Principles of Differential Diagnosis and Biopsy.pdf

PART V Management of Oral @LibraryEDent ‫ﻣﻛﺗﺑﺔ طب اﻷﺳﻧﺎن‬ Pathologic Lesions Pathologic growths and lesions frequently develop in the mouth and adjacent structures. General dentists encounter m...

PART V Management of Oral @LibraryEDent ‫ﻣﻛﺗﺑﺔ طب اﻷﺳﻧﺎن‬ Pathologic Lesions Pathologic growths and lesions frequently develop in the mouth and adjacent structures. General dentists encounter more frequent and repetitive exposures to the tissues in patients’ oral cavities and contiguous structures than any other health care provider. Although most of these lesions are benign and not threatening to the patient’s well-being, dentists nevertheless have the profes- sional responsibility for the maintenance and overall health of their patients’ oral and perioral structures. Whether by referral to another health care provider or by directly assuming responsibility for the surgical management of these hard and soft tissue pathologic entities, the dentist is the “gateway” provider who initially recognizes any departure from normal, coordinates the needed definitive care, ensures adequate patient follow-up, and provides any required dental restorative support. The unique role of general dentists as oral health experts requires them to be constantly vigilant for any abnormalities in the bony and soft tissues of the head and neck area during their routine care of patients. General dentists must be observant clinicians and astute diagnosti- cians and must remain knowledgeable about the natural history of the more common oral and maxillofacial disease manifestations. Early diagnosis and treatment is always the best practice for managing these pathologic entities. Chapters 22 and 23 describe the potential roles of the general dentist in the comprehensive management of a patient’s pathologic conditions. The most important aspect of this care begins with performing a thorough oral, head, and neck examination; formulating a rational tentative diagnosis; and providing needed treatment or appropriate referrals when indicated. Chapter 22 covers these topics in detail, with emphasis on the role of a general dentist. Chapter 23 describes the surgical management of more complex pathologic lesions of the oral cavity and contiguous https: / / t.me / LibraryEDent structures. Expanded details on surgical technique are provided for management of less complex lesions that might be managed by general dentists. The surgical management of more complex and difficult pathologic conditions, cysts, and tumors of the oral-maxillofacial region are also presented, with emphasis on the general dentist’s supportive roles in patient management and referral to specialists. 450 22 Principles of Differential Diagnosis and Biopsy @LibraryEDent ‫ﻣﻛﺗﺑﺔ طب اﻷﺳﻧﺎن‬ EDWARD ELL IS III AND MICHAELL A. HUBER CHAPTER OUTLINE Examination and Diagnostic Methods Examination and Diagnostic Methods, 451 Lesions of the oral cavity and perioral areas must be identified and Health History, 451 accurately diagnosed so that appropriate therapy can eliminate History of the Specific Lesion, 452 them. When abnormal tissue growth is discovered, several important Clinical Examination, 453 and orderly steps should be undertaken to identify and characterize Diagnostic Adjuncts, 456 it (Fig. 22.1). These steps include a comprehensive health history, Cytology-Based Adjuncts, 458 history of the identified lesion(s), clinical and radiographic examina- Vital Stain–Based Adjuncts, 458 tions, and relevant laboratory testing if indicated. These steps lead Light-Based Adjuncts, 458 to a period of close observation, referral to another health care Molecular-Based Adjuncts, 459 provider when indicated, and initiation of surgical procedures to Radiographic Examination, 459 obtain a specimen for histologic examination (biopsy), which, in Laboratory Investigation, 459 turn, will lead to appropriate treatment decisions. Presumptive Clinical Differential Diagnosis, 460 When the dentist discovers or confirms the presence of a lesion, Prebiopsy Monitoring, 460 the information must be discussed with the patient in a sensitive Basic Tenets of Follow-up and Referral, 460 manner that conveys the importance of urgent attention to the Biopsy or Referral, 461 problem without alarming the patient. Words such as lesion, tumor, Informed Consent and Shared Risk, 461 growth, and biopsy can carry terrifying connotations for many Postbiopsy Monitoring, 461 patients. The empathetic dentist can spare patients undue anxiety and emotional trauma by carefully wording the discussion relating General Principles of Biopsy, 461 to the lesion and reminding the patient that most discovered lesions Incisional Biopsy, 462 in the head and neck region are benign and that the steps being Excisional Biopsy, 462 taken are merely precautionary. https: / / t.me / LibraryEDent Aspiration Biopsy, 462 Soft Tissue Biopsy Techniques and Surgical Principles, 462 Anesthesia, 465 Health History Tissue Stabilization, 465 Discerning the overall medical status of the patient is important Hemostasis, 465 during the diagnostic stages. Recent findings have led to a growing Incisions, 465 realization that frequently a close interrelationship exists between Wound Closure, 465 the medical and dental health of patients and that oral lesions can Handling of Tissues; Specimen Care, 467 be a reflection of, or contributers to, systemic health problems. Suture Tagging of Specimens; Margin Identification, 468 Therefore documentation of a detailed and annotated health history Submission of Specimens, 468 coupled with a thorough clinical evaluation (including medical Biopsy Submission Data Form, 469 consultation when necessary), is essential for two basic reasons: Intraosseous (Hard Tissue) Biopsy Techniques and Principles, 1. A preexisting medical problem may affect or be affected by 471 the dentist’s treatment of the patient. As outlined in Chapters Mucoperiosteal Flaps, 471 1 and 2, patients with certain medical conditions (e.g., those Precautionary Aspiration, 471 with hypertension or certain cardiac conditions, those taking Osseous Window, 471 potentially interactive medications, those taking anticoagulants, Specimen Management, 473 and those with implanted orthopedic or cardiovascular prosthe- Postbiopsy Follow-up, 475 ses) 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. 