MetLife designates this activity for 2.0 continuing education credit for the review of this Quality Resource Guide and successful Quality Resource Guide completion of the post test. FIRST EDITION White Lesions of the Oral Cavity

change, while potentially overlapping with several of Author Acknowledgements Educational Objectives the conditions covered in this document, should be Paul Edwards, MSc DDS FRCD(C) considered under their respective categories2 and are not Following this unit of instruction, the practitioner Professor - should be able to: included in this discussion. Oral Pathology, Medicine & Radiology Indiana University 1. Outline the range of common and clinically Oral mucosa may present with a white appearance for School of Dentistry important white lesions affecting the oral a number of reasons, ranging from (an Indianapolis, Indiana cavity. increase in the thickness of the surface layer) to Dr. Edwards has no relevant financial 2. Describe the steps involved in the initial epithelial hyperplasia (an increase in the thickness of the relationships to disclose. assessment of a white lesion of indeterminate epithelial layer itself). White mucosal change may likewise The following commentary highlights etiology. result from intracellular edema (a buildup of fluid between fundamental and commonly accepted 3. Categorize white lesions of the oral cavity by epithelial cells, as seen in leukoedema), reduced sub- practices on the subject matter. The category of disease process (INERTIA). surface vascularity (increased collagen deposition seen information is intended as a general overview and is for educational purposes only. This with the use of certain brands of smokeless tobacco) and 4. Describe the rationale for developing a information does not constitute legal advice, extrinsic surface changes such as debris accumulation differential diagnosis for all white lesions of which can only be provided by an attorney. the oral cavity. (materia alba, ) or chemical or thermal cautery © Metropolitan Life Insurance Company, (dentifrice-associated sloughing, cinnamon reaction). New York, NY. All materials subject to this copyright may be photocopied for the 5. Define and explain the etiology, significance, This latter group of conditions is characterized by the and management of “idiopathic leukoplakias” noncommercial purpose of scientific or ability to remove the white material with vigorous wiping, educational advancement. in the oral cavity. or resolution of the lesion within several days following Originally published September 2014. 6. Appreciate the challenges involved in the removal of the offending agent(s). Expiration date: December 2017. The management of potentially preneoplastic white content of this Guide is subject to change as new scientific information becomes lesions of the oral cavity. The initial step in assessing any lesion of indeterminate available. etiology is to carefully evaluate it with respect to duration, size, location, surface texture, borders, and distribution. Background Commonly, chronic lesions involving multiple quadrants are associated with systemic mucocutaneous conditions hite lesions of the oral cavity comprise a MetLife is an ADA CERP Recognized Provider. such as . group of lesions of diverse etiology, ranging ADA CERP is a service of the American Dental Association to assist dental professionals from reactive lesions to squamous cell With these findings in mind, it is critical that the clinician W in identifying quality providers of continuing carcinoma (Table 1). The lesions in this disparate group then formulate a thorough differential diagnosis, dental education. ADA CERP does not approve of conditions often overlap in appearance, potentially representing a list of both the most likely and the or endorse individual courses or instructors, leading to under-diagnosis. A thorough knowledge nor does it imply acceptance of credit hours by most clinically significant diagnostic possibilities, for boards of dentistry. of their clinical presentations and significance allows the lesion in question. The differential diagnosis will Concerns or complaints about a CE provider management of these lesions as a critical part of the guide patient management by directing what additional may be directed to the provider or to ADA 1 practice of dentistry. This Quality Resource Guide will investigation, if any, is needed in order to arrive at a CERP at www.ada.org/goto/cerp. discuss the most common and/or clinically significant definitive diagnosis. The use of a mnemonic that prompts Accepted Program Provider FAGD/MAGD white lesions that may appear in the oral cavity. Credit 11/01/12 - 12/31/16. the clinician to consider all general etiologic causes of For the purpose of this Guide, a white lesion is defined disease (idiopathic, neoplastic, etc.) should be considered Address comments to: [email protected] as a readily identifiable distinct white color change (when when developing the differential diagnosis (Table 1). In MetLife Dental compared to the adjacent unaffected mucosa), localized addition to helping assure that all possible etiologies Quality Initiatives Program or generalized on the oral mucosal surface, which does are considered in the differential diagnosis, mnemonics 501 US Highway 22 Bridgewater, NJ 08807 not readily rub off. Lesions with ulceration or red color may also reduce the likelihood of a “rush to diagnosis”. www.metdental.com Quality Resource Guide – White Lesions of the Oral Cavity

Table 1 Common and Clinically Important White Lesions of the Oral Cavity Grouped by Category of Disease Process (Mnemonic: INERTIA)

Prevalence Category Specific Clinical Clinical In General of Disease Condition/ Specific Etiology Management Comments Presentation Significance Dental Diagnosis Process Practice

