- Email: [email protected]
A retrospective survey of oral lichenoid lesions: Revisiting the diagnostic process for oral lichen planus
A retrospective survey of oral lichenoid lesions: Revisiting the diagnostic process for oral lichen planus Sandra L. Myers, DMD,a Nelson L. Rhodus, DMD, MPH,b Heather M. Parsons, BS,c James S. Hodges, PhD,d and Shanti Kaimal, MDS,e Minneapolis, Minn, and Pondicherry, India UNIVERSITY OF MINNESOTA SCHOOL OF DENTISTRY AND MAHATMA GANDHI DENTAL COLLEGE AND HOSPITAL
Objective. We sought to investigate patient demographics and diagnostic trends in biopsies in patients with final diagnoses of oral lichen planus or lichenoid over 4 decades. Methods. Archived biopsy reports from 248 patients were examined for 1966, 1976, 1986, and 1996. Data were collected for patient age and sex, significant medical and dental history, description of lesion, and clinical and histopathologic diagnoses. Results. Oral lichen planus made up a declining portion of total final diagnoses over the decades. The number of cases with less-than-definitive diagnoses and using modifying terminology (eg, probable, possible, suggestive of ) increased. In addition, the age at diagnosis for female patients increased by 1.2 years per decade on average, whereas the age for male patients decreased by 3.5 years per decade on average. Conclusions. The diagnosis of oral lichen planus appears to have been extended by the use of modifying terminology to include lesions that have less than definitive features. Comprehensive clinical histories and investigations can help limit the inclusion of such lesions. (Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2002;93:676-81)
Lesions of oral lichen planus (OLP) and other lichenoid conditions often present a diagnostic dilemma for dental clinicians and pathologists. Many articles in the literature have attempted to bring these lesions into perspective and create a definition for “true” OLP.1-3 Since the time of Wilson4 and Wickham5 in the late 1800s, lichen planus has been recognized as a chronic mucocutaneous inflammatory condition. Although the cause of OLP remains unknown, a cell-mediated immune response is suspected.6 OLP has most often been reported in middle-aged patients, affecting more women than men.7-13 Any location in the oral cavity may be affected, with the most Dr Hodges was supported by NIH/NIDCR grant P30-DE09737. a Assistant Professor, Department of Oral Sciences, University of Minnesota School of Dentistry, Minneapolis. b Associate Professor, Department of Diagnostic and Surgical Sciences, University of Minnesota School of Dentistry. c Fourth-Year Dental Student, University of Minnesota School of Dentistry, Minneapolis. d Senior Research Associate, Division of Biostatistics, School of Public Health, and Director, Biostatistics Core, Minnesota Oral Health Clinical Research Center, University of Minnesota School of Dentistry, Minneapolis. e Lecturer, Department of Oral Medicine, Mahatma Gandhi Dental College and Hospital, Pondicherry, India. Received for publication Sep 17, 2001; accepted for publication Oct 15, 2001. Copyright © 2002 by Mosby, Inc. 1079-2104/2002/$35.00 ⫹ 0 7/13/121281 doi:10.1067/moe.2002.121281
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common site being the posterior buccal mucosa.12 Bilateral lesions are considered a key diagnostic feature and unilateral lesions a contradiction, rendering true OLP less likely.1,14 Clinical presentations of OLP are highly variable, with atrophic, bullous, erosive, papular, plaquelike, and reticular types described.11,12,15 Lesions indistinguishable clinically and histologically from OLP may be produced by systemic medications and diseases and by local factors such as metallic restorative materials.1,16 The provisional clinical diagnosis of OLP has been and still is applied to a wide spectrum of red or white lesions of diverse causes in all locations of the oral cavity. Subtle dysplastic or premalignant tendencies in OLP lesions may be hard to detect clinically and histologically.17,18 A number of studies have investigated squamous cell carcinoma (SCC) arising within or adjacent to OLP or lichenoid lesions.19-22 Investigators have attempted to demonstrate that OLP has premalignant potential and can progress to SCC.23-25 Specific diagnostic criteria to histologically differentiate lichenoid lesions and lichenoid lesions with dysplastic features from OLP have been developed.17,26 However, specific clinical diagnostic guidelines to differentiate lichenoid lesions from OLP have not been clearly delineated. This study examined biopsy reports of lesions diagnosed as OLP or lichenoid submitted to the University of Minnesota School of Dentistry Oral Pathology Laboratory Service over 4 decades. All biopsies with a diagnosis of OLP or lichenoid were included, along
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Table I. Sex of patients with OLP & lichenoid lesions Female Male Total/Decade Ratio F:M
1966
1976
1986
1996
Total
12 7 19 1.71
17 14 31 1.38
52 20 72 2.05
75 51 126 1.39
156 92 248 1.7:1
