Oral soft-tissue lesions are frequently observed in patients treated by general dentists as well as specialists. It is imperative that all soft-tissue lesions, even those that appear benign, be appropriately monitored to determine if there is resolution or if the lesion progresses or changes. Lack of resolution or progression of the lesion is indication for biopsy or referral. The standard of care is to diagnose all lesions, so it is important for dentists to be diligent when examining the oral mucosa.
When a lesion is observed, it may be warranted to observe the lesion for 10 to 14 days, but definitive care should not be delayed beyond this time period. Unfortunately, some lesions that may have been biopsied in the past and shown to be noncancerous are not adequately followed. Dentists should understand that over time many lesions can undergo a malignant transformation. In addition, it’s not just older patients. Recent studies have shown a nearly fivefold increase in the incidence of oral cancer in those under 40, many of whom had no traditional risk factors.1 Approximately 1% of benignly presenting lesions in the mouth will prove to be malignant.2
Oral lesions may be detected during a treatment appointment or during an oral cancer examination that is part of an initial or periodic dental examination. Early detection of oral cancer is extremely important. When detected late, the overall 5-year survival rate is approximately 50%.3
In the United States, oral malignancies represent about 3% of all cancers in males and 2% in females, and are responsible for 2% of the annual cancer deaths in males and 1% in females. Each year approximately 30,000 new cases are diagnosed in the United States.4 Worldwide, oral cancer is the sixth most common cancer, and more than 90% of oral-pharyngeal cancers are squamous cell carcinoma.3 Squamous cell carcinoma, sometimes known as epidermoid carcinoma, is defined as a malignant neoplasm derived from or exhibiting the morphologic features of squamous epithelium. It is often the end-stage of alteration in stratified squamous epithelium, beginning as an epithelial dysplasia and progressing until the dysplastic epithelial cells breach the basement membrane and invade the connective tissue. This cancer may also arise directly from the overlying stratified squamous epithelium and not have a prolonged premalignant phase.4 Because of these factors, the standard of care is to diagnose all lesions.5
This article discusses the various manifestations of oral cancer, indications for biopsy, biopsy techniques, and the materials and methods necessary to improve screening for and early diagnosis of soft-tissue lesions, with an emphasis on oral cancer. All dentists are encouraged to be proactive in detecting, diagnosing, and, when required, treating all oral soft-tissue lesions.
ORAL LESIONS OF CONCERN
Any change in the appearance of the oral mucosa that can be defined as an oral lesion should be evaluated. Nevertheless, some oral lesions are more likely to be malignant than others. Kratochvil defines these lesions as “oral lesions of concern.”6 He describes them as follows:
(1) ulcers that cannot be related to trauma or infection;
(2) leukoplakia on the floor of the mouth or ventral surface of the tongue;
(4) palatal soft-tissue masses; and
(5) mucocele-like lesions in locations other than the lower lip, floor of the mouth, or ventral surface of the anterior tongue.
In reference to oral lesions, these 5 characteristics should be considered to be of special significance. Nonhealing ulcers, leukoplakias, and erythroplakias raise the possibility of squamous cell carcinoma. Palatal softtissue masses and mucocele-like lesions at unusual locations suggest the possibility of salivary gland neoplasms.6
Regarding asymptomatic invasive squamous cell carcinoma, there is a variation in appearance. Lesions can present with the following array of surface characteristics:7
(1) Texture: smooth (39%), granular (60%), fissured (1%).
(2) Integrity: nonulcerated (88%), ulcerated (12%).
(3) Elevation: not elevated (53%), ≥ 1-mm elevation (33%), > 1-mm elevation (14%).
(4) Induration: not indurated (88%), indurated (12%).
