Oral lichen planus: controversies surrounding malignant transformation

Studies of the malignant potential of oral lichen planus (OLP) have been hampered by inconsistencies in the diagnostic criteria used for OLP, the criteria adopted to identify a true case of malignant transformation in OLP, the risk factors for malignant transformation and the optimum management of patients to ensure the early diagnosis of transformation. Consensus remains elusive, and leading workers in this field have recently published conflicting reports on the malignant potential of OLP and on the important question of the advisability of excluding patients with epithelial dysplasia or a tobacco habit from studies on this issue. The present review outlines these debates and proposes a possible a molecular basis for the malignant transformation in this disease.     

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口腔扁平苔藓(oral lichen planus,OLP)是一种常见的口腔黏膜慢性炎性疾病,WHO将其列入潜在恶性病变(potentially malignant disorders)的范畴。有关OLP癌变的研究目前主要集中在流行病学调查、癌变危险性预测、癌变机制、化学预防等方面,而对其是否癌变近年产生疑问和争议。本文就OLP癌变的相关研究进展进行综述。     

A clinical study of 674 patients with oral lichen planus in China

BACKGROUND: Oral lichen planus (OLP) is a chronic inflammatory disease with different clinical presentations that can be classified as reticular, atrophic or erosive. Although OLP is a relatively common disorder, the reports comprising large numbers of OLP patients with specific character are lacking in the literature. The purpose of this paper was to describe the clinical characteristics of OLP in 674 Chinese patients. METHODS: A total of 674 charts of patients with histologically confirmed OLP were collected from Stomatological Hospital of Wuhan University between 1963 and 2003. RESULTS: Of the 674 patients, 65.9% were women and 34.1% were men. The most common clinical presentation was the reticular type (51.3%), and symptomatic OLP was noted in 67.5% of the patients, mainly in those with the erosive form. The erosive presentations showed significantly longer duration, more sites affected and a much greater old patients predominance than reticular or atrophic ones. About 90.9% of the patients had multiple oral sites of involvement and isolated lower lip lichen planus were observed in 60 cases (8.9%) and isolated gingiva lichen in only one case (0.2%). Skin involvement of lichen planus was found in 11.4% of patients. No statistically significant differences could be identified between OLP and diabetes, cardiovascular disease, smoking or alcohol use. Precipitating factors that resulted in an exacerbation of the disease were frequently noted and included foods, stress, dental cusp and poor oral hygiene. The transformation of OLP into malignancy was observed in four patients at sites previously diagnosed by clinical examination as erosive or atrophic lichen planus. CONCLUSIONS: Patients with OLP in China usually present with distinctive clinical morphology and characteristic distribution and few may display lesions with a confusing array of forms mimicking other diseases. A long time follow up is of utmost importance to detect its malignant transformation.     

细胞自噬在口腔扁平苔藓恶变中作用的研究进展

口腔扁平苔藓(OLP)是一种常见的口腔黏膜炎症性疾病,易复发并存在恶变的可能,具体的病因和发病机制尚不清楚。细胞自噬是真核细胞生物中高度保守的生命现象,作为程序性细胞死亡的方式之一,在维持细胞内环境的稳态方面起到重要作用。目前关于细胞自噬与OLP发病及恶变的关系的相关报道较少,本文就细胞自噬与口腔扁平苔藓的联系作一探讨。     

Factors predicting malignant transformation in oral potentially malignant disorders among patients accrued over a 10‐year period in South East England

