User:Ian Furst/leukoplakia sign

User:Ian Furst/Dysplasia (mouth) User:Ian Furst/leukoplakia

Definition
The word leukoplakia means "white patch", and is derived from the Greek words λευκός - "white" and πλάξ - "plate". Leukoplakia is a diagnosis of exclusion, meaning that what lesions are included depends upon what diagnoses are currently considered acceptable. Accepted definitions of leukoplakia have changed over time and are still controversial. It is possible that the definition will be further revised as new knowledge becomes available.

In 1984 an international symposium agreed upon the following definition: "a whitish patch or plaque, which cannot be characterized clinically or pathologically as any other disease, and is not associated with any physical or chemical agent except the use of tobacco." There were however problems and confusion in applying this definition. At a second international symposium held in 1994 it was argued that whilst tobacco was a likely causative factor in the development of leukoplakia, some white patches could be linked directly to the local effects of tobacco by virtue of their disappearance following smoking cessation, suggesting that this kind of white patch represents a reactive lesion to local tissue irritation rather than a lesion caused by carcinogens in cigarette smoke, and could be better termed to reflect this etiology, e.g. smokers' keratosis. The second internal symposium therefore revised the definition of leukoplakia to: "a predominantly white lesion of the oral mucosa that cannot be characterized as any other definable lesion." This description is supported by the World Health Organization.

The term has been incorrectly used to describe white patches of any cause (rather than specifically referring to idiopathic white patches) and also to refer only to white patches which have a risk of malignant transformation. It has been suggested that leukoplakia is an unhelpful term since there is so much inconsistency surrounding its use, and some clinicians now avoid using it at all.

Associated medical conditions
There are many known conditions which present with a white lesion of the oral mucosa, but the majority of oral white patches have no known cause. These are termed leukoplakia once other likely possibilities have been ruled out. There are also few recognized subtypes of leukoplakia, described according to the clinical appearance of the lesion.

Almost all oral white patches are usually the result of keratosis. For this reason oral white patches are sometimes generally described as keratoses, although a minority of oral white lesions are not related to hyperkeratosis, e.g. epithelial necrosis and ulceration caused by a chemical burn (see: Oral ulceration). In keratosis, the thickened keratin layer absorbs water from saliva in the mouth and appears white in comparison with normal mucosa. Normal oral mucosa is a red-pink color due the underlying vasculature in the lamina propria showing through the thin layer of epithelium. Melanin produced in the oral mucosa also influences the color, with a darker appearance being created by higher levels of melanin in the tissues (associated with racial/physiologic pigmentation, or with disorders causing melanin overproduction such as Addison's disease). Other endogenous pigments can be overproduced to influence the color, e.g. bilirubin in hyperbilirubinemia or hemosiderin in hemochromatosis, or exogenous pigments such as heavy metals can be introduced into the mucosa, e.g. in an amalgam tattoo.

Almost all white patches are benign, i.e. non-malignant. The differential diagnosis of a white lesion in the mouth can be considered according to a surgical sieve (see table).

Leukoplakia cannot be rubbed off the mucosa, distinguishing it readily from white patches such as pseudomembraneous candidiasis, where a white layer can be removed to reveal an erythematous, sometimes bleeding surface underneath. The white color associated with leukoedema disappears when the mucosa is stretched. A frictional keratosis will generally be adjacent to a sharp surface such as a broken tooth or rough area on a denture and will disappear when the causative factor is removed. Some have a suggested as general rule that any lesion that does not show signs of healing within 2 weeks should be biopsied. Morsicatio buccarum and linea alba are located at the level of the occlusal plane (the level at which the teeth meet). A chemical burn has a clear history of placing an aspirin tablet (or other caustic substance such as eugenol) against the mucosa in an attempt to relieve toothache. Developmental white patches usually are present from birth or become apparent earlier in life, whilst leukoplakia generally affects middle aged or elderly people. Other causes of white patches generally require pathologic examination of a biopsy specimen to distinguish with certainty from leukoplakia.

Classification
Leukoplakia could be classified as mucosal disease, and also as a premalignant condition. Although the white color in leukoplakia is a result of hyperkeratosis (or acanthosis), similarly appearing white lesions that are caused by reactive keratosis (smoker's keratosis or frictional keratoses e.g. morsicatio buccarum) are not considered to be leukoplakias. Leukoplakia could also be considered according to the affected site, e.g. oral leukoplakia, leukoplakia of the urinary tract, including bladder leukoplakia or leukoplakia of the penis, vulvae, cervix or vagina. Leukoplakia may also occur in the larynx, possibly in association with gastro-esophageal reflux disease. Oropharyngeal leukoplakia is linked to the development of esophageal squamous cell carcinoma, and sometimes this is associated with tylosis, which is thickening of the skin on the palms and soles of the feet (see: Leukoplakia with tylosis and esophageal carcinoma). Dyskeratosis congenita may be associated with leukoplakia of the oral mucosa and of the anal mucosa.

