Thu. Nov 25th, 2021

    LEUKOPLAKIA

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    Leukoplakia is a firmly attached white patch on a mucous membrane which is associated with an increased risk of cancer.[4][5] The edges of the lesion are typically abrupt and the lesion changes with time.[4][6] Advanced forms may develop red patches.[6] There are generally no other symptoms.[8] It usually occurs within the mouth, although sometimes mucosa in other parts of the gastrointestinal tracturinary tract, or genitals may be affected.[9][10][11]

    The cause of leukoplakia is unknown.[6] Risk factors for formation inside the mouth include smoking, chewing tobacco, excessive alcohol, and use of betel nuts.[4][7] One specific type is common in HIV/AIDS.[12] It is a precancerous lesion, a tissue alteration in which cancer is more likely to develop.[4] The chance of cancer formation depends on the type, with between 3–15% of localized leukoplakia and 70–100% of proliferative leukoplakia developing into squamous cell carcinoma.[4]

    Leukoplakia is a descriptive term that should only be applied after other possible causes are ruled out.[6] Tissue biopsy generally shows increased keratin build up with or without abnormal cells, but is not diagnostic.[4][6] Other conditions that can appear similar include yeast infectionslichen planus, and keratosis due to repeated minor trauma.[4] The lesions from a yeast infection can typically be rubbed off while those of leukoplakia cannot.[4][13]

    Treatment recommendations depend on features of the lesion.[4] If abnormal cells are present or the lesion is small surgical removal is often recommended; otherwise close follow up at three to six month intervals may be sufficient.[4] People are generally advised to stop smoking and limit the drinking of alcohol.[3] In potentially half of cases leukoplakia will shrink with stopping smoking;[5] however, if smoking is continued up to 66% of cases will become more white and thick.[6] The percentage of people affected is estimated at 1–3%.[4] Leukoplakia becomes more common with age, typically not occurring until after 30.[4] Rates may be as high as 8% in men over the age of 70.

    TREATMENT

    A systematic review found that no treatments commonly used for leukoplakia have been shown to be effective in preventing malignant transformation. Some treatments may lead to healing of leukoplakia, but do not prevent relapse of the lesion or malignant change.[8] Regardless of the treatment used, a diagnosis of leukoplakia almost always leads to a recommendation that possible causative factors such as smoking and alcohol consumption be stopped,[35] and also involves long term review of the lesion,[35] to detect any malignant change early and thereby improve the prognosis significantly.

    Predisposing factors and review[edit]

    Beyond advising smoking cessation, many clinicians will employ watchful waiting rather than intervene. Recommended recall intervals vary. One suggested program is every 3 months initially, and if there is no change in the lesion, then annual recall thereafter. Some clinicians use clinical photographs of the lesion to help demonstrate any changes between visits. Watchful waiting does not rule out the possibility of repeated biopsies.[3] If the lesion changes in appearance repeat biopsies are especially indicated.[2] Since smoking and alcohol consumption also places individuals at higher risk of tumors occurring in the respiratory tract and pharynx, “red flag” symptoms (e.g. hemoptysis – coughing blood) often trigger medical investigation by other specialties.[3]

    Surgery[edit]

    Surgical removal of the lesion is the first choice of treatment for many clinicians. However, the efficacy of this treatment modality cannot be assessed due to insufficient available evidence.[8] This can be carried out by traditional surgical excision with a scalpel, with lasers, or with eletrocautery or cryotherapy.[35] Often if biopsy demonstrates moderate or severe dysplasia then the decision to excise them is taken more readily. Sometimes white patches are too large to remove completely and instead they are monitored closely. Even if the lesion is completely removed, long term review is still usually indicated since leukoplakia can recur, especially if predisposing factors such as smoking are not stopped.[2]

    Medications[edit]

    Many different topical and systemic medications have been studied, including anti-inflammatoriesantimycotics (target Candida species), carotenoids (precursors to vitamin A, e.g. beta carotene), retinoids (drugs similar to vitamin A), and cytotoxics, but none have evidence that they prevent malignant transformation in an area of leukoplakia.[8]Vitamins C and E have also been studied with regards a therapy for leukoplakia.[2] Some of this research is carried out based upon the hypothesis that antioxidant nutrients, vitamins and cell growth suppressor proteins (e.g. p53) are antagonistic to oncogenesis.[2] High doses of retinoids may cause toxic effects.[8] Other treatments that have been studied include photodynamic therapy.[8]

    Prognosis[edit]

    White patch on left buccal mucosa. Biopsy showed early squamous cell carcinoma. The lesion is suspicious because of the presence of nodulesNodular leukoplakia in right commissure. Biopsy showed severe dysplasia

    The annual malignant transformation rate of leukoplakia rarely exceeds 1%,[8] i.e. the vast majority of oral leukoplakia lesions will remain benign.[30] A number of clinical and histopathologic features are associated with varying degrees of increased risk of malignant transformation, although other sources argue that there are no universally accepted and validated factors which can reliably predict malignant change.[30] It is also unpredictable to an extent if an area of leukoplakia will disappear, shrink or remain stable.[36]

    • Presence and degree of dysplasia (mild, moderate or severe/carcinoma in situ). While the degree of dysplasia has been shown to be an important predictor of malignant change,[3] many have challenged its use due to the low predictive value from the lack of objectivity of grading dysplasia.[37][38][39] While 10% of leukoplakia lesions show dysplasia when biopsied,[8] as many as 18% of oral lesions undergo malignant change in the absence of dysplasia.[40]
    • Leukoplakia located on the floor of the mouth, the posterior and lateral tongue, and the retromolar areas (the region behind the wisdom teeth) have higher risk, whereas white patches in areas such as the top surface of the tongue and the hard palate do not have significant risk.[3] Although these “high risk” sites are recognized, statistically, leukoplakia is more common on the buccal mucosa, alveolar mucosa, and the lower labial mucosa.[28] Leukoplakia of the floor of the mouth and tongue accounts for over 90% of leukoplakias showing dysplasia or carcinoma on biopsy.[2] This is thought to be due to pooling of saliva in the lower part of the mouth, exposing these areas to more carcinogens held in suspension.
    • Red lesions (erythroplasia) and mixed red and white lesions (erythroleukoplakia/”speckled leukoplakia”) have a higher risk of malignant change than homogenous leukoplakia.[14]
    • Verrucous or nodular areas have a higher risk.[3]
    • Although smoking increases risk of malignant transformation, smoking also causes many white patches with no dysplasia.[3] This means that statistically, white patches in non smokers have a higher risk.[2]
    • Older people with white patches are at higher risk.[3]
    • Larger white patches are more likely to undergo malignant transformation than smaller lesions.[3]
    • White patches which have been present for a long period of time have higher risk.[3]
    • Persons with a positive family history of cancer in the mouth.[3]
    • Candida infection in the presence of dysplasia has a small increased risk.[3]
    • A change in the appearance of the white patch, apart from a change in the color, has a higher risk.[3] Changes in the lesion such as becoming fixed to underlying tissues, ulceration, cervical lymphadenopathy (enlargement of lymph nodes in the neck), and bone destruction may herald the appearance of malignancy.[27]
    • White patches present in combination with other conditions that carry a higher risk (e.g. oral submucous fibrosis), are more likely to turn malignant.[3]
    • Although overall, oral cancer is more common in males, females with white patches are at higher risk than men.[3]
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