Varix (plural: varices)

DESCRIPTION:  Varices appear as red, blue, or deep purple broad-based elevations in  oral mucosa. The size is usually less than 5 mm. The buccal mucosa is a common place to find them, however, they are also found in lip mucosa and ventral and lateral mucosa of the tongue and floor of the mouth. On ventral tongue they are apt to be multiple and the term "caviar tongue" has been commonly used to describe them. They are seen more commonly in the elderly.

ETIOLOGY:  A varix is a distended vein that elevates the overlying mucosa.  The reason  for  venous  distention  is unclear  but  may  be  related  to  weakening  of  the  vessel wall secondary to aging.

TREATMENT:  None usually required. They often thrombose but this is of little clinical consequence.

PROGNOSIS:  Good

DIFFERENTIAL DIAGNOSIS:  Mucocele, hemangioma and angina bullosa hemorragica. 

Snuff lesion (smokeless tobacco lesion)

DESCRIPTION:  The lesion develops on the mucosa where smokeless tobacco is held.  The usual appearance is white, wrinkled or corrugated mucosa. Gingival recession is a  common manifestation with cervical erosion of teeth a less frequent finding. Symptoms are uncommon.

ETIOLOGY:    Prolonged  use  of  smokeless  tobacco  produces such as chewing tobacco or snuff.

TREATMENT:  Biopsy should be done to rule out dysplasia, otherwise no treatment is necessary.

PROGNOSIS:  Verrucous and squamous carcinomas arise in smokeless tobacco lesions more than chance alone can explain. One article noted almost a 50-fold increased risk of cancers of the gingival  and  buccal  mucosa in females who were chronic users. The duration necessary   to   induce   dysplastic   or   malignant   change   is unknown but appears to be at least 20 years.

DIFFERENTIAL  DIAGNOSIS:   The clinical appearance of the  lesion  plus  a  history  of  using  smokeless  tobacco establishes the diagnosis.

Acquired immune deficiency syndrome (AIDS) and its oral manifestations

Description:  Acquired immune deficiency syndrome is characterized by relentless destruction of CD4 T lymphocytes, key cells of the immune system. The eventual collapse of both the cellular and humoral arms of immunity leaves the host vulnerable to  a wide variety of pathogenic organisms including bacteria, viruses, fungi and protozoa.  It is important for health care workers to recognize that it is difficult to transmit the AIDS virus in the health care setting, from patient to worker or the reverse. However, opportunistic infectious diseases that AIDS patients are apt to have including tuberculosis, herpes-virus infections, hepatitis B and hepatitis C are readily transmissible.

Etiology:  The causes of AIDS is an RNA  retrovirus of the lentivirus group. It is designated the human immunodeficiency virus (HIV) and there are several variants:  HIV- 1 is the most common cases of AIDS. The virus attaches to the surface of cells that bear the  CD4  receptor  including  helper  T  lymphocytes,  B  lymphocytes  and  macrophages.

Although they lack a CD4 receptor, microglia, skin fibroblasts, and bowel epithelium become  infected.  The  virus  destroys  the  infected  cells.  With  gradual  depletion  of  the cells of immunity, especially T-helper lymphocytes and macrophages, the host becomes increasingly vulnerable to pathogenic organisms.

Oral Manifestations:

Candidiasis  -  Colonization  and  infection  of  the  oral  mucosa  by  Candida  species  is among the earliest and most common findings in HIV-infected patients. In one study, 88% had oral candidiasis. Lesions range from white to red or red/white combinations.

Fig. 1 illustrates the typical appearance of candidiasis. The lesions may be asymptomatic or there may be mild discomfort. For stubborn infection, fluconazole is recommended.  