Normal More common in developmental Bilateral buccal None; clinical black patients, I Leukoedema variant associated mucosa; diffuse presentation is No treatment needed but also seen in Idiopathic with intraepithelial subtle white change pathognomonic lighter skinned edema individuals

Idiopathic ; Exposure to epithelial dysplasia; carcinogens modified Biopsy and definitive treatment Can also be Varies depending on by host susceptibility Potentially based on histopathologic categorized proliferative condition. Generally Varies N (Tobacco, alcohol, preneoplastic diagnosis. Indefinite recall (q6 under verrucous single site. leukoplakia; rarely immuno- months) in absence of dysplasia “Idiopathic” Neoplastic oral submucous suppression) (includes fibrosis preneoplastic, benign and Confirmatory biopsy followed malignant) squamous cell Tobacco, alcohol, Varies; evidence of by definite surgical excision, carcinoma; rarely immuno- Malignant neoplasm Uncommon surface change and/or radiation therapy and/or supression verrucous carcinoma chemotherapy

Rare. Included as Ammonia production Abrupt onset of example of E from degradation of white [plaques in Underlying renal failure Most likely to Uremic stomatitis Address underlying renal failure “Endocrine/ elevated serum patient with acute or is life-threatening see in severely Endocrine/ Metabolic” by oral flora? chronic renal failure ill hospitalized metabolic patient etiology

May be mistaken for Chemical burn; White sloughing of other white lesions and Somewhat R Direct tissue damage thermal burn exposed oral tissues possibly bullous lesions common Reactive such as pemphigoid

If frictional etiology not clearly Frictional May be Retromolar pad; evident and/or if thick, papillary or hyperkeratosis; linea indistinguishable T Repetitive friction buccal mucosa; verrucous in appearance and/or if Common alba; Morsicatio clinically from lateral tongue other changes, incisional biopsy to Traumatic linguarum idiopathic leukoplakia rule out dysplasia is mandatory.

Biopsy to confirm; investigation May signify to rule out HIV-related Corrugated white undiagnosed HIV immunosuppression if no clinical I Oral hairy EBV infection of patch(es) lateral disease. Often history of medication-induced Rare leukoplakia superficial epithelium tongue; often misdiagnosed clinically immuno-suppression. May be Inflammatory bilateral as “tongue chewing” or seen in patients on high potency or Infectious “idiopathic leukoplakia” corticosteroid inhalers for COPD or asthma.

Biopsy required if unilateral Varies: “classic” Immune-mediated Many other processes presentation, or in presence of bilateral white striae Somewhat Lichen planus mucocutaneous present with similar , ulceration or other on buccal mucosa to common disease clinical appearance “non-classical” appearance widespread erosions A (see text). Autoimmune Associated with chronic Rare in overall (immune- Resembles lichen GVHD. Most patients on Biopsy if atypical presentation population. mediated) Graft versus host Allogeneic bone planus. Dorsal immuno-suppressive (thick, granular, persistent Common after disease marrow transplant tongue often therapy, increasing risk ulceration). bone marrow involved. of oral cancer. transplant.