451 452 PART V Management of Oral Pathologic Lesions Lesion detection Health and lesion histories, clinical and radiograph examinations, laboratory testing Differential diagnosis @LibraryEDent ‫ﻣﻛﺗﺑﺔ طب اﻷﺳﻧﺎن‬ Observation or Observation or nonsurgical nonsurgical treatment treatment not indicated; high for 10-14 days suspicion of malignancy Improvement No improvement Decision to biopsy Perform biopsy Refer to specialist No further Diagnosis indicates treatment required need for further treatment/surgery Needs are within Need for referral capabilities of a to specialist general dentist Patient monitoring/follow-up/support Fig. 22.1 Decision tree for treatment of oral lesions. 2. The lesion under investigation may be the oral manifestation of lesion that has been present for several years might be congenital https: / / t.me / LibraryEDent a significant systemic disease. For example, certain conditions and is more likely benign, whereas a rapidly developing lesion (e.g., agranulocytosis, leukemia, Crohn disease) may often present is considered more ominous. Although establishing the duration with oral lesions. Surface ulcerations in a chronic smoker should of a lesion provides valuable information, duration must be alert the dentist to the possibility of oral or pharyngeal cancer. taken in context with other elements of the history because it A number of systemic disease processes can manifest as oral is possible that the lesion was present for an extended period lesions, so the dentist must always maintain awareness of these before the patient became aware of its presence. relationships. 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 History of the Specific Lesion be malignant, whereas a slower-growing lesion suggests a possibly An old saying in medicine is “If you listen to the patient long benign condition. By combining information on the growth enough, he or she will generally lead you to the diagnosis.” The rate with findings regarding the duration of presence, one can art of history taking sometimes gets lost in modern medicine in make a more accurate assessment of the nature of the lesion. the rush to get to the next patient. A generally accepted axiom in 3. Has the lesion changed in character or features (e.g., a lump medicine is that many systemic diseases (up to 85% to 90%) can becoming an ulcer or an ulcer starting as a vesicle)? Noting be diagnosed by gathering a detailed, annotated medical history. changes in the physical characteristics of a lesion can often assist The same can be true of many oral lesions when the diagnostician in the diagnosis. For example, if an ulcer began as a vesicle, it is familiar with the natural history of the more common diseases. could suggest a localized or systemic vesiculobullous or viral Questioning of the patient who has a pathologic condition should disease. include the following: 4. What symptoms are associated with the lesion (e.g., pain, altered 1. How long has the lesion been present? The duration of a lesion function, anesthesia or paresthesia, abnormal taste or odors, may provide valuable insight into its nature. For example, a dysphagia, or tenderness of cervical lymph nodes)? If painful,  CHAPTER 22 Principles of Differential Diagnosis and Biopsy 453 is the pain acute or chronic, constant or intermittent? What An examination is classically described as a process that includes increases or decreases the pain? Lesions with an inflammatory inspection, palpation, percussion, and auscultation. In the head component are most often associated with pain. Cancers, and neck region, inspection and palpation are more commonly erroneously thought by many to be painful, are actually often used as diagnostic modalities, with inspection always preceding painless unless secondarily infected. Sensory nerve changes such palpation. Early inspection facilitates description of the lesion before as numbness or tingling often occur with a malignant or inflam- it is handled because some lesions are so fragile that manipulation matory process unless other identifiable causes can be ascertained. of any kind can result in hemorrhage or rupture of a fluid-filled Dysphagia can suggest changes in the floor of the mouth or in lesion or loss of loosely attached surface tissues, which would the parapharyngeal tissues. Swelling can often result from and compromise any subsequent examinations. Percussion is reserved @LibraryEDent ‫ﻣﻛﺗﺑﺔ طب اﻷﺳﻧﺎن‬ occur with oral lesions, indicating an expansile process from for examination of the dentition. Auscultation is infrequently used any of a number of causes, including inflammation, infection, but is important when examining suspected vascular lesions. The cysts, or tumor formation. The patient may indicate feeling a following are some important additional points to be considered sensation of fullness even before the doctor can actually visualize during the inspection of a lesion. or verify the swelling during clinical examination. Painful lymph 1. Anatomic location of the lesion. Pathologic lesions can arise nodes usually indicate an inflammatory or infectious cause but from any tissue within the oral cavity, including the epithelium, may also be a manifestation of malignancy. subcutaneous and submucosal connective tissues, muscle, 5. What anatomic locations are involved? Certain lesions have a tendon, nerve, bone, blood vessels, lymphatic vessels, or salivary predilection for certain anatomic areas or tissues. Noting whether glands. The dentist should attempt to ascertain, as much as the lesion is confined to keratinized or nonkeratinized tissues, possible, which tissues are contributing to the lesion based on regions with salivary gland tissues or areas of neural or vascular the anatomic location of the lesion. For example, if a mass anatomy can sometimes provide clues to the diagnosis. appears on the dorsum of the tongue, the dentist would logically 6. Are there any associated systemic symptoms (e.g., fever, nausea, or consider an epithelial, connective tissue, lymphatic, vascular, malaise)? Has the patient noted any similar or concurrent changes glandular, neural, or muscular origin. Similarly, a mass on the elsewhere in the body or had similar lesions in the oral or inner aspect of the lower lip would prompt the dentist to perioral tissues in the past? The dentist should look for possible include a minor salivary gland origin in the differential relationships or manifestations from related systemic diseases diagnosis, along with connective tissue origin and other pos- or conditions. For example, many systemic viral conditions sibilities. Certain lesions may have unique anatomic charac- (e.g., measles, mumps, mononucleosis, herpes, acquired immu- teristics, such as the linear tendencies of herpes zoster lesions nodeficiency syndrome) can cause oral manifestations concurrent as they follow neural pathways. The possible role of trauma with the systemic involvement. Autoimmune conditions may should always be entertained as possible sources of the lesion also manifest with oral lesions. Many oral ulcerative conditions (ill-fitting dental appliances, parafunctional habits such as can also present lesions elsewhere in the body (e.g., pemphigus, cheek biting, sharp edges on teeth or restorations, and trauma lichen planus, erythema multiforme, sexually transmitted from acts of domestic or other types of violence). Finally, infections). Other factors could include drug abuse or injuries pulpal, periapical, and periodontal pathologic or inflammatory from domestic violence. conditions also cause a significant percentage of oral lesions. 