Kaposi's  sarcoma  -  AIDS  patients  are  vulnerable  to  a  variety  of  oral  malignancies including Kaposi's sarcoma, malignant lymphoma and squamous carcinoma. Kaposi's sarcoma is the most common. In one study, 20% of AIDS patients had Kaposi's sarcoma and of these, the tumor was in the oral cavity in 1 of every 5 patients; the palate is the most common site. In the early stage, the tumor appears as a red to purple bruise (Fig. 2). The tumor grows and eventually appears as a hemorrhagic mass (Fig. 3). The cell of origin  is  endothelium;  thus  Kaposi's  sarcoma  is  a  variety  of  angiosarcoma.  They  are locally invasive, cause pain and bleeding and interfere with normal function. Low-dose radiation  therapy  and  intralesional  or  systemic  chemotherapy  are  the  treatments  of choice. Herpes virus type VIII is thought to play a role in the pathogenesis of this tumor.

Hairy leukoplakia  -  This  variety  of  leukoplakia  was  first  recognized  in  HIV-infected patients but has been encountered in other immune deficiency states such as organ transplant patients who are intentionally immune suppressed. The lateral tongue is the most common location (Fig. 4). Lesions are of rough texture, adherent and asymptomatic. The diagnosis of hairy leukoplakia can be suspected on routine biopsy specimens, but confirmation requires demonstration of the presence of the causative virus, the Epstein-Barr herpesvirus. This is ordinarily achieved by DNA in situ hybridization. A word of caution: hairy leukoplakia may be confused with candidiasis. A patient who presents with a white lesion should be treated with antifungal therapy first. If it fails to heal, it most likely is hairy leukoplakia.

Gingival and periodontal lesions  - HIV-infected patients are vulnerable to necrotizing gingivitis and periodontitis (Fig. 5). The organisms recovered from these lesions are the same as those in non-HIV-positive patients. Lesions are treated by dental prophylaxis, debridement, and metronidazole. Good oral hygiene and daily rinses with chlorhexidine are beneficial.

Others - HIV patients also develop major aphthous-like lesions that respond to tetracycline and topical steroid therapy.

Thalidomide has been used successfully in their management. The human papillomavirus has also been found in both condylomas and focal epithelial hyperplasia. Cytomegalovirus infections and several fungal infections such as histoplasmosis  and  coccidiodomycosis  are  also  common.  Lastly,  xerostomia  secondary  to  salivary  gland  destructions  has  been reported. 

Leukoedema

Leukoedema was first described in 1953 by Sandstead and Lowe. 

DESCRIPTION:   Leukoedema id characterized by a widespread whitening of the inner lining of the cheek oe other mouth tissues, due to an increase in the amount of fluid being retained by the skin’s cells. Leukoedema is persistant, and is most common in indivuals with dark skin. The cause of this condition is unknown.

Leukoedema is much like another abnormal condition, leukoplakia, in that both give the inner mouth tissues a white appearance. A simple test t overify the condition is to streatch the skin over the fingers; is the normal pink colour returns, it is leukoema. It is important that we distinguish leukoedema from leukoplakia, as leukoplakia can be pre-cancerous condition and should be biopsied for accurate diagnosis.

Leukoedema appears as a filmy, opaque, and white to slate gray discoloration of mucosa, chiefly buccal mucosa. Redundancy of the mucosa may impart a folded or wrinkled appearance to the relaxed mucous membrane. It partially disappears when the mucosa is stretched. It is stated to be seen in 90% of Blacks and 10-90% in Whites. This variation may be due to the difficulty in observation of leukoedema in  non-pigmented mucosa. Leukoedema is accentuated in smokers.

ETIOLOGY:   Leukoedema  is  a  variation  of  normal  that  should   not   be   confused   with   something   ominous.  Intracellular edema of the superficial epithelial cells coupled with retention of superficial parakeratin is thought to  account for the white appearance. Microscopic examination  reveals  superficial  squamous  cells  have  a  clear, seemingly  empty  cytoplasm  but  it  has  not  been  shown that there is an increase in intracellular water. Thus, the  term edema is questionable.

TREATMENT:  None required.

PROGNOSIS:  Good

DIFFERENTIAL DIAGNOSIS:  White sponge nevus, hereditary benign intraepithelial dyskeratosis, and dyskeratosis  congenital. All are extremely rare. 