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Specific Lesions Thick, corrugated or verrucous appearing white Histologically, idiopathic leukoplakias represent patches, lesions with irregular borders or variations a spectrum (Figures 3A-C) ranging from simple Frictional Hyperkeratosis in the degree or intensity of whiteness should be hyperkeratosis to SCC, with upwards of 15% of oral Repetitive friction is one of the most common treated with a high index of suspicion, as should leukoplakic lesions harboring epithelial dysplasia causes of a localized white surface change in the all localized white patches occurring in areas not (mild, moderate or severe) and 5-10% SCC on initial oral cavity. This reactive process is characterized generally prone to repetitive friction, such as the biopsy. The likelihood of epithelial dysplasia or histologically by an increase in the thickness of the dentate gingival alveolar tissue, ventral tongue, carcinoma is greatest for lesions involving the lower surface keratin, somewhat analogous to a callus floor of the mouth, vermillion border of the lower lip, floor of the mouth and tongue; with leukoplakias on the skin. Intraorally, these lesions develop in lip and the soft palate. at these sites having a 25-45% likelihood of areas most likely to be traumatized by the teeth, dysplasia or SCC at initial biopsy. including the area of greatest prominence of the While true reactive hyperkeratoses are not lateral tongue and along the occlusal plane on associated with an increased risk of malignant Scalpel incisional biopsy and histopathological the buccal mucosa. As a result, a diagnosis of transformation,4 their importance lies in not examination of formalin-fixed tissue from frictional hyperkeratosis should only be confidently under-diagnosing a potentially preneoplastic white representative areas of all cases clinically made in those areas at highest risk of repeated lesion (“idiopathic leukoplakia”) as a frictional diagnosed as idiopathic leukoplakia is mandatory. trauma. response. As described above, location and clinical Multiple areas may need to be sampled in patients presentation are two important factors to consider with large areas of leukoplakia. Areas with the A variant of frictional hyperkeratosis, seen along when making this determination. In the absence of most prominent change, or with a mixed red-white the mandibular edentulous alveolar ridge, has convincing evidence pointing to a frictional etiology, appearance, should be chosen for biopsy. been referred to as “benign alveolar ridge white lesions should be managed as idiopathic (BARK)”.3 This designation reflects the leukoplakias and, as described below, assessed by While a number of adjunct tools are commercially observation that these lesions are generally free biopsy for evidence of epithelial change. available to assist in evaluating suspicious intraoral of epithelial dysplasia on biopsy, particularly when epithelial lesions, the benefit of these tests have absent any worrisome clinical features such as Idiopathic Leukoplakia primarily been evaluated in studies looking at significant thickness or variation in color intensity. Idiopathic leukoplakia is a clinical term describing high-risk populations, such as patients previously BARK is believed to result from repetitive trauma a white patch or plaque that cannot be rubbed off treated for cancer of the upper aerodigestive to the alveolar mucosa from a food bolus being and cannot be definitively characterized clinically tract.6 As a result, their routine use in low-risk pushed against the edentulous ridge by opposing as another process (figure 2). Leukoplakic lesions populations is questioned due to their lower natural or artificial teeth. of the oral cavity are considered to be preneoplastic positive predictive value when used in the typical because as a group, they are associated with a Clinically, white patches of frictional etiology general dental setting characterized by low greater likelihood of developing cancer, specifically generally present as well-defined thin linear areas disease prevalence.7 Nevertheless, there are data squamous cell carcinoma (SCC), when compared of hyperkeratosis that do not extend beyond the to suggest the possible benefits of employing some to normal-appearing tissue.5 area of potential trauma (figure 1), and often exhibit of these diagnostic aids to determine the optimal a rough, macerated surface that can sometimes site for taking a biopsy of a large heterogeneous Figure 2 be partially removed with tissue forceps. lesion. Cytology-based diagnostic tests (“brush biopsy”), loosely analogous to the cervical pap smear, Figure 1 are generally not a substitute for traditional scalpel biopsy because the harvested cells are disaggregated, thereby lacking the necessary architectural information to histologically assess and grade dysplastic epithelial lesions.8 While cytology-based assessment can accurately identify Leukoplakic lesion of the right lateral-ventral lesions with dysplastic change, a traditional biopsy tongue in a 55-year-old male with a 35-pack year history of tobacco use - the lesion does not is still required in these cases. Performing both involve a typical site for trauma, and exhibits procedures can be argued as unnecessarily Subtle white linear lesion with well-defined an irregular surface morphology, with areas of increasing the patient’s costs. distribution along the buccal mucosa consistent prominent thickening - clinically, this represents with frictional hyperkeratosis - the area of white an idiopathic leukoplakia - on incisional biopsy, Screening tests, if used, are probably best restricted change does not extend appreciably past the area this was found histologically to represent severe to assessing minimally suspicious white lesions of the occlusal plane. epithelial dysplasia. involving low risk sites (the edentulous mandibular www.metdental.com Page 3 Quality Resource Guide – White Lesions of the Oral Cavity alveolar ridge). These approaches may eventually post-intervention morbidity due to location. This risk of malignant transformation.11 Therefore, supplement the use of scalpel biopsy for the uncertainty is further tempered by the disparate even in the absence of dysplasia on initial biopsy, evaluation of leukoplakic change when new tests data regarding the effectiveness of surgical careful long-term follow-up, with repeat biopsies are developed that assess cytologic preparations intervention at reducing the progression of mild as necessary, is mandatory. for the expression of specific molecular markers 10 epithelial dysplasia to invasive carcinoma. Tobacco smoking is the strongest independent predictive of cancer risk. Estimates suggest that surgical excision reduces risk factor linked to the development of oral Once a biopsy has been performed, further the risk of malignant transformation across all leukoplakia.12 There is no definitive data showing treatment is based on the specific histopathological grades of OED by approximately 50%. that smoking cessation is associated with diagnosis. If oral epithelial dysplasia (OED) is Complete excision is generally considered to be a reduced likelihood of long-term malignant present, treatment is dictated by the degree of the standard of care for oral lesions exhibiting transformation in patients with oral leukoplakic dysplasia, clinical presentation, location of the moderate to severe epithelial dysplasia, lesions, however, there is obvious biologic lesion (with “high risk” sites, such as the floor regardless of lesional size. This approach reflects plausibility to support such a recommendation. of the mouth and ventral tongue where white the belief that progression from dysplasia to Regardless of histopathological diagnosis, all patches are most likely to exhibit preneoplastic invasive squamous cell carcinoma involves a patients presenting with idiopathic leukoplakia of or neoplastic change, being candidates for more step-wise process involving the accumulation the oral cavity should be counseled regarding risk aggressive intervention), as well as lesion size of multiple genetic aberrations, eventually factors and encouraged to enroll in a smoking and surgical accessibility. Studies suggest that leading to loss of cell-cycle regulation and cessation program. 5-30+% of OEDs ultimately progress to invasive inhibition of normal cellular senescence. In Interestingly, genetic polymorphisms in enzymes carcinoma, with cases of mild OED exhibiting a other words, epithelium harboring moderate to involved in both the detoxification of carcinogens transformation rate approximating 5%.9 Ideally, severe dysplastic change has accumulated a and DNA repair appear to contribute to an lesions diagnosed as mild epithelial dysplasia greater number of molecular alterations on the increased risk of developing oral leukoplakia should be removed in their entirety, provided continuum to invasive carcinoma, and therefore and SCC in tobacco users. As the cost of that these can be excised with minimal patient fewer additional changes are needed to progress whole genome DNA sequencing continues to to frank invasion. morbidity. However, it can be questioned whether drop, heralding the era of “personalized oral a 5% likelihood of progression to SCCA represents It is also important to recognize, from a and maxillofacial medicine”, clinicians may a high enough threshold to recommend complete management perspective, that a variable, though soon be better able to predict which patients surgical excision of all mild OEDs as routine small, percentage of leukoplakic lesions that fail with idiopathic leukoplakia and oral epithelial protocol, especially with larger lesions and/ to demonstrate evidence of epithelial dysplasia dysplasia are at greatest risk for developing or those associated with a greater likelihood of on initial biopsy are associated with a long-term cancer.13

