Oral Diseases (2015) 21, 478–482 doi:10.1111/odi.12306 © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd All rights reserved www.wiley.com
ORIGINAL ARTICLE
Clinical characteristics of lichen and dysplasia vs lichen planus cases and dysplasia cases R Czerninski1, S Zeituni2, A Maly3, J Basile4 1
Department of Oral Medicine, Hebrew University-Hadassah School of Dental Medicine, Jerusalem, Israel; 2Hebrew UniversityHadassah School of Dental Medicine, Jerusalem, Israel; 3Department of Pathology, Hadassah Medical Center, Jerusalem, Israel; 4 Department of Oncology and Diagnostic Sciences, University of Maryland Dental School, Baltimore, MD, USA
OBJECTIVES: To compare the clinical characteristics of lichen planus with dysplasia (LD) cases with oral dysplasia (DYS), and LP/lichenoid reaction (LP/LR). METHODS: Patients treated at the Department of Oral Medicine with a histological diagnosis were included. Patient information (age, gender, ethnicity, smoking habits, and medical status) and parameters of oral manifestation (lesions’ distribution, site, and type) were compared. RESULTS: Two hundred and thirty five patients were included. 54% were never smokers and 25% were current smokers. The LD group (n = 79) had more bilateral cases when compared to the DYS group (n = 30), 70% to 40.7%, respectively (P = 0.008), and a lower average age [56–62, respectively (P = 0.043)]. All other parameters were similar. When compared to LR patients, the LD group had a higher percentage of men [41.8–27.9%, respectively (P = 0.08)] while all other parameters were similar. CONCLUSIONS: As clinical characteristics of LD are more similar to the LP and LR group than to dysplasia, these findings may indicate that LD should be considered as part of the lichen planus disorder spectrum rather than a separate entity, although further analysis of larger groups is warranted. These results support the need for clinical follow-up among patients diagnosed with lichenoid changes. Oral Diseases (2015) 21, 478–482 Keywords: mucosal diseases; pre-cancer; oncology; lichen planus
Correspondence: Rakefet Czerninski, DMD, The Department of Oral Medicine, Hebrew University –Hadassah School of Dental Medicine, POB 12272, Jerusalem 91120, Israel. Tel: (9722) 6776141, Fax: (9722) 6447919, E-mail: [email protected] Received 1 October 2014; revised 17 November 2014; accepted 30 November 2014
Introduction Oral lichen planus (OLP) is a chronic oral and cutaneous inflammatory disease found in 0.5–2.2% of the general population (Al-Hashimi et al, 2007). Lichenoid reaction (LR) has some clinical and histopathological similarities to LP and some consider it a variant of OLP (Ismail et al, 2007). Oral dysplasia usually has a different patient profile and is diagnosed microscopically. The management of dysplastic lesions is controversial, but the majority of studies favor surgical excision and a follow-up due to its potential to become malignant even after excision (van der Waal, 2010). The potential of LP and lichenoid lesions in general for malignant transformation is controversial (Lodi et al, 2005; van der Waal, 2014). Currently, the common practice is to have a close follow-up among patients diagnosed with LP or lichenoid lesions to detect malignant transformation at early stages, as clinical and histological overlap with true premalignant lesions often makes for a difficult diagnosis (Gale et al, 2005; Le Cleach and Chosidow, 2012). Some consider that true transformations occur, while others think that the diagnosis of lichenoid lesions with dysplastic changes is a distinct pathology (Eisenberg, 2000) and not part of the LP spectrum. Recently, it was reported that histologically lichenoid features are found in oral dysplasia and squamous cell carcinoma (Fitzpatrick et al, 2014). The authors also claim that the criteria for lichenoid lesions are subjective and might contribute to the inconsistent diagnosis. As the approach to treating LP and lichen planus with dysplasia (LD) is an unsolved question and a clinical dilemma, we wanted to learn whether LD is a distinct pathological entity or part of a group of LP/lichenoid diseases. As the histological diagnosis is not objective and there are no standardized or molecular tests available, we decided to study the clinical features of these conditions. Our objective was to compare the clinical characteristics of LD cases to oral dysplasia only (DYS), LP only, and LR only cases.