Leukoedema

Leukoplakia-Definition, Epidemiology, Clinical presentation, Aetiopathogenisis, Diagnosis, Treatment, Prognosis and complication, Prevention

Definition

Leukoplakia is the most common premalignant or "potentially malignant" lesion of the oral mucosa.

Leukoplakia is a predominantly white lesion of the oral mucosa than cannot be clinicopathologically characterized as any other definable lesion.

The term leukoplakia is a clinical descriptor only and should not be used once histological information is available. On the other hand, the terms keratosis and dyskeratosis are histological features and should not be used as clinical terms.

Based on clinical examinations a provisional diagnosis of leukoplakia is made when the lesion cannot be clearly diagnosed as any other disease of the oral mucosa with a white appearance. A definitive diagnosis is made as a result of the identification, and if possible elimination, of suspected etiological factors and, in the case of persistent lesions, histopathological examination confirm the diagnosis.

Epidemiology

The incidence and prevalence of leukoplakia vary in different parts of the world.

In general the reported prevalence ranges from 0.2 to 5%, with remarkable regional differences: India (0.2-4.9%), Sweden (3.6%), Germany (1.6%), Holland (1.4%).

Leukoplakia is seen most frequently in middle-aged and older men.

Gender distribution is also variable. Men are more affected in some countries, while this is not the case in the Western world.

Clinical presentation

Leukoplakia can be either solitary or multiple.

Leukoplakia may appear on any site of the oral cavity, the most common sites being: buccal mucosa, alveolar mucosa, floor of the mouth, tongue, lips and palate.

Classically two clinical types of leukoplakia are recognised: homogeneous and non-homogeneous, which can co-exist.

Homogeneous leukoplakia is defined as a predominantly white lesion of uniform flat and thin appearance that may exhibit shallow cracks and that has a smooth, wrinkled or corrugated surface with a consistent texture throughout. This type is usually asymptomatic.

Non-homogeneous leukoplakia has been defined as a predominant white or white-and-red lesion ("eritroleukoplakia") that may be either irregularly flat, nodular ("speckled leukoplakia) or exophytic ("exophytic or verrucous leukoplakia"). These types of leukoplakia are often associated with mild complaints of localised pain or discomfort.

Proliferative verrucous leukoplakia is an aggressive type of leukoplakia that almost invariably develops into malignancy. This type is characterised by widespread and multifocal appearance, often in patients without known risk factors.

In general, non-homogeneous leukoplakia has a higher malignant transformation risk, but oral carcinoma may develop from any leukoplakia.

Aetiopathogenesis

The aetiology of leukoplakia is still unclear. Although, tobacco seems to be the major inductor factor, its association cannot be determined in all cases.

A variety of smokeless tobacco habits have been reported as leukoplakia inductors: e.g. snuff, chewing. These lesions have shown to have a low malignant transformation risk.

A higher malignant transformation rate has been reported in Candida-infected leukoplakias. However, there is not an agreement of how this lesion should be named "Candida-leukoplakia" or "hyperplastic candidosis", and whether Candida infection is the cause of leukoplakia or is an infection superimposed in a pre-existing lesion.

The possible implication of human papillomavirus (HPV) and others virus has been studied. High risk HPV (16 and 18) have been associated with oral cancer.

Other factors such as alcohol, inadequate diet, vitamin deficiency (e.g. vitamin A and C), areca nut (betel), different mouthwashes, chronic traumatic irritation, poor oral hygiene, poor socio-economic status, galvanism, and even genetic factors have considered and studied in leukoplakia.

Diagnosis

Leukoplakia diagnosis has clinical and histopathological approaches.

- Provisional Clinical Diagnosis: clinical evidence from a single visit, using inspection and palpation as the only diagnostic means.

- Definitive Clinical Diagnosis: clinical evidence obtained by lack of changes after eliminating suspected etiologic factors during a follow-up period of 2-4 weeks (In some cases the time may be longer).

