Oral Cancer and Precancerous Lesions - Topic 2: Clinical & Histological Features of Oral Cancers


2.1   Introduction

Oral cancer may appear in different stages, with different physical findings, and in different sites. However, certain locations are more common than others.



2.2   Estimated Percentages of Sites for Oral Cancer

This is the general clinical distribution of oral cancer by sites. As you see, you need to carefully inspect under patient’s tongue and the floor of the mouth. The lateral tongue is also a common site. The lower lip is considered by some a skin site because it is exposed to actinic radiation and therefore has a separate co-factor that is carcinogenic. An important physical finding demonstrating actinic damage is loss of the vermilion border of the mouth.



2.3   Clinical Features of Oral Cancer

Oral cancer may show up clinically in different stages, and with multiple different appearances. It may look like a white area, or leukoplakia; a red patch or erythroplakia, or a combination of the two, an ulcer, a mass, or just a sore area with a submucosal component. Another common feature of late stage cancer is paresthesia, because there is eventual perineural and intraneural invasion.

Here is a carcinoma of the palate, which is not among the most common locations, but it is important to see some of the unusual presentations so you are aware of the possibilities.



2.4   Leukoplakia

The term leukoplakia is a controversial term. In oral pathology it is considered to be a white plaque of the oral mucosa that cannot be wiped off and cannot be clinically diagnosed as any other disease.



2.5   Leukoplakia

Depending on the definition we use for leukoplakia, a variable, but significant amount of people will have it. Most of the cases represent hyperkeratosis microscopically, which is analogous to a callus of the skin. A few of the leukoplakias will be premalignant or malignant when examined histologically.

As noted, leukoplakia is a descriptive clinical term that should not imply any specific diagnosis. The most common etiology for a leukoplakia is frictional trauma, especially in edentulous areas where there is a lot of friction against food or a denture.

The more worrisome cases are those involving epithelial dysplasia or carcinomas, and those account for approximately 5-15% of the cases, most commonly in smokers. This is another example of the carcinogenic effect of tobacco. These lesions should be biopsied because clinical presentation does not really correlate with the histology in all cases. So as not to miss relevant lesions we do a lot of biopsies.



2.6   Leukoplakia

So, when do we biopsy a leukoplakia? The rule of thumb is to try to find a mechanical cause for the friction or trauma, and remove it. If the lesion does not resolve in 3 weeks, or if you cannot find a traumatic cause, refer for biopsy. Three weeks is enough time for a reactive lesion to resolve after removal of the cause, and it is not too much time to wait if the leukoplakia turns out to be dysplasia or cancer. Assure, however, that your patient is not lost to follow up.



2.7   Conditions Clinically Similar to Leukoplakias

Here is a non-all-inclusive list of other conditions that may present clinically as leukoplakias. The trick is to try to figure out which you are dealing with, and if there is the least doubt of the diagnosis, biopsy the lesion. In fact, biopsy is required to confirm many of these diagnoses.



2.8   Leukoplakia

This patient presented to dentistry for another complaint, and upon clinical evaluation this lesion was discovered. It was biopsied and turned out to be severe dysplasia already! This photo is to remind you that the lesions may not be overt, and you need to be looking for them, since there are plenty of areas of the mouth where they can hide easily.



2.9   Hyperkeratosis

Most cases of leukoplakia represent hyperkeratosis microscopically, which is analogous to a callus of the skin. Hyperkeratosis is a microscopic term, since we cannot see the thickness of the keratin layer clinically. We may suspect that is the condition, but we can only diagnose it histologically. It represents an excessive accumulation of the keratin layer, analogous to the stratum corneum of the epidermis. It usually looks white clinically because wet and clean keratin looks like that, similar to what happens with wet fibrin versus an eschar. If the keratin has nuclei we call it parakeratin, and if it does not and exhibits a granular cell layer, it is termed orthokeratosis.

A singular term is pseudoepitheliomatous hyperplasia. This is a microscopic term that represents a cancer-mimicking condition associated with other lesions that may stimulate the proliferation of epithelium. Some common entities associated with this condition are granular cell tumors and deep fungal infections.



2.10   Hyperkeratosis and Epithelial Dysplasia

This is a photomicrograph of severe epithelial dysplasia and hyperkeratosis. This lesion clinically would have looked white, and would not rub off, therefore you could have described it as a leukoplakia. Just as in real estate, location is important. If the lesion is in an anatomic location that is considered “high risk” and if the patient has a history of alcohol or tobacco use, this raises a red flag and biopsy should be expedited.



2.10.1   Sites for Oral Cancer

Sites for Oral Cancer

Lower lip 35%
Lateral/ventral tongue 25%
 Floor of mouth 20%
Soft palate 15%
Gingiva/alveolar ridge 04%
Buccal mucosa 01%
 



2.11   Erythroplakia

Erythroplakia is also a clinical term. It represents a red patch. This is like leukoplakia, but is red. The difference is that these red lesions are more often the clinical presentation of more severe epithelial changes, or more advanced disease. Especially important is biopsy of erythroplakia that has a velvet-like texture on high risk areas and high risk patients.

There may be combination lesions, the coexistence of leukoplakia and erythroplakia. This is called erythro-leukoplakia of speckled leukoplakia. For biopsy purposes, you should sample both components of the lesion.

The example at the top turned out to be carcinoma in situ, and the one at the bottom turned out to be just mucositis of the soft/hard palate in the midline.



2.12   Erythroplakia

The majority of erythroplakias turn out to be significant disease. The older the patient and a history of tobacco and alcohol consumption are associated with a greater chance of serious dysplasia or carcinoma in situ.



2.13   Histological Features of Oral Cancer

With dysplasia, we use the same general concepts of gynecology for cervical neoplasia when evaluating the features:

Eventually, sophisticated genetic studies will probably be incorporated in the mix, but we are not quite there yet. Ploidy studies are probably the most advanced studies so far, but are not utilized on a large scale.



2.14   Histological Features of Oral Cancer

A dysplasia that involves the entire thickness of the epithelium is termed carcinoma in situ, or CIS. By definition there is no evidence of invasion into the connective tissue. Treatment is the same as for dysplasia, i.e., excision with clean margins. Follow up of any patient with diagnosis of dysplasia or CIS is mandatory and forever.



2.15   Histological Features of Oral Cancer

On a microscope, the tumors can be graded based on agreed-upon criteria, but still are subject to observer-related variations. We rank the degree of differentiation based on how much it resembles normal squamous epithelium: well-very similar; moderate-so so; and poorly differentiated is barely discernible. The undifferentiated category is usually a diagnosis made with the help of immunohistochemical phenotyping of the tissue. The degree of keratinization may also correlate with the degree of differentiation, and may in some cases correlate with prognosis.



2.16   Histological Features of Oral Cancer

This is a well-differentiated, keratinizing squamous cell carcinoma of the oral cavity at medium magnification. The pinker or more eosinophilic areas are keratin whorls or pearls. The neoplastic epithelium is more pink-purple or basophilic because it stains with hematoxilin.