with those prefaced with adjectives such as possible, probable, or suggestive of. Patient demographics and trends in diagnoses for OLP and lichenoid lesions were examined for significant differences. The use of qualifying and disqualifying features in formulating clinical and final histologic diagnoses was examined. This study emphasizes the need to correlate both the clinical and histologic findings in the formulation of a final diagnosis. It also points out the need for increased clarity in communications between clinicians and pathologists to determine what may or may not be “true” OLP. MATERIAL AND METHODS Demographics Data were collected from biopsy reports generated from cases submitted to the Oral Pathology Laboratory Service at the University of Minnesota School of Dentistry from the years 1966, 1976, 1986, and 1996. The University of Minnesota Institutional Review Board granted approval for the use of the existing data on subjects with oral lichen planus and lichenoid lesions. The availability of an archived patient database provided a unique opportunity to study trends of OLP and lichenoid lesions over 4 decades. Information was recorded from all cases with OLP or lichenoid lesion as the final diagnosis. Data included the following: patient age and sex, significant reported medical and dental history, clinical description of lesion, and provisional clinical and definitive histologic diagnoses. Statistical methods The Pearson chi-square test was used to test whether the sex ratio of cases examined changed over the four decades considered. Multiple linear regression was used to analyze how the age of the patients changed over the decades, treating the year as a continuous predictor and including patient sex and the sex-by-year interaction. RESULTS The Division of Oral Pathology received and processed 8884 biopsies at the University of Minnesota School of Dentistry during the years 1966, 1976, 1986, and 1996. Of these, a total of 248 biopsies
were recorded as OLP or lichenoid lesions. There were 156 female and 92 male patients ranging in age from 17 to 82 years (Table I). Women outnumbered men (1.7:1) for OLP and lichenoid lesions in all decades, with no significant change in sex ratio over the decades. A decrease in mean age for male patients and increase in mean age for female patients was observed over the years studied (Fig 1). The average age was 57.2 years for female patients and 51.8 years for male patients. The average age at diagnosis for women increased by 1.2 years per decade on average, whereas the age for men decreased by 3.5 years per decade on average. The terminology used by clinicians to describe the lesions was analyzed for common descriptive words. The most common adjectives used by contributing dentists to describe the oral lesion(s) biopsied are listed in Table II. In 138 cases, none of these descriptors were used, and in 14 cases no description at all was provided. The most common location cited for the oral lesions (alone or in combination with other sites) was buccal mucosa/vestibule (152 cases), followed by tongue (48 cases) and gingiva/alveolar ridge (49 cases). The locations in order of frequency and bilateral versus unilateral distribution are shown in Table III. Eight oral pathologists generated 248 final histologic diagnoses of OLP, lichenoid or containing modifiers such as possible, probable, suggestive of or consistent with OLP (Fig 2). A declining portion of the total final diagnoses that were “true” OLP was observed over the decades. However, an increase in the number of cases with less-than-definitive diagnoses was evident. In 1966, the histologic diagnosis for 16 of 19 lesions was OLP and there were three diagnoses of “consistent with OLP (cwLP).” By 1976, 5 of 31 lesions were recognized as having lichenoid features, and the modifier “suggestive of OLP (soLP)” was used to characterize 3 cases. For the years 1986 and 1996, use of lichenoid and all modifiers including “probable OLP (proLP)” and “possible OLP (posLP),” but not soLP, increased. A comparison was made between 212 clinical diagnoses given by clinicians and 248 final diagnoses by the pathologists (Table IV). The clinical diagnosis, when provided, matched the final histologic diagnosis in ap-
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Table III. Location of oral lesion(s) [n ⫽ 248 biopsies]
Fig 1. Mean age and sex of patients who had biopsies in years sampled.
Table II. Descriptive terms used by clinicians* Term White/whitish Lace-like/lacey Striae/striations/striated (Wickham’s striae ⫽ 6) Red and white Erythema/erythematous/red Hyperkeratosis/leukoplakia/white patch(es) Ulcer/ulceration/ulcerated Descriptors not given Erosive/eroded LP/ LP-like/ lichenoid Vesicles/blisters/blistering Denuded/sloughing/desquamation Induration
Total (n ⫽ 248 biopsies) 97 (39%) 47 (19%) 41 (17%) 35 (14%) 34 (14%) 32 (13%) 26 (10%) 14 (6%) 13 (5%) 10 (4%) 6 (2%) 4 (2%) 4 (2%)
For 138 biopsies (56%), none of these descriptors was used. Other descriptors used included firm, friable, normal appearing flat, annular and hemorrhagic.