Figure 3a Figure 3b Figure 3c

Photomicrographs depicting the spectrum of epithelial change evident in idiopathic leukoplakia (hematoxylin and eosin stain) a) Oral mucosa with hyperorthokeratosis - histologic features include ordered maturation of the epithelial layer, a prominent granular cell layer, and a markedly thickened layer of orthokeratin. b) Oral mucosa demonstrating an abrupt transition from mild epithelial dysplasia (left; characterized by mild cytological changes and architectural disturbances limited to the basal third of the epithelium) to severe dysplasia (middle; characterized by architectural disturbances extending to the superior third of the epithelium) and carcinoma in situ (right side; full thickness change) - histologic features of dysplasia include disordered maturation of the epithelial layer, premature keratinization, an increased nuclear-to-cytoplasmic ratio, significant nuclear pleomorphism, hyper- chromatic nuclei, an increased number of mitotic features, many with abnormal mitoses, and drop shaped rete ridges. c) Superficially invasive squamous cell carcinoma characterized by invasion of islands of atypical epithelium through the basement membrane into the underling lamina propria. www.metdental.com Page 4 Quality Resource Guide – White Lesions of the Oral Cavity

Actinic Cheilitis (AC) erythema or ulceration, initial treatment involves Figure 4 Actinic cheilitis (AC) represents a preneoplastic counseling the patient to discontinue or modify process involving the skin and vermillion of the the location of placement of the ST followed by lower lip resulting from chronic sun exposure.14 reassessment in 3-4 weeks. It is essentially analogous to the spectrum of change seen in idiopathic oral leukoplakia, the Oral submucous fibrosis17 is a progressive change main differences being the location of the lesion and of the oral mucosa characterized by fibrosis of the underlying etiologic agent (ultraviolet mediated the submucosal tissues and a marked tendency DNA damage versus carcinogens such as tobacco for malignant transformation in response to long- and ethanol). White to mixed red-white surface term exposure to carcinogens in betel quid (a Actinic cheilitis - A 72-year-old man with change is seen in AC, often accompanied by flaking. generalized thickening and loss of definition of combination of betel leaf, areca nut, and slaked In more advanced stages, there is blurring of the the vermillion border of the lower lip - subtle vermillion border, thickening and swelling of the lip lime that varies in formulation depending on leukoplakia is evident on the patient’s right side. geographic location). When tobacco is added, and ulceration (figure 4). Histologically, epithelial Figure 5 changes mimic the spectrum seen in idiopathic the product is referred to as gutka. Betel quid/ leukoplakia, ranging from hyperkeratosis to invasive gutka is used extensively in large areas of South squamous cell carcinoma. Biopsy of any areas and Southeast Asia in a manner analogous exhibiting evidence of sun damage is needed to to chewing tobacco. The characteristic clinical assess the degree of epithelial damage and to guide presentation is that of generalized mucosal treatment. In the presence of dysplasia, treatment pallor, oral burning and loss of elasticity of the options include cryotherapy, electrosurgery, the use oral mucosa and oropharynx, eventually leading of topical chemotherapeutic agents and surgical to trismus and decreased ability to open the vermillionectomy. With upward of 10% of AC cases mouth (figure 6). In light of the significant rate Proliferative verrucous hyperplasia - 72-year- of oral SCC development in patients with oral progressing to invasive carcinoma, counseling on old male with a thickened granular leukoplakia the use of sunblock combined with long-term submucous fibrosis, a high index of suspicion for involving the right lateral and ventral tongue clinical follow up is essential. all white and mixed red-white lesions is required extending onto the floor of the mouth and the in patients with a history of betel quid use. lingual alveolar process - the possibility of ver- Proliferative Verrucous Leukoplakia (PVL) rucous carcinoma or squamous cell carcinoma Epithelial Malignancies should also be considered in the clinical differ- Proliferative verrucous leukoplakia (PVL)15 ential diagnosis- the lesion had reportedly been represents a more prominent form of oral (Squamous Cell Carcinoma) slowly increasing in size over the last several leukoplakia, presenting as large white thickened Epithelial malignancies of the oropharynx, years, and had previously been surgically excised primarily squamous cell carcinoma, represent on two prior occasions - multiple biopsies failed verrucous-appearing patches involving contiguous to identify evidence of epithelial dysplasia. oral sites (figure 5) and frequently presenting at the sixth most common type of cancer in North multiple separate intraoral sites. Histologically, PVL