Esophageal leukoplakia
Leukoplakia of the esophagus is rare compared to oral leukoplakia. The relationship with esophageal cancer is unclear because the incidence of esophageal leukoplakia is so low. It usually appears as a small, nearly opaque white lesion that may resemble early esophageal squamous cell carcinoma. The histologic appearance is similar to oral leukoplakia, with hyperkeratosis and possible dysplasia.

Leukoplakia of the bladder
In the context of lesions of the mucous membrane lining of the bladder, leukoplakia is a historic term used to describe a visualized white patch which histologically represents keratinization in an area of squamous metaplasia. The symptoms may include frequency, suprapubic pain (pain felt above the pubis), hematuria (blood in the urine), dysuria (difficult urination or pain during urination), urgency, and urge incontinence. The white lesion may be seen during cystoscopy, where it appears as a whitish-gray or yellow lesion, on background of inflamed urothelium and there may be floating debris in the bladder. Leukoplakia of the bladder may undergo malignant transformation, so biopsy and long term follow up are usually indicated.

Oral leukoplakia
Within the mouth, leukoplakia is sometimes further classified according to the site involved, e.g. leukoplakia buccalis (leukoplakia of the buccal mucosa) or leukoplakia lingualis (leukoplakia of the lingual mucosa). There are two main clinical variants of oral leukoplakia, namely homogenous leukoplakia and non-homogenous (heterogenous) leukoplakia, which are described below. The word leukoplakia is also included within the nomenclature of other oral conditions which present as white patches, however these are specific diagnoses which are generally considered separate from leukoplakia, with the notable exception of proliferative verrucous leukoplakia, which is a recognized sub-type of leukoplakia.

Homogenous leukoplakia
Homogenous leukoplakia (also termed "thick leukoplakia") is usually well defined white patch of uniform, flat appearance and texture, although there may be superficial irregularities. Homogenous leukoplakia is usually slightly elevated compared to surrounding mucosa, and often has a fissured, wrinkled or corrugated surface texture, with the texture generally consistent throughout the whole lesion. This term has no implications on the size of the lesion, which may be localized or extensive. When homogenous leukoplakia is palpated, it may feel leathery, dry, or like cracked mud.

Non-homogenous leukoplakia
Non-homogenous leukoplakia is a lesion of non-uniform appearance. The color may be predominantly white or a mixed white and red. The surface texture is irregular compared to homogenous leukoplakia, and may be flat (papular), nodular or exophytic. "Verrucous leukoplakia" (or "verruciform leukoplakia") is a descriptive term used for thick, white, papillary lesions. Verrucous leukoplakias are usually heavily keratinized and are often seen in elderly people. Some verrucous leukoplakias may have an exophytic growth pattern, and some may slowly invade surrounding mucosa, when the term proliferative verrucous leukoplakia may be used. Non-homogenous leukoplakias have a greater risk of malignant transformation than homogenous leukoplakias.

Proliferative verrucous leukoplakia
Proliferative verrucous leukoplakia (PVL) is a recognized high risk subtype of non-homogenous leukoplakia. It is uncommon, and usually involves the buccal mucosa and the gingiva (the gums). This condition is characterized by (usually) extensive, papillary or verrucoid keratotic plaques that tends to slowly enlarge into adjacent mucosal sites. An established PVL lesion is usually thick and exophytic (prominent), but initially it may be flat. Smoking does not seem to be as strongly related as it is to leukoplakia generally, and another dissimilarity is the preponderance for women over 50. There is a very high risk of dysplasia and transformation to OSCC or to verrucous carcinoma.

Erythroleukoplakia
Erythroleukoplakia (also termed speckled leukoplakia, erythroleukoplasia or leukoerythroplasia) is a non-homogenous lesion of mixed white (keratotic) and red (atrophic) color. Erythroplakia is an entirely red patch that cannot be attributed to any other cause. Erythroleukoplakia can therefore be considered a variant of either leukoplakia or erythroplakia since its appearance is midway between. Erythroleukoplakia frequently occurs on the buccal mucosa in the commisural area (just inside the cheek at the corners of the mouth) as a mixed lesion of white nodular patches on an erythematous background, although any part of the mouth may be affected. Erythroleukoplakia and erythroplakia have a higher risk of malignant transformation than homogeneous leukoplakia.