J Oral Pathol Med (2011) 40 : 677–683 Objective: The aims of the study were to determine how frequently oral potentially malignant disorders (OPMDs) transform to cancer and to identify clinical and histological factors determining the rates of transformation. Methods: The study included 1357 patients with biopsy‐confirmed OPMDs seen at Guy’s Hospital between 1990 and 1999 and followed up until 2005. The patients’ details (name, date of birth, gender and any other relevant information) were matched to the Thames Cancer Registry (TCR) database and Office for National Statistics (ONS) to identify patients who subsequently developed oral cancer (ICD‐10 C00–C06). From each patient’s record, we identified their highest grade of dysplasia, graded as none, mild, moderate or severe. The outcome of principal interest was transformation to oral squamous cell carcinoma. To avoid co‐existing malignancies, follow‐up was started 6 months after the date of the index biopsy. Kaplan–Meier estimates and Cox proportional hazard analysis were undertaken to explore the factors associated with the time to transformation to oral cancer. Results: One thousand three hundred and fifty‐seven patients were included in the study. The majority of patients were women (60.9%), and ∼30% were under 47 years of age. The most common OPMD was lichen planus/lichenoid reaction. Among all OPMDs, 204 (15.1%) had oral epithelial dysplasia (30 severe, 70 moderate and 104 mild). Thirty‐five patients developed oral cancer over the follow‐up period (2.6%). There was an association between dysplasia grade and time to transformation. Patients with severe dysplasia had a higher risk of transformation to oral cancer [HR 35.4 95% CI (14.2–88.3)] compared to those with no dysplasia. This association remained significant although attenuated [HR 21.6 95% CI (5.8–80.5)] following adjustment for sex, age, anatomical site of OPMD and diagnosis. A significant trend over dysplasia grades was evident (P < 0.0001). Transformation to oral cancer was also associated with increasing age (P = 0.0390). Conclusions: In 2.6% of cases, OPMDs transformed to invasive cancer for a total person follow‐up time of 12 273 years (mean 9.04 years). The severity of dysplasia is a significant predictor for malignant transformation.     

Telomerase activity in oral lichen planus

The purpose of this study was to determine the expression of telomerase in refractory oral lichen planus. Using a polymerase chain reaction-based telomerase activity assay, we investigated telomerase activity in 20 oral lichen planus specimens (erosive 9, atrophic 11). Telomerase activity was detected in 14 cases (erosive 7, atrophic 7). Furthermore, 13 cases of lichen planus with mild dysplasia proved telomerase-positive in eight specimens and six of seven cases devoid of dysplasia were also positive in the telomerase assay. The data indicate that, in general, telomerase activity might be frequently detectable in OLP. The data also suggest that telomerase activity might not be particularly associated with the premalignant phenotype in OLP.     

Mast cell expression in oral lichen planus: A systematic review

Lichen planus is a common chronic, inflammatory, immune‐mediated mucocutaneous disorder affecting the skin and mucosa. The role of mast cells in the genesis of lichen planus has been debated. Establishing a definitive part played by mast cells and its degranulation would possibly provide a permanent, cost‐effective treatment modality for oral lichen planus (OLP). This review aims to study the expression of mast cells qualitatively and quantitatively in OLP. The research questions were framed to assess the mast cell count, localization within the epithelium basement membrane zone and degranulation of mast cells. We performed a systematic search of PubMed, Medline, Cochrane and Web of Science. We found a total of 120 studies from which 12 were found suitable for the review. There is a marked increase in the number of mast cells in OLP. The mast cells were seen in increased numbers in the epithelial and connective tissue junction at areas of basement membrane disruption. There was also an increase in the degranulation of mast cells. It is evident that there is an increase in the mast cell number in lichen planus and its subsequent degranulation.     

A multicenter study of oral lichen planus in Thai patients

Abstract Aim: Oral lichen planus is an oral mucosal disease that affects middle‐aged patients. The characteristics of oral lichen planus in Thai patients from a multicenter were studied. Methods: Data of 533 patients from the oral medicine clinics at Chulalongkorn and Mahidol (central Thailand), Chiang Mai (northern Thailand), and Khon Kaen (northeastern Thailand) universities during 2002–2007 were analyzed. The diagnosis of patients with oral lichen planus was clinically and/or histopathologically confirmed. Results: There was a greater number of female patients than males (4:1). There were significant differences in age, sex, and some systemic diseases among the oral lichen planus patients from the three centers. Burning sensation was the most common symptom (72.9%), followed by pain (26.5%), roughness (6.4%), and then no other symptoms (7.9%). The most common site of lesions was found at the buccal mucosa (87.1%). Atrophic oral lichen planus was common in Thai patients. There were significant differences in the types of oral lichen planus, including reticular, atrophic, and ulcerative oral lichen planus among these patients from the three centers (P = 0.000). Nine cases (1.7%) showed dysplasia, but one case (0.2%) developed squamous cell carcinoma. Conclusion: Patients with oral lichen planus from the central, northern, and northeastern parts of Thailand presented with distinct characteristics. The malignant transformation of oral lichen planus was low in Thai patients.     