Characteristics of lichen, dysplasia, and combination
R Czerninski et al
479
Paents with biopsies & histopathologic diagnosis 2007-2012
Patients and Methods This retrospective study included patients treated at the Department of Oral Medicine between 2007 and 2012 who had a biopsy during these years with a histological diagnosis of LP, LR, DYS, or LD (patients diagnosed with graft-vs-host disease were not included in the study). All histopathology diagnoses were conducted at the Department of Pathology at the Hadassah medical center. Patient information collected from the medical files included gender, age (years) at the day of the biopsy, ethnic origin (Israel, Europe and USA, Africa, Asia, Post-Soviet States, Arab, and others), smoking habits (none, past smoker (over 10 years ago), or current smoker [smoking or stopped up to 10 years ago)], medical background with main disorder groups (endocrinopathic, cardiovascular, neoplastic, autoimmune, others), and number of medications (more or >5 medications per day, not including nutritional supplement and vitamins). Oral lesion’s characteristics (from which the biopsy was taken) included type (erosive/red, reticular/white, or combined) and size in mm (diameter or longest dimension as evaluated by the clinician). The oral manifestation of the disease was also recorded as unilateral or bilateral, the location and number of involved sites (tongue (ventral, lateral, or dorsal), hard palate, gingival, buccal, lips, and/or floor of mouth).
Ethical approval The study was approved by the institutional review board of Hadassah Medical Center, which determined that patient consent was not required as no identifiers were obtained in the retrospective medical record review protocol, and was performed in accordance with the ethical standards laid down in the Declaration of Helsinki.
Statistical analysis Data were entered into EXCEL software and then SPSS 21.0 for data analysis. Associations between variables were tested using the Pearson chi-squared test, independent t-test, and ANOVA when appropriate. The level of significance was set at 5%.
Results Seven hundred fifty eight patients had biopsies and histopathological diagnosis between 2007 and 2012. Only those with a diagnosis of LP, LR, DYS, or LD were included in the study (Figure 1). A total of 235 patients (92 men and 143 women) with 235 biopsies were included. The average age of the patients was 56 (age range 13–86). 54% were never smokers and 25% were current smokers. Sixty-seven patients (25%) were free of major chronic diseases (such as diabetes and hypertension), while others (n = 168) reported chronic diseases. Of this group, 58% (n = 98) had more than one chronic disease; the major groups of diseases were cardio-vascular (50%), endocrinopathies (43%), previous malignancy (24%), and autoimmune disease (18%). 38 patients were taking more than five medications per day. There were no statistically significant differences between the subgroups. Fifty-one percent (n = 121) of the biopsied lesions were reticular (with significant difference between the subgroups), 13% were erosive, and the rest were combined (Table 1). More than half of the biopsies (57%) were taken from the buccal mucosa, a fifth (21%) from the tongue, and the rest from other sites in the mouth, with significant difference between the groups (Table 1). The average size of these lesions was 12 mm (13 mm in the LD group, 11 mm in the LP group, 12 mm for the LR group and 11 mm of the DYS group), without significant differences between the groups.
N = 758 Included in the study Paents diagnosed with LP DYS or LD LP, LR LR, DYS,
Excluded from the study Paents diagnosed with Any other pathology
N = 523
N = 235
LP 1
N = 57 1 2
LR 1
N = 69
LD 1,2
N = 79
DYS 2
N = 30
Total diagnosed with lichenoid features N = 205 Total diagnosed with dysplasc changes N = 109
Figure 1 Subjects included and excluded from the study
Study group 109 of the 758 cases were diagnosed with dysplasia. Of these, a minority of 30 cases (27.5%) were dysplasia only (DYS group) and 79 cases showed dysplastic changes with lichen planus or lichenoid reaction (LD group). 205 of 758 patients presented with histological lichenoid features. Sixty nine cases were diagnosed as lichenoid reaction (LR) and 57 as lichen planus (LP) (Figure 1). The demographic characteristics of the LD group were compared to each of the other groups. Subjects in the LD group had a lower average age when compared to the DYS group (56–62 years, respectively (P = 0.043), Figure 2) and similar average age as the other groups. The gender ratio in the LD group was similar to others except for the LR group, which had a lower percentage of men compared to other groups (41.8–27.9%, respectively (P = 0.08), Figure 3). All of the other demographic parameters (ethnic origin, smoking history, medical background, percentage of patients taking more than five medications per day) were similar, with no statistically significant differences between the study groups. The clinical characteristics of the disorders were also compared. The percentage of cases with multiple sites (which could be unilateral) was over 75% at all groups, with a statistically significant difference between the LD and LP groups (77.2–94.7%, respectively (P = 0.021), Figure 4). The LD group had a high percentage of bilateral cases, similar to the LP and LR groups, and significantly higher than DYS cases (70% vs 40.7%, respectively (P = 0.008), Figure 5). All other clinical characteristics were similar among the groups.