Sublingual keratosis
Sometimes this term is used to describe leukoplakia of the floor of mouth or under the tongue. It is not universally accepted to be a distinct clinical entity from idiopathic leukoplakia generally, as it is distinguished from the latter by location only. Usually sublingual keratoses are bilateral and possesses a parallel-corrugated, wrinkled surface texture described as "ebbing tide".

Candidal leukoplakia
Candidal leukoplakia is usually considered to be a largely historical synonym for a type of oral candidiasis, now more commonly termed chronic hyperplastic candidiasis, rather than a subtype of true leukoplakia. However, some sources use this term to describe leukoplakia lesions that become colonized secondarily by Candida species, thereby distinguishing it from hyperplastic candidiasis.

Oral hairy leukoplakia
Oral hairy leukoplakia is a corrugated ("hairy") white lesion on the sides of the tongue caused by opportunistic infection with Epstein-Barr virus on a systemic background of immunodeficiency, almost always human immunodeficiency virus (HIV) infection. This condition is not considered to be a true idiopathic leukoplakia since the causative agent has been identified. It is one of the most common oral lesions associated with HIV infection, along with pseudomembraneous candidiasis. The appearance of the lesion often heralds the transition from HIV to acquired immunodeficiency syndrome (AIDS).

Syphilitic leukoplakia
This term refers to a white lesion associated with syphilis, specifically in the tertiary stage of the infection. It is not considered to be a type of idiopathic leukoplakia, since the causative agent Treponema pallidum is known. It is now rare, but when syphilis was more common, this white patch usually appeared on the top surface of the tongue and carried a high risk of malignant transformation.


 * Pathophysiology or Mechanism

Diagnostic approach or Evaluation
CONSIDER MOVING APPEARANCE IN HERE AFTER TALKING WITH EXPERT Tissue biopsy is usually indicated to rule out other causes of white patches and also to enable a detailed histologic examination to grade the presence of any epithelial dysplasia. This is an indicator of malignant potential and usually determines the management and recall interval. The sites of a leukoplakia lesion that are preferentially biopsied are the areas that show induration (hardening) and erythroplasia (redness), and erosive or ulcerated areas. These areas are more likely to show any dysplasia than homogenous white areas.

Brush biopsy/exfoliative cytology is an alternative to incisional biopsy, where a stiff brush is scraped against the lining of the mouth to remove a sample of cells. This is then made into a smear which can be examined microscopically. Sometimes the biopsy site can be selected with adjunct methods which aim to highlight areas of dysplasia. Toluidine blue staining, where the dye is preferentially retained by dysplastic tissue, is sometimes used, but there is high false positive rate. Other methods involve the use of illuminescence, relying on either the property of normal autoflorescent molecules in mucosa such as collagen and keratin which is lost from areas of dysplasia or carcinoma under blue light, or by initially staining of the mucosa with toluidine blue or dilute acetic acid and examination under white light.


 * Treatment or Management (for the symptom itself, if any: e.g., analgesics for pain)
 * Epidemiology (incidence, prevalence, risk factors)

History
(of the science, not of the patient: e.g., "The oldest surviving description is in a medical text written by Avicenna.") The term "leukoplakia" was coined in 1861 by Rokintansky, who used it to describe white lesions of the urinary tract. In 1877 Schwimmer first used the term to describe an oral white lesion. It is now thought that this white lesion on the tongue represented syphilitic glossitis, a condition not included in the modern definitions of oral leukoplakia. Since, the word leukoplakia has been incorporated into the names for several other oral lesions (e.g. "candidal leukoplakia", now more usually termed hyperplastic candidiasis). In 1930 it was shown experimentally that leukoplakia could be induced in rabbits that were subjected to tobacco smoke for 3 minutes per day. According to one source from 1961, leukoplakia can occur on multiple different mucous membranes of the body, including in the urinary tract, rectum, vagina, uterus, vulva, paranasal sinuses, gallbladder, esophagus, eardrums, and pharynx. Generally, oral leukoplakia is the only context where the term is in common usage in modern medicine. In 1988, a case report used the term "acquired dyskeratotic leukoplakia" to describe an acquired condition in a female where dyskeratotic cells were present in the epithelia of the mouth and genitalia.


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