Lack of clinicopathologic correlation in the diagnosis of oral lichen planus based on the presently available diagnostic criteria and suggestions for modifications

INTRODUCTION: Confirmation of a clinical diagnosis of oral lichen planus (OLP) by means of histopathologic study of a biopsy specimen is generally advised. However, hardly any data exist about the correlation between clinical and histopathologic diagnoses of OLP. The aim of the present investigation was to study the correlation between the clinical and histopathologic assessment of OLP, and to propose diagnostic refinements, if appropriate. METHODS: Clinical and histopathologic data of two previously published studies were used for this purpose. The number of clinical cases in which all clinicians agreed as well as the number of microscopic slides on which all reviewing pathologists agreed were calculated and compared with each other in order to assess the clinicopathologic correlation. RESULTS: In 42% of the cases in which all clinicians agreed about the clinical diagnosis being diagnostic of OLP, there appeared to be no consensus on the histopathologic diagnosis. Conversely, in 50% of the cases in which all pathologists agreed about the histopathologic diagnosis being diagnostic of OLP there was a lack of consensus on the clinical diagnosis. CONCLUSION: Based on the findings of the present study, there appears to be a lack of clinicopathologic correlation in the diagnostic assessment of OLP. We therefore propose a set of revised diagnostic criteria of OLP and oral lichenoid lesions, based on the WHO definition of OLP, including clinical as well as histopathologic aspects.     

The role of histopathological characteristics in distinguishing amalgam-associated oral lichenoid reactions and oral lichen planus

OBJECTIVES: To identify histological features that distinguish amalgam-associated oral lichenoid reactions (AAOLR) from oral lichen planus (OLP). METHODS: Oral pathologists provided their opinion as to the possibility of distinguishing AAOLR and OLP histologically, the features important in distinguishing AAOLR from OLP and the diagnosis of 12 AAOLR and 12 OLP cases including the features that drew them to their conclusion. RESULTS: There was considerable variation between pathologists in their ability to distinguish the AAOLR and OLP cases. The sensitivity and specificity for histological diagnosis were 40% and 32% respectively. There were four features that were used most commonly to discriminate between AAOLR and OLP: an inflammatory infiltrate located deep to superficial infiltrate in some or all areas; a focal perivascular infiltrate; plasma cells in the connective tissue and neutrophils in the connective tissue. Each was independently predictive of AAOLR or OLP (P < 0.028). CONCLUSIONS: This study confirms the uncertainty of the diagnostic histological differences between AAOLR and OLP. Distinguishing these conditions should not rely on histology alone, but should be based on a synthesis of all available information including history, examination, histopathology and skin patch testing.     

ALDH1在OLP和LK组织中的表达及其意义

目的：通过检测干细胞标记物ALDH1在口腔扁平苔藓（OLP）和白斑（LK）中的表达水平,评价其与癌变的关系。方法：采用免疫组织化学SP法检测ALDH1在10例正常口腔黏膜,30例OLP,60例LK,10例口腔鳞癌（OS－CC）中表达水平;再检测ALDH1在30例癌变与30例未癌变LK中的表达差异。结果：ALDH1在正常口腔黏膜中不表达,在OLP、LK和OSCC中的表达率分别为26．7％,63．3％和90．0％（P＜0．05）;ALDH1在未癌变和癌变LK中的表达率分别是43．3％和83．3％（P＜0．01）。结论：ALDH1与口腔黏膜恶性潜能程度相关,可能是预测癌变的分子标记物。     

Autoimmune disorders in oral lichen planus: A systematic review and meta-analysis

Objectives

The association of OLP with other autoimmune processes points to the possibility that OLP-affected patients are actually developing an autoimmune status that predisposes them to autoaggression against different targets. This systematic review and meta-analysis aim to evaluate the current evidence on the prevalence of autoimmune disorders in patients with OLP and their magnitude of association.

