Oral lichen planus: Malignant potential and diagnosis

Oral lichen planus (OLP) is one of the most common diseases of the oral mucosa. Clinically, it has specific and clearly identifiable features; bilateral symmetric presentation showing a lace-like network of fine white lines (known as Wickham's striae) is an essential element of OLP even if the lesion exhibits a mainly atrophic and erosive pattern. There are various lesions that resemble OLP clinically and histologically. These lesions are widely referred to as lichenoid reactions or lichenoid lesions (OLLs). OLLs include contact hypersensitivity to dental materials, drug-induced lichenoid lesions, lichenoid reactions in chronic graft-versus-host disease, and other lesions that resemble OLP. The risk of malignant transformation of OLP is the subject of ongoing debate in the literature. Some authors have suggested that only OLLs, but not OLP, are of a premalignant nature and thus, should be categorized as “other dysplastic conditions.” Contrary to this suggestion, many cases of oral squamous cell carcinoma (OSCC) developing in patients with OLP presenting with no epithelial dysplasia have been reported. In addition, it has been reported that multiple events including multifocal dysplasia and/or OSCC subsequently occurred in some patients with OLP, suggesting possible field cancerization in OLP. In this paper, differential diagnosis between OLP and OLLs and their malignant potential are reviewed.     

Squamous cell carcinoma arising in an oral lichenoid lesion

BACKGROUND: Oral lichen planus, or OLP, is a chronic inflammatory mucocutaneous disease that frequently involves the oral mucosa. Lichenoid dysplasia, or LD, refers to lesions that could be mistaken clinically for OLP but have histologic features of dysplasia and a true malignant predisposition. Published case reports of OLP conversion to squamous cell carcinoma, or SCC, have created a great deal of controversy about the true nature of OLP, highlighting the need to verify its clinical diagnosis histologically. CASE DESCRIPTION: The authors document the development of SCC in a 58-year-old woman with an oral lesion diagnosed clinically as OLP and described histologically as having lichenoid features with dysplastic changes. The time from the initial diagnosis of oral lichenoid lesions to the patient's return visit to the medical center with clinically evident cancer was three years and eight months. The SCC developed in the labial mucobuccal fold and left mandibular edentulous ridge, which had undergone multiple biopsy procedures. CLINICAL IMPLICATIONS: This case does not provide answers to the ongoing controversy about the innate propensity of OLP to become malignant. However, in view of both the common occurrence of OLP and unresolved issues regarding its premalignant potential, this case report illustrates the need for histologic confirmation and close follow-up of patients with clinical lesions that have lichenoid features.     

Histochemical analysis of pathological alterations in oral lichen planus and oral lichenoid lesions

Lichen planus is a dermatologic disease of unknown etiology characterized by keratotic plaques on the skin. Many patients also harbor white lesions of the oral mucosa. The literature contains numerous reports of lichen planus-like lesions evolving in conjunction with the administration of a variety of pharmacologic agents. It is difficult, if not impossible, to distinguish such lesions from one another. The present study evaluated the epithelial and basement membrane thickness, mast cells (intact cells and degranulated cells subepithelially) and the presence or absence of blood vessels in oral lichen planus and oral lichenoid lesions. The evaluation was done using the periodic acid-schiff (PAS) and toluidine blue staining techniques on 20 cases each of oral lichen planus and oral lichenoid lesions and 5 control specimens of normal buccal mucosa. The results showed an increased number of degranulated mast cells in areas of basement membrane degeneration, increased vascularity and increased PAS-positive basement membrane thickness in oral lichen planus as compared with oral lichenoid lesions. Reduced epithelial thickness was found in oral lichen planus. The present study emphasizes the importance of these parameters in differentiating oral lichen planus from oral lichenoid lesions using special staining techniques.     