proximately 72% of cases. One hundred and fifty-three of 212 cases had a clinical diagnosis of OLP. Fifty-nine cases had other clinical diagnoses in the differential, such as leukoplakia, squamous cell carcinoma, pemphigus, hyperkeratosis, metal sensitivity, pemphigoid, etc.). In 66 of the 212 cases, clinicians submitted two or more entities for the clinical differential diagnosis. Thirty-eight cases mentioned or listed dysplasia, carcinoma in situ, or squamous cell carcinoma alone or in the clinical differential diagnosis. In 18 of these 38 cases (47%), the final histologic diagnosis was OLP or consistent with OLP. For the remaining 20 cases (53%), the final diagnosis was lichenoid or contained the modifiers probable, possible, or suggestive of. Follow-up of such lesions, containing less-than-definitive final diagnoses, becomes critical, especially when the clinical
Buccal mucosa Gingiva/alveolar ridge Tongue Retromolar/tuberosity Vestibule Palate Not given Floor of mouth Lip Bilateral Left side only Right side only Side not given Other
139 (56%) 49 (20%) 48 (19%) 17 (7%) 13 (52%) 12 (5%) 9 (4%) 3 (1%) 1 (.04%) 60 (24%) 82 (33%) 66 (27%) 36 (15%) 4 (2%)
differential diagnosis includes malignant or premalignant entities. DISCUSSION This study reviewed clinical and histopathologic features of lesions that had OLP or lichenoid in the final diagnoses submitted to an oral pathology biopsy service over 4 decades. Changing trends in patient and lesion demographics, provisional clinical diagnoses and descriptions, and final histologic diagnoses were examined. The sex ratio over the decades was consistent with that of a number of previous studies reported in the literature. However, a trend for male patient age to decrease and female patient age to increase, as observed in this study, has not been previously reported. Factors that may have partially contributed to this trend include improved detection of as well as increased tendency to biopsy suspicious lesions of unknown cause in men and women of all ages. In addition, advances in medicine that have lengthened the life expectancy of patients, including those with chronic debilitating or systemic diseases, may have been a factor. Increased and more frequent use of medications and multiple complex drug regimens are also capable of producing OLP-like lesions in skin and oral mucosa. Clinicians may identify OLP features in these lesions and reflect this in their clinical descriptions and diagnoses. Further investigations are needed to determine more precise reasons for the observed sex-related age changes over time. Many of the clinical descriptions provided with the cases contained generic terminology such as white/ whitish, red and white, hyperkeratosis, and leukoplakia. These terms may describe clinical conditions other than OLP, ranging from chronic cheek chewing (morsicatio buccarum) to tobacco-pouch keratosis and verrucous carcinoma (snuff dipper’s cancer). Some clini-
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Fig 2. Diagnoses of oral lichen planus and lichenoid lesions in years sampled.
Table IV. Final histopathologic diagnosis versus clinical diagnosis Total biopsies (final histopathologic diagnosis)* Clinical diagnosis not given Clinical diagnosis given by dentist Clinical diagnosis OLP Clinical diagnosis-other†
1966
1976
1986
1996
Total
19 1 (5%) 18 (95%) 11 (58%) 7 (37%)
31 2 (6%) 29 (94%) 20 (65%) 9 (29%)
72 15 (21%) 57 (79%) 42 (58%) 15 (21%)
126 18 (14%) 108 (86%) 80 (64%) 28 (22%)
248 36 (14%) 212 (86%) 153 (62%) 59 (24%)
OLP, oral lichen planus. *Includes lichenoid and diagnoses with modifiers consistent with LP, possible LP, probable LP, and suggestive of LP. † Other clinical diagnoses included leukoplakia, squamous cell carcinoma, pemphigus, etc.
cians supported their provisional clinical diagnosis by providing definitive descriptions, such as striae of Wickham, and specifying a location for the oral lesions. The clinical appearance and location, in combination with medical and dental findings, are valuable clues for clinicians formulating and justifying provisional and differential clinical diagnoses. They are also valuable considerations for pathologists in rendering definitive final diagnoses. Provisional clinical diagnoses provided by clinicians may bias the pathologist in the formulation of a definitive histologic diagnosis. The reverse is also true, with the definitive histologic diagnosis influencing clinicians. The use of terminology such as lichenoid lesion or possible, and probable in definitive final diagnoses when the findings are less than classic may be misleading to clinicians formulating treatment options and follow-up care. Clinicians may consider all these lesions to be close enough to OLP to treat them all the same way. This could impede or prevent further investigation of lesions that mimic OLP but have a different cause that ultimately could be identified. The opposite circumstances might also exist, where the use of modifiers
might spur the clinician to undertake further investigations to identify an underlying cause and make a more definitive clinical diagnosis. Use of modifiers in the terminology of a final diagnosis has not been studied, and the long-term impact of these terms on treatment and follow-up is unknown. The final histopathologic diagnoses of cases submitted over the decades demonstrated change over time. The percentage of lesions with a histopathologic diagnosis of “true” OLP decreased, while the percentage of lichenoid lesions and those descriptions prefaced with modifiers increased. This trend may indicate that reporting oral pathologists are using more stringent criteria to make a diagnosis of “true” OLP, separating out lesions with atypical findings or subtle dysplastic features. It could also indicate an increased tendency to recognize “lichenoid” features in lesions that may have a recognized underlying cause, such as those related to medication use or systemic disease. Over time, lesions both resembling OLP and containing less than classic features of OLP have been identified and had the term “lichenoid” applied to them. Some of these lesions have been associated with the use
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Table V. Qualifying and disqualifying factors for oral lichen planus Disqualifying factors
Qualifying factors
Local
Systemic
Hypersensitivity (metals, flavorings)
Medications (side effects, reactions) Immune disorders (LE, EM, GVHD, AIDS)* Infections (candidiasis, 2° syphilis)
Histologic Dysplasia/carcinoma-in-situ
Clinical
Histologic
Appearance (striae of Wickham) Location (bilateral) Cutaneous LP lesions (violaceous papules)
Inflammation (bandlike, lymphoreticular) Liquefaction degeneration (basal layer of epithelium)
*LE, lupus erythematosus; EM, erythema multiforme; GVHD, graft-versus-host disease; AIDS, acquired immune deficiency syndrome.
