such as the buccal mucosa and the palate (Figure 38-20). However, these patients almost always have lesions on the tongue. In addition, lesions of migratory glossitis are often seen in conjunction with deep fissures on the tongue dorsum (fissured tongue) (Figure 38-21). Occasionally, patients report lesion-free periods.
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The lesions of geographic tongue are generally asymptomatic; however, tingling or burning sensation may be reported in association with spicy or acidic foods or brushing of the tongue with toothpaste. Other than reassuring the patient on the benign nature of geographic tongue, treatment is not necessary. For symptomatic patients, especially those who complain of burning sensation or pain, topical fluocinonide 0.05% gel may be used. Also there are case reports advocating the use of zinc sulfate 200 mg 3 times/day or vitamin B complex supplementations. A diagnostic biopsy may be performed in cases of inability to exclude geographic tongue from other conditions that may share similar clinical features including erythroleukoplakia.
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Candidiasis of the oral mucosa is caused by C. albicans which presents in two forms, yeast and hyphae, the former being generally innocuous while the latter can invade the host tissue.11 Other forms of Candida that can be identified in the mouth, however, far less frequently, include C. glabrata, C. tropicalis, C. krusei, C. parapsilosis, and C. dubliniensis. Among all fungal infections, oral candidiasis is by far the most common. The organism is present in the mouth of 30% to 50% of individuals without causing disease and its presence in the mouth increases with age. Factors that have been associated with the development of clinical disease include the immune status of the host, the strain of Candida, and the environment of the mouth. For example, patients with iron deficiency or pernicious anemia, on long-term antibiotics and steroids (topical, inhaled, or systemic), those with HIV infection or AIDS, and dry mouth can develop candidiasis. Smoking has also been related to the hyperplastic form of candidiasis. However, healthy individuals can also be affected.
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Clinically, there are four forms of candidiasis: pseudomembranous, erythematous, hyperplastic, and mucocutaneous.
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Pseudomembranous candidiasis (thrush) is a common form and it is usually acute. It affects approximately 5% of infants and 10% of debilitated older adults as well as patients on long-term antibiotics or those with dry mouth or immunocompromised patients. The term pseudomembranous is misleading since there is no pseudomembrane present. Instead, creamy white or yellow, easily detached aggregates of yeast and desquamated epithelial cells are seen on the oral soft tissues (Figure 38-22) of the palate, buccal mucosa, and tongue. They are easily removed with a tongue blade, dry gauze or a cotton-tipped applicator leaving behind normal or erythematous oral mucosa. If bleeding occurs during this procedure, an underlying disease, such as lichen planus/lichenoid mucositis or a neoplastic epithelial process, should be suspected and excluded by biopsy. In most cases of thrush there are no symptoms; however, burning sensations and altered taste have been reported.
Erythematous candidiasis is characterized by red patchy areas with minimal or no white plaques of fungal aggregates. Erythematous candidiasis can have several clinical presentations that include acute atrophic candidiasis, central papillary atrophy of the tongue (median rhomboid glossitis), angular cheilitis, and denture stomatitis.
Acute atrophic candidiasis (Figure 38-23) is usually seen in patients on long-term antibiotic treatment, with xerostomia, blood dyscrasias, or immunosuppression. Patients usually complain of a burning sensation (scalded mouth). When the tongue is affected, there is loss of the filiform papillae ("bald tongue").
Central papillary atrophy of the tongue, also referred to as rhomboid glossitis, is a mostly asymptomatic, chronic form of candidiasis, presenting as a depapillated, usually symmetrical area on the middle and posterior central aspect of the tongue that appears smooth or less frequently lobulated. Lesions may also occur on the palate ("kissing" effect) or the buccal mucosa (Figure 38-24). This is referred to as chronic multifocal candidiasis.
Angular cheilitis (perlèche) presents with fissures and cracks in the commissures of the lip (Figure 38-25). Typically it is seen in older patients with reduced vertical occlusal dimension (superior–inferior relationship of the maxilla to the mandible when the teeth are fully occluded), usually denture wearers, as well as patients with multifocal candidiasis. While in some instances only Candida is present, the majority of lesions harbor also Staphylococcus aureus, while some are caused only by this bacterium. Candida in angular cheilitis can spread to lips and perioral tissues.