Dysplasia in oral lichen planus: relevance,controversies and challenges. A position paper

Background Patients with oral lichen planus (OLP) have an increased risk of oral cancer. For this reason, OLP is classified as an oral potentially malignant disorder. However, the precise personal (or individual) risk is unknown. Recent meta-analytical studies have reported that dysplastic OLP may transform to cancer in around 6% of cases, while the rate of transformation is lower (<1.5%) in non-dysplastic cases. The presence of epithelial dysplasia has emerged as the most powerful indicator for assessing cancer risk in oral potentially malignant disorders in routine practice. However, the general acceptance of epithelial dysplasia as an accompanying histologic feature in OLP is subject to great controversy. Many pathologists consider the presence of dysplasia as a criterion to exclude OLP when routinely reporting on this disease. This practice, widespread among oral pathology professionals, has resulted in the underestimation of the potential for malignancy of OLP.Material and Methods A review of the literature was carried out in order to critically analyze the relevance, controversies and challenges encountered across the diagnosis of epithelial dysplasia in OLP.Results 12 studies have been published examining dysplastic changes in OLP, reporting Figures ranging from 0.54% to 25% of cases with dysplasia in the first diagnostic biopsy. The diagnosis of dysplasia in the OLP poses an additional difficulty due to the fact that the affected oral epithelium per se develops changes related to autoimmune aggression. Among the most frequent histological features of OLP that develops dysplasia are basal cell hyperplasia with basaloid appearance, loss of basal cells polarity, cellular and nuclear pleomorphism and irregular stratification.Conclusions Epithelial dysplasia should not be considered an exclusion criterion for OLP; its evaluation requires experienced pathologists in this field. Key words:Oral lichen planus, epithelial dysplasia, oral cancer.     

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.     

Involucrin as a diagnostic marker in oral lichenoid lesions

Thirty-eight biopsy specimens were examined for involucrin reactivity by an immunoperoxidase technique. The sampling consisted of specimens diagnosed as normal oral mucosa, reactive epithelial hyperplasia, lichen planus (LP), nonspecific lichenoid stomatitis (NLS), lichenoid dysplasia (LD), carcinoma in situ, and squamous cell carcinoma (SCCa) on routine hematoxylin and eosin examination. Findings were consistent with prior observations of involucrin reactivity in skin and cervical-vaginal mucosa. Specifically, conditions characterized by predominance of mature squamous epithelial cells (superficial layers of normal and hyperplastic oral epithelium, NLS, and LP) exhibited strong involucrin reactivity in such areas. In contrast, atypical or dysplastic lichenoid lesions (LD), as well as carcinoma in situ, despite squamoid differentiation, demonstrated irregular distribution of involucrin, suggesting disturbances in terminal differentiation. Invasive components of SCCa revealed markedly diminished involucrin expression. These findings support prior evidence that LP and LD are biologically distinct lesions. Clinically and microscopically, both may be morphologically similar. However, involucrin reactivity should be helpful in distinguishing difficult cases. Accordingly, we suggest that the use of involucrin immunoreactivity may prove to be a valuable adjunct in the separation of similar lichenoid oral conditions.     

Oral lichen planus: progress in understanding its malignant potential and the implications for clinical management

Oral lichen planus (OLP) is an inflammatory lesion that has malignant potential, but few cases of OLP progress to malignancy. A diagnosis of OLP should be confirmed on the basis of historical, clinical, and histologic data. The presence of dysplasia in an OLP-like lesion increases the risk of malignant transformation, mandating management and close follow-up. A molecular assessment of OLP may provide the best evidence of malignant risk and will likely become available for clinical use. In addition, exfoliated cells may be examined for loss of heterozygosity and may become a valuable clinical tool for patient follow-up. The treatment of OLP should include elimination of tissue irritants and recurring exposure to oral carcinogens. If OLP is symptomatic, appropriate treatment with immunosuppressive medications, particularly corticosteroids, should be undertaken. For lesions with dysplastic changes, management may include attention directed to the inflammatory change and follow-up biopsies to assess residual histologic changes that may represent dysplasia. Dysplastic OLP may be best treated as other oral dysplastic conditions; thus, regular, more frequent follow-up is required.     