Methods

We searched PubMed, Embase, Web of Science, Scopus databases for the studies published before May 2021, with no limitation in regards to their publication date or language. We evaluated the quality of studies, carried out meta-analyses and performed heterogeneity, subgroups, meta-regression, and small-study effects analyses.

Results

Inclusion criteria were met by 153 studies (23,327 patients). Our results indicate the existence of high prevalence and a frequent association between OLP and some autoimmune disorders, especially in regards to thyroid disease (PP = 7.96%, 95% CI = 6.32–9.75; OR = 1.99, 95% CI = 1.60–2.49, p < 0.001) and diabetes mellitus (PP = 9.41%,95% CI = 8.16–10.74; OR = 1.64, 95% CI = 1.34–2.00, p < 0.001).

Conclusions

Our study demonstrates the existence of a comorbidity between autoimmune thyroid diseases as well as between diabetes mellitus and OLP respectively. Quality of evidence should be upgraded on other autoimmune diseases (fibromyalgia, gastrointestinal disorders, rheumatic diseases, Sjogren's syndrome, lupus erythematosus, and dermatological diseases) for which the current data do not allow us to know whether they are really associated with OLP.     

Pathogenesis of oral lichen planus – a review

J Oral Pathol Med (2010) 39 : 729–734 Oral lichen planus (OLP) is a T‐cell‐mediated chronic inflammatory oral mucosal disease of unknown etiology. OLP presents as white striations, white papules, white plaques, erythema, erosions, or blisters affecting predominantly the buccal mucosa, tongue and gingiva. Both antigen‐specific and non‐specific mechanisms are hypothesized to be involved in the pathogenesis of oral lichen planus (OLP). Antigen‐specific mechanisms in OLP include antigen presentation by basal keratinocytes and antigen‐specific keratinocyte killing by CD8⁺ cytotoxic T cells. Non‐specific mechanisms include mast cell degranulation and matrix metalloproteinase activation in OLP lesions. These mechanisms may combine to cause T cell accumulation in the superficial lamina propria, basement membrane disruption, intra‐epithelial T cell migration and keratinocyte apoptosis in OLP. The various hypotheses proposed for pathogenesis of oral lichen planus are discussed in this review.     

Studies of the inflammatory process and malignant potential of oral mucosal lichen planus

Oral mucosal lichen planus (OMLP) is a well recognized mucosal disease with unknown aetiology. Considerable controversy exists as to whether OMLP is intrinsically premalignant, or if the disorder facilitates the development of oral mucosal squamous cell carcinoma (OMSCC) by external factors.
The aim of the present studies was to investigate the expression of c-erbB-2 protein in the keratinocytes of the initial biopsies of oral mucosal disorders diagnosed as OMLP with no evidence of epithelial dysplasia and to compare the results with the expression of c-erbB-2 protein in subsequent biopsies obtained from the same patients. These results were compared with the findings from another 26 biopsies from patiente with OMLP and control groups (patiente with dysplasia with no evidence of OMLP, patients with OMSCC with no evidence of OMLP and normal oral mucosa).
The expression of the c-erbB-2 protein was evaluated by Immunohistochemical staining of the gene product with the avidin-biotin-complex method using both fresh frozen and paraffin-embedded tissue sections.
Five of the initial biopsies from patients with OMLP expressed the c-erbB-2 protein and one did not. None of the OMLP cases that subsequently showed evidence of dysplasia expressed the c-erbB-2 protein and of the OMSCC specimens from the patients with OMLP, 2 were negative and 1 expressed c-erbB-2 protein. Within the other group of OMLP specimens 3 (3/26) were negative for c-erbB-2 staining. The specimens from the control groups all expressed the c-erbB-2 protein.
The results indicated the probability of the absence of c-erbB-2 staining being an indication of a potential for neoplastic transformation in OMLP with dysplastic changes.