Clinical Features

WSN presents as an asymptomatic, folded, white lesion that may affect several mucosal sites (Fig. 3-2; Box 3-1). Lesions tend to be thickened and have a spongy consistency. The presentation intraorally is almost always bilateral and symmetric and usually appears early in life, typically before puberty. The characteristic clinical manifestations of this particular form of keratosis are usually best observed on the buccal mucosa, although other areas such as the tongue and vestibular mucosa may also be involved. The conjunctival mucosa is usually spared, but mucosa of the esophagus, anus, vulva, and vagina may be affected.

Histopathology

Microscopically, the epithelium is greatly thickened, with marked spongiosis, acanthosis, and parakeratosis (Fig. 3-3). Within the stratum spinosum, marked hydropic or clear cell change may be noted, often beginning in the parabasal region and extending very close to the surface. Perinuclear eosinophilic condensation of cytoplasm is characteristic of prickle cells in WSN. It is often possible to see columns of parakeratin extending from the spinous layer to the surface.

Differential Diagnosis

The differential diagnosis includes hereditary benign epithelial dyskeratosis, lichen planus, lichenoid drug reaction, lupus erythematosus (LE), cheek chewing, and possibly candidiasis (Table 3-1). Once tissue diagnosis is confirmed, no additional biopsies are necessary.

Treatment

No treatment is necessary for this condition because it is asymptomatic and benign. Some may elect to manage this condition with tetracycline mouth rinses with good but transient effect.

Clinical Features

HBID presentation includes early onset (usually within the first year of life) of bulbar conjunctivitis, conjunctival plaques at the corneal limbus, and oral white lesions. Preceding the bulbar conjunctivitis are foamy gelatinous plaques that represent the ocular counterpart of the oral mucosal lesions.

Oral lesions consist of soft, asymptomatic, white folds and plaques of spongy mucosa. Areas characteristically involved include the buccal and labial mucosa and the labial commissures, as well as the floor of the mouth and lateral surfaces of the tongue, gingiva, and palate. The dorsum of the tongue is usually spared. Oral lesions are generally detected within the first year of life, with a gradual increase in intensity until mid-adolescence.

In some patients ocular lesions may vary seasonally, with spontaneous shedding of conjunctival plaques. Patients may complain of photophobia, especially in early life. Blindness, resulting from corneal vascularization, has been reported.

Histopathology

Similarities between oral and conjunctival lesions are noted microscopically. Epithelial hyperplasia and acanthosis are present with intracellular edema. Enlarged hyaline keratinocytes are the dyskeratotic elements that are present in the superficial half of the epithelium. Normal cellular features are noted within the lower spinous and basal layers. Inflammatory cell infiltration within the lamina propria is minimal, and the epithelium–connective tissue junction is well defined.

Treatment

No treatment is necessary because this condition is self-limiting and benign. It appears to pose no risk of malignant transformation. Genetic counseling may be sought.

Clinical Features

Onset occurs between the ages of 6 and 20 years. The disease has a predilection for the skin, with 13% of patients demonstrating oral lesions. Skin manifestations are characterized by small, skin-colored papular lesions symmetrically distributed over the face, trunk, and intertriginous areas. The papules eventually coalesce and feel greasy because of excessive keratin production. The coalesced areas subsequently form patches of vegetating to verrucous growths that have a tendency to become infected and malodorous. Lesions may also occur unilaterally or in a zosteriform pattern. Thickening of the palms and soles (hyperkeratosis palmaris et plantaris) by excessive keratotic tissue is not uncommon. Fingernail changes may include fragility, splintering, and subungual keratosis. Nail changes are often helpful in establishing a diagnosis.

The extent of the oral lesions may parallel the extent of skin involvement. Favored oral mucosal sites include the attached gingiva and hard palate. Lesions typically appear as small, whitish papules, producing an overall cobblestone appearance. Papules range from 2 to 3 mm in diameter and may become coalescent. Extension beyond the oral cavity into the oropharynx and pharynx may occur.

Histopathology

Oral lesions closely resemble the cutaneous lesions. Features include (1) formation of suprabasal lacunae (clefts) containing acantholytic epithelial cells, (2) basal layer proliferation immediately below and adjacent to the lacunae or clefts, (3) formation of vertical clefts that show a lining of parakeratotic and dyskeratotic cells, and (4) the presence of specific benign dyskeratotic cells—corps ronds and grains. Corps ronds are large, keratinized squamous cells with round, uniformly basophilic nuclei and intensely eosinophilic cytoplasm. Grains are smaller parakeratotic cells with pyknotic, hyperchromatic nuclei.

Treatment and Prognosis

Vitamin A analogs or retinoids have been used effectively, but long-term therapy is tolerated poorly. The disease is chronic and slowly progressive; remissions may be noted in some patients.