of medications such as antihypertensives, antidepressants, and antidiabetics. Others were observed adjacent to metallic restorative materials and were associated with the use of flavoring agents. Lichenoid lesions have also been seen in conjunction with systemic conditions such as lupus erythematosus, graft-versus-host disease, erythema multiforme, and infections. The use of qualifying and disqualifying factors to rule in or rule out identifiable causes can substantially narrow the clinical and histopathologic diagnosis of lesions considered “true” OLP (Table V). Some lichenoid lesions possess dysplastic features, and a few have reportedly undergone malignant transformation. In addition, a small number of OLP and lichenoid lesions without dysplasia have reportedly progressed to squamous cell carcinoma. Inclusion of such diverse lesions under a single diagnostic umbrella of OLP is perilous and has made the identification of “true” OLP a challenge. CONCLUSIONS This study points out the need for further refinement in the diagnosis of “true” OLP based on a more extensive consideration of clinical and histopathologic findings. A more comprehensive diagnostic process, with more detailed etiologic investigations and increased exchange of information between clinicians and pathologists, is needed. The diverse clinical and histologic findings in the spectrum of lesions diagnosed as OLP or lichenoid lesion points to an underlying immune-mediated mechanism that may or may not be cause-specific. This immune mechanism may be the sign of a disease process rather than pathognomonic for OLP. Just as with signs such as anemia, jaundice, cyanosis, and fever, investigation into the cause of the underlying
disease process is requisite. Clinicians bear the responsibility to thoroughly evaluate the medical and dental status of patients and report these findings to the assigned pathologist. This report must include a valid and detailed description of the lesions biopsied, including the locations affected. Such information can then be judiciously considered by the pathologist along with the histopathologic findings to formulate a final diagnosis. We recommend restricting the use of confusing, nonspecific terms such as lichenoid and the modifiers possible, probable, consistent with, and suggestive of in the final diagnoses. For lesions lacking classic OLP features, descriptive histopathologic terminology or terminology linked to the underlying causative factor should be used. This will help differentiate and better define lesions that may be considered “true” OLP from those lesions that do not fit the classic picture of OLP. Ongoing research into OLP and lichenoid lesions at the molecular level will help characterize the underlying immune mechanism or mechanisms responsible for this group of disorders. This should result in improved diagnostic parameters, which will help pathologists to formulate more definitive final histopathologic diagnoses and in turn will facilitate the formulation of patient treatment and follow-up care by clinicians. REFERENCES 1. Boyd AS, Neldner KH. Lichen planus. J Am Acad Dermatol 1991;25:593-619. 2. Scully C, Beyli M, Ferreiro M, Ficarra G, Gill Y, Griffiths M, et al. Update on oral lichen planus: etiopathogenesis and management. Crit Rev Oral Biol Med 1998;9:86-122. 3. Scully C, el-Kom M. Lichen planus: Review and update on pathogenesis. J Oral Pathol 1985;14:431-58. 4. Wilson E. On lichen planus. J Cutan Med Dis Skin 1869;3:11732. 5. Wickham LF. Sur un signe pathognomonique de lichen du Wil-
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6. 7. 8. 9. 10.
11. 12. 13.
14. 15. 16. 17. 18.
son (lichen plan) stries et ponctuations grisatres. Ann Dermatol Syph 1895;6:517-20. Arndt KA, ed. Disorders of the dermal-epidermal interface and the dermis. 3rd ed. New York: McGraw-Hill; 1986:967-73. Allen CM, Beck FM, Rossie KM, Kaul TJ. Relation of stress and anxiety to oral lichen planus. Oral Surg Oral Med Oral Pathol 1986;61:44-6. Lacy MF, Reade PC, Hay KD. Lichen planus: a theory of pathogenesis. Oral Surg Oral Med Oral Pathol 1983;56:521-26. Fulling HJ. Cancer development in oral lichen planus. Arch Dermatol 1973;108:667-69. Silverman S, Gorsky M, Lozada-Nur F. A prospective follow-up study of 570 patients with oral lichen planus: persistence, remission, and malignant association. Oral Surg Oral Med Oral Pathol 1985;60:30-4. Vincent SD, Fotos PG, Baker KA, Williams TP. Oral lichen planus: The clinical, historical, and therapeutic features of 100 cases. Oral Surg Oral Med Oral Pathol 1990;70:165-71. Lozada-Nur F, Miranda C. Oral lichen planus: epidemiology, clinical characteristics and associated diseases. Sem Cutan Med Surg 1997;16:273-77. Onofre MA, Sposto MR, Navarro CM, Motta ME, Turatti E, Almeida RT. Potentially malignant epithelial oral lesions: discrepancies between clinical and histological diagnosis. Oral Dis 1997;3:148-52. Eisenberg E. Clinicopathologic patterns of oral lichenoid lesions. In: Oral & Maxillofacial Surgery Clinics of North America. Philadelphia: WB Saunders; 1994:445-63. Andreasen JO. Oral lichen planus. 1. A clinical evaluation of 115 cases. Oral Surg Oral Med Oral Pathol 1968;25:31-42. Eversole L, Ringer M. The role of dental restorative metals in the pathogenesis of oral lichen planus. Oral Surg Oral Med Oral Pathol 1984;57:383-87. Krutchkoff DJ, Eisenberg E. Lichenoid dysplasia: a distinct histopathologic entity. Oral Surg Oral Med Oral Pathol 1985;30: 308-15. Lovas J, Harsanyi BB, ElGeneidy AK. Oral lichenoid dysplasia: a clinicopathologic analysis. Oral Surg Oral Med Oral Pathol 1989;68:57-63.