Number V Oral lichen planus: clinical features and management

Oral lichen planus (OLP) is a relatively common chronic inflammatory disorder affecting stratified squamous epithelia. Whereas in the majority of instances, cutaneous lesions of lichen planus (LP) are self-limiting and cause itching, oral lesions in OLP are chronic, rarely undergo spontaneous remission, are potentially premalignant and are often a source of morbidity. Current data suggest that OLP is a T cell-mediated autoimmune disease in which auto-cytotoxic CD8+ T cells trigger apoptosis of oral epithelial cells. The characteristic clinical aspects of OLP may be sufficient to make a correct diagnosis if there are classic skin lesions present. An oral biopsy with histopathologic study is recommended to confirm the clinical diagnosis and mainly to exclude dysplasia and malignancy. The most commonly employed and useful agents for the treatment of lichen planus (LP) are topical corticosteroids but other newer agents are available.     

Evaluation on Malignant Transformation of Oral Lichen Planus

目的：口腔扁平苔藓（oral lichen planus,OLP)是否属于癌前病变，至今仍存在较大的争论。本文的目的在于评估OLP的癌变性质。方法：报告1995－2002年之间9例OLP的癌变病例。结果：5例OLP患者同时或继发为口腔鳞状细胞癌，1例为疣状癌，3例为上皮异常增生。其中7例发生在原OLP存在的部位，1例发生在其它部位，1例在同一部位同时存在OLP和鳞状细胞癌。OLP的癌变常发生在糜烂型和萎缩型，发生于颊粘膜，舌或牙龈。根据所制定的OLP的诊断及癌变标准，4例OLP患者发生了癌变。结论：OLP具有一定的癌变潜力，对OLP患者应每年随访2－4次，尤其是对发生在颊粘膜，舌或牙龈的糜烂型和萎缩型的患者。     

Oral lichen planus: A disease or a spectrum of tissue reactions? Types,causes, diagnostic algorhythms,prognosis, management strategies

Oral lichen planus and lichenoid lesions comprise a group of disorders of the oral mucosa that likely represent a common reaction pattern to 1 or more unknown antigens. The coexistence of hyperkeratotic striation/reticulation, varying degrees of mucosal inflammation from mild erythema to severe widespread ulceration, and a band‐like infiltrate of mononuclear inflammatory cells including activated T lymphocytes, macrophages, and dendritic cells, are considered suggestive of oral lichen planus and lichenoid lesions. Several classification systems of oral lichen planus and lichenoid lesions have been attempted, although none seem to be comprehensive. In this paper, we present a classification of oral lichen planus and lichenoid lesions that includes oral lichen planus, oral lichenoid contact lesions, oral lichenoid drug reactions, oral lichenoid lesions of graft vs. host disease, discoid lupus erythematosus, and systemic lupus erythematosus, lichen planus‐like variant of paraneoplastic pemphigus/paraneoplastic autoimmune multiorgan syndrome, chronic ulcerative stomatitis, lichen planus pemphigoides, solitary fixed drug eruptions, and lichen sclerosus. We present the clinical and diagnostic aspects of oral lichen planus and lichenoid lesions, and discuss related treatment options.     

Oral lichen planus: clinical presentation and management

Oral lichen planus (OLP) is a chronic mucosal condition commonly encountered in clinical dental practice. Lichen planus is believed to represent an abnormal immune response in which epithelial cells are recognized as foreign, secondary to changes in the antigenicity of the cell surface. It has various oral manifestations, the reticular form being the most common. The erosive and atrophic forms of OLP are less common, yet are most likely to cause symptoms. Topical corticosteroids constitute the mainstay of treatment for symptomatic lesions of OLP. Recalcitrant lesions can be treated with systemic steroids or other systemic medications. However, there is only weak evidence that these treatments are superior to placebo. Given reports of a slightly greater risk of squamous cell carcinoma developing in areas of erosive OLP, it is important for clinicians to maintain a high index of suspicion for all intraoral lichenoid lesions. Periodic follow-up of all patients with OLP is recommended.     

