Premalignant Oral Lesions

Precancerous Oral Lesions

Precancerous Lesion

It is a benign, morphologically altered tissue that has a greater than normal risk of malignant transformation.
Leukoplakia Erythroplakia Erythroleukoplakia

Leukoplakia (leuko-white; plakia-patch)

Oral leukoplakia is defined by the WHO as a white patch or plaque that cannot be characterized clinically or pathologically as any other disease. Thus a diagnosis by exclusion. The term is strictly a CLINICAL one and does not imply a specific histopathologic tissue alteration. Leukoplakia is the most common oral precancer. How common is it according to Bouquots study???

Leukoplakia: Why is it White?

The clinical color (white) results from a thickened surface keratin layer (which appears white when wet) or a thickened spinous layer, which masks the normal vascularity (redness) of the underlying connective tissue.

Leukoplakia: A Premalignant or Precancerous Lesion

Although leukoplakia is not associated with a specific histopathologic diagnosis, it is considered to be a premalignant lesion for the risk of malignant transformation is greater in a leukoplakic lesion than that associated with normal or unaltered mucosa.

Leukoplakia

Despite the fact that leukoplakia is a premalignant lesion it should be noted that not every lesion shows histopathologic evidence of epithelial dysplasia or frank malignancy (squamous cell carcinoma). In fact, dysplastic epithelium or invasive carcinoma is found in only 5 to 25 % of the biopsy samples of leukoplakia.

Leukoplakia: Malignant Transformation Potential

Overall, the malignant transformation potential of leukoplakia is 4 % (estimated lifetime risk). However, specific clinical subtypes are associated with much high potential malignant transformation rates (as high as 47 %).

Leukoplakia: How Common Is It?

Leukoplakia is by far the most common oral precancer, accounting for 85 % of such lesions. (Note: this statement is not saying that leukoplakia has the highest malignant transformation risk of the premalignant group of lesions for erythroplakia [erythroplasia] does). Leukoplakia is also a relatively common lesion for it is estimated that approximately 3 % of all white adults will be affected at some time. Additionally, Bouquot in his study of oral mucosal lesions found it to be the most common of all.

Leukoplakia: Who Develops It?

There is a strong male predilection (70%), except in parts of the country where females use tobacco products more than males. Overall, there has been a slight decrease in the proportion of males affected over the past few decades. In general, leukoplakia is diagnosed more frequently now than in the past, probably because of enhance awareness.

Leukoplakia: Etiology

The cause of leukoplakia remains unknown. Over the years the following have been considered: tobacco, alcohol, sanguinaria, ultraviolet radiation, microorganisms and trauma.

Etiology of Leukoplakia: The Role of Tobacco

The habit of tobacco smoking appears most closely associated with leukoplakia development. 80 % of patients with leukoplakia are smokers. Smokers are much more likely to have leukoplakia than non-smokers. Heavier smokers have greater numbers of and larger lesions than light smokers. A large proportion of leukoplakias in peresons who stop smoking either disappear or become smaller soon after discontinuing the habit.

Etiology of Leukoplakia: The Role of Alcohol and Sanguinaria

Alcohol, which seems to have a strong synergistic effect with tobacco in oral cancer development, has not been associated with leukoplakia. Sanguinaria (blood root) is a herbal extract that has been used in toothpaste and moutwash. Over 80 % of the patients with vestibular/maxillary alveolar leukoplakias have a history of using a sanguinaria containing product as compared to 3 % of the normal population; some lesions have persisted after the patient stopped using the product.

Etiology of Leukoplakia: The Role of Ultraviolet Radiation

Ultraviolet radiation has been associated with leukoplakia of the vermilion of the lower lip. This leukoplakia is usually associated with actinic cheilosis.

Etiology of Leukoplakia: The Role of Microorganisms

Treponema pallidum has been implicated in leukoplakia of the dorsal surface of the tongue in patients with syphilis. Candida albicans has been demonstrated histologically in the hyperplastic/dysplastic epithelium of lesions termed candidal leukoplakia and candidal hyperplasia.

Etiology of Leukoplakia: The Role of Microorganisms Continued

Human papillomavirus (HPV), particularly subtypes 16 and 18, have been identified in some oral leukoplakias. However, HPV has also been demonstrated in normal oral epithelial cells.