7. Is there any historical event associated with the onset of the lesions 2. Overall physical characteristics of the lesion. Appropriate medical (e.g., trauma, recent treatment, exposure to toxins or allergens, terminology should always be used to describe clinical findings visits to foreign countries)? One of the initial steps the dentist in the record because lay terminology can be misleading and should take when a lesion is noted is to seek a possible explana- nonspecific. Terms such as “ulcer” or “nodule” may be inter- tion based on the patient’s medical, dental, family, or social preted differently by different examiners. High-quality digital https: / / t.me / LibraryEDent histories. Frequently oral and perioral lesions can be caused by photographs may also be printed and enclosed with the biopsy parafunctional habits, hard or hot foods, application of medica- specimen or can be emailed separately to the pathologist. tions not intended for topical use, recent trauma, conditions Photographs are helpful in demonstrating the clinical char- involving the dentition (e.g., caries, periodontal disease, fractured acteristics of the lesion. Box 22.1 lists several common physical teeth), or an identified event or exposure. 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 Clinical Examination lesion. Lay terms such as “swelling” and “sore” are generally When a lesion is discovered, careful clinical and radiographic not helpful and may be subject to misinterpretation. examinations and palpation of regional lymph nodes is mandatory. 3. Single versus multiple lesions. The presence of multiple lesions Once the examination is complete, a detailed description of all is an important feature. When multiple ulcerations are found objective and subjective findings should be documented in the within the mouth, the dentist should think of specific possibili- patient’s chart. A drawing or a graphic schematic of the location, ties for the differential diagnosis. To find multiple or bilateral orientation, general shape, and dimensions of the lesion in the neoplasms in the mouth is unusual, whereas vesiculobullous, patient record is helpful. The use of standardized illustrations can bacterial, and viral diseases commonly present such a pattern. simplify the documentation (Fig. 22.2). Additionally, good-quality Similarly, an infectious process may exhibit outward spread as digital photographs are useful for documentation if the dentist one lesion infects the adjacent tissues with which it has had has the appropriate camera and accessories. Details, descriptions, contact. and drawings allow the dentist or subsequent referral specialists 4. Size, shape, and growth presentation of the lesion. Documentation to evaluate the course of the lesion over time and determine whether of the size and shape of the lesion should be made, as noted it is enlarging, its features are changing, or new lesions are appearing previously. A small metric ruler made of a material that can in different anatomic areas. be disinfected (e.g., metal or plastic) is useful to have on hand. 454 PART V Management of Oral Pathologic Lesions @LibraryEDent ‫ﻣﻛﺗﺑﺔ طب اﻷﺳﻧﺎن‬ A B https: / / t.me / LibraryEDent C D Fig. 22.2 Illustrations of the oral cavity and perioral areas, which are useful for indicating size and loca- tion of oral lesions.  CHAPTER 22 Principles of Differential Diagnosis and Biopsy 455 @LibraryEDent ‫ﻣﻛﺗﺑﺔ طب اﻷﺳﻧﺎن‬ E Fig. 22.2, cont’d BOX 22.1 Descriptive Pathology Terminology and margins should be recorded. Margins of an ulcer may be flat, rolled, raised, or everted. The base of the ulcer may be Bulla (pl. bullae): a blister an elevated, circumscribed, fluid-containing smooth, granulated, or covered with fibrin membrane or slough lesion of skin or mucosa or hemorrhagic crust (scab) or it may have the fungating Crusts (crusted): dried or clotted serum on the surface of the skin or appearance that is characteristic of some malignancies. mucosa 6. Lesion coloration. The surface color(s) of a lesion can reflect Dysplasia (dysplastic): any abnormal development of cellular size, shape, or organization in tissue various characteristics and even the origin of many lesions. Erosion: a shallow, superficial ulceration A dark bluish swelling that blanches on pressure suggests Hyperkeratosis: an overgrowth of the cornified layer of epithelium a vascular lesion, whereas a lighter-colored, bluish lesion Hyperplasia (hyperplastic): an increased number of normal cells that does not blanch may suggest a mucus-retaining cyst. A Hypertrophy (hypertrophic): an increase in size caused by an increase in pigmented lesion within the mucosa may suggest a “traumatic the size of cells, not in the number of cells tattoo” of restorative material or a more ominous melanotic Keratosis (keratotic): An overgrowth and thickening of cornified (horned tumor. Keratinized white lesions can reflect a reaction to layer) epithelium repetitive local tissue trauma or represent potentially prema- Leukoplakia: a slowly developing change in mucosa characterized by lignant changes. An erythematous (or mixed red and white) firmly attached thickened white patches lesion may represent an even more ominous prognosis for Macule: a circumscribed nonelevated area of color change that is distinct from ad acent tissues dysplastic changes than a white lesion. Inflammation can be Malignant: anaplastic a cancer that is potentially invasive and metastatic superimposed on areas of mechanical trauma or ulceration, Nodule: a large, elevated, circumscribed and solid palpable mass of the resulting in a varied presentation from one examination to skin or mucosa the next. Papule: a small, elevated, circumscribed and solid palpable mass of the 7. Sharpness of lesion borders and mobility. If a mass is present, the skin or mucosa dentist should determine whether it is fixed to the surrounding https: / / t.me / LibraryEDent