Clinical Features

Friction-induced hyperkeratoses occur in areas that are commonly traumatized, such as the lips, lateral margins of the tongue, buccal mucosa along the occlusal line, and edentulous alveolar ridges (Figs. 3-4 to 3-7; Box 3-2). Chronic cheek or lip chewing may result in opacification (keratinization) of the affected area. Chewing on edentulous alveolar ridges produces the same effect.

Histopathology

As the name indicates, the primary microscopic change is hyperkeratosis (Fig. 3-8). A few chronic inflammatory cells may be seen in the subjacent connective tissue.

Diagnosis

Careful history taking and examination should indicate the nature of this lesion. If the practitioner is clinically confident of a traumatic cause, no biopsy may be required. Patients should be advised to discontinue the causative habit, or the offending tooth or denture should be smoothed. The lesion should resolve or at least should be reduced in intensity over time, confirming the clinical diagnosis. Resolution of the lesion would allow unmasking of any underlying lesion that may not be related to trauma (Table 3-2). If the clinical diagnosis is in doubt, a biopsy should be taken.

Treatment

Observation is generally all that is required for simple frictional hyperkeratotic lesions. Control of the habit causing the lesion should result in clinical improvement. No malignant potential exists.

Etiology

A causal relationship has been documented between smokeless tobacco and white tissue changes. Although all forms of smokeless tobacco may cause alterations in the oral mucosa, snuff (particulate, finely divided, or shredded tobacco) appears to be much more likely to cause oral lesions than does chewing tobacco. Oral mucosa responds to the topically-induced effects of tobacco with inflammation and keratosis. At the molecular level, altered cell signaling and subsequent cell damage have been demonstrated. Dysplastic changes may follow, with a low potential risk of malignant change. Smokeless tobacco–induced alterations in tissues are thought to be a response to tobacco constituents and perhaps other agents that are added for flavoring or moisture retention. Carcinogens such as nitrosonornicotine, an organic component of chewing tobacco and snuff, have been identified in smokeless tobacco. The pH of snuff, which ranges between 8.2 and 9.3, may be another factor that contributes to the alteration of mucosa.

Duration of exposure to smokeless tobacco that is necessary to produce mucosal damage is measured in terms of years. It has been demonstrated that leukoplakia can be predicted with the use of three tins of tobacco per week or duration of the habit of longer than 2 years.

Clinical Features

White lesions associated with smokeless tobacco develop in the immediate area where the tobacco is habitually placed (Figs. 3-9 and 3-10; Box 3-3). The most common area of involvement is the mucobuccal fold of the mandible in the incisor or the molar region. The mucosa develops a granular to wrinkled appearance. In advanced cases, a heavy, folded character may be seen. Less often, an erythroplakic or red component may be admixed with the white keratotic component. The lesions are generally painless and asymptomatic, and their discovery is often incidental to routine oral examination.

Histopathology

Slight to moderate parakeratosis, often in the form of spires or chevrons, is noted over the surface of the affected mucosa (Fig. 3-11). Superficial epithelium may demonstrate vacuolization or edema. A slight to moderate chronic inflammatory cell infiltrate is typically present. Epithelial dysplasia may occasionally develop in these lesions, especially among long-time users of smokeless tobacco. On occasion, a diffuse zone of basophilic stromal alteration may be seen, usually adjacent to inflamed minor salivary glands.

Treatment and Prognosis

With discontinuation of smokeless tobacco use, some lesions may disappear after several weeks. It would be prudent to perform a biopsy on persistent lesions. A long period of exposure to smokeless tobacco increases the risk of transformation to verrucous or squamous cell carcinoma, although this risk is probably low.

Clinical Features

The palatal mucosa initially responds with an erythematous change followed by keratinization (Box 3-4). Subsequent to opacification or keratinization of the palate, red dots surrounded by white keratotic rings appear (Figs. 3-12 and 3-13). The dots represent inflammation surrounding the minor salivary gland excretory ducts.

Histopathology

Nicotine stomatitis is characterized by epithelial hyperplasia and hyperkeratosis (Fig. 3-14). The minor salivary glands in the area show inflammatory change, and excretory ducts may show squamous metaplasia.

Treatment and Prognosis

This condition rarely evolves into malignancy, except in individuals who reverse smoke. Although the risk of carcinoma development in the palate is minimal, nicotine stomatitis is a marker or indicator of intense tobacco use and hence may indicate increased risk of epithelial dysplasia and neoplasia elsewhere in the oral cavity, oropharynx, and respiratory tract. Therefore, nicotine stomatitis should be viewed as a potential indicator of significant epithelial change at sites other than the hard palate.