Etiology of Leukoplakia: The Role of Trauma

Several keratotic lesions, which until recently have been viewed as variants of leukoplakia, are now considered not to be premalignant. Included in this group are lesions termed nicotine stomatitis and frictional keratosis. The keratoses are readily reversible after the elimination of the trauma or chronic irritation.

Leukoplakia: Clinical Features

Leukoplakia usually affects people over the age of 40 years (average age is 60 years). Prevalence increases rapidly with age particularly in males. Approximately 8 % of the males over the age of 70 years are reportedly affected.

Leukoplakia: Clinical Features Continued

Approximately 70 % of the oral leukoplakias are found on the lip vermilion, buccal mucosa and gingiva. Note: Lesions of the tongue, lip vermilion and floor of the mouth account for more than 90 % of those that show dysplasia or carcinoma upon histologic examination.

Leukoplakia: Clinical Features Continued

Individual lesions vary in clinical appearance and tend to change over time. Early/mild lesions usually appear as slightly elevated gray or gray-white plaques, which may appear translucent, fissured or wrinkled and are typically soft and flat. Early/mild lesions are usually well demarcated but may blend into the surrounding normal mucosa.

Leukoplakia: Clinical Features Continued

Early/mild thin leukoplakia, which seldom shows dysplasia on biopsy, may disappear or continue unchanged. If the cause (s) of the lesion are not removed, many lesions will gradually become thicker and larger. The clinical appearance (s) of leukoplakia and the anticipated underlying histopathologic changes are presented in the following diagram.

Proliferative Verrucous Leukoplakia (PVL)

PVL is a special high risk form of leukoplakia. It is characterized by multiple keratotic plaques with rough surface projections although initially beginning as a simple flat hyperkeratosis. PVL plaques tend to spread slowly, yet progressively. PVL usually transforms into a squamous cell carcinoma within about 8 years. PVL has a strong female predilection (1:4 male to female) and minimal association with tobacco usage.

Leukoplakia: Histopathologic Features

Leukoplakia is characterized by a thickened keratin layer (hyperkeratosis) with or without a thickened spinous layer (acanthosis). Some leukoplakias show surface hyperkeratosis but with atrophy or thinning of the underlying epithelium. Variable numbers of chronic inflammatory cells are typically noted within the underlying connective tissue.

Leukoplakia: Histopathologic Features Continued

While most leukoplakias show no dysplasia on biopsy, some 5 to 25 % of the cases do show evidence of epithelial dysplasia (or squamous cell carcinoma). The histopathologic alterations of dysplastic epithelial cells are outlined in the next slide.

Histopathologic Alterations of Dysplastic Epithelial Cells

Enlarged nuclei and cells. Large and prominent nucleoli. Increased nuclear-cytoplasmic ratio. Hyperchromatic (dark-staining) nuclei. Pleomorphic (abnormally shaped) nuclei and cells. Dyskeratosis (premature keratinization) Increased mitotic activity and abnormal mitotic figures

Histopathologic Alterations of Dysplastic Epithelium Continued

Bulbous or teardrop-shaped rete ridges. Loss of polarity (lack of progressive maturation toward the surface). Keratin or epithelial pearls. Loss of typical epithelial cell cohesiveness.

Leukoplakia: Treatment and Prognosis

Leukoplakia represents a clinical diagnosis and therefore the first step in treatment is to arrive at a definitive diagnosis via biopsy and histologic examination of the tissue. Treatment depends upon the diagnosis and any leukoplakia exhibiting moderate epithelial dysplasia or worse warrants complete removal if possible. Treatment of lesions exhibiting less severe changes is guided by the size of the lesion and its response to more conservative measures such as eliminating tobacco use.

Leukoplakia: Treatment and Prognosis Continued

Leukoplakia not exhibiting dysplasia often is not excised but clinical evaluation every 6 months is recommended. Additional biopsies are recommended if smoking continues or if clinical changes increase in severity. The following diagram represents the various clinical appearance of oral leukoplakia and the anticipated underlying associated histopathologic changes.

Leukoplakia: Treatment and Prognosis Continued

Complete removal of oral leukoplakia can be accomplished with equal effectiveness by surgical excision, electrocautery, cryosurgery or laser ablation. Long-term follow-up after removal is mandatory because of recurrence potential and because new leukoplakias may occur. Malignant transformation potential is related to clinical appearance and the degree of dysplasia present.

Erythroplakia: Definition

Erythroplakia is defined as a red patch that cannot be clinically or pathologically diagnosed as any other condition. Erythroplasia is occasionally used as a synonym for erythroplakia although it was originally used by Queyrat to describe a precancerous red lesion of the penis.