America. Forty-one thousand cases are predicted Figure 6 lacks evidence of dysplasia, but is characterized to be diagnosed in the United States during 2014, by continued lateral spread of the lesion and a with close to 8000 of these individuals dying of propensity to malignant transformation. Definitive their disease.18 An additional 275,000 living men therapy is complicated by a marked tendency for and women have a prior diagnosis of cancer in lesions to recur following excision. the oral or pharyngeal regions. A child born today has an estimated 1.1% lifetime risk of developing Smokeless Tobacco Keratosis oral or pharyngeal cancer. The stage at which Smokeless tobacco (ST) use is characterized by oral cancer is diagnosed has a significant effect white change and edema of mucosa that is in on survival. Localized disease, representing a Oral submucous fibrosis - 60 year old male with prolonged direct contact with the ST. The degree and lesion confined to the primary oral cavity site, 40+ year history of betel quid use presented with nature of change, both clinically and histologically, sensitivity to spicy foods and generalized pallor of is associated with an 83% 5-year survival rate. and the risk of subsequent oral SCC development, the oral mucosa - note the black stain involving The 5-year survival drops to 60% and 36% the gingival margins of the teeth - no evidence of varies depending on the type and brand of ST respectively in the presence of regional lymph dysplasia was found on biopsy - long-term close product used.16 In the absence of verrucous surface node involvement or distant metastasis. clinical follow-up is required due to the increased morphology, extreme thickening or associated risk of squamous cell carcinoma development.

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As a malignancy of epithelial origin, SCC will Lichen Planus Oral manifestations resembling lichen planus are generally exhibit clinical evidence of surface Lichen planus is a chronic mucocutaneous common in cGVHD. Diagnosis is made in correlation change, with early lesions often presenting as condition that can present with variable with the patient’s medical history and a thorough white lesions clinically indistinguishable from involvement of the oral mucosa, skin and assessment of the overall clinical presentation. In idiopathic leukoplakia. Ulceration, erythema and, bed.20 Its classic intraoral presentation is that of cases in which the differential diagnosis includes in more advanced lesions, surface nodularity, are asymptomatic bilateral white striae (Wickham’s’ the possibility of OED or SCC, based upon the also commonly present (figure 7). striae), involving the buccal mucosa and/or lateral clinical presentation, an incisional biopsy may tongue (figure 8a). When presenting bilaterally in be prudent (figure 10). This is particularly true in Figure 7 these “classic” areas, and with no evidence patients on long-term immunosuppressive therapy of verrucous surface change, erythema or for cGVHD, which is associated with an increased ulceration, a strong presumptive diagnosis may risk of oral SCC development.22 be rendered based on the clinical presentation; Oral Hairy Leukoplakia (OHL) biopsy may not be required. Involvement of Oral hairy leukoplakia (OHL) is an Epstein Barr intraoral sites other than the lateral tongue or virus-mediated process characterized by white buccal mucosa, lesions presenting without a corrugated thickening involving the lateral tongue bilaterally symmetrical distribution or lesions bilaterally. Although 80% of cases are reported exhibiting irregular white thickening (figure 8b), Squamous cell carcinoma - 55-year old male, in HIV-positive patients,23 it is also seen in erythema (figure 8c) or ulceration necessitate a non-smoker presenting with a 6x5 mm leuko- conjunction with medication-induced systemic plakic area with a central area of ulceration on confirmatory incisional biopsy to rule out lichen or local immunosuppressive states (figure 11).24 the left ventral lateral tongue - patient reports planus mimickers (figure 9). that he believes he accidentally traumatized Clinically, it is commonly misdiagnosed as habitual the area 6 months prior secondary to a cracked Chronic Graft versus Host Disease tongue chewing (“morsicatio linguarum”) or tooth - the clinical differential diagnosis included (cGVHD) idiopathic leukoplakia. Biopsy is confirmatory. In chronic traumatic , chronic hyperplastic candidiasis with ulceration, versus dysplasia/ Chronic graft-versus-host disease (cGVHD) is a the absence of an explanatory medical history, all squamous cell carcinoma - a biopsy was per- frequent complication of allogeneic hematopoietic patients with a biopsy diagnosis of OHL should be formed, revealing a well-differentiated superfi- bone marrow transplantation,21 often used in the referred for further assessment to rule out HIV cially invasive squamous cell carcinoma. treatment of various hematologic malignancies. disease.