Clinical Features

Hairy leukoplakia presents as a well-demarcated white lesion that varies in architecture from a flat and plaquelike to a papillary/filiform or corrugated lesion (Figs. 3-15 and 3-16; Box 3-6). It may be unilateral or bilateral. A vast majority of cases have been located along the lateral margins of the tongue, with occasional extension onto the dorsal surface. Rarely, hairy leukoplakia may be seen on the buccal mucosa, the floor of the mouth, or the palate. Lesions have not been seen in the vaginal or anal mucosa.

In general, no associated symptoms have been reported, although associated infection with Candida albicans might call attention to the presence of this condition. In more severe cases, the patient may become visually aware of the lesion.

Histopathology

The characteristic microscopic feature of hairy leukoplakia is found in the nuclei of upper level keratinocytes (Fig. 3-17). Viral inclusions or peripheral displacement of chromatin with a resultant smudgy nucleus is evident. This is seen in the context of a markedly hyperparakeratotic surface, often with the formation of keratotic surface irregularities and ridges. C. albicans hyphae are often seen extending into the superficial epithelial cell layers. Beneath the surface, within the spinous cell layer, cells show ballooning degeneration and perinuclear clearing. A general paucity of subepithelial inflammatory cells has been noted, and Langerhans cells are scant.

In situ hybridization studies have demonstrated the presence of EBV within cells, showing nuclear inclusions and basophilic homogenization. Further confirmation has been accomplished by ultrastructural demonstration of intranuclear virions of EBV.

Differential Diagnosis

The clinical differential diagnosis of hairy leukoplakia includes idiopathic leukoplakia, frictional hyperkeratosis (tongue chewing), and leukoplakia associated with tobacco use. Other entities that might be considered are lichen planus, lupus erythematosus, and hyperplastic candidiasis.

Treatment and Prognosis

No specific treatment is available for hairy leukoplakia. For patients whose immune status is unknown and in whom biopsy findings indicate hairy leukoplakia, investigation for HIV infection or other causes of immunosuppression should be undertaken. Some discretion is required because a small percentage of patients with hairy leukoplakia is not associated with AIDS.

For cosmetic reasons, patients may request treatment of their lesions. Responses to acyclovir, ganciclovir, famciclovir, tretinoin, and podophyllum have been reported, with return of lesions often noted on discontinuation of therapy.

Approximately 10% of individuals with diagnosed hairy leukoplakia have AIDS at the time of diagnosis, and an additional 20% develop this disease in the following year. The probability that AIDS will develop in untreated HIV-positive individuals with HIV-associated hairy leukoplakia is approximately 50% within 1.5 years; within 2.5 years the probability is 80%.

Etiology

Numerous initiating or predisposing factors for hairy tongue have been identified. Broad-spectrum antibiotics, such as penicillin, and systemic corticosteroids are often identified in the clinical history of patients with this condition. In addition, oxygenating mouth rinses containing hydrogen peroxide, sodium perborate, and carbamide peroxide have been cited as possible etiologic agents in this condition. Hairy tongue may also be seen in individuals who are intense smokers, in those who have undergone radiotherapy to the head and neck region for malignant disease, and in patients who have undergone hematopoietic stem cell transplantation. The basic problem is believed to be related to an alteration in microbial flora, with attendant proliferation of fungi and chromogenic bacteria, along with papillary overgrowth.

Clinical Features

The clinical alteration translates to asymptomatic hyperplasia of the filiform papillae, with concomitant retardation of the normal rate of desquamation. The result is a thick, matted surface that serves to trap bacteria, fungi, cellular debris, and foreign material (Fig. 3-18; Box 3-7).

Hairy tongue is predominantly a cosmetic problem because symptoms are generally minimal. However, when extensive elongation of the papillae occurs, a gagging or a tickling sensation may be felt. The color may range from white to tan to deep brown or black, depending on diet, oral hygiene, oral medications, and the composition of the bacteria inhabiting the papillary surface.

Histopathology

Microscopic examination of a biopsy specimen confirms the presence of elongated filiform papillae over the dorsum of the tongue, with surface contamination by clusters of microorganisms and fungi. The underlying lamina propria is generally mildly inflamed.

Diagnosis

Because the clinical features of this lesion are usually quite characteristic, confirmation by biopsy is not necessary. Cytologic or culture studies are of little value.

Treatment and Prognosis

Identification of a possible etiologic factor, such as antibiotics or oxygenating mouth rinses, is helpful. Discontinuing one of these agents should result in improvement within a few weeks. In other patients, brushing with a slurry of sodium bicarbonate (baking soda) in water or gentle once-daily scraping of the dorsum of the tongue may be beneficial. In individuals who have undergone radiotherapy with resultant xerostomia and altered bacterial flora, management is more difficult. Brushing the tongue and maintaining fastidious oral hygiene should be of some benefit (application of a 1% solution of podophyllum resin with thorough rinsing has also been described as a useful treatment). It is important to emphasize to patients that this process is entirely benign and self-limiting, and that the tongue should return to normal after physical debridement and proper oral hygiene have been instituted.