19. van der Meij E, Schepman K, Smeele L, van der Wal J, Bezemer P, van der Waal I. A review of the recent literature regarding malignant transformation of oral lichen planus. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1999;88:307-10. 20. Katz RW, Brahim JS, Travis WD. Oral squamous cell carcinoma arising in a patient with long-standing lichen planus. Oral Surg Oral Med Oral Pathol 1990;70:282-85. 21. Duffey D, Eversole L, Abemayor E. Oral lichen planus and its association with squamous cell carcinoma: an update on pathogenesis and treatment implications. Laryngoscope 1996;106:35762. 22. Camisa C, Hamaty F, Gay J. Squamous cell carcinoma of the tongue arising in lichen planus: a case report and review of the literature. Cutis 1998;62:175-78. 23. Barnard NA, Scully C, Eveson JW, Cunningham S, Porter SR. Oral cancer development in patients with oral lichen planus. J Oral Pathol Med 1993;22:421-24. 24. Markopoulos AK, Antoniades D, Papanayotou P, Trigonidis G. Malignant potential of oral lichen planus: a follow-up study of 326 patients. Oral Oncol 1997;33:263-69.AQ1—Au: Please spell out what MGDCH stands for. 25. Lo Muzio L, Mignogna MD, Favia G, Procaccini M, Testa NF, Bucci E. The possible association between oral lichen planus and oral squamous cell carcinoma: a clinical evaluation on 14 cases and a review of the literature. Oral Oncol 1998;34:239-46. 26. Eisenberg E. Lichen planus and oral cancer: is there a connection between the two? J Am Dent Assoc 1992;123:104-8. Reprint requests: Sandra L. Myers Department of Oral Sciences School of Dentistry University of Minnesota Malcolm Moos Health Sciences Tower 16-122 515 Delaware Street South East Minneapolis, Minn USA 55455 [email protected]
Objective. We sought to investigate patient demographics and diagnostic trends in biopsies in patients with final diagnoses of oral lichen planus or lichenoid over 4 decades. Methods. Archived biopsy reports from 248 patients were examined for 1966, 1976, 1986, and 1996. Data were collected for patient age and sex, significant medical and dental history, description of lesion, and clinical and histopathologic diagnoses. Results. Oral lichen planus made up a declining portion of total final diagnoses over the decades. The number of cases with less-than-definitive diagnoses and using modifying terminology (eg, probable, possible, suggestive of ) increased. In addition, the age at diagnosis for female patients increased by 1.2 years per decade on average, whereas the age for male patients decreased by 3.5 years per decade on average. Conclusions. The diagnosis of oral lichen planus appears to have been extended by the use of modifying terminology to include lesions that have less than definitive features. Comprehensive clinical histories and investigations can help limit the inclusion of such lesions. (Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2002;93:676-81)
Lesions of oral lichen planus (OLP) and other lichenoid conditions often present a diagnostic dilemma for dental clinicians and pathologists. Many articles in the literature have attempted to bring these lesions into perspective and create a definition for “true” OLP.1-3 Since the time of Wilson4 and Wickham5 in the late 1800s, lichen planus has been recognized as a chronic mucocutaneous inflammatory condition. Although the cause of OLP remains unknown, a cell-mediated immune response is suspected.6 OLP has most often been reported in middle-aged patients, affecting more women than men.7-13 Any location in the oral cavity may be affected, with the most Dr Hodges was supported by NIH/NIDCR grant P30-DE09737. a Assistant Professor, Department of Oral Sciences, University of Minnesota School of Dentistry, Minneapolis. b Associate Professor, Department of Diagnostic and Surgical Sciences, University of Minnesota School of Dentistry. c Fourth-Year Dental Student, University of Minnesota School of Dentistry, Minneapolis. d Senior Research Associate, Division of Biostatistics, School of Public Health, and Director, Biostatistics Core, Minnesota Oral Health Clinical Research Center, University of Minnesota School of Dentistry, Minneapolis. e Lecturer, Department of Oral Medicine, Mahatma Gandhi Dental College and Hospital, Pondicherry, India. Received for publication Sep 17, 2001; accepted for publication Oct 15, 2001. Copyright © 2002 by Mosby, Inc. 1079-2104/2002/$35.00 ⫹ 0 7/13/121281 doi:10.1067/moe.2002.121281
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common site being the posterior buccal mucosa.12 Bilateral lesions are considered a key diagnostic feature and unilateral lesions a contradiction, rendering true OLP less likely.1,14 Clinical presentations of OLP are highly variable, with atrophic, bullous, erosive, papular, plaquelike, and reticular types described.11,12,15 Lesions indistinguishable clinically and histologically from OLP may be produced by systemic medications and diseases and by local factors such as metallic restorative materials.1,16 The provisional clinical diagnosis of OLP has been and still is applied to a wide spectrum of red or white lesions of diverse causes in all locations of the oral cavity. Subtle dysplastic or premalignant tendencies in OLP lesions may be hard to detect clinically and histologically.17,18 A number of studies have investigated squamous cell carcinoma (SCC) arising within or adjacent to OLP or lichenoid lesions.19-22 Investigators have attempted to demonstrate that OLP has premalignant potential and can progress to SCC.23-25 Specific diagnostic criteria to histologically differentiate lichenoid lesions and lichenoid lesions with dysplastic features from OLP have been developed.17,26 However, specific clinical diagnostic guidelines to differentiate lichenoid lesions from OLP have not been clearly delineated. This study examined biopsy reports of lesions diagnosed as OLP or lichenoid submitted to the University of Minnesota School of Dentistry Oral Pathology Laboratory Service over 4 decades. All biopsies with a diagnosis of OLP or lichenoid were included, along
