Premalignant or precancerous (also referred to as “potentially malignant”) oral lesions involve the skin lining of the mouth (known as the epithelium) and may be at risk for becoming (transforming into) an oral cancer, although it is difficult to predict which lesions will transform and how long it will take (see below)
As we grow older our risk of developing cancer increases. The same is true for premalignant lesions. Most lesions are detected in people over the age of 40 and those with similar risk factors for oral cancer, such as tobacco and/or heavy alcohol use, although such lesions can also be found in younger individuals and/or those without classic risk factors.
1- Patches that are, red, white or mixed red/white in color, or that may also be ulcerated (ie an area where the lining epithelium is lost), especially when found on “high-risk” sites such as the side (lateral surface), underside of the tongue (ventral surface), floor of mouth, or at the back of mouth/top of the throat (oropharynx).
2- A white patch that cannot be wiped off with gauze and for which an explanation is not obvious to the dentist may be defined as a leukoplakia. Similarly, reddish patches with no obvious cause can be defined as erythroplakia and mixed red and white areas termed erythroleukoplakia .
3- Lesions with a red component carry the highest potential for being premalignant or becoming malignant. Some dentists use additional technologies to look for or characterize suspicious lesions (known as diagnostic adjuncts). It is essential to establish an accurate diagnosis for all such lesions that raise suspicion.
There are three possible outcomes: benign (most frequently), premalignant, or cancer. The pathology report will use pathologic diagnoses such as epithelial hyperplasia/hyperkeratosis or other benign diagnoses, epithelial dysplasia (for premalignant lesions), or squamous cell carcinoma (the most common type of cancer seen in the oral cavity). In epithelial dysplasia, the cells making up the layers of the epithelium look abnormal (atypia), and depending on the amount of abnormal cells seen microscopically, dysplasia may be graded as mild, moderate, severe, or carcinoma in situ (where the atypical cells are in all layers of the epithelium). In squamous cell carcinoma these abnormal cells are no longer confined just to the epithelium but have invaded below the epithelium into deeper tissues
Oral epithelial dysplasia is not associated with any specific clinical appearance. However, leukoplakia and erythroplakia are the lesions classically associated with dysplastic changes. Thus white, red, or mixed white and red changes are those most frequently revealing epithelial dysplasia. The frequency of epithelial dysplasia in leukoplakia varies between < 1 and > 30%
Patients with high-grade dysplasia (severe or carcinoma-in- situ) generally have a higher chance for malignant transformation than those with lower-grade dysplasias. It is extremely important that patients with oral epithelial dysplasia be followed by a specialist who is trained to manage these types of lesions. Eliminating high-risk behaviors and promoting protective behaviors (such as a healthy diet) are essential. Surgical removal of a premalignant lesion may or may not be warranted. Regardless of removal, periodic close follow-up of the patient for any visual changes to the lesion site is critical because lesions can recur and transformation into a malignant lesion is possible at anytime.
Loss of polarity of basal cells The presence of more than one layer of cells having a basaloid appearance Increased nuclear-cytoplasmic ratio Drop-shaped rete ridges Irregular epithelial stratification Increased number of mitotic figures Mitotic figures that are abnormal in form The presence of mitotic figures in the superficial half of the epithelium Cellular and nuclear pleomorphism Nuclear hyperchromatism Enlarged nuclei Loss of intercellular adherence Keratinization of single cells or cell groups in the prickle cell layer
Leukoplakia The term leukoplakia is sometimes used inappropriately to indicate a premalignant condition. In fact, the term describes a white plaque that does not rub off and cannot be clinically identified as another entity. Most cases of leukoplakia are a hyperkeratotic response to an irritant and are asymptomatic, but about 20% of leukoplakic lesions show evidence of dysplasia or carcinoma at first clinical recognition.
However, some anatomic sites (floor of mouth andventral tongue) have rates of dysplasia or carcinoma ashigh as 45%. There is no reliable correlation betweenclinical appearance and the histopathologic presenceof dysplastic changes except that the possibility ofepithelial
dysplasia increases in leukoplakic lesions with interspersed red areas. In one large study, lesions with an erythroplakic component had a 23.4% malignant transformation rate, compared with a 6.5% rate for lesions that were homogeneous. The term erythroleukoplakia has been used to describe leukoplakias with a red component.
Figure 1. Biopsy of leukoplakia in floor of mouth showing severe dysplasia/carcinoma in situ. Note normal epithelium in left side. The dysplastic area is especially characterized by an increased nuclear-cytoplasmic ratio, an increased number of mitotic figures including abnormal mitoses and mitoses occurring in the middle and upper parts of the epithelium, nuclear hyperchromatism, and enlarged nuclei. H&E, X90 Figure 2. Biopsy of leukoplakia at lateral border of the tongue showing mild to moderate epithelial dysplasia. Note normal stratification and cytology in superficial half of the epithelium. H&E, X190.
Erythroplakia An erythroplakia is a red lesion that cannot be classified as another entity. Far less common than leukoplakia, erythroplakia has a much greater probability (91%) of showing signs of dysplasia or malignancy at the time of diagnosis.(3) Such lesions have a flat, macular, velvety appearance and may be speckled with white spots representing foci of keratosis.
The premalignant or malignant potential of lichen planus is in dispute. Some believe that the occasional epithelial dysplasia or carcinoma found in patients with this relatively common lesion may be either coincidental or evidence that the initial diagnosis of lichen planus was erroneous. It is frequently difficult to differentiate lichen planus from epithelial dysplasia; one study found that 24% of oral lichen planus cases had 5 of the 12 World Health Organization (WHO) diagnostic criteria for epithelial dysplasia, and only 6% had no histologic features suggestive of that disorder.
However, Oral Cancer Background Papers as many reports on lichen planus patients followed over time indicate a higher than expected rate of malignant transformation, it is prudent practice to biopsy the lesion at the initial visit to confirm the diagnosis and to monitor it thereafter for clinical changes suggesting a premalignant or malignant change.
Conventional clinical (subtype of leukoplakia) and histopathological (presence or absence of epithelial dysplasia) characteristics are still the most important parameters for the prediction of malignant transformation in oral pre-malignant lesions in routine diagnostic oral pathology. Thus, careful oral examination and a biopsy are usually required for optimal management to be determined. In particular, a non-homogeneous type of leukoplakia and the presence of distinct epithelial dysplasia are indications of a lesion at risk for malignant change
The use of molecular biological markers for predicting malignant transformation of oral pre-malignant lesions is intriguing and rapidly evolving. So far, these studies have not demonstrated methods that are readily applicable for routine diagnostic work. There is little doubt, however, that future developments will render these biological markers as valuable diagnostic tools