Principles of Differential Diagnosis and Biopsy

Health History

Discerning the overall medical status of the patient is important during the diagnostic stages. Recent findings have led to a growing realization that frequently a close interrelationship exists between the medical and dental health of patients and that oral lesions can be a reflection of, or contributers to, systemic health problems. Therefore documentation of a detailed and annotated health history coupled with a thorough clinical evaluation (including medical consultation when necessary), is essential for two basic reasons:

• 1

  A preexisting medical problem may affect or be affected by the dentist's treatment of the patient. As outlined in Chapters 1 and 2 , patients with certain medical conditions (e.g., those with hypertension or certain cardiac conditions, those taking potentially interactive medications, those taking anticoagulants, and those with implanted orthopedic or cardiovascular prostheses) may require special management precautions when invasive dental surgery is required. In addition, surgical intervention may upset the delicate balance between health and disease in a fragile patient or one with a poorly controlled condition, such as a patient who has diabetes or one who is immunocompromised.

• 2

  The lesion under investigation may be the oral manifestation of a significant systemic disease. For example, certain conditions (e.g., agranulocytosis, leukemia, Crohn disease) may often present with oral lesions. Surface ulcerations in a chronic smoker should alert the dentist to the possibility of oral or pharyngeal cancer. A number of systemic disease processes can manifest as oral lesions, so the dentist must always maintain awareness of these relationships.

History of the Specific Lesion

An old saying in medicine is “If you listen to the patient long enough, he or she will generally lead you to the diagnosis.” The art of history taking sometimes gets lost in modern medicine in the rush to get to the next patient. A generally accepted axiom in medicine is that many systemic diseases (up to 85% to 90%) can be diagnosed by gathering a detailed, annotated medical history. The same can be true of many oral lesions when the diagnostician is familiar with the natural history of the more common diseases. Questioning of the patient who has a pathologic condition should include the following:

• 1

  How long has the lesion been present? The duration of a lesion may provide valuable insight into its nature. For example, a lesion that has been present for several years might be congenital and is more likely benign, whereas a rapidly developing lesion is considered more ominous. Although establishing the duration of a lesion provides valuable information, duration must be taken in context with other elements of the history because it is possible that the lesion was present for an extended period before the patient became aware of its presence.

• 2

  Has the lesion changed in size? A change in the radiographic or clinical size of a lesion, or both, is an important piece of information. An aggressive, enlarging lesion is more likely to be malignant, whereas a slower-growing lesion suggests a possibly benign condition. By combining information on the growth rate with findings regarding the duration of presence, one can make a more accurate assessment of the nature of the lesion.

• 3

  Has the lesion changed in character or features (e.g., a lump becoming an ulcer or an ulcer starting as a vesicle)? Noting changes in the physical characteristics of a lesion can often assist in the diagnosis. For example, if an ulcer began as a vesicle, it could suggest a localized or systemic vesiculobullous or viral disease.

• 4

  What symptoms are associated with the lesion (e.g., pain, altered function, anesthesia or paresthesia, abnormal taste or odors, dysphagia, or tenderness of cervical lymph nodes) ? If painful, is the pain acute or chronic, constant or intermittent? What increases or decreases the pain? Lesions with an inflammatory component are most often associated with pain. Cancers, erroneously thought by many to be painful, are actually often painless unless secondarily infected. Sensory nerve changes such as numbness or tingling often occur with a malignant or inflammatory process unless other identifiable causes can be ascertained. Dysphagia can suggest changes in the floor of the mouth or in the parapharyngeal tissues. Swelling can often result from and occur with oral lesions, indicating an expansile process from any of a number of causes, including inflammation, infection, cysts, or tumor formation. The patient may indicate feeling a sensation of fullness even before the doctor can actually visualize or verify the swelling during clinical examination. Painful lymph nodes usually indicate an inflammatory or infectious cause but may also be a manifestation of malignancy.