Plaque: any flat, slightly elevated superficial lesion deep tissues or freely movable. Determining the boundaries of Pustule: a small, cloudy, elevated and circumscribed pus-containing vesicle the surface lesion will aid in establishing whether the mass is on the skin or mucosa fixed to adjacent bone, arising from bone and extending into Scale: a thin, compressed, superficial flake of cornified (keratinized) adjacent soft tissues, or only infiltrating the soft tissue. epithelium Stomatitis: any generalized inflammatory condition of the oral mucosa 8. Consistency of the lesion to palpation. Consistency can be Ulcer: a crater-like circumscribed surface lesion resulting from necrosis of described as soft or compressible (e.g., a lipoma or abscess), the epithelium firm or indurated (e.g., a fibroma or neoplasm), or hard (e.g., Vesicle: a small blister a small circumscribed elevation of skin or mucosa torus or exostosis). Fluctuant is a term used to describe the containing serous fluid 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 The ruler is valuable for measuring the diameters of clinically feels the impulse transmitted through the fluid-filled cavity. evident lesions, which measurements can then be entered into 9. Presence of pulsation. Palpation of a mass may reveal a rhythmic the record with the drawing. The growth presentation should pulsation that is suggestive of a significant vascular component. also be noted: whether the lesion is flat or slightly elevated, This sensation can be subtle and is especially significant when endophytic (growing inward) or exophytic (growing outward dealing with intrabony lesions. The pulsation can be accom- from the epithelial surface), and sessile (broad based) or panied by a palpable vibration, called a thrill. If a thrill is pedunculated (on a stalk). palpated, auscultation of the area with a stethoscope may 5. Surface appearance of the lesion. The epithelial surface of a reveal a bruit, or audible murmur, in the area. Invasive pro- lesion may be smooth, lobulated (verruciform), or irregular. cedures on lesions with thrills, bruits, or both should be avoided, If ulceration is present, the characteristics of the ulcer base and patients should be referred to specialists for treatment 456 PART V Management of Oral Pathologic Lesions because life-endangering hemorrhage can result if surgical (3) presence of pain or tenderness, (4) degree of fixation (fixed, intervention (biopsy) is attempted. matted, or movable), and (5) texture (soft, firm, or hardened). 10. Examination of regional lymph nodes. No evaluation of an oral When multiple nodes are slightly enlarged but barely palpable, lesion is complete without a thorough examination of the they can feel like bird shot and are described as “shotty nodes.” regional lymph nodes. This examination should be accomplished The lymph node examination should be methodical and should before any biopsy procedure. Sometimes lymphadenitis develops include the following groups: (1) occipital, (2) preauricular and in the regional nodes following a surgical procedure such as postauricular; (3) mandibular, submandibular, and submental; (4) biopsy, thus creating a subsequent diagnostic dilemma. It can deep anterior cervical chain; (5) superficial cervical nodes (along then become difficult to differentiate between reactive lym- the sternocleidomastoid muscle); (6) deep posterior cervical chain; @LibraryEDent ‫ﻣﻛﺗﺑﺔ طب اﻷﺳﻧﺎن‬ phadenitis as a surgical sequela, coincidental regional infection and (7) supraclavicular nodes. Buccal lymph nodes may or may or inflammation, or metastatic spread of the tumor in question. not be routinely palpable. Fig. 22.3 illustrates the primary lymph nodes of significance in the cervicofacial region. The standard examination of lymph nodes requires only simple Diagnostic Adjuncts inspection and palpation. Comparison of left and right sides, using A variety of adjunctive diagnostic aids have been promoted to the middle three fingers for light palpation, is often useful. Move- the practitioner to screen for and identify oral and pharyngeal ments during palpation should be slow and gentle, with the fingers cancers (OPCs) and oral premalignant lesions at their earliest moving lightly across each area in vertical and horizontal directions presentation (Tables 22.1 and 22.2).1-15 They are all marketed as well as in a rotary motion. In adults, normal lymph nodes are as aids for the clinician to use in addition to, not in lieu of, the not palpable unless they are enlarged by inflammation or neoplasia, accomplishment of the conventional head and neck examination but cervical nodes of up to 1 cm in diameter can often be palpated and are often promoted as advanced “must-have” products. Some in children up to the age of 12 years and are generally not considered adjuncts are marketed as “discovery” or “screening” enhancements, an abnormal finding. In recording lymph node findings, the fol- whereas others are marketed as case assessment utilities to further lowing five characteristics should be routinely documented: (1) assess a visually identified lesion. The use of these products in the location, (2) size (preferably recording the diameters in centimeters), profession remains a topic of much debate. As there is currently Preauricular Maxillary Buccal Postauricular https: / / t.me / LibraryEDent Mandibular Submental Occipital Submandibular Deep cervical Superficial cervical Supraclavicular Infraclavicular A Fig. 22.3 (A) Anatomic location of cervicofacial lymph nodes.  CHAPTER 22 Principles of Differential Diagnosis and Biopsy 457 @LibraryEDent ‫ﻣﻛﺗﺑﺔ طب اﻷﺳﻧﺎن‬ B C https: / / t.me / LibraryEDent Fig. 22.3, cont’d (B) Anterior approach to cervical lymph node examination. Gently move the fingers in a circular motion along the full length of the sternocleidomastoid muscle. (C) Posterior approach to cervical lymph node exam- ination. It is generally helpful for the patient to move the head from side to side and to tilt the head forward to make the lymph nodes more palpable. (D) Bimanual palpation of floor D of mouth and submandibular lymph nodes. 