(5) Bleeding: no bleeding (98%), bleeding (2%). Ulcers.
|Figure 1. Adult female patient with a persistent ulcer on the left ventral surface of the tongue. The diagnosis was invasive squamous cell carcinoma. (Photo courtesy of Charles Dunlap, DDS, University of Missouri-Kansas City School of Dentistry, Department of Oral and Maxillofacial Pathology, Radiology, and Medicine.)||
Figure 2. Lower right posterior buccal mucosa in a 23-year-old male who chews tobacco. The histological report was this: Hyperparakeratosis without evidence of epithelial dysplasia, and mild chronic mucositis consistent with snuff dippers keratosis. According to Ries, LA, et al, leukoplakia with chronic inflammation in a patient who uses alcohol and tobacco has an approximately 5% to 17% risk of malignant transformation to squamous cell carcinoma. (SEER Cancer Statistic Review, 1975-2000. Bethesda, Md. National Cancer Institute. 2003.)
|Figure 3. This adult male presented with an asymptomatic mixed leukoplakia/erythroplakia on the buccal mucosa. The tissue diagnosis was a superficially invasive squamous cell carcinoma. (Photo courtesy of Charles Dunlap, DDS, University of Missouri-Kansas City School of Dentistry, Department of Oral and Maxillofacial Pathology, Radiology, and Medicine.)|
Erythroplakia is a flat red patch or lesion in the mouth that clinically cannot be attributed to any other pathology. As with leukoplakia, the term is a clinical description that requires a biopsy and histological diagnosis as tissue in a normal range versus precancerous dysplasia (mild, moderate, severe) or frank carcinoma (Dr. Gary Ellis, Pathology Department, University of Utah, personal communication, May 18, 2006). Erythroplakia is less common than leukoplakia but has a higher likelihood of malignancy.3 Microscopically, erythroplakia exhibits epithelial dysplasia, carcinoma-insitu, or invasive squamous cell carcinoma in 90% of cases.11 Surgical excision and histologic examination is the treatment of choice in order to obtain a definitive diagnosis.
According to Reichart and Philipsen,12 only the true, velvety, red homogeneous oral erythroplakia has been clearly defined, while the terminology for mixed red and white lesions is complex, ill-defined, and confusing. Nevertheless, the combination red/white (erythroleukoplakic) inflammatory lesion is often described in the literature as a clinical feature of squamous cell carcinoma13,14,15 (Figure 3).
A palatal mass that is not osseous or inflammatory in appearance should be considered a salivary gland neoplasm until histological findings prove otherwise. More than 50% of palatal salivary gland tumors are cancerous.16
Mucocele-like lesions found in atypical locations (other than the lower lip, floor of the mouth, or anterior ventral surface of the tongue) may be salivary gland neoplasms—most likely a low-grade mucoepidermoid adenocarcinoma.6 While typical mucoceles found in the lower lip, floor of the mouth, or anterior ventral surface of the tongue are not as likely to be a problem, appropriate evaluation and treatment are still required.
PREPARING FOR A DIAGNOSIS
To establish a diagnosis, the following steps should be taken: (1) obtain a thorough history of the lesion, (2) review the patient’s health history, (3) complete an examination of the oral cavity and contiguous structures such as head and neck (including lymph nodes), and (4) examine the patient’s radiographs for possible hard-tissue abnormalities. The health history should record past and current medical/dental conditions including medications, diet, and oral habits. Proper questioning of the patient may elicit the probable cause for the lesion, and may direct the clinician toward the diagnosis, leading to proper treatment.17 Appropriate questions regarding an oral lesion might include the following:
(1) How long has the lesion been present?
(2) Has the lesion changed in size, shape, or color?
(3) Are there local (intraoral) symptoms associated with the lesion? Are there any remote signs or symptoms, including enlarged lymph nodes or systemic involvement (eg, fever)?
(4) Is there a history of trauma?
Table 1. Clinical Descriptions of Lesions.
|Bulla - Compartmentalized fluid in or under the epithelium of skin or mucosa. A large blister, greater than 5 mm in diameter.
Crusts - Dried or clotted serum protein on the surface of skin or mucosa.
Cyst - A pathologic, epithelium-lined cavity often filled with liquid or semisolid contents.
Ecchymosis - A nonelevated area of hemorrhage. Larger than petechia.
Erosion - Superficial ulceration (excoriation).
Fissure - A narrow, slit-like ulceration or groove.
Granuloma - A focal area of chronic inflammation composed of vascularized granulation tissue.
Macule - Circumscribed area of color change without elevation.
Multilocular - A radiolucent lesion composed of multiple compartments.
Nodule - A large, palpable mass elevated above the epithelial surface. Larger than 5 mm in diameter.