Figure 8a Figure 8b Figure 8c

Classic lichen planus - 67-year old woman Atypical appearance in a 59-year-old male with a Atypical leukoplakia associated with the attached with white lace-like areas (“Wickham’s striae”) long-standing history of biopsy-confirmed lichen gingiva spanning from the bilateral mandibular involving the buccal mucosa bilaterally. planus - the irregular white thickening evident in second molar to the distal papillae of the canine this case is not consistent with a classic with white verrucous surface morphology and lichenoid appearance, mandating a biopsy to peripheral erythema - several other areas of rule out the possibility of dysplastic change. involvement were noted throughout the oral cavity - the patient had previously been assessed clinically without the benefit of a tissue biopsy - incisional biopsy demonstrated moderate epithelial dysplasia.

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Figure 9 Figure 10 Figure 11

Squamous cell carcinoma mimicking erosive Chronic graft-versus-host disease (cGVHD) - a Oral hairy leukoplakia in a patient using topical lichen planus – a 67-year-old male, non-smoker, 57-year-old woman treated with autogenous corticosteroids for management of an unrelated presented with a 1-month history of discomfort bone marrow transplant for acute myeloid leuke- immune-mediated vesiculobullous disease af- involving the left lateral tongue - patient believed mia 3 years prior - she developed cGVHD at ap- fecting the oral cavity - note the thick corrugated that the area of ulceration was related to irritation proximately 6 months, and was on rituximab and surface texture - similar change was evident on from a rough restoration on one of his mandibu- cyclosporine - oral lesions clinically resembling the left lateral tongue - testing for candidiasis lar molars - he was being treated with topical erosive lichen planus were distributed through- and HIV were negative - the lesions resolved on corticosteroids for a presumptive diagnosis of out the oral cavity. discontinuation of the topical corticosteroids. “erosive lichen planus” - no prior biopsy had been performed - examination revealed a 5x3 cm area exhibiting a combination of white thickened surface morphology with focal erythema and a REFERENCES and neck cancer: pooled analysis in the International central 1.5x0.7 cm ulcer with relatively well-de- Head and Neck Cancer Epidemiology Consortium. fined margins - the white thickened area extends 1. Edwards PC. Oral Cancer Screening for Asymptomatic Cancer Epidemiol Biomarkers Prev 2009;18:541-50. Adults: Do the United States Preventive Services Task 13. Edwards PC. Towards Predictive Oral and Maxillofacial onto the left posterior buccal mucosa and the Force Draft Guidelines Miss the Proverbial for the Medicine: Perspective on Zavras et al. Oral Surg Oral posterior vestibule. Trees? Oral Surg Oral Med Oral Pathol Oral Radiol Med Oral Pathol Oral Radiol 2012;114:549-51. 2013;116:131-4. 14. Kaugars GE, Pillion, Svirsky JA, et al. Actinic cheilitis: 2. Kanjirath PP, Edwards PC. Red and white tongue mass. A review of 152 cases. Oral Surg Oral Med Oral Pathol Am Fam Physician 2010;81:785-6. Oral Radiol Endod 1999;88:181-6. 3. Chi AC, Lambert PR 3rd, Pan Y, Li R, et al. Is alveolar 15. Fettig A, Pogrel MA, Silverman Jr S, et al. Proliferative ridge keratosis a true leukoplakia? A clinicopathologic verrucous leukoplakia of the gingiva. Oral Surg Oral Summary comparison of 2,153 lesions. J Am Dent Assoc Med Oral Pathol Oral Radiol Endod 2000;90:723-30. s outlined in this guide, a large 2007;138:641-51. 