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Table I. Sex of patients with OLP & lichenoid lesions Female Male Total/Decade Ratio F:M
1966
1976
1986
1996
Total
12 7 19 1.71
17 14 31 1.38
52 20 72 2.05
75 51 126 1.39
156 92 248 1.7:1
with those prefaced with adjectives such as possible, probable, or suggestive of. Patient demographics and trends in diagnoses for OLP and lichenoid lesions were examined for significant differences. The use of qualifying and disqualifying features in formulating clinical and final histologic diagnoses was examined. This study emphasizes the need to correlate both the clinical and histologic findings in the formulation of a final diagnosis. It also points out the need for increased clarity in communications between clinicians and pathologists to determine what may or may not be “true” OLP. MATERIAL AND METHODS Demographics Data were collected from biopsy reports generated from cases submitted to the Oral Pathology Laboratory Service at the University of Minnesota School of Dentistry from the years 1966, 1976, 1986, and 1996. The University of Minnesota Institutional Review Board granted approval for the use of the existing data on subjects with oral lichen planus and lichenoid lesions. The availability of an archived patient database provided a unique opportunity to study trends of OLP and lichenoid lesions over 4 decades. Information was recorded from all cases with OLP or lichenoid lesion as the final diagnosis. Data included the following: patient age and sex, significant reported medical and dental history, clinical description of lesion, and provisional clinical and definitive histologic diagnoses. Statistical methods The Pearson chi-square test was used to test whether the sex ratio of cases examined changed over the four decades considered. Multiple linear regression was used to analyze how the age of the patients changed over the decades, treating the year as a continuous predictor and including patient sex and the sex-by-year interaction. RESULTS The Division of Oral Pathology received and processed 8884 biopsies at the University of Minnesota School of Dentistry during the years 1966, 1976, 1986, and 1996. Of these, a total of 248 biopsies
were recorded as OLP or lichenoid lesions. There were 156 female and 92 male patients ranging in age from 17 to 82 years (Table I). Women outnumbered men (1.7:1) for OLP and lichenoid lesions in all decades, with no significant change in sex ratio over the decades. A decrease in mean age for male patients and increase in mean age for female patients was observed over the years studied (Fig 1). The average age was 57.2 years for female patients and 51.8 years for male patients. The average age at diagnosis for women increased by 1.2 years per decade on average, whereas the age for men decreased by 3.5 years per decade on average. The terminology used by clinicians to describe the lesions was analyzed for common descriptive words. The most common adjectives used by contributing dentists to describe the oral lesion(s) biopsied are listed in Table II. In 138 cases, none of these descriptors were used, and in 14 cases no description at all was provided. The most common location cited for the oral lesions (alone or in combination with other sites) was buccal mucosa/vestibule (152 cases), followed by tongue (48 cases) and gingiva/alveolar ridge (49 cases). The locations in order of frequency and bilateral versus unilateral distribution are shown in Table III. Eight oral pathologists generated 248 final histologic diagnoses of OLP, lichenoid or containing modifiers such as possible, probable, suggestive of or consistent with OLP (Fig 2). A declining portion of the total final diagnoses that were “true” OLP was observed over the decades. However, an increase in the number of cases with less-than-definitive diagnoses was evident. In 1966, the histologic diagnosis for 16 of 19 lesions was OLP and there were three diagnoses of “consistent with OLP (cwLP).” By 1976, 5 of 31 lesions were recognized as having lichenoid features, and the modifier “suggestive of OLP (soLP)” was used to characterize 3 cases. For the years 1986 and 1996, use of lichenoid and all modifiers including “probable OLP (proLP)” and “possible OLP (posLP),” but not soLP, increased. A comparison was made between 212 clinical diagnoses given by clinicians and 248 final diagnoses by the pathologists (Table IV). The clinical diagnosis, when provided, matched the final histologic diagnosis in ap-
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Table III. Location of oral lesion(s) [n ⫽ 248 biopsies]
Fig 1. Mean age and sex of patients who had biopsies in years sampled.