Papillary - A tumor or growth exhibiting numerous surface projections.
Papule - A small, palpable mass elevated above the epithelial surface. Less than 5 mm in diameter.
Pedunculated - A tumor or growth whose base is narrower than the widest part of the lesion.
Petechia - A round, pinpoint area of hemorrhage.
Plaque - A flat, elevated lesion. The confluence of papules.
Pustule - A cloudy or white vesicle, the color of which results from the presence of polymorphonuclear leukocytes (pus).
Scale - A macroscopic accumulation of keratin.
Sessile - A tumor or growth whose base is the widest part of the lesion.
Telangiectasia - A vascular lesion caused by dilatation of a small, superficial blood vessel.
Ulcer - Loss of epithelium.
Unilocular - A radiolucent lesion having a single compartment.
Verrucous - Describing a tumor or growth exhibiting a rough, warty surface.
Vesicle - A small loculation of fluid on or under the epithelium. A small blister less than 5 mm in diameter.
The dentist should record a thorough description of the lesion covering many observed characteristics: location, size, shape, color, texture, consistency, overall character, single or multiple locations, ulcerations, mobility or fixation to adjacent structures, fluctuance, inflammation, and associated lymphadenopathy. When describing a lesion, accepted medical terms should be used in order to convey an accurate description in a language common to all who may examine or evaluate the patient (Table 1). A photograph is useful to aid in documentation. It is important that all information gathered at the examination be accurately recorded in the patient’s chart, providing a baseline in the event that the lesion is to be followed over a period of time.
The clinician must recognize that many oral lesions are manifestations of systemic conditions. Reviewing a patient’s current and past medical history with creative questioning sometimes suggests a possible systemic origin for the lesion. Being aware of these conditions and how they present is an important part of the process in establishing a differential diagnosis. Common examples of systemic diseases with oral manifestations include but are not limited to the following:
(1) Crohn’s Disease (CD) is a chronic inflammatory bowel disease of uncertain etiology, but with a hereditary component. It is characterized by transmural inflammation and granuloma formation, usually in the lower part of the small intestine. Several theories regarding the etiology of Crohn’s disease have been proposed, one of which is infection with Mycobacterium avium subspecies paratuberculosis (M. paratuberculosis), which causes a similar disease in animals and is present in the human food chain.18 Plauth, et al19 evaluated 79 cases for morphology and site of oral and intestinal manifestations. Oral CD was the presenting symptom in more than half the patients. They exhibited a characteristic morphologic appearance frequently preceding intestinal symptoms—mostly in adolescents and young adults. From a total of 228 oral lesions in 79 patients, they found that the most common types of oral lesions exhibited edema (62), ulcers (57), and polypoid papulous hyperplastic mucosa (45). The most common locations were on the lips (57), buccal mucosa (45), gingiva (40), and vestibular sulci (31). Oral CD may cause disabling pain and facial distortion. Treatment, whether topical and/or systemic, is not always successful.
(2) Behcet’s Disease is a multisystem inflammatory disorder. It is caused by an auto-immune process manifested by a chronic relapsing vasculitis. Initial symptoms are generally numerous and painful oral aphthous ulcers. The disease has a genetic component but may have microbial or chemical environmental triggers. It follows that the dentist should be aware that the presence of multiple oral aphthous ulcers could be the first symptom of the disease. Although considered rare in the United States, it is a major cause of blindness in Turkey, Japan, the Middle East, and the Far East. Early detection and treatment can delay the onset or prevent vision problems as well as neurological and cardiovascular complications. It is not uncommon for practitioners to confuse Behcet’s disease with oral herpetic lesions. A rheumatologist can assist in diagnosis and general medical management.20
(3) Sjogren’s Syndrome (SS) is a chronic autoimmune disease mainly affecting women. In a study of 50 patients with SS,21 oral dryness was perceived as intense and oral health was considered poor. Oral symptoms most commonly expressed were sensitivity to acids (68%), difficulty eating dry foods (66%), and sensitivity to spicy foods (58%). Oral findings in these patients included cervical or atypical caries (83%), oral candidiasis (74%), and fissured erythematous tongue (70%). Adequate management of dry mouth, mainly for the modifiable components such as decay and candidiasis, was not achieved, making it all the more important to implement good prevention and treatment plans to help reduce discomfort and dental conditions associated with oral dryness.