Denture stomatitis refers to erythematous lesions in the areas covered by the dentures, or other removable dental prosthetic appliances, especially if they are continuously worn (Figure 38-26). These lesions are generally asymptomatic. Interestingly, a biopsy most often does not feature any evidence of fungus. In such cases candida is found in the pores of the dentures; however, similar lesions can be caused by bacteria.
Hyperplastic candidiasis is an unusual form seen primarily in smokers. It is most commonly seen on the buccal mucosa (Figure 38-27) or the tongue. In this form of candidiasis, nonremovable white plaques are present. Although it is known that candida can induce epithelial proliferation, it is not entirely clear if some lesions of hyperplastic candidiasis represent leukoplakias suprainfected by candida. Occasionally, lesions disappear after antifungal treatment thus confirming the cause and effect role of candida in their development. Leukoplakias suprainfected with candida can also have a speckled appearance, that is, speckled mixed white and red lesions (speckled leukoplakia). In such instances, antifungal treatment may improve the appearance of the leukoplakia to a smoother, more homogenous white lesion.
Mucocutaneous candidiasis12 is a relatively rare immunologic disorder in which patients develop lesions affecting the mouth (hyperplastic candidiasis and other forms), nails, skin, and other mucosal surfaces. In some patients, mutations in the autoimmune regulator (AIRE) gene have been identified. Lesions appear early in life and persist. However, they are not invasive and they can be controlled with continuous antifungal treatment. There is also association of mucocutaneous candidiasis with endocrinopathies and rarely there is associated ectodermal dysplasia. Associated endocrinopathies include hypothyroidism, primary Addison's disease, diabetes mellitus, and hypoparathyroidism. In these patients there is increased risk for the development of oral or esophageal carcinoma.
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The treatment of oral candidiasis involves elimination of factors, if possible, that contribute to persistent infection. It is important for patients to maintain a high level oral hygiene. Topical treatments for adults include the following.
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Clotrimazole troches (imidazole agent) one 10 mg troche slowly dissolved in the mouth 5 times per day for 10 to 14 days.
Nystatin oral (polyene agent) 1 or 2 lozenges (pastilles) 200,000 to 400,000 IU dissolved slowly in the mouth 4 to 5 times per day for 10 to 14 days.
Itraconazole oral solution (triazole agent) 10 mL vigorously swished and swallowed twice daily for 1 to 2 weeks.
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When systemic treatment is needed for adults, fluconazole (triazole agent) 200 mg tablets the first day and then 100 mg per day for 1 to 2 weeks should be the first choice. Depending on the form of the disease and in patients with resistant candida species, ketoconazole capsules (imidazole agent) 200 mg once or twice a day for 1 to 4 weeks or for 3 to 5 days after lesions resolve. Ketoconazole should not be used as initial therapy.
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Oral lichen planus (OLP) is a relatively common chronic T-cell-mediated autoimmune disease affecting 1% to 2% of the population.13 In contrast to cutaneous lichen planus that is usually self-limiting, OLP is generally a chronic disease, which may be difficult to palliate and rarely spontaneously resolves. Also and more importantly, lesions of OLP may infrequently undergo neoplastic transformation thus causing morbidity and mortality. The premalignant potential has varies in studies between 0.4% and over 5%.
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Patients with OLP may have concomitant extraoral manifestations and 15% of patients with OLP develop subsequently extraoral disease. The severity of OLP does not, in general, correlate with the extent of cutaneous disease. Also known is the association of OLP of the gingiva with vulvovaginal or penile LP.
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OLP is seen primarily in the 5th and 6th decades of life and it is twice as common in females as in males. Lesions of OLP can also be seen in children and adolescents. Patients with OLP have higher levels of anxiety and those with erosive forms have higher depression scores. Also an association of OLP with hepatitis C has been reported.13
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Clinical Presentation
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There are three well-recognized forms: reticular, atrophic, and erosive. Reticular OLP (Figure 38-28) is the most common form and is characterized by multiple papules or plaques that coalesce forming striations (Wickham striae). Interestingly, lesions of reticular OLP rarely cause symptoms and frequently patients are unaware of their existence. Atrophic and erosive forms (Figure 38-29) are less common. However, these forms are the most frequently encountered in clinical practice because they cause varying degrees of discomfort. The erosive form is mostly used as a clinical term when ulcerated lesions are encountered. Histopathologically, true erosions are infrequently encountered. These forms may be associated with reticular lesions (Figure 38-30) and occasionally erythematous, atrophic, and ulcerated lesions feature radiating white striations. Rarely, vesicles and bullae (bullous LP) may be seen. The most frequent sites of OLP are the posterior buccal mucosa bilaterally, dorsolateral tongue, gingiva, palate, and lip vermillion. Occasionally, lesions of OLP are associated with candidiasis which alters their clinical appearance especially those of the reticular form. In cases of reticular OLP with candida superinfection, patients may complain of burning sensation. The characteristic striations of OLP are seen after the candida infection is treated.