Table II. Descriptive terms used by clinicians* Term White/whitish Lace-like/lacey Striae/striations/striated (Wickham’s striae ⫽ 6) Red and white Erythema/erythematous/red Hyperkeratosis/leukoplakia/white patch(es) Ulcer/ulceration/ulcerated Descriptors not given Erosive/eroded LP/ LP-like/ lichenoid Vesicles/blisters/blistering Denuded/sloughing/desquamation Induration
Total (n ⫽ 248 biopsies) 97 (39%) 47 (19%) 41 (17%) 35 (14%) 34 (14%) 32 (13%) 26 (10%) 14 (6%) 13 (5%) 10 (4%) 6 (2%) 4 (2%) 4 (2%)
For 138 biopsies (56%), none of these descriptors was used. Other descriptors used included firm, friable, normal appearing flat, annular and hemorrhagic.
proximately 72% of cases. One hundred and fifty-three of 212 cases had a clinical diagnosis of OLP. Fifty-nine cases had other clinical diagnoses in the differential, such as leukoplakia, squamous cell carcinoma, pemphigus, hyperkeratosis, metal sensitivity, pemphigoid, etc.). In 66 of the 212 cases, clinicians submitted two or more entities for the clinical differential diagnosis. Thirty-eight cases mentioned or listed dysplasia, carcinoma in situ, or squamous cell carcinoma alone or in the clinical differential diagnosis. In 18 of these 38 cases (47%), the final histologic diagnosis was OLP or consistent with OLP. For the remaining 20 cases (53%), the final diagnosis was lichenoid or contained the modifiers probable, possible, or suggestive of. Follow-up of such lesions, containing less-than-definitive final diagnoses, becomes critical, especially when the clinical
Buccal mucosa Gingiva/alveolar ridge Tongue Retromolar/tuberosity Vestibule Palate Not given Floor of mouth Lip Bilateral Left side only Right side only Side not given Other
139 (56%) 49 (20%) 48 (19%) 17 (7%) 13 (52%) 12 (5%) 9 (4%) 3 (1%) 1 (.04%) 60 (24%) 82 (33%) 66 (27%) 36 (15%) 4 (2%)
differential diagnosis includes malignant or premalignant entities. DISCUSSION This study reviewed clinical and histopathologic features of lesions that had OLP or lichenoid in the final diagnoses submitted to an oral pathology biopsy service over 4 decades. Changing trends in patient and lesion demographics, provisional clinical diagnoses and descriptions, and final histologic diagnoses were examined. The sex ratio over the decades was consistent with that of a number of previous studies reported in the literature. However, a trend for male patient age to decrease and female patient age to increase, as observed in this study, has not been previously reported. Factors that may have partially contributed to this trend include improved detection of as well as increased tendency to biopsy suspicious lesions of unknown cause in men and women of all ages. In addition, advances in medicine that have lengthened the life expectancy of patients, including those with chronic debilitating or systemic diseases, may have been a factor. Increased and more frequent use of medications and multiple complex drug regimens are also capable of producing OLP-like lesions in skin and oral mucosa. Clinicians may identify OLP features in these lesions and reflect this in their clinical descriptions and diagnoses. Further investigations are needed to determine more precise reasons for the observed sex-related age changes over time. Many of the clinical descriptions provided with the cases contained generic terminology such as white/ whitish, red and white, hyperkeratosis, and leukoplakia. These terms may describe clinical conditions other than OLP, ranging from chronic cheek chewing (morsicatio buccarum) to tobacco-pouch keratosis and verrucous carcinoma (snuff dipper’s cancer). Some clini-
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Fig 2. Diagnoses of oral lichen planus and lichenoid lesions in years sampled.
Table IV. Final histopathologic diagnosis versus clinical diagnosis Total biopsies (final histopathologic diagnosis)* Clinical diagnosis not given Clinical diagnosis given by dentist Clinical diagnosis OLP Clinical diagnosis-other†
1966
1976
1986
1996
Total
19 1 (5%) 18 (95%) 11 (58%) 7 (37%)
31 2 (6%) 29 (94%) 20 (65%) 9 (29%)
72 15 (21%) 57 (79%) 42 (58%) 15 (21%)
126 18 (14%) 108 (86%) 80 (64%) 28 (22%)
248 36 (14%) 212 (86%) 153 (62%) 59 (24%)
OLP, oral lichen planus. *Includes lichenoid and diagnoses with modifiers consistent with LP, possible LP, probable LP, and suggestive of LP. † Other clinical diagnoses included leukoplakia, squamous cell carcinoma, pemphigus, etc.