458 PART V Management of Oral Pathologic Lesions TABLE 22.1 Available Cytology-Based, Vital Stain– The CytID case assessment adjunct utilizes a liquid cytology Based, and Light-Based Adjunctive sampling technique; its recommendation for use is similar to that of the previously described Oral CDx BrushTest for assessing lesions Diagnostic Technologies1–12 when biopsy is not warranted or possible.19 The appropriate CDT Product Contact code to use is D7287, “oral cytology brush.”17 The use of liquid cytology is claimed to provide a more accurate sampling compared Cytology-based OralCDx rush Test CDx Diagnostics CytID orward Science with the Oral CDx BrushTest.20,21 Tested lesions that receive a “malignancy” or “atypical” result with CytID must undergo a scalpel ital stain based Toluidine chloride stain Den-Mat oldings biopsy to determine the definitive diagnosis. @LibraryEDent ‫ﻣﻛﺗﺑﺔ طب اﻷﺳﻧﺎن‬ (component of izi ite The clinical value of using cytology to assess suspicious lesions Plus with T lue) remains controversial, and many consider cytology an unnecessary Ora lu AdDent, Inc. intermediate procedure.22-28 Cytology is not diagnostic and all ight-based izi ite T lue Den-Mat oldings “positive” or “atypical” reports must undergo a scalpel biopsy to Microlux D AdDent, Inc. establish a firm diagnosis. Furthermore, lesions that report back as scope x D Dental negative but that persist clinically will often have to undergo biopsy Sapphire Plus Den-Mat oldings to obtain a diagnosis. In a recent study addressing the efficacy of Identafi Dental the BrushTest in assessing 41 small cancerous lesions (carcinoma io/Screen AdDent, Inc. in situ and ≤2 cm), the authors determined the sensitivity of the DO S it Dent ight Inc. OralID orward Science brush technique to be 74.5%.29 Thus when this test is used, as izi ite PRO Den-Mat oldings, marketed, to “test common oral spots,” OPC may be missed. C Vital Stain–Based Adjuncts Vital staining with toluidine blue has been advocated for decades as a method to better assess suspicious mucosal lesions.23,30,31 It TABLE 22.2 Available Molecular-Based Adjuncts to uses a topically applied metachromatic dye that has an affinity for Diagnose Oral Premalignant Lesions/Oral tissues expressing high cellular activity (e.g., dysplasia, neoplasia, inflammatory, regenerative). Tissues that retain the dye appear and Pharyngeal Cancer12–15 dark blue clinically. False-positive results are common and are Product Company Biomarkers Assessed primarily associated with inflammatory lesions and healing ulcers, which also have high cellular metabolic rates.22,32 As a consequence, OraRisk P OralD A abs P strains a, , , , , , Complete , , , , , operator experience is essential for proper interpretation. enotype , , Toluidine blue is not currently approved by the U.S. Food and Drug Administration (FDA) as a stand-alone adjunctive screening OraRisk P OralD A abs P strains , , , , , aid. It is marketed as a case assessment marking aid to the ViziLite / / R , , , , , , , , TBlue, Bio/Screen, and MicroLux DL light-based adjuncts (see further on), where it is used as a case assessment marker to further MOP PC Molecular P , cytology, cellular changes enhance the visualization of an area initially identified by the light-based adjunct.2,9 The appropriate CDT code to apply in using SaliMark OSCC PeriRx, C D SP , SAT, and OA toluidine blue is D0431, “adjunctive prediagnostic test that aids in detection of mucosal abnormalities including premalignant and https: / / t.me / LibraryEDent HPV, Human papillomavirus. malignant lesions, not to include cytology or biopsy procedures.”17 Light-Based Adjuncts insufficient evidence to draw a firm conclusion, clinicians should From the perspective of the FDA, the light-based adjuncts are all be both cautious in choosing to use such devices and aware of cleared for marketing by the FDA as illumination devices.33 All their limitations. are marketed to help the practitioner discover new or potentially overlooked mucosal abnormalities. Some are also marketed to help Cytology-Based Adjuncts the surgeon define appropriate surgical margins for excision.23,34 Available since 1999, the Oral CDx BrushTest is specifically These devices can be categorized into two basic groups according marketed to the dental professional to “test common oral spots to the manner in which a specific spectrum of light is used to (subtle red or white spots) that may appear in your mouth from interrogate the tissue. time to time.”16 As such it is a case assessment adjunct. This The ViziLite TBlue and Microlux DL use a blue-white light adjunctive test is a refinement of the pap smear technique used (spectral wavelengths of 430 and 580 nm) to assess the tissues. in gynecology, in which a special sampling brush is used to harvest The blue-white light for the ViziLite TBlue product is generated a full transepithelial specimen that is forwarded to a centralized via chemiluminescence, whereas a battery powered light-emitting laboratory for assessment. The appropriate CDT code to use is diode is used to generate the blue-white light for the Microlux D7288, “brush biopsy—transepithelial sample collection.”17 At DL product. A 60-second prerinse with a 1% acetic acid solution the laboratory, a sophisticated computer protocol is employed that is used to remove the surface glycoprotein layer and improve helps the pathologist render a final report. Variants of this technology visualization with either product.22,35 The examination is performed (WATS3D, EndoCDx TNE—Transnasal Esophagoscopy, EndoCDx in a darkened room or with the use of special eyewear to negate LP—Laryngeal) are marketed to gastroenterologists and the effects of ambient light. Normal cells absorb the blue-white otolaryngologists.18 light, whereas dysplastic cells with abnormal nuclei and high nuclear/  CHAPTER 22 Principles of Differential Diagnosis and Biopsy 459 cytoplasmic ratios reflect the blue-white back to the examiner as markers DUSP1, SAT, and OAZ1. The company claims that the “aceto-white.”35-37 sensitivity and specificity of the SaliMark for oral squamous cell The VELscope Vx, Sapphire Plus, Identafi, BioScreen, DOE carcinomas are 91.7% and 59.0%, respectively.51 However, the Oral Exam System, OralID, and ViziLite PRO products use light performance of this product in assessing the variety of nonmalignant spectra in the 390- to 460-nm range to assess the autofluorescent oral lesions encountered in general practice remains unknown. This character of the mucosal tissues. Narrow-band filtration (either in test, like cytology, is marketed as a negative predictor; patients the device’s viewfinder or via eyewear) further highlights the with moderate or high test results should be referred for further autofluorescent character of the lesion. Dysplastic or carcinogenic evaluation and/or biopsy, whereas patients with low risk results tissues are associated with a decrease in natural fluorophore con- should be followed up to ensure resolution. However, a biopsy @LibraryEDent ‫ﻣﻛﺗﺑﺔ طب اﻷﺳﻧﺎن‬ centration and an increased absorption and scattering of light.35 will often be necessary