• 5

  What anatomic locations are involved? Certain lesions have a predilection for certain anatomic areas or tissues. Noting whether the lesion is confined to keratinized or nonkeratinized tissues, regions with salivary gland tissues or areas of neural or vascular anatomy can sometimes provide clues to the diagnosis.

• 6

  Are there any associated systemic symptoms (e.g., fever, nausea, or malaise) ? Has the patient noted any similar or concurrent changes elsewhere in the body or had similar lesions in the oral or perioral tissues in the past? The dentist should look for possible relationships or manifestations from related systemic diseases or conditions. For example, many systemic viral conditions (e.g., measles, mumps, mononucleosis, herpes, acquired immunodeficiency syndrome) can cause oral manifestations concurrent with the systemic involvement. Autoimmune conditions may also manifest with oral lesions. Many oral ulcerative conditions can also present lesions elsewhere in the body (e.g., pemphigus, lichen planus, erythema multiforme, sexually transmitted infections). Other factors could include drug abuse or injuries from domestic violence.

• 7

  Is there any historical event associated with the onset of the lesions (e.g., trauma, recent treatment, exposure to toxins or allergens, visits to foreign countries) ? One of the initial steps the dentist should take when a lesion is noted is to seek a possible explanation based on the patient's medical, dental, family, or social histories. Frequently oral and perioral lesions can be caused by parafunctional habits, hard or hot foods, application of medications not intended for topical use, recent trauma, conditions involving the dentition (e.g., caries, periodontal disease, fractured teeth), or an identified event or exposure.

Clinical Examination

When a lesion is discovered, careful clinical and radiographic examinations and palpation of regional lymph nodes is mandatory. Once the examination is complete, a detailed description of all objective and subjective findings should be documented in the patient's chart. A drawing or a graphic schematic of the location, orientation, general shape, and dimensions of the lesion in the patient record is helpful. The use of standardized illustrations can simplify the documentation ( Fig. 22.2 ). Additionally, good-quality digital photographs are useful for documentation if the dentist has the appropriate camera and accessories. Details, descriptions, and drawings allow the dentist or subsequent referral specialists to evaluate the course of the lesion over time and determine whether it is enlarging, its features are changing, or new lesions are appearing in different anatomic areas.

An examination is classically described as a process that includes inspection, palpation, percussion, and auscultation. In the head and neck region, inspection and palpation are more commonly used as diagnostic modalities, with inspection always preceding palpation. Early inspection facilitates description of the lesion before it is handled because some lesions are so fragile that manipulation of any kind can result in hemorrhage or rupture of a fluid-filled lesion or loss of loosely attached surface tissues, which would compromise any subsequent examinations. Percussion is reserved for examination of the dentition. Auscultation is infrequently used but is important when examining suspected vascular lesions. The following are some important additional points to be considered during the inspection of a lesion.

• 1

  Anatomic location of the lesion. Pathologic lesions can arise from any tissue within the oral cavity, including the epithelium, subcutaneous and submucosal connective tissues, muscle, tendon, nerve, bone, blood vessels, lymphatic vessels, or salivary glands. The dentist should attempt to ascertain, as much as possible, which tissues are contributing to the lesion based on the anatomic location of the lesion. For example, if a mass appears on the dorsum of the tongue, the dentist would logically consider an epithelial, connective tissue, lymphatic, vascular, glandular, neural, or muscular origin. Similarly, a mass on the inner aspect of the lower lip would prompt the dentist to include a minor salivary gland origin in the differential diagnosis, along with connective tissue origin and other possibilities. Certain lesions may have unique anatomic characteristics, such as the linear tendencies of herpes zoster lesions as they follow neural pathways. The possible role of trauma should always be entertained as possible sources of the lesion (ill-fitting dental appliances, parafunctional habits such as cheek biting, sharp edges on teeth or restorations, and trauma from acts of domestic or other types of violence). Finally, pulpal, periapical, and periodontal pathologic or inflammatory conditions also cause a significant percentage of oral lesions.