(4) HIV oral manifestations can include candidiasis (that may be deeply penetrating); acute, nonspecific ulcerations; atypical, erythematous gingival inflammation involving several teeth; focal areas of advanced gingival recession that are the result of acute, necrotizing, ulcerative periodontitis; and purplish macular lesions (Kaposi’s sarcoma).22 A study by Patton, et al23 helps reveal the relative incidence of these and other characteristics. They examined 238 HIV-infected adults and found that 48% of the individuals had one or more oral lesions. Specific lesion prevalence was hairy leukoplakia (26.5%), candidiasis (20%), HIV-associated periodontal disease (8.8%), aphthous ulcers (4.2%), papillomas (2.5%), herpes simplex (2.1%), HIV salivary gland disease (2.1%), Kaposi’s sarcoma (1.7%), and others (1.3%). This data was obtained largely before patients were on HAART (highly active antiretroviral therapy), although a few may have been on some clinical trials. This makes it even more appropriate for diagnostic purposes.
MAKING A DIAGNOSIS
Table 2. Oral Cancer Statistics.*
*Oral Health in America: A Report of the Surgeon General. Reuters Health. 2000.
After data collection and a description of the lesion have been completed, a differential diagnosis is established. Then the clinician must make a professional judgment on how to proceed. In some cases where local irritation is thought to be the cause of the problem, the lesion in question is treated by eliminating the cause. Examples of nonsurgical treatment would include smoothing a sharp edge of tooth, relief of acrylic or clasp adjustment on a denture, or observing an area where it is suspected that sharp or hot food injured the tissue. In this situation a watch-and-wait period of two weeks would be prudent. If, in fact, the lesion is due to trauma, the area should heal within this period of time. However, if after this time the lesion persists, then it must be assumed the cause is not traumatic in nature, and a more definitive workup would be indicated. Depending on the nature of the lesion and comfort level of the clinician, either biopsy or referral is indicated.
It is important to note that most oral cancers are asymptomatic in their early stages. The consequence is that many cases are not taken seriously (detected, diagnosed, and treated) until classic signs of malignancy appear late in the course of the disease. Unfortu-nately, these signs are often associated with advanced disease, and significant morbidity and mortality (Table 2). Failure to diagnose is also a cause of major legal claims against US dentists.24
BIOPSY OF LESIONS
Three types of biopsy and an additional technique that helps visualize lesions with chemoluminescent light will be discussed. These 4 procedures are (1) excisional biopsy, (2) incisional biopsy, (3) brush biopsy, and (4) oral speculoscopy.
|Figure 4a. Elliptical incision lines for an excisional biopsy that demonstrate a margin of normal tissue adjacent to the lesion. (Figure from Manual of Minor Oral Surgery for the General Dentist. Ed: K.R. Koerner. Blackwell Publishing. Ames, IA. 2006. Used with permission.)||Figure 4b. Elliptical incisions (as shown in Figure 4a) that meet underneath the lesion. Traction is placed on the lesion with tissue pick-ups or a suture to facilitate tissue control and enable the clinician to get beneath the lesion. (Figure from Manual of Minor Oral Surgery for the General Dentist. Ed: K.R. Koerner. Blackwell Publishing. Ames, IA. 2006. Used with permission.)|
|Figure 5a. Small lesion on the dorsum of the tongue. (Figure from Manual of Minor Oral Surgery for the General Dentist. Ed: K.R. Koerner. Blackwell Publishing. Ames, IA. 2006. Used with permission.)||Figure 5b. With traction on the lesion, a scalpel is ready to make the first elliptical incision on one side. (Figure from Manual of Minor Oral Surgery for the General Dentist. Ed: K.R. Koerner. Blackwell Publishing. Ames, IA. 2006. Used with permission.)|
|Figure 5c. After an incision on both sides of the lesion—incisions that meet underneath while traction is being applied—the lesion is removed. The defect is ready to suture. (Figure from Manual of Minor Oral Surgery for the General Dentist. Ed: K.R. Koerner. Blackwell Publishing. Ames, IA. 2006. Used with permission.)||Figure 5d. The defect is sutured. (Figure from Manual of Minor Oral Surgery for the General Dentist. Ed: K.R. Koerner. Blackwell Publishing. Ames, IA. 2006. Used with permission.)|
|Figure 5e. The lesion has been placed in a specimen jar, the report has been filled out, and it is ready to be mailed to the oral pathology laboratory. The lesion was found to be a squamous papilloma. (Figure from Manual of Minor Oral Surgery for the General Dentist. Ed: K.R. Koerner. Blackwell Publishing. Ames, IA. 2006. Used with permission.)|
Scalpel removal of tissue followed by histologic evaluation of the lesion remains the gold standard for a definitive diagnosis of an oral lesion. An excisional biopsy is the removal of the entire lesion including a representative portion of normal tissue at the border. This procedure is both diagnostic and therapeutic in nature in that the entire lesion is removed for examination and diagnosis. In most instances, these lesions will not need further surgical intervention.