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The diagnosis of lichen planus is established clinically and histopathologically. The differential diagnosis includes the following.
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Contact hypersensitivity reaction to dental materials, flavoring food agents such as cinnamon or mints (Figures 38-31 and 38-32). In the later, characteristic Wickham striae are not encountered.
Lichenoid drug reaction (Figure 38-33), graft versus host disease (GVHD), and oral lesions of lupus erythematosus may have similar or indistinguishable clinicopathologic features with lichen planus. Therefore the clinician should exclude such possibilities prior to establishing the diagnosis of OLP.
Chronic ulcerative stomatitis and vesiculobullous diseases.
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Treatment of OLP is needed for the symptomatic forms. Patients with reticular OLP may be followed every 6 to 12 months. If patients are symptomatic, they may have a candida infection and antifungal medications should resolve the symptoms. Because of the autoimmune nature of LP and depending on the severity of lesions, topical and/or systemic corticosteroids may be indicated. Topical steroids including fluocinonide, betamethasone dipropionate, or clobetasol propionate 0.05% gels may be used. For widely distributed lesions, dexamethasone 0.5 mg/5 mL rinse may be used. Secondary candidiasis that may develop as a side effect to topical corticosteroid treatment can be eliminated by antifungal agents as described above. Topical tacrolimus ointment has been used in recalcitrant cases. Systemic treatment with prednisone may be needed in severe cases of erosive OLP. Other systemic medications that have been used for the treatment of OLP include azathioprine, dapsone, levamisole, and thalidomide.
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Leukoplakia is defined by the World Health Organization (WHO) as "a white patch or plaque that cannot be characterized clinically or pathologically as any other disease." It is a term that does not define a specific entity, but excludes a wide variety of white lesions that present distinct clinical and/or histopathologic characteristics. It is a strictly clinical term that should be used by clinicians to communicate the presence of a white lesion, are unaware of. Table 38-3 lists lesions that should be included and excluded from the term leukoplakia.
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Note among those lesions, the entity referred to as hairy leukoplakia (Figure 38-34). This is a type of white lesion exhibiting specific clinicopathologic features, caused by Epstein–Barr virus (EBV). It is frequently suprainfected by candida and seen mostly in immunosuppressed patients and those with HIV/AIDS. This is but an example of the confusion that the term leukoplakia can cause.
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Etiologic factors for the development of leukoplakic lesions include all forms of tobacco, alcohol abuse, ultraviolet light (for labial lesions), Candida albicans, sanguinaria (bloodroot, a plant used in some nonprescription products). Of these factors, tobacco is most frequently associated with the development of leukoplakias. It is known that around 80% of patients with leukoplakia are smokers and that heavier smokers have greater numbers of lesions and larger lesions compared to light smokers. Also, smoking cessation leads to a decrease in size or disappearance of leukoplakias in many patients. However, one should note that some patients with leukoplakias never smoked and that nonsmokers with leukoplakia have higher risk for the development of squamous cell carcinoma compared to smokers.
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Leukoplakia is considered a premalignant lesion. However only 5% to 25% of the cases have definitive histopathologic criteria to support premalignancy (intraepithelial neoplasia). The premalignant nature of leukoplakia has been established by clinical investigations and long-term monitoring of lesions. These studies have confirmed a malignant transformation potential of about 4% to 5%, which increases in certain subtypes of leukoplakia (erythroleukoplakia, proliferative verrucous leukoplakia) to up to 47%. The progression and time of the development of histologically recognizable dysplasia in leukoplakic lesions are uncertain and occasionally invasive squamous cell carcinoma can occur without evidence of recognizable dysplasia.