• 2

  Overall physical characteristics of the lesion. Appropriate medical terminology should always be used to describe clinical findings in the record because lay terminology can be misleading and nonspecific. Terms such as “ulcer” or “nodule” may be interpreted differently by different examiners. High-quality digital photographs may also be printed and enclosed with the biopsy specimen or can be emailed separately to the pathologist. Photographs are helpful in demonstrating the clinical characteristics of the lesion. Box 22.1 lists several common physical descriptions that are useful in describing oral and maxillofacial pathologic entities. Terms such as those listed in Box 22.1 should generally be used to describe the characteristics of a lesion. Lay terms such as “swelling” and “sore” are generally not helpful and may be subject to misinterpretation.

  Box 22.1

  Descriptive Pathology Terminology

  • Bulla (pl. bullae): a blister; an elevated, circumscribed, fluid-containing lesion of skin or mucosa

  • Crusts (crusted): dried or clotted serum on the surface of the skin or mucosa

  • Dysplasia (dysplastic): any abnormal development of cellular size, shape, or organization in tissue

  • Erosion: a shallow, superficial ulceration

  • Hyperkeratosis: an overgrowth of the cornified layer of epithelium

  • Hyperplasia (hyperplastic): an increased number of normal cells

  • Hypertrophy (hypertrophic): an increase in size caused by an increase in the size of cells, not in the number of cells

  • Keratosis (keratotic): An overgrowth and thickening of cornified (horned layer) epithelium

  • Leukoplakia: a slowly developing change in mucosa characterized by firmly attached thickened white patches

  • Macule: a circumscribed nonelevated area of color change that is distinct from adjacent tissues

  • Malignant: anaplastic; a cancer that is potentially invasive and metastatic

  • Nodule: a large, elevated, circumscribed and solid palpable mass of the skin or mucosa

  • Papule: a small, elevated, circumscribed and solid palpable mass of the skin or mucosa

  • Plaque: any flat, slightly elevated superficial lesion

  • Pustule: a small, cloudy, elevated and circumscribed pus-containing vesicle on the skin or mucosa

  • Scale: a thin, compressed, superficial flake of cornified (keratinized) epithelium

  • Stomatitis: any generalized inflammatory condition of the oral mucosa

  • Ulcer: a crater-like circumscribed surface lesion resulting from necrosis of the epithelium

  • Vesicle: a small blister; a small circumscribed elevation of skin or mucosa containing serous fluid

• 3

  Single versus multiple lesions. The presence of multiple lesions is an important feature. When multiple ulcerations are found within the mouth, the dentist should think of specific possibilities for the differential diagnosis. To find multiple or bilateral neoplasms in the mouth is unusual, whereas vesiculobullous, bacterial, and viral diseases commonly present such a pattern. Similarly, an infectious process may exhibit outward spread as one lesion infects the adjacent tissues with which it has had contact.

• 4

  Size, shape, and growth presentation of the lesion. Documentation of the size and shape of the lesion should be made, as noted previously. A small metric ruler made of a material that can be disinfected (e.g., metal or plastic) is useful to have on hand. The ruler is valuable for measuring the diameters of clinically evident lesions, which measurements can then be entered into the record with the drawing. The growth presentation should also be noted: whether the lesion is flat or slightly elevated, endophytic (growing inward) or exophytic (growing outward from the epithelial surface), and sessile (broad based) or pedunculated (on a stalk).

• 5

  Surface appearance of the lesion. The epithelial surface of a lesion may be smooth, lobulated (verruciform), or irregular. If ulceration is present, the characteristics of the ulcer base and margins should be recorded. Margins of an ulcer may be flat, rolled, raised, or everted. The base of the ulcer may be smooth, granulated, or covered with fibrin membrane or slough or hemorrhagic crust (scab) or it may have the fungating appearance that is characteristic of some malignancies.