to diagnose a low-risk lesion, rendering Normal or healthy tissue appears pale green utilizing autofluores- use of the SaliMark an often unnecessary intermediate procedure. cence, whereas suspect tissues appear dark (loss of fluorescence).38 The Identafi product includes an additional green-amber light (545 nm) option to better visualize the increase in angiogenesis Radiographic Examination associated with carcinoma.39,40 Radiographs are useful diagnostic adjuncts after completion of the Although light-based adjuncts do offer the clinician a different history and clinical examination, especially for lesions occurring perspective in viewing a given lesion (e.g., assessment utility), their within or adjacent to bone. When soft tissue lesions are close to value and efficacy as screening adjuncts remain unproven.35,38,41 bone, radiographs may indicate whether the lesion is causing an In a recent report of 14 available studies addressing the effectiveness osseous reaction, eroding into the bone, or arising from an intraos- of the VELscope, ViziLite, and Microlux DL adjuncts, the authors seous origin. Various radiographic techniques may be used depending determined that the adjuncts demonstrated widely variable sensitivi- on the anatomic location of the lesion. Most pathologic conditions ties and specificities and did not effectively discriminate between of the mandible or maxilla can be adequately viewed on routine high- and low-risk lesions.35 plain views (e.g., periapical, occlusal, or panoramic), but occasionally Practitioners choosing to use any of the available visualization specialized imaging techniques are needed—including computed adjuncts in assessing their patients should understand their limita- tomography (CT; with the newer cone-beam CT) or magnetic tions and ensure that an appropriate referral and/or biopsy is resonance imaging (MRI) views—to fully delineate the exact nature accomplished for any lesion deemed suspicious. The appropriate and location of intrabony lesions. CDT code to apply in using one of these adjunctive aids is D0431, The radiographic appearance may frequently give clues to the “adjunctive prediagnostic test that aids in detection of mucosal diagnosis of a lesion. For example, a cyst usually appears as a abnormalities including premalignant and malignant lesions, not radiolucency with sharp borders (Fig. 22.4A–B), whereas a radio- to include cytology or biopsy procedures.”17 lucency with ragged, irregular borders might indicate a malignant or more aggressive lesion (see Fig. 22.4C–D). In viewing a Molecular-Based Adjuncts radiograph, if an intraosseous area shows a deviation from normal The assessment of saliva to identify potential tumor biomarkers structures or appearance, the dentist must determine whether the (e.g., nonorganic compounds; proteins and peptides; DNA, mRNA, change is pathologic or simply an atypical presentation of a normal and miRNA; carbohydrates; and other metabolites) is being aggres- anatomic structure. This is particularly true in viewing certain sively researched.42-44 The number of potential biomarkers associated projections of the maxilla and the mandible in which the complex with OPC exceeds 800, and the challenge will be to identify the adjacent anatomy leads to superimpositions of contiguous structures unique molecular fingerprint of OPC.45 Four molecular-based such as the paranasal sinus cavities. adjunctive tests (see Table 22.2) have been introduced as putative In unique diagnostic situations, radiopaque dyes or markers https: / / t.me / LibraryEDent aids to assess for OPC or OPC risk. may be used in conjunction with routine or specialized radiographs. The OraRisk human papillomavirus (HPV) Complete Genotype For example, sialography involves the injection of radiopaque dye and the OraRisk HPV 16/18/HR are two saliva-based polymerase into glandular ducts to produce an indirect image of the gland chain reaction (PCR)–based tests available for determining the architecture and delineate any pathologic lesions within the gland. presence of HPV.12,13 The value of routinely using either of these Cysts may be injected to assist in determining the true extent of tests in clinical practice remains unknown, as the prognostic value their anatomic boundaries. Radiopaque markers such as needles of current or persistent HPV detection in oral rinses to predict or metal spheres can be used to localize a foreign object or pathologic the risk for OPC is unknown and there are available therapies to lesion. address chronic HPV infection.46,48 In a recent analysis the authors estimated that 10,500 patients would need to be tested to detect one case of OPC.48 The use of this test is likely to generate significant Laboratory Investigation anxiety for those who screen positive for a high risk HPV.49 In certain instances supplementary laboratory tests can assist The MOP screening test from PCG Molecular claims to test in lesion identification. Certain oral lesions may be manifesta- for oral cancer risk earlier than traditional testing methods by tions of a systemic disease process such as hyperparathyroidism, assessing for HPV, cytologic changes, and DNA damage.50 Informa- multiple myeloma, leukemia, and certain lymphomas. To cite an tion on this test appears to be restricted to its promotional website, example of the role of laboratory testing, examination of a patient and there is no peer-reviewed literature addressing the overall clinical with multiple lytic lesions and loss of lamina dura bone might value of this product. suggest hyperparathyroidism. This diagnosis could be clarified by The SaliMark oral squamous cell carcinoma adjunctive test is the dentist requesting serum calcium, phosphorus, and alkaline a commercially available assessment utility intended to help the phosphatase tests. Guidance for requesting such tests can be found practitioner stratify the risk of malignancy for a clinically discovered in leading oral and maxillofacial pathology textbooks and other oral lesion.15 The test interrogates for the levels of the putative cancer resources. 