Discussion The aim of the current study was to add a clinical aspect to the discussion of the nature of LP and dysplasia cases by comparing them with dysplasia only cases or LP/LR only cases. We analyzed clinical and epidemiological features of 235 patients. Most of the patients had a medical backOral Diseases
Characteristics of lichen, dysplasia, and combination
R Czerninski et al
480
ground which can be related to an average age of 56, with no significant difference between the groups. The percentage of current smokers reflected the percentage of smokers in Israel, which is 21% of the population (Ministry of Health, 2012), and was not different among the groups. 205 of 758 newly diagnosed patients presented with histological lichenoid features. This distribution reflects
the patient distribution in oral medicine clinics in which lichen-related diseases are the most common disease. It is commonly recommended that these patients be closely monitored, due to the potential for malignant transformation, which means a life-long follow-up (Greaney et al, 2014; van der Waal, 2014). The potential for malignant transformation of LP and LR lesions is controversial
Table 1 Biopsied lesions’ characteristics Study groups (%)
Lesion’s type
Reticular Combined Erosive Total Buccal mucosa Tongue (lateral & ventral) Gingiva Lips Palate Tongue (dorsal) Floor of mouth Total
Lesion’s site
64
DYS
LD
LP
LR
P
53 20 27 100% 37 43 10 10 0 0 0 100%
44 18 38 100% 56 29 6 4 2 1 3 100%
68 3 29 100% 72 9 14 2 2 0 1 100%
48 14 38 100% 52 10 19 9 7 3 0 100%
0.049 0.486 0.070
*
62 60
100
**
**
58
**
80
56
60
54
40
52
*
0.002
** 94.7
88.4
LP
LR
77.2
76.7
20
50
DYS LD *P = 0.043,**P > 0.05
LP
LR
Figure 2 Average age by study groups
0
DYS LD *P = 0.021, ** P > 0.05
Figure 4 Percentage of cases with multiple involved sites
100 80 60 40
** **
*
80%
20
80
82
40.7
20%
DYS LD *P = 0.08,**P > 0.05
Figure 3 Men distribution by study groups Oral Diseases
70
**
60% 40%
0
**
*
100%
LP
LR
0%
DYS LD *P = 0.008,**P > 0.05
LP
Figure 5 Percentage of cases with bilateral involvement
LR
Characteristics of lichen, dysplasia, and combination
R Czerninski et al
among clinicians and researchers, however (Le Cleach and Chosidow, 2012; Greaney et al, 2014), although some think that it might represent a true transformation of a lichenoid lesion. In that case, a lesion with lichenoid features and dysplasia could be showing the beginnings of carcinogenesis and therefore every lesion, LP or LR, could be at risk. Others think that transformation is simply related to the similarities in clinical and histological appearance between LP and dysplasias that appear ‘lichenoid’ (Van der Meij et al, 2003 Fitzpatrick et al, 2014). Clearly, understanding the nature of ‘lichen and dysplasia’ as a subgroup of dysplasia or part of lichen planus diseases has a clinical importance related to management protocol. The histological diagnosis of lichen planus, lichenoid lesions, and lichenoid dysplasia might be too similar and based on subjective measures (Van der Waal, 2009; van der Waal, 2014). Therefore, an analysis of the clinical aspect of these conditions may contribute to the discussion. Of the 235 biopsies studied, 109 were with dysplasia, and more than two-thirds of them had lichenoid features (LD group). When comparing the demographic features of the LD group with other groups, the average age was found to be similar to LP and LR, with the only significant difference arising when compared to the DYS group, which had a higher average age, as was also reported by others (Arduino et al, 2009; Ho et al, 2012). Comparison by gender showed that the LD group falls between DYS patients, which had the highest percentage of males, and the LR group, which had the lowest percentage, although the differences were not large. The slightly higher percentage of females for the lichen planus group of diseases is in accordance with the literature reporting a higher percentage of women among LP and LR patients (Van der Waal, 2009; Le Cleach and Chosidow, 2012). The majority of lesions biopsied were of the reticular or white type, reflecting the common clinical features of the lichen planus/lichenoid reaction pathologies (Le Cleach and Chosidow, 2012) and also oral dysplasia (Ho et al, 2012). The high percentage for buccal mucosa as the biopsy site is due to the fact that it is the most common site for this lesion (Van der Waal, 2009) and the easiest to tolerate for the patient when a diagnostic biopsy is needed in a multisite condition. The majority of tongue biopsies were from the dysplasia subgroups (DYS and LD) as they were performed to diagnose a suspected lesion. For the other groups, a biopsy was done for confirmation of the clinical diagnosis of lichen planus and the site could be chosen. In these cases, clinicians usually prefer to take the biopsy from the buccal mucosa, which is more readily tolerable for the patient. The clinical characteristics were also compared. The majority of cases for all groups had multiple oral sites involved, which were either unilateral or bilateral. In the DYS cases, this could be explained as the result of smoking, while in the lichen group of diseases, multiple lesions are a common feature. In the small range of 77% to 95% of multiple sites, the LD group was more similar to DYS cases, but when comparing the percentage of oral bilateral cases, the LD group is significantly closer to the results of the LP/LR cases than to DYS.