- Histopathologically Proven Diagnosis: definitive clinical diagnosis complemented by biopsy in which, histopathologically, no other definable lesion is observed.

Differential diagnosis includes lichen planus, lupus, leukoedema, candidosis, white sponge naevus, frictional lesions, morsicatio lesions, contact lesions, and smoker’s palate.

Histopathological study of leukoplakia allows the clinician: 1.- to exclude any other definable lesions; and 2.- to establish the degree of epithelial dysplasia, if present.

It may be hazardous to just observe a white lesion without having taken a biopsy. It is important to biopsy the clinically most suspicious areas, especially the non-homogeneous zones or any associated red areas.

Other diagnostic methods such toluidine blue staining or Lugol’s iodine, mycological culture and cytology might be helpful, but they do not replace the biopsy.

Treatment

There are different treatments for leukoplakia, which have shown different results.

However, the risk of malignant transformation is not completely eliminated by any of the current therapies.

Initial treatment of a white oral lesion is the elimination of the possible aetiological factors: e.g. trauma, Candida, tobacco use etc. Complete and definitive cessation of tobacco is obligatory in patients with leukoplakia.

Presence of epithelial dysplasia in persistent lesions is a crucial aspect to consider, although measurement of DNA ploidy may be more reliable.

Complete surgical removal (leaving free-lesion borders) is recommended in cases with epithelial dysplasia. In cases without epithelial dysplasia the decision concerning further treatment or not, is influenced by the extent and location of the lesion as well as the patient ‘s medical condition.

Apart from surgical excision, other treatment modalities available include cryosurgery, laser surgery, retinoids, beta-carotene, bleomycin, calcipotriol, photodynamic therapy, etc.

The major drawbacks for most current agents are the frequency of adverse effects and the recurrence of lesions when treatment is discontinued.

Prognosis and complication

The malignant transformation rate of oral leukoplakia varies from 0 to 33%. Overall, 3 to 8% of leukoplakias develop malignant transformation in a average follow-up period of five years.

Any leukoplakia could transform into a carcinoma, even those which did not show epithelial dysplasia initially (or in which dysplasia happened to be absent from the biopsy taken). The main problem is that the malignant transformation cannot be reliably predicted yet. Nonetheless, some data could help identifying the possible risk. Leukoplakias show a high transformation risk when they: 1.- affect women; 2.- persist for long periods; 3.- appear in non smokers, 4.- are located on the floor of the mouth or tongue; 5.- are seen in patients with a previous head and neck carcinoma; 6.- are non- homogenous; 7.- are infected by Candida; 8.- show epithelial dysplasia, 9.- show DNA aneuploidy. Of all these factors the presence of epithelial dysplasia still seems to be the most important indicator of malignant potential but ploidy may soon be more useful.

Some leukoplakias show an increased recurrence rate (proliferative verrucous leukoplakia; PVL). On the other hand, some leukoplakias disappear spontaneously without any specific therapy.

Regular check-up of these patients is essential, probably every 3, 6 and then 12 months, both in treated and untreated patients.

Prevention

There is no known therapy to prevent development of oral leukoplakia and there is no known therapy to prevent oral squamous cell carcinoma developing from oral leukoplakia;.

It has been demonstrated that a healthy life style and the abstinence of tobacco are the best way to prevent both.

Fresh fruits and vegetables may have a protective effect in the primary prevention of oral cancer and precancer.

Early diagnosis and treatment of leukoplakia, can reduce the high rates of oral cancer morbidity and mortality in many countries.

Screening programs for oral cancer and precancer may be indicated in individuals at risk, such as predetermined age (40-70 years), gender (males in some countries), risk habits (tobacco/alcohol users) and in certain geographic areas with a high incidence of oral cancer.

Leukoplakia of the buccal mucosa

Leukoplakia of the gingiva

Leukoplakia of the lateral tongue

Leukoplakia, histological aspect

Leukoplakia, verrucous variant