Ideally, the excisional biopsy technique should be utilized. However, this procedure is not practical for every lesion and situation. For general dentists, it is best suited for lesions that (1) are 1 cm or less in diameter, (2) are surgically accessible, and (3) do not appear malignant in nature (Figures 4a and 4b, 5a to 5e).
|Figure 6. The incisional biopsy on the left side of the lesion correctly shows the ideal removal of cells below the most inferior border of the lesion. The wedge on the right demonstrates an incision that does not capture the entire dimension of the lesion. It is better to incise narrow and deep than wide and shallow. (Figure from Manual of Minor Oral Surgery for the General Dentist. Ed: K.R. Koerner. Blackwell Publishing. Ames, IA. 2006. Used with permission.)|
Incisional biopsy is the removal of a representative portion of a lesion for histologic examination. This type of biopsy is primarily used on large, diffuse, or malignant-appearing lesions. The intent of this procedure is to remove a portion of the tissue in question along with a sample of normal adjacent tissue for comparative purposes. The incisional biopsy, although not complicated, requires more forethought and planning for proper execution than the excisional biopsy. A pie-shaped wedge incision is usually made, starting 2 to 3 mm within normal tissue and extending into an adjacent portion of abnormal tissue. It is a common mistake to incise tissue too superficially in relation to the actual depth of the lesion. Histologic changes are most easily detected not in the superficial tissue that can be necrotic, but in the deeper tissues located toward the center of the lesion (Figure 6).
|Figure 7a. Oral CDx (Oral CDx Laboratories, Inc.) brush near an oval lesion with a white border on the right lateral dorsum of the tongue. (Figure from Manual of Minor Oral Surgery for the General Dentist. Ed: K.R. Koerner. Blackwell Publishing. Ames, IA. 2006. Used with permission.)||Figure 7b. Cells being smeared on a slide prior to adding the fixative. The lab reported that the cellular representation consisted of superficial, intermediate, and basal cells. In this case the diagnosis was of benign epithelial cells, singly and in clusters, negative for premalignant or malignant epithelial changes. (Figure from Manual of Minor Oral Surgery for the General Dentist. Ed: K.R. Koerner. Blackwell Publishing. Ames, IA. 2006. Used with permission.)|
A computer-assisted method of tissue analysis is offered by the brush biopsy technique. This procedure provides an adjunct to the visual assessment of an oral lesion. The purpose of the oral brush biopsy is to identify lesions that otherwise appear harmless but, in fact, histologically exhibit atypical cells, dysplasia, or frank carcinoma. In a laboratory, the full-thickness tissue sample that the brush obtains is examined by computer and also evaluated microscopically by a pathologist. The brush biopsy bridges the gap between an inappropriately long observation period and the incisional or excisional biopsy. Even though original clinical trials and other studies demonstrated positive predictive results, more recently controversy has come to light concerning its ability to identify all the potentially malignant cells in a lesion.25,26 Therefore, if clinical suspicion persists regarding a lesion that persists for a prolonged period of time, standard scalpel biopsy must be considered3 (Figure 7a and 7b).
|Figure 8a. ViziLite (Zila Pharmaceuticals) vial of acetic acid, light stick, and light stick holder. This product helps the dentist visualize and evaluate oral mucosal abnormalities. (Figure from Manual of Minor Oral S