In conclusion, we have determined that the clinical characteristics of LD are more similar to the LP and LR group than to DYS and therefore may indicate that LD should be considered as part of the lichen planus disorder spectrum rather than a separate entity, although further analysis of larger groups is warranted. Our results support the concept of clinical management of the lichenoid diseases as premalignant conditions and suggest that careful follow-up is required to monitor for transformation.
481
Author contributions Rakefet Czerninski – the clinical PI for the study, designed the study, analyzed results, conducted the literature review, and co-wrote the final draft and revision. Shelly Zeituni collected the data, and made the tables and figures. Alexander Maly made the pathological diagnosis and reviewed the final draft and revision. John Basile analyzed results and co-wrote the final draft and revision. References Al-Hashimi I, Schifter M, Lockhart PB et al (2007). Oral lichen planus and oral lichenoid lesions: diagnostic and therapeutic considerations. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 103 Suppl:S25:e1–e12. Arduino PG, Surace A, Carbone M et al (2009). Outcome of oral dysplasia: a retrospective hospital-based study of 207 patients with a long follow-up. J Oral Pathol Med 38: 540–544. Eisenberg E (2000). Oral lichen planus: a benign lesion. J Oral Maxillofac Surg 58: 1278–1285. Fitzpatrick SG, Honda KS, Sattar A, Hirsch SA (2014). Histologic lichenoid features in oral dysplasia and squamous cell carcinoma. Oral Surg Oral Med Oral Pathol Oral Radiol 117: 511–520. Gale N, Pilch BZ, Sidransky D et al (2005). Epithelial precursor lesions. In: Barnes L, Eveson J, Reichart P, Sidransky D eds. Pathology and genetics of tumors of the head and neck. Lyon, France: International Agency for Research on Cancer (IARC), pp. 177–181. Greaney L, Brennan PA, Kerawala C, Cascarini L, Godden D, Coombes D (2014). Why should I follow up my patients with oral lichen planus and lichenoid reactions? Br J Oral Maxillofac Surg 52: 291–293. Ho MW, Risk JM, Woolgar JA et al (2012). The clinical determinants of malignant transformation in oral epithelial dysplasia. Oral Oncol 48: 969–976. Ismail SB, Kumar SK, Zain RB (2007). Oral Lichen planus and lichenoid reaction. etiopathogenesis, diagnosis, management and malignant transformation. J Oral Sci 49: 89–106. Le Cleach L, Chosidow O (2012). Lichen planus. N Engl J Med 366: 723–732. Lodi G, Scully C, Carrozzo M, Griffiths M, Sugerman PB, Thongprasom K (2005). Current controversies in oral lichen planus: report of an international consensus meeting. Part 2. Clinical management and malignant transformation. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 100: 164–178. Ministry of Health (2012). Annual report –smoking in Israel, published May 2013 http://www.health.gov.il/PublicationsFiles/smoking-2012.pdf [accessed on 15 December 2014] Van der Meij EH, Schepman KP, Van der Waal I (2003). The possible premalignant character of oral lichen planus and oral
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lichenoid lesions: a prospective study. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 96: 164–171. Van der Waal I (2009). Oral lichen planus and oral lichenoid lesions` a critical appraisal with emphasis on the diagnostic aspects. Med Oral Patol Oral Cir Bucal 14: E310–E314.