No evidence of hypersensitivity to dental restorative metals in oral lichen planus

Abstract – Twelve patients with oral lichen planus (OLP) suspected of dental restorative metal allergy were examined. All patients were patch tested with several metals including six different mercury compounds. One (8%) patient showed a positive patch test to two mercury compounds whereas no mercury allergy was found in a reference group of 17 patients suspected of dental restorative material allergy but without OLP lesions. The mercury allergic OLP patient was further tested on palatal mucosa but no reactions developed. Moreover, the energy dispersive X-ray microanalysis failed to show any contaminating metals in his OLP lesion. Mucosal biopsies were taken in close contact with amalgam fillings from nine OLP patients but these disclosed no evidence of lichenoid or dysplastic alterations. In OLP lesions, the immunofluorescence findings showed fibrinogen deposition, altered basement membrane and elastic fiber staining and intense Ulex europeaus I lectin fluorescence through all epithelial cell layers. Therefore, the present patch tests did not reveal increased frequency of mercury or other metal allergy in OLP patients and the mucosal biopsies failed to show any histologic or immunofluorescence alterations deviating from idiopathic OLP lesions.     

No evidence of hypersensitivity to dental restorative metals in oral lichen planus

Twelve patients with oral lichen planus (OLP) suspected of dental restorative metal allergy were examined. All patients were patch tested with several metals including six different mercury compounds. One (8%) patient showed a positive patch test to two mercury compounds whereas no mercury allergy was found in a reference group of 17 patients suspected of dental restorative material allergy but without OLP lesions. The mercury allergic OLP patient was further tested on palatal mucosa but no reactions developed. Moreover, the energy dispersive X-ray microanalysis failed to show any contaminating metals in his OLP lesion. Mucosal biopsies were taken in close contact with amalgam fillings from nine OLP patients but these disclosed no evidence of lichenoid or dysplastic alterations. In OLP lesions, the immunofluorescence findings showed fibrinogen deposition, altered basement membrane and elastic fiber staining and intense Ulex europeaus I lectin fluorescence through all epithelial cell layers. Therefore, the present patch tests did not reveal increased frequency of mercury or other metal allergy in OLP patients and the mucosal biopsies failed to show any histologic or immunofluorescence alterations deviating from idiopathic OLP lesions.     

Oral lichen planus and related lesions. What should we accept based on the available evidence?

Recent new terminologies have been proposed for lesions in the sphere of oral lichen planus (OLP) that theoretically present unique aetiological, clinical, prognostic or management characteristics different from those of the so-called typical forms of OLP. We aimed to critically analyse what concepts and terminologies related to OLP should we accept based on the available evidence. A review of the literature was carried out in order to critically analyse the concepts and terminologies related to OLP. New concepts and terminologies include oral lichenoid lesions; contact lichenoid reactions, drug lichenoid reactions or those in the context of graft-versus-host disease; chronic ulcerative stomatitis; lichen planus pemphigoid; and some lesions that are difficult to categorise, such as OLP with features of proliferative verrucous leukoplakia and lichenoid lesions of the upper labial mucosa. A multidisciplinary, multicontinent working group has recently published a guideline with recommendations for modifying definitions and terminologies associated with a disease, among which a reasoned, evidence-based justification for the proposed change is considered essential. An in-depth analysis of the newly proposed terms for OLP-related lesions shows that many of them are not justified. In this paper, we set out our position on the basis of the existing evidence on the appropriateness of the use of these new terms.     

Oral dysplasia and in situ carcinoma: clinicopathologic correlations of eight patients.

Eight patients with multiple oral dysplastic epithelial lesions were followed by clinical examinations and serial biopsies for periods varying from four to 22 years. The dysplasias and in situ carcinomas were characterized by persistence, recurrence, and eventual progression to invasive squamous cell carcinoma. It could not be determined whether dysplasia and in situ carcinoma were separate clinical-pathologic entities with similar end points or whether they were part of a continuum in a spectrum of epithelial neoplasia. The need for close clinical observation and local excision was emphasized because of the multiplicity of lesions and because of the protracted clinical course. Treatment of these patients was problematic because of similarities of the disease to lichen planus. It is possible that they had a premalignant disease process that mimicked lichen planus, or that they had an unusual form of lichen planus for which criteria have not been established. The progressive nature of the disease was exemplified by one death, one patient with cervical metastasis, and one with generalized remote metastatic disease.     

MAGE-A antigens in lesions of the oral mucosa

Oral squamous cell carcinoma develops continuously out of predamaged oral mucosa. For