460 PART V Management of Oral Pathologic Lesions @LibraryEDent ‫ﻣﻛﺗﺑﺔ طب اﻷﺳﻧﺎن‬ A B R C D Fig. 22.4 (A–B) Radiographic appearance of cysts. (A) Note the peripheral condensing osteitis around radiolucent center. (B) Large unilocular radiolucency in left mandible with well-defined peripheral border. (C–D) Radiographic appearance of bone destruction by malignancy. (C) Squamous cell carcinoma has eroded into the right mandible. Note the ragged appearance and lack of cortication (arrows). (D) Intraos- seous malignancy has completely destroyed the normal architecture of the right mandibular ramus and produced a pathologic fracture. In the majority of cases, screening laboratory studies are con- because up to 15% to 20% of those areas (and 100% of erythro- sidered unnecessary because they often have a low diagnostic yield plakia lesions) can exhibit histologic evidence of dysplasia or frank per total cost involved in performing such tests. Once the surgical malignancy.52 High-risk areas of the mouth include the floor of biopsy has provided a definitive diagnosis, however, laboratory the mouth, the lateral and ventral surfaces of the tongue, and the testing can contribute meaningful information that is relevant to buccal and lower lip mucosa. Areas of redness or pebbling within the subsequent management of the lesion. areas of leukoplakia are especially troubling. Incisional biopsies from one or more of such suspicious areas are generally https: / / t.me / LibraryEDent indicated. Presumptive Clinical Differential Diagnosis During subsequent examinations, the patient record should After completing the initial dental, medical, and lesion histories provide details on whether the observed lesion has improved or and clinical, radiographic, and laboratory examinations (as indi- not improved and the dentist’s plan for subsequent management cated), the dentist next should compile a presumptive list of reason- (i.e., continued observation on a structured timetable, continued able differential diagnoses. These diagnoses convey the clinician’s local treatment, biopsy, or referral). impression to the pathologist regarding what the dentist feels the lesion most likely is on the basis of the total assessment. These Basic Tenets of Follow-up and Referral diagnoses may or may not ultimately be consistent with the final histologic diagnosis but are, nonetheless, important because the Failure to diagnose and refer a patient with a possible pathologic pathologist rules out entities that may have similar clinical and condition in a timely manner has become one of the leading causes pathologic presentations. of litigation in the medical profession. Over the years, numerous articles and textbook chapters have provided guidance on how to Prebiopsy Monitoring obtain biopsies of lesions and to formulate differential diagnoses. Little guidance has been provided on the proper follow-up protocols Any undiagnosed or suspicious change in oral tissues that cannot for “suspicious” lesions and guidelines for appropriate referrals be explained by localized trauma (and the source corrected) or between practitioners. One article has attempted to provide this other factors should be followed up in 7 to 14 days, with or needed guidance without imposing a legal precedent that could without local treatment. If the lesion enlarges or expands, develops be construed as a legal standard.53 an altered appearance, or does not respond as expected to local The dentist should not delegate examination of patients for therapy, biopsy is usually indicated. Areas of leukoplakia (which pathologic conditions to auxiliary staff such as dental hygienists. is used as a clinical and not a pathology term) can be problematic, Although most hygienists are well trained to be observant with  CHAPTER 22 Principles of Differential Diagnosis and Biopsy 461 regard to soft tissue changes in the oral cavity, the ultimate compromised its clinical features. Biopsy can also produce reactive responsibility for the detection of pathologic conditions (including lymph nodes that are possibly unrelated to the original lesion. oral cancer screening) rests with the dentist. Delegation of this Allowing the referral specialist to evaluate the patient before duty is not permitted by law in most if not all, states. If the dentist biopsy helps obtain a more accurate diagnosis and simplifies does not follow up on the hygienist’s discovery of abnormal tissues, the formulation of a suitable treatment plan. the patient record should reflect the rationale for that decision. If the dentist decides to refer the patient for a second opinion or specialty management, the referral appointment should ideally Informed Consent and Shared Risk be arranged before the patient leaves the office. If left to make the Some clinicians argue that all lesions should be removed, a biopsy @LibraryEDent ‫ﻣﻛﺗﺑﺔ طب اﻷﺳﻧﺎن‬ appointment themselves, many patients may fail to do so because should be obtained, or both should be done. In some clinical situ- of fear, denial, or procrastination. The arranged appointment should ations, however, patients and their dentists may jointly elect to be followed up with a letter, fax, or email from the referring general observe periodically any innocent-appearing lesions that occur in dentist to the specialist outlining the details of the case, the concerns, low-risk areas in low-risk patients (e.g., nonsmokers). However, and the requested procedures. A copy of this correspondence should lesions demonstrating any dysplastic changes on histopathologic be placed in the patient’s record. Copies of the specialist’s findings, examination should always be removed in their entirety. It must recommendations, procedures, and biopsy findings should also be be remembered that observation over time may be a calculated placed in the patient’s record. These formal exchanges provide risk. Many life-threatening conditions can initially masquerade as precise documentation that prevents miscommunications between innocuous lesions, and many different lesions can present similar offices and may provide some element of protection if litigation clinical appearances. The dentist should err on the side of caution is initiated later. Returned reports from the pathologist should be and must always ensure that the patient is fully informed of the acted on promptly. The patient should be notified of the results, risks, rationales, and alternatives before deciding that a lesion should and if the results are unexpected or positive, requiring further not be removed. The patient must understand that he or she is treatment, the patient should be counseled in person by the dentist. sharing the responsibility for that decision, and the discussions on which the decision is based should be well documented in the patient’s record. If the dentist advises removal and the patient Biopsy or Referral declines, that discussion and decision should likewise be thoroughly Clinicians vary in their surgical interests, training, and skills. Some documented, reflecting the patient’s understanding of the potential dentists may feel comfortable performing many biopsy procedures negative consequences of the decision. on their patients, whereas others may refer their patients to other specialists. This is a personal choice and should take several points Postbiopsy Monitoring into consideration. 