Oral Diseases
van der Waal I (2010). Potentially malignant disorders of the oral and oropharyngeal mucosa; present concepts of management. Oral Oncol 46: 423–425. van der Waal I (2014). Oral potentially malignant disorders: is malignant transformation predictable and preventable. Med Oral Patol Oral Cir Bucal 19: 386–390.
ORIGINAL ARTICLE
Clinical characteristics of lichen and dysplasia vs lichen planus cases and dysplasia cases R Czerninski1, S Zeituni2, A Maly3, J Basile4 1
Department of Oral Medicine, Hebrew University-Hadassah School of Dental Medicine, Jerusalem, Israel; 2Hebrew UniversityHadassah School of Dental Medicine, Jerusalem, Israel; 3Department of Pathology, Hadassah Medical Center, Jerusalem, Israel; 4 Department of Oncology and Diagnostic Sciences, University of Maryland Dental School, Baltimore, MD, USA
OBJECTIVES: To compare the clinical characteristics of lichen planus with dysplasia (LD) cases with oral dysplasia (DYS), and LP/lichenoid reaction (LP/LR). METHODS: Patients treated at the Department of Oral Medicine with a histological diagnosis were included. Patient information (age, gender, ethnicity, smoking habits, and medical status) and parameters of oral manifestation (lesions’ distribution, site, and type) were compared. RESULTS: Two hundred and thirty five patients were included. 54% were never smokers and 25% were current smokers. The LD group (n = 79) had more bilateral cases when compared to the DYS group (n = 30), 70% to 40.7%, respectively (P = 0.008), and a lower average age [56–62, respectively (P = 0.043)]. All other parameters were similar. When compared to LR patients, the LD group had a higher percentage of men [41.8–27.9%, respectively (P = 0.08)] while all other parameters were similar. CONCLUSIONS: As clinical characteristics of LD are more similar to the LP and LR group than to dysplasia, these findings may indicate that LD should be considered as part of the lichen planus disorder spectrum rather than a separate entity, although further analysis of larger groups is warranted. These results support the need for clinical follow-up among patients diagnosed with lichenoid changes. Oral Diseases (2015) 21, 478–482 Keywords: mucosal diseases; pre-cancer; oncology; lichen planus
Correspondence: Rakefet Czerninski, DMD, The Department of Oral Medicine, Hebrew University –Hadassah School of Dental Medicine, POB 12272, Jerusalem 91120, Israel. Tel: (9722) 6776141, Fax: (9722) 6447919, E-mail: [email protected] Received 1 October 2014; revised 17 November 2014; accepted 30 November 2014
Introduction Oral lichen planus (OLP) is a chronic oral and cutaneous inflammatory disease found in 0.5–2.2% of the general population (Al-Hashimi et al, 2007). Lichenoid reaction (LR) has some clinical and histopathological similarities to LP and some consider it a variant of OLP (Ismail et al, 2007). Oral dysplasia usually has a different patient profile and is diagnosed microscopically. The management of dysplastic lesions is controversial, but the majority of studies favor surgical excision and a follow-up due to its potential to become malignant even after excision (van der Waal, 2010). The potential of LP and lichenoid lesions in general for malignant transformation is controversial (Lodi et al, 2005; van der Waal, 2014). Currently, the common practice is to have a close follow-up among patients diagnosed with LP or lichenoid lesions to detect malignant transformation at early stages, as clinical and histological overlap with true premalignant lesions often makes for a difficult diagnosis (Gale et al, 2005; Le Cleach and Chosidow, 2012). Some consider that true transformations occur, while others think that the diagnosis of lichenoid lesions with dysplastic changes is a distinct pathology (Eisenberg, 2000) and not part of the LP spectrum. Recently, it was reported that histologically lichenoid features are found in oral dysplasia and squamous cell carcinoma (Fitzpatrick et al, 2014). The authors also claim that the criteria for lichenoid lesions are subjective and might contribute to the inconsistent diagnosis. As the approach to treating LP and lichen planus with dysplasia (LD) is an unsolved question and a clinical dilemma, we wanted to learn whether LD is a distinct pathological entity or part of a group of LP/lichenoid diseases. As the histological diagnosis is not objective and there are no standardized or molecular tests available, we decided to study the clinical features of these conditions. Our objective was to compare the clinical characteristics of LD cases to oral dysplasia only (DYS), LP only, and LR only cases.