16. Nitrosamines. In: IARC Monographs on the Evaluation of 4. Woo SB, Lin D. Morsicatio mucosae oris-a chronic oral Carcinogenic Risks to International Agency for Research number of conditions of disparate frictional keratosis, not a leukoplakia. J Oral Maxillofac on Cancer. Smokeless tobacco and tobacco-specific etiology can present as primarily Surg 2009;67:140-6. nitrosamines. In: IARC Monographs on the Evaluation A 5. Bouquot JE, Gorlin RJ. Leukoplakia, lichen planus, and of Carcinogenic Risks to Humans. Lyon, France: IARC; white areas involving the oral mucosa. other oral keratoses in 23,616 white Americans over 2007;89:41-583. Absent a strong presumptive clinical the age of 35 years. Oral Surg Oral Med Oral Pathol 17. Javed F, Chotai M, Mehmood A, Almas K. Oral mucosal 1986;61:373-81. disorders associated with habitual gutka usage: a diagnosis that the lesion in question is 6. Rethman MP, Carpenter W, Cohen EE, et al. American review. Oral Surg Oral Med Oral Pathol Oral Radiol of reactive etiology, biopsy of all white Dental Association Council on Scientific Affairs Expert Endod 2010;109:857-64. Panel on Screening for Oral Squamous Cell Carcinomas. 18. From Surveillance Epidemiology and End Results, National lesions should be strongly considered. Evidence-based clinical recommendations regarding Cancer Institute, U.S. National Institutes of Health. Although the majority of these lesions screening for oral squamous cell carcinomas. J Am Available at: http://seer.cancer.gov/csr/1975_2010/ Dent Assoc 2010;141:509-20. results_single/sect_01_table.01.pdf. Accessed April will prove not to be malignant on biopsy, 7. McNamara KK, Martin BD, Evans EW, Kalmar JR. The 21, 2014. role of direct visual fluorescent examination (VELscope) 19. Data estimated on January 1, 2010, Surveillance it is recommended that the biopsy be in routine screening for potentially malignant oral Epidemiology and End Results, National Cancer scheduled within as short a time frame mucosal lesions. Oral Surg Oral Med Oral Pathol Oral Institute, U.S. National Institutes of Health. Available Radiol 2012;114:636-43. at: http://seer.cancer.gov/csr/1975_2009_pops09/ as possible (1-2 weeks), to reduce both 8. Edwards PC. Point of care: oral pathology and oral results_merged/topic_lifetime_risk.pdf. Accessed April patient anxiety and the likelihood of the medicine. Question 1 What are the indications for using 21, 2014. diagnostic aids such as Orascan, Oral CDx and Vizilite 20. Edwards PC, Kelsch R. Oral lichen planus: clinical patient being lost to follow-up. in the evaluation of oral lesions? J Can Dent Assoc presentation and management J Can Dent Assoc 2002; 2003;69:677-8. 68: 494-9. 9. Dost F, LeCao K, Ford PJ, et al. Malignant transformation 21. Nakamura S, Hiroki A, Shinohara M, et al. Oral of oral epithelial dysplasia: a real-world evaluation of involvement in chronic graft-versus-host disease after histopathologic grading. Oral Surg Oral Med Oral Pathol allogeneic bone marrow transplantation. Oral Surg Oral Radiol 2014;117:343-52. Oral Med Oral Pathol Oral Radiol Endod 1996;82:556- 10. Mehanna HM, Rattay T, Smith J. McConkey. Treatment 63. and follow-up of oral dysplasia: a systematic review and 22. Abdelsayed RA, Sumner T, Allen CM, et al. Oral meta-analysis. Head Neck 2009;31:1600-9. precancerous and malignant lesions associated with 11. Edwards PC. The Natural History of Oral Epithelial graft-versus-host disease: Report of 2 cases. Oral Surg Dysplasia: Perspective on Dost et al. Oral Surg Oral Med Oral Med Oral Pathol Oral Radiol Endod 2002;93:75-80. Oral Pathol Oral Radiol 2014;117:263-6. 23. Sciubba J, Brandsma J, Schwartz M, Barrezueta N. Hairy 12. Hashibe M, Brennan P, Chuang SC, et al. Interaction leukoplakia: an AIDS-associated opportunistic infection. between tobacco and alcohol use and the risk of head Oral Surg Oral Med Oral Pathol 1989;67:404-10. www.metdental.com Page 7 Quality Resource Guide – White Lesions of the Oral Cavity

POST-TEST Internet Users: This page is intended to assist you in fast and accurate testing when completing the “Online Exam.” We suggest reviewing the questions and then circling your answers on this page prior to completing the online exam. (2.0 CE Credit Contact Hour) Please circle the correct answer. 70% equals passing grade.