Erythroplakia

Almost all true erythroplakias demonstrate significant epithelial dysplasia, carcinoma in situ or invasive squamous cell carcinoma. The cause (s) of erythroplakias are unknown but presumed to be the same as those associated with squamous cell carcinoma.

Erythroplakia

Erythroplakia is far less common than leukoplakia but has a much greater potential to be severely dysplastic at the time of biopsy or to develop invasive malignancy at a later time. Erythroplakia can occur in conjunction with leukoplakia and has been found concurrently with a large proportion of early invasive oral carcinomas.

Erythoplakia: Clinical Features

It is predominantly a disease of older males with a peak prevalence between the ages of 65 and 74 years. The floor of the mouth, tongue and soft palate are the most commonly involved sites. Multiple lesions may occur. Early erythroplakias appear as well-demarcated erythematous macules or plaques with a soft velvety texture. Unfortunately, it is usually asymptomatic.

Erythroplakia: Histopathologic Features

Approximately 90 % of these lesions represent either severe epithelial dysplasia, carcinoma in situ, or superficially invasive carcinoma. Typically the epithelium shows a lack of keratin production and is often atrophic. This lack of keratinization, coupled with epithelial thinness allows the underlying microvasculature to show through imparting the red appearance.

Erythroplakia: Treatment and Prognosis

As with leukoplakia, the treatment is guided by the definitive diagnosis obtained by biopsy. Lesions exhibiting moderate dysplasia or worse must be completely removed. Recurrence and multifocal oral mucosal involvement necessitates long-term follow-up.

Erythroleukoplakia

This term is used for lesions that have both a red (Erythroplakia) and white (Leukoplakia) component. Formerly called either speckled erythroplakia or speckled leukoplakia depending upon which (red or white) accounted for the majority component.

Precancerous Oral Conditions

A precancerous condition is a disease or patient habit that does not necessarily alter the clinical appearance of the local tissue but is associated with a greater than normal risk of a precancerous lesion or cancer developing in that tissue.

Plummer-Vinson Syndrome (Paterson-Kelly Syndrome)

This is an uncommon condition characterized by an iron-deficiency anemia with an associated glossitis and dysphagia. It is of significance because of its association with a high frequency of oral and esophageal squamous cell carcinoma.

Plummer-Vinson Syndrome: Clinical Features

This syndrome is most common in females between the ages of 30 and 50 years. It is more common in patients of Scandinavian and northern European background. Patients complain of a burning tongue/mouth. Angular cheilitis and a smooth red tongue are often presenting features. Dysplasia (difficulty) or pain on swallowing are often manifestations of esophageal webs (abnormal tissue bands in the esophagus).

Plummer-Vinson Syndrome: Clinical Features Continued

Another sign involves the nails, which are often spoon-shaped (koilonychia) and may be brittle. The symptoms of anemia such as fatigue, shortness of breath and weakness often lead the patient to seek medical care.

Plummer-Vinson Syndrome: Laboratory & Microscopic Features

Hematologic studies show a hypochromic, microcytic anemia consistent with irondeficiency anemia. Biopsy of the oral mucosa reveals epithelial atrophy with submucosal inflammation. In advanced case one may see epithelial atypia, dysplasia, carcinoma in situ or frank squamous cell carcinoma.

Plummer-Vinson Syndrome: Treatment and Prognosis

Treatment centers on correcting the irondeficiency anemia and if this is successful, the glossodynia and esophageal symptoms improve. Patients should be evaluated periodically for oral, pharyngeal and esophageal cancer. The frequency of malignancy in these patients has ranged from 5 to 50 % in the literature.

Oral Submucous Fibrosis: Clinical Features

Oral lesions appear as areas of opacification with loss of elasticity. Fibrous bands may occur. Any region of the oral cavity may be affected.

Oral Submucous Fibrosis: Cause

This lesion may be a result of a hypersensitivity reaction to dietary constituents such as betel nut, capsaicin, etc.

Oral Submucous Fibrosis: Treatment

No treatment has been consistently effective. Intralesional corticosteroids, surgical splitting or excision of the fibrous band have been helpful in some cases.

Oral Submucous Fibrosis: Significance

The greatest significance is that oral submucous fibrosis is a high-risk precancerous condition. Additionally, these fibrous lesions are not reversible restricting many oral movements.