Characteristics of lichen, dysplasia, and combination
R Czerninski et al
479
Paents with biopsies & histopathologic diagnosis 2007-2012
Patients and Methods This retrospective study included patients treated at the Department of Oral Medicine between 2007 and 2012 who had a biopsy during these years with a histological diagnosis of LP, LR, DYS, or LD (patients diagnosed with graft-vs-host disease were not included in the study). All histopathology diagnoses were conducted at the Department of Pathology at the Hadassah medical center. Patient information collected from the medical files included gender, age (years) at the day of the biopsy, ethnic origin (Israel, Europe and USA, Africa, Asia, Post-Soviet States, Arab, and others), smoking habits (none, past smoker (over 10 years ago), or current smoker [smoking or stopped up to 10 years ago)], medical background with main disorder groups (endocrinopathic, cardiovascular, neoplastic, autoimmune, others), and number of medications (more or >5 medications per day, not including nutritional supplement and vitamins). Oral lesion’s characteristics (from which the biopsy was taken) included type (erosive/red, reticular/white, or combined) and size in mm (diameter or longest dimension as evaluated by the clinician). The oral manifestation of the disease was also recorded as unilateral or bilateral, the location and number of involved sites (tongue (ventral, lateral, or dorsal), hard palate, gingival, buccal, lips, and/or floor of mouth).
Ethical approval The study was approved by the institutional review board of Hadassah Medical Center, which determined that patient consent was not required as no identifiers were obtained in the retrospective medical record review protocol, and was performed in accordance with the ethical standards laid down in the Declaration of Helsinki.
Statistical analysis Data were entered into EXCEL software and then SPSS 21.0 for data analysis. Associations between variables were tested using the Pearson chi-squared test, independent t-test, and ANOVA when appropriate. The level of significance was set at 5%.
Results Seven hundred fifty eight patients had biopsies and histopathological diagnosis between 2007 and 2012. Only those with a diagnosis of LP, LR, DYS, or LD were included in the study (Figure 1). A total of 235 patients (92 men and 143 women) with 235 biopsies were included. The average age of the patients was 56 (age range 13–86). 54% were never smokers and 25% were current smokers. Sixty-seven patients (25%) were free of major chronic diseases (such as diabetes and hypertension), while others (n = 168) reported chronic diseases. Of this group, 58% (n = 98) had more than one chronic disease; the major groups of diseases were cardio-vascular (50%), endocrinopathies (43%), previous malignancy (24%), and autoimmune disease (18%). 38 patients were taking more than five medications per day. There were no statistically significant differences between the subgroups. Fifty-one percent (n = 121) of the biopsied lesions were reticular (with significant difference between the subgroups), 13% were erosive, and the rest were combined (Table 1). More than half of the biopsies (57%) were taken from the buccal mucosa, a fifth (21%) from the tongue, and the rest from other sites in the mouth, with significant difference between the groups (Table 1). The average size of these lesions was 12 mm (13 mm in the LD group, 11 mm in the LP group, 12 mm for the LR group and 11 mm of the DYS group), without significant differences between the groups.
N = 758 Included in the study Paents diagnosed with LP DYS or LD LP, LR LR, DYS,
Excluded from the study Paents diagnosed with Any other pathology
N = 523
N = 235
LP 1
N = 57 1 2
LR 1
N = 69
LD 1,2
N = 79
DYS 2
N = 30
Total diagnosed with lichenoid features N = 205 Total diagnosed with dysplasc changes N = 109
Figure 1 Subjects included and excluded from the study
Study group 109 of the 758 cases were diagnosed with dysplasia. Of these, a minority of 30 cases (27.5%) were dysplasia only (DYS group) and 79 cases showed dysplastic changes with lichen planus or lichenoid reaction (LD group). 205 of 758 patients presented with histological lichenoid features. Sixty nine cases were diagnosed as lichenoid reaction (LR) and 57 as lichen planus (LP) (Figure 1). The demographic characteristics of the LD group were compared to each of the other groups. Subjects in the LD group had a lower average age when compared to the DYS group (56–62 years, respectively (P = 0.043), Figure 2) and similar average age as the other groups. The gender ratio in the LD group was similar to others except for the LR group, which had a lower percentage of men compared to other groups (41.8–27.9%, respectively (P = 0.08), Figure 3). All of the other demographic parameters (ethnic origin, smoking history, medical background, percentage of patients taking more than five medications per day) were similar, with no statistically significant differences between the study groups. The clinical characteristics of the disorders were also compared. The percentage of cases with multiple sites (which could be unilateral) was over 75% at all groups, with a statistically significant difference between the LD and LP groups (77.2–94.7%, respectively (P = 0.021), Figure 4). The LD group had a high percentage of bilateral cases, similar to the LP and LR groups, and significantly higher than DYS cases (70% vs 40.7%, respectively (P = 0.008), Figure 5). All other clinical characteristics were similar among the groups.