1. Which of the following lesions should be considered potentially 6. Which of the following conditions is associated with the lowest “preneoplastic” (associated with an increased risk of progression likelihood of malignant transformation? to squamous cell carcinoma)? a. Oral lichen planus a. Frictional hyperkeratosis b. Actinic cheilitis b. Idiopathic leukoplakia c. Proliferative verrucous leukoplakia c. Oral hairy leukoplakia d. Idiopathic leukoplakia on the floor of the mouth d. Dentifrice-associated sloughing 7. Which of the following are at highest risk for developing 2. Which of the following lesions does NOT typically require a squamous cell carcinoma in an area of leukoplakia, size and biopsy? appearance being similar? a. A well-defined linear subtle hyperkeratotic patch with a macerated a. Buccal mucosa surface along the buccal mucosa at the occlusal plane in a dentate b. Mandibular anterior vestibule patient c. Ventral tongue and floor of the mouth b. A 9x5 mm single thick white patch with a corrugated surface d. Buccal gingiva located on the mandibular buccal gingiva c. A 4x4 mm well-circumscribed white lesion involving the left buccal 8. Approximately how many individuals are diagnosed in the United mucosa in a patient with a 20-year history of betel quid use States with oral cavity or pharyngeal cancer each year? d. A patient with extensive corrugated white hyperkeratotic change a. 4,000,000 involving the lateral tongue bilaterally. b. 400,000 c. 40,000 3. Oral hairy leukoplakia is associated with infection with of the d. 4,000 following organisms?

a. Human papilloma virus (HPV) b. Candida albicans 9. What is the most appropriate treatment for a patient with a long- c. Human immunodeficiency virus (HIV) standing history of oral lichen planus who presents with a 20x6 d. Epstein Barr virus (EBV) mm white patch with a thickened verrucous surface appearance and irregular margins on the left ventral tongue? 4. A patient presents with asymptomatic subtle white lace-like a. Incisional biopsy hyperkeratosis involving the entire buccal mucosa bilaterally. b. Excisional biopsy There is no evidence of erythema, or ulceration. What is the most c. Exfoliate cytology likely diagnosis? d. Reassess in 2-3 weeks a. Oral hairy leukoplakia b. Oral lichen planus 10. What is the most appropriate treatment for an otherwise c. Idiopathic leukoplakia apparently healthy 40-year-old male who presents with thickened d. Frictional hyperkeratosis corrugated white areas involving the bilateral tongue that is 5. What is the likelihood that a child born in 2014 will develop oral clinically suspicious for oral hairy leukoplakia? cavity or pharyngeal squamous cell carcinoma at some point in a. Advise the patient to stop chewing the sides of his tongue and his/her life? reassess in 2-3 weeks a. 50% b. Refer him to his primary care physician for HIV testing b. 10% c. Refer him to his primary care physician to assess for Epstein Barr c. 1% virus (EBV) d. 0.1% d. Perform an incisional biopsy to confirm your clinical impression*

www.metdental.com Page 8 REGISTRATION/CERTIFICATION INFORMATION (Necessary for proper certification) Name (Last, First, Middle Initial):______PLEASE PRINT CLEARLY Street Address:______Suite/Apt. Number______City: ______State:______Zip:______Telephone: ______Fax:______Date of Birth:______Email: ______State(s) of Licensure:______License Number(s):______Preferred Dentist Program ID Number:______Check Box If Not A PDP Member AGD Mastership: Yes No AGD Fellowship: Yes No Date:______Please Check One: General Practitioner Specialist Dental Hygienist Dental Assistant Other

Quality Resource Guide – White Lesions of the Oral Cavity

Providing dentists with the opportunity for continuing dental education is an essential part of MetLife’s commitment to helping dentists improve the oral health of their patients through education. You can help in this effort by providing feedback regarding the continuing education offering you have just completed.

Please respond to the statements below by checking the appropriate box, 1 = POOR 5 = Excellent using the scale on the right. 1 2 3 4 5

1. How well did this course meet its stated educational objectives? 2. How would you rate the quality of the content? 3. Please rate the effectiveness of the author. 4. Please rate the written materials and visual aids used. 5. The use of evidence-based dentistry on the topic when applicable. N/A 6. How relevant was the course material to your practice? 7. The extent to which the course enhanced your current knowledge or skill? 8. The level to which your personal objectives were satisfied. 9. Please rate the administrative arrangements for this course. 10. How likely are you to recommend MetLife’s CE program to a friend or colleague? (please circle one number below:)

10 9 8 7 6 5 4 3 2 1 0 extremely likely neutral not likely at all

What is the primary reason for your score?

11. Please identify future topics that you would like to see:

Thank you for your time and feedback.

To comple the program traditionally, please mail your post-test and evaluation form to: MetLife Dental Quality Initiatives Program 501 US Highway 22 Bridgewater, NJ 08807 www.metdental.com