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The estimated prevalence of leukoplakia is between 1% and 4% and, recently, there appears to be gender parity, although in last years approximately 70% of the patients were males. The most frequent sites of occurrence are the vestibule and buccal mucosa followed by the palate, alveolar ridge, lower lip, tongue, and floor of mouth. The sites in the mouth in which leukoplakias present high risk for the development of dysplasia and squamous cell carcinoma are, in descending order the floor of mouth, ventrolateral tongue, lower lip, palate, buccal mucosa, vestibule, and retromolar mucosa.
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Clinical Presentation
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Clinically, leukoplakic lesions vary in clinical appearance from thin and homogeneous to thick irregular, leathery patches that may have distinct borders or blend with the surrounding tissues (Figures 38-35, 38-36, 38-37). Variations within the same lesion also occur. Occasionally, an erythematous component is present (erythroleukoplakia) (Figure 38-38). Such lesions have a higher risk for being dysplastic or invasive squamous cell carcinoma at the time of diagnosis. Proliferative verrucous leukoplakia (PVL),14 a subtype of leukoplakia, is characterized by the development of more than one lesions that exhibit various patterns of maturation even within the same patient (Figures 38-39A and B). Lesions of PVL have a very high risk for the development of verrucous or squamous cell carcinoma. They occur more frequently in women and less than one-third of the patients are smokers.
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In the concept of oral premalignancy/squamous cell carcinoma one should include erythroplakia.21 This is defined as a red patch that cannot be clinically or pathologically diagnosed as any other condition (Figure 38-40). However, this definition is misleading because at the time of biopsy lesions of erythroplakia show severe dysplasia, carcinoma in situ, or invasive squamous cell carcinoma. Erythroplakia is less common than leukoplakia. It occurs in middle aged to older adults and the sites of predilection are the floor of mouth, tongue, and soft palate.
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The gold standard for the diagnosis of clinically identified suspicious oral lesions is surgical biopsy.
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Surgical excision is the treatment of choice for leukoplakic lesions. Laser ablation is also used. Photodynamic therapy15 using 5-aminolevulinic acid is a promising alternative for treatment of dysplastic lesions. Cryosurgery and administration of 13-cis-retinoic acid have been used with limited results.
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Oral Squamous Cell Carcinoma
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Oral cancer accounts for less than 3% of all cancers in the United States. Over 20,000 cases are diagnosed per year with more than 5000 patients dying of this disease annually. Oral squamous cell carcinoma (OSCC) represents approximately 95% of all types of malignancy affecting the oral cavity. Most patients are older than 60 years. However, there is an alarming increase in the number of younger patients without the traditional risk factors. Based on incidence rates less than 1% of men and women will be diagnosed with OSCC during their lifetime. The male-to-female ratio is approximately 2.5:1.
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The major etiologic factors include tobacco and alcohol. All forms of smoked tobacco have been associated with increased risk. However, in smokeless tobacco, the association with the development of OSCC remains weak and controversial. In contrast, chewing of betel quid (paan, pan supari; combination of tobacco, areca nut, and slake lime) is a major cause for OSCC in the Indian subcontinent. Also, combination of heavy smoking and alcohol abuse results in a synergistic effect and increases the risk further.
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Besides smoking and alcohol abuse, human papillomavirus (HPV) has been implicated in cases of tonsillar (oropharyngeal). However, association of HPV with the development of OSCC of the oral mucosa proper has not been determined. Squamous cell carcinoma with tumors is associated with HPV having a better prognosis.16 Patients with severe iron deficiency (Plummer–Vinson syndrome) have an elevated risk for development of esophageal and oropharyngeal squamous cell carcinoma.
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Clinical Presentation
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There is a variety of clinical appearances of OSSC. Tumors can be ulcerated, endophytic, exophytic, leukoplakic, or erythroleukoplakic (Figures 38-41 and 38-42). While some tumors are clinically obvious, there are occasions where lesions are small (Figure 38-43), painless, and mimicking inflammatory processes (Figure 38-44). Such is the case of lesions seen in association with dental prostheses or presenting as "inflamed" gingiva. In such cases, consultation with dental professionals may be necessary.
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Diagnostic biopsies should be obtained of all lesions that present with the aforementioned characteristics. Treatment of oral cancer involves a team of physicians that include ear, nose, and throat/oral surgery and maxillofacial specialists, oncologists, and prosthodontists.