• 6

  Lesion coloration. The surface color(s) of a lesion can reflect various characteristics and even the origin of many lesions. A dark bluish swelling that blanches on pressure suggests a vascular lesion, whereas a lighter-colored, bluish lesion that does not blanch may suggest a mucus-retaining cyst. A pigmented lesion within the mucosa may suggest a “traumatic tattoo” of restorative material or a more ominous melanotic tumor. Keratinized white lesions can reflect a reaction to repetitive local tissue trauma or represent potentially premalignant changes. An erythematous (or mixed red and white) lesion may represent an even more ominous prognosis for dysplastic changes than a white lesion. Inflammation can be superimposed on areas of mechanical trauma or ulceration, resulting in a varied presentation from one examination to the next.

• 7

  Sharpness of lesion borders and mobility. If a mass is present, the dentist should determine whether it is fixed to the surrounding deep tissues or freely movable. Determining the boundaries of the surface lesion will aid in establishing whether the mass is fixed to adjacent bone, arising from bone and extending into adjacent soft tissues, or only infiltrating the soft tissue.

• 8

  Consistency of the lesion to palpation. Consistency can be described as soft or compressible (e.g., a lipoma or abscess), firm or indurated (e.g., a fibroma or neoplasm), or hard (e.g., torus or exostosis). Fluctuant is a term used to describe the wave-like motion felt during bidigital palpation of a lesion with nonrigid walls that contains fluid. This valuable sign can be elicited by palpating with two or more fingers in a rhythmic fashion. As one finger exerts pressure, the opposing finger feels the impulse transmitted through the fluid-filled cavity.

• 9

  Presence of pulsation. Palpation of a mass may reveal a rhythmic pulsation that is suggestive of a significant vascular component. This sensation can be subtle and is especially significant when dealing with intrabony lesions. The pulsation can be accompanied by a palpable vibration, called a thrill . If a thrill is palpated, auscultation of the area with a stethoscope may reveal a bruit , or audible murmur, in the area. Invasive procedures on lesions with thrills, bruits, or both should be avoided, and patients should be referred to specialists for treatment because life-endangering hemorrhage can result if surgical intervention (biopsy) is attempted.

• 10

  Examination of regional lymph nodes. No evaluation of an oral lesion is complete without a thorough examination of the regional lymph nodes. This examination should be accomplished before any biopsy procedure. Sometimes lymphadenitis develops in the regional nodes following a surgical procedure such as biopsy, thus creating a subsequent diagnostic dilemma. It can then become difficult to differentiate between reactive lymphadenitis as a surgical sequela, coincidental regional infection or inflammation, or metastatic spread of the tumor in question. Fig. 22.3 illustrates the primary lymph nodes of significance in the cervicofacial region.

  

The standard examination of lymph nodes requires only simple inspection and palpation. Comparison of left and right sides, using the middle three fingers for light palpation, is often useful. Movements during palpation should be slow and gentle, with the fingers moving lightly across each area in vertical and horizontal directions as well as in a rotary motion. In adults, normal lymph nodes are not palpable unless they are enlarged by inflammation or neoplasia, but cervical nodes of up to 1 cm in diameter can often be palpated in children up to the age of 12 years and are generally not considered an abnormal finding. In recording lymph node findings, the following five characteristics should be routinely documented: (1) location, (2) size (preferably recording the diameters in centimeters), (3) presence of pain or tenderness, (4) degree of fixation (fixed, matted, or movable), and (5) texture (soft, firm, or hardened). When multiple nodes are slightly enlarged but barely palpable, they can feel like bird shot and are described as “shotty nodes.”

The lymph node examination should be methodical and should include the following groups: (1) occipital, (2) preauricular and postauricular; (3) mandibular, submandibular, and submental; (4) deep anterior cervical chain; (5) superficial cervical nodes (along the sternocleidomastoid muscle); (6) deep posterior cervical chain; and (7) supraclavicular nodes. Buccal lymph nodes may or may not be routinely palpable.

Diagnostic Adjuncts

A variety of adjunctive diagnostic aids have been promoted to the practitioner to screen for and identify oral and pharyngeal cancers (OPCs) and oral premalignant lesions at their earliest presentation ( Tables 22.1 and 22.2 ). They are all marketed as aids for the clinician to use in addition to, not in lieu of, the accomplishment of the conventional head and neck examination and are often promoted as advanced “must-have” products. Some adjuncts are marketed as “discovery” or “screening” enhancements, whereas others are marketed as case assessment utilities to further assess a visually identified lesion. The use of these products in the profession remains a topic of much debate. As there is currently insufficient evidence to draw a firm conclusion, clinicians should be both cautious in choosing to use such devices and aware of their limitations.

Radiographic Examination

Radiographs are useful diagnostic adjuncts after completion of the history and clinical examination, especially for lesions occurring within or adjacent to bone. When soft tissue lesions are close to bone, radiographs may indicate whether the lesion is causing an osseous reaction, eroding into the bone, or arising from an intraosseous origin. Various radiographic techniques may be used depending on the anatomic location of the lesion. Most pathologic conditions of the mandible or maxilla can be adequately viewed on routine plain views (e.g., periapical, occlusal, or panoramic), but occasionally specialized imaging techniques are needed—including computed tomography (CT; with the newer cone-beam CT) or magnetic resonance imaging (MRI) views—to fully delineate the exact nature and location of intrabony lesions.

The radiographic appearance may frequently give clues to the diagnosis of a lesion. For example, a cyst usually appears as a radiolucency with sharp borders ( Fig. 22.4A–B ), whereas a radiolucency with ragged, irregular borders might indicate a malignant or more aggressive lesion (see Fig. 22.4C–D ). In viewing a radiograph, if an intraosseous area shows a deviation from normal structures or appearance, the dentist must determine whether the change is pathologic or simply an atypical presentation of a normal anatomic structure. This is particularly true in viewing certain projections of the maxilla and the mandible in which the complex adjacent anatomy leads to superimpositions of contiguous structures such as the paranasal sinus cavities.

In unique diagnostic situations, radiopaque dyes or markers may be used in conjunction with routine or specialized radiographs. For example, sialography involves the injection of radiopaque dye into glandular ducts to produce an indirect image of the gland architecture and delineate any pathologic lesions within the gland. Cysts may be injected to assist in determining the true extent of their anatomic boundaries. Radiopaque markers such as needles or metal spheres can be used to localize a foreign object or pathologic lesion.

Laboratory Investigation

In certain instances supplementary laboratory tests can assist in lesion identification. Certain oral lesions may be manifestations of a systemic disease process such as hyperparathyroidism, multiple myeloma, leukemia, and certain lymphomas. To cite an example of the role of laboratory testing, examination of a patient with multiple lytic lesions and loss of lamina dura bone might suggest hyperparathyroidism. This diagnosis could be clarified by the dentist requesting serum calcium, phosphorus, and alkaline phosphatase tests. Guidance for requesting such tests can be found in leading oral and maxillofacial pathology textbooks and other resources.

In the majority of cases, screening laboratory studies are considered unnecessary because they often have a low diagnostic yield per total cost involved in performing such tests. Once the surgical biopsy has provided a definitive diagnosis, however, laboratory testing can contribute meaningful information that is relevant to the subsequent management of the lesion.

Presumptive Clinical Differential Diagnosis

After completing the initial dental, medical, and lesion histories and clinical, radiographic, and laboratory examinations (as indicated), the dentist next should compile a presumptive list of reasonable differential diagnoses. These diagnoses convey the clinician's impression to the pathologist regarding what the dentist feels the lesion most likely is on the basis of the total assessment. These diagnoses may or may not ultimately be consistent with the final histologic diagnosis but are, nonetheless, important because the pathologist rules out entities that may have similar clinical and pathologic presentations.