1. Health of the patient. The patient pool in the United States is Following an incisional biopsy for diagnosis, a positive pathology getting older, and a growing number of older patients are seeking report (indicating dysplastic changes or malignancy) generally treatment in dental offices. Many of these patients have a history mandates appropriate surgical excision of the lesion and contiguous of systemic diseases, multiple medications, or physical com- tissues as indicated by the histopathologic diagnosis. This might promise that pose an increased surgical risk or potential hazards. necessitate referral to an oral-maxillofacial surgeon or other head These conditions are outlined and discussed in Chapters 1 and and neck specialist who is experienced in the management of 2; they may complicate any planned surgical procedures, includ- malignancies. A negative biopsy report, however, should never be ing biopsy. The presence of such conditions, however, should taken at face value but interpreted with clinical and historical not significantly delay biopsy or referral in most cases. Patients findings in mind. If doubt exists, a second biopsy might be indicated. https: / / t.me / LibraryEDent can be referred to specialists who are trained to deal with patients At the very least, plans should be developed for a structured schedule with special medical needs so that the procedure is carried out of continued close observation at appropriate intervals. Generally as safely as possible. it is prudent to reexamine the patient within 1 month and then 2. Surgical difficulty. If any of the basic surgical principles outlined at 3, 6, and 12 months during the first year. Thereafter, if clinical in Chapter 3 (such as access, lighting, anesthesia, tissue stabiliza- and radiographic findings are unchanged, the interval between tion, and instrumentation) pose a problem for the dentist in follow-up visits can be increased to 6 and then 12 months, as terms of treatment, referral should be considered. Similarly, as appropriate. Patients should always be counseled to contact the the size of a lesion increases or its position encroaches on dentist immediately if any clinical changes or new symptoms are significant anatomic structures, the potential for significant noted between visits. complications (e.g., bleeding and nerve damage) increases. Each dentist must judge whether the biopsy is within his or her General Principles of Biopsy surgical abilities or whether the patient would be better managed by a more highly trained specialist. The term biopsy indicates removal of tissue from a living body for 3. Malignant potential. The dentist who suspects that a lesion is microscopic diagnostic examination. Biopsy is the most precise malignant has two choices: (1) perform a surgical biopsy after and accurate of all diagnostic tissue procedures and should be completion of a comprehensive diagnostic workup or (2) before performed whenever a definitive diagnosis cannot be obtained a biopsy is performed, refer the patient to a specialist who is using less invasive procedures. The primary purpose of biopsy is able to provide definitive treatment if the lesion is shown to to determine the diagnosis precisely so that proper treatment can be malignant. The latter choice usually represents better service be provided because many different lesions have similar clinical to the patient if the referral can be executed in a prompt and or radiographic appearances. In actuality, a biopsy is more likely timely manner. In such cases it is better for the referral specialist to rule out malignancy than to diagnose cancer because the majority to evaluate the lesion before any surgical intervention has of oral and odontogenic lesions are benign. Nevertheless, the term 462 PART V Management of Oral Pathologic Lesions biopsy leads many patients to a perception that the dentist suspects the sample (Figs. 22.6 and 22.7). Central areas of a large lesion malignancy, so discussions that include that word must be carefully are often necrotic and therefore of little diagnostic value to the phrased so that it will not cause undue alarm or anxiety. pathologist, whereas active growth is taking place at the perimeter; Indications for biopsy are summarized in Box 22.2. The typical therefore inclusion of the lesion interface with normal-appearing characteristics of lesions that should raise the dentist’s suspicion tissue can demonstrate many significant cellular changes. Care of malignancy are listed in Box 22.3. Fig. 22.5 shows examples must be taken to include an adequate depth of tissue as well so of lesions that should be considered suspect. The four major types that cellular features from the base of the lesion are included. of biopsy generally performed in and around the oral cavity include Generally it is better to take a narrow, deep specimen than a broad, a (1) cytologic biopsy, (2) incisional biopsy, (3) excisional biopsy, shallow one. Care should be taken not to compromise significant @LibraryEDent ‫ﻣﻛﺗﺑﺔ طب اﻷﺳﻧﺎن‬ and (4) aspiration biopsy. adjacent anatomic structures such as nerves and major blood vessels unless they seem to have a relationship with the origins or pathology Incisional Biopsy of the lesion. An incisional biopsy is a biopsy procedure that removes only a small portion of a lesion. If the lesion is large or demonstrates Excisional Biopsy differing characteristics in different locations, then more than one An excisional biopsy implies removal of a lesion in its entirety, to area of the lesion may require sampling. Incisional sampling is include a 2- to 3-mm perimeter of normal tissue around the lesion used if the lesion is large (>1 cm in diameter), is located in a risky (Fig. 22.8). The width of the perimeter of normal tissue may vary or hazardous location, or whenever a definitive histopathologic depending on the presumptive diagnosis. An additional 2 to 3 mm diagnosis (e.g., for suspected malignancy) is desired before planning in tissues may be required for specimens suspected of malignancy, a complex removal or other treatment. including some pigmented lesions and lesions already diagnosed The biopsy is generally excised as a wedge of tissues in such a as having dysplastic or malignant cells. Complete excision often manner as to include normal- and abnormal-appearing tissues in constitutes definitive treatment of the lesion biopsied. Excisional biopsy is reserved for smaller lesions (