cians supported their provisional clinical diagnosis by providing definitive descriptions, such as striae of Wickham, and specifying a location for the oral lesions. The clinical appearance and location, in combination with medical and dental findings, are valuable clues for clinicians formulating and justifying provisional and differential clinical diagnoses. They are also valuable considerations for pathologists in rendering definitive final diagnoses. Provisional clinical diagnoses provided by clinicians may bias the pathologist in the formulation of a definitive histologic diagnosis. The reverse is also true, with the definitive histologic diagnosis influencing clinicians. The use of terminology such as lichenoid lesion or possible, and probable in definitive final diagnoses when the findings are less than classic may be misleading to clinicians formulating treatment options and follow-up care. Clinicians may consider all these lesions to be close enough to OLP to treat them all the same way. This could impede or prevent further investigation of lesions that mimic OLP but have a different cause that ultimately could be identified. The opposite circumstances might also exist, where the use of modifiers
might spur the clinician to undertake further investigations to identify an underlying cause and make a more definitive clinical diagnosis. Use of modifiers in the terminology of a final diagnosis has not been studied, and the long-term impact of these terms on treatment and follow-up is unknown. The final histopathologic diagnoses of cases submitted over the decades demonstrated change over time. The percentage of lesions with a histopathologic diagnosis of “true” OLP decreased, while the percentage of lichenoid lesions and those descriptions prefaced with modifiers increased. This trend may indicate that reporting oral pathologists are using more stringent criteria to make a diagnosis of “true” OLP, separating out lesions with atypical findings or subtle dysplastic features. It could also indicate an increased tendency to recognize “lichenoid” features in lesions that may have a recognized underlying cause, such as those related to medication use or systemic disease. Over time, lesions both resembling OLP and containing less than classic features of OLP have been identified and had the term “lichenoid” applied to them. Some of these lesions have been associated with the use
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Table V. Qualifying and disqualifying factors for oral lichen planus Disqualifying factors
Qualifying factors
Local
Systemic
Hypersensitivity (metals, flavorings)
Medications (side effects, reactions) Immune disorders (LE, EM, GVHD, AIDS)* Infections (candidiasis, 2° syphilis)
Histologic Dysplasia/carcinoma-in-situ
Clinical
Histologic
Appearance (striae of Wickham) Location (bilateral) Cutaneous LP lesions (violaceous papules)
Inflammation (bandlike, lymphoreticular) Liquefaction degeneration (basal layer of epithelium)
*LE, lupus erythematosus; EM, erythema multiforme; GVHD, graft-versus-host disease; AIDS, acquired immune deficiency syndrome.
of medications such as antihypertensives, antidepressants, and antidiabetics. Others were observed adjacent to metallic restorative materials and were associated with the use of flavoring agents. Lichenoid lesions have also been seen in conjunction with systemic conditions such as lupus erythematosus, graft-versus-host disease, erythema multiforme, and infections. The use of qualifying and disqualifying factors to rule in or rule out identifiable causes can substantially narrow the clinical and histopathologic diagnosis of lesions considered “true” OLP (Table V). Some lichenoid lesions possess dysplastic features, and a few have reportedly undergone malignant transformation. In addition, a small number of OLP and lichenoid lesions without dysplasia have reportedly progressed to squamous cell carcinoma. Inclusion of such diverse lesions under a single diagnostic umbrella of OLP is perilous and has made the identification of “true” OLP a challenge. CONCLUSIONS This study points out the need for further refinement in the diagnosis of “true” OLP based on a more extensive consideration of clinical and histopathologic findings. A more comprehensive diagnostic process, with more detailed etiologic investigations and increased exchange of information between clinicians and pathologists, is needed. The diverse clinical and histologic findings in the spectrum of lesions diagnosed as OLP or lichenoid lesion points to an underlying immune-mediated mechanism that may or may not be cause-specific. This immune mechanism may be the sign of a disease process rather than pathognomonic for OLP. Just as with signs such as anemia, jaundice, cyanosis, and fever, investigation into the cause of the underlying
disease process is requisite. Clinicians bear the responsibility to thoroughly evaluate the medical and dental status of patients and report these findings to the assigned pathologist. This report must include a valid and detailed description of the lesions biopsied, including the locations affected. Such information can then be judiciously considered by the pathologist along with the histopathologic findings to formulate a final diagnosis. We recommend restricting the use of confusing, nonspecific terms such as lichenoid and the modifiers possible, probable, consistent with, and suggestive of in the final diagnoses. For lesions lacking classic OLP features, descriptive histopathologic terminology or terminology linked to the underlying causative factor should be used. This will help differentiate and better define lesions that may be considered “true” OLP from those lesions that do not fit the classic picture of OLP. Ongoing research into OLP and lichenoid lesions at the molecular level will help characterize the underlying immune mechanism or mechanisms responsible for this group of disorders. This should result in improved diagnostic parameters, which will help pathologists to formulate more definitive final histopathologic diagnoses and in turn will facilitate the formulation of patient treatment and follow-up care by clinicians. REFERENCES 1. Boyd AS, Neldner KH. Lichen planus. J Am Acad Dermatol 1991;25:593-619. 2. Scully C, Beyli M, Ferreiro M, Ficarra G, Gill Y, Griffiths M, et al. Update on oral lichen planus: etiopathogenesis and management. Crit Rev Oral Biol Med 1998;9:86-122. 3. Scully C, el-Kom M. Lichen planus: Review and update on pathogenesis. J Oral Pathol 1985;14:431-58. 4. Wilson E. On lichen planus. J Cutan Med Dis Skin 1869;3:11732. 5. Wickham LF. Sur un signe pathognomonique de lichen du Wil-
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