Discussion The aim of the current study was to add a clinical aspect to the discussion of the nature of LP and dysplasia cases by comparing them with dysplasia only cases or LP/LR only cases. We analyzed clinical and epidemiological features of 235 patients. Most of the patients had a medical backOral Diseases
Characteristics of lichen, dysplasia, and combination
R Czerninski et al
480
ground which can be related to an average age of 56, with no significant difference between the groups. The percentage of current smokers reflected the percentage of smokers in Israel, which is 21% of the population (Ministry of Health, 2012), and was not different among the groups. 205 of 758 newly diagnosed patients presented with histological lichenoid features. This distribution reflects
the patient distribution in oral medicine clinics in which lichen-related diseases are the most common disease. It is commonly recommended that these patients be closely monitored, due to the potential for malignant transformation, which means a life-long follow-up (Greaney et al, 2014; van der Waal, 2014). The potential for malignant transformation of LP and LR lesions is controversial
Table 1 Biopsied lesions’ characteristics Study groups (%)
Lesion’s type
Reticular Combined Erosive Total Buccal mucosa Tongue (lateral & ventral) Gingiva Lips Palate Tongue (dorsal) Floor of mouth Total
Lesion’s site
64
DYS
LD
LP
LR
P
53 20 27 100% 37 43 10 10 0 0 0 100%
44 18 38 100% 56 29 6 4 2 1 3 100%
68 3 29 100% 72 9 14 2 2 0 1 100%
48 14 38 100% 52 10 19 9 7 3 0 100%
0.049 0.486 0.070
*
62 60
100
**
**
58
**
80
56
60
54
40
52
*
0.002
** 94.7
88.4
LP
LR
77.2
76.7
20
50
DYS LD *P = 0.043,**P > 0.05
LP
LR
Figure 2 Average age by study groups
0
DYS LD *P = 0.021, ** P > 0.05
Figure 4 Percentage of cases with multiple involved sites
100 80 60 40
** **
*
80%
20
80
82
40.7
20%
DYS LD *P = 0.08,**P > 0.05
Figure 3 Men distribution by study groups Oral Diseases
70
**
60% 40%
0
**
*
100%
LP
LR
0%
DYS LD *P = 0.008,**P > 0.05
LP
Figure 5 Percentage of cases with bilateral involvement
LR
Characteristics of lichen, dysplasia, and combination
R Czerninski et al
among clinicians and researchers, however (Le Cleach and Chosidow, 2012; Greaney et al, 2014), although some think that it might represent a true transformation of a lichenoid lesion. In that case, a lesion with lichenoid features and dysplasia could be showing the beginnings of carcinogenesis and therefore every lesion, LP or LR, could be at risk. Others think that transformation is simply related to the similarities in clinical and histological appearance between LP and dysplasias that appear ‘lichenoid’ (Van der Meij et al, 2003 Fitzpatrick et al, 2014). Clearly, understanding the nature of ‘lichen and dysplasia’ as a subgroup of dysplasia or part of lichen planus diseases has a clinical importance related to management protocol. The histological diagnosis of lichen planus, lichenoid lesions, and lichenoid dysplasia might be too similar and based on subjective measures (Van der Waal, 2009; van der Waal, 2014). Therefore, an analysis of the clinical aspect of these conditions may contribute to the discussion. Of the 235 biopsies studied, 109 were with dysplasia, and more than two-thirds of them had lichenoid features (LD group). When comparing the demographic features of the LD group with other groups, the average age was found to be similar to LP and LR, with the only significant difference arising when compared to the DYS group, which had a higher average age, as was also reported by others (Arduino et al, 2009; Ho et al, 2012). Comparison by gender showed that the LD group falls between DYS patients, which had the highest percentage of males, and the LR group, which had the lowest percentage, although the differences were not large. The slightly higher percentage of females for the lichen planus group of diseases is in accordance with the literature reporting a higher percentage of women among LP and LR patients (Van der Waal, 2009; Le Cleach and Chosidow, 2012). The majority of lesions biopsied were of the reticular or white type, reflecting the common clinical features of the lichen planus/lichenoid reaction pathologies (Le Cleach and Chosidow, 2012) and also oral dysplasia (Ho et al, 2012). The high percentage for buccal mucosa as the biopsy site is due to the fact that it is the most common site for this lesion (Van der Waal, 2009) and the easiest to tolerate for the patient when a diagnostic biopsy is needed in a multisite condition. The majority of tongue biopsies were from the dysplasia subgroups (DYS and LD) as they were performed to diagnose a suspected lesion. For the other groups, a biopsy was done for confirmation of the clinical diagnosis of lichen planus and the site could be chosen. In these cases, clinicians usually prefer to take the biopsy from the buccal mucosa, which is more readily tolerable for the patient. The clinical characteristics were also compared. The majority of cases for all groups had multiple oral sites involved, which were either unilateral or bilateral. In the DYS cases, this could be explained as the result of smoking, while in the lichen group of diseases, multiple lesions are a common feature. In the small range of 77% to 95% of multiple sites, the LD group was more similar to DYS cases, but when comparing the percentage of oral bilateral cases, the LD group is significantly closer to the results of the LP/LR cases than to DYS.
In conclusion, we have determined that the clinical characteristics of LD are more similar to the LP and LR group than to DYS and therefore may indicate that LD should be considered as part of the lichen planus disorder spectrum rather than a separate entity, although further analysis of larger groups is warranted. Our results support the concept of clinical management of the lichenoid diseases as premalignant conditions and suggest that careful follow-up is required to monitor for transformation.
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Author contributions Rakefet Czerninski – the clinical PI for the study, designed the study, analyzed results, conducted the literature review, and co-wrote the final draft and revision. Shelly Zeituni collected the data, and made the tables and figures. Alexander Maly made the pathological diagnosis and reviewed the final draft and revision. John Basile analyzed results and co-wrote the final draft and revision. References Al-Hashimi I, Schifter M, Lockhart PB et al (2007). Oral lichen planus and oral lichenoid lesions: diagnostic and therapeutic considerations. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 103 Suppl:S25:e1–e12. Arduino PG, Surace A, Carbone M et al (2009). Outcome of oral dysplasia: a retrospective hospital-based study of 207 patients with a long follow-up. J Oral Pathol Med 38: 540–544. Eisenberg E (2000). Oral lichen planus: a benign lesion. J Oral Maxillofac Surg 58: 1278–1285. Fitzpatrick SG, Honda KS, Sattar A, Hirsch SA (2014). Histologic lichenoid features in oral dysplasia and squamous cell carcinoma. Oral Surg Oral Med Oral Pathol Oral Radiol 117: 511–520. Gale N, Pilch BZ, Sidransky D et al (2005). Epithelial precursor lesions. In: Barnes L, Eveson J, Reichart P, Sidransky D eds. Pathology and genetics of tumors of the head and neck. Lyon, France: International Agency for Research on Cancer (IARC), pp. 177–181. Greaney L, Brennan PA, Kerawala C, Cascarini L, Godden D, Coombes D (2014). Why should I follow up my patients with oral lichen planus and lichenoid reactions? Br J Oral Maxillofac Surg 52: 291–293. Ho MW, Risk JM, Woolgar JA et al (2012). The clinical determinants of malignant transformation in oral epithelial dysplasia. Oral Oncol 48: 969–976. Ismail SB, Kumar SK, Zain RB (2007). Oral Lichen planus and lichenoid reaction. etiopathogenesis, diagnosis, management and malignant transformation. J Oral Sci 49: 89–106. Le Cleach L, Chosidow O (2012). Lichen planus. N Engl J Med 366: 723–732. Lodi G, Scully C, Carrozzo M, Griffiths M, Sugerman PB, Thongprasom K (2005). Current controversies in oral lichen planus: report of an international consensus meeting. Part 2. Clinical management and malignant transformation. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 100: 164–178. Ministry of Health (2012). Annual report –smoking in Israel, published May 2013 http://www.health.gov.il/PublicationsFiles/smoking-2012.pdf [accessed on 15 December 2014] Van der Meij EH, Schepman KP, Van der Waal I (2003). The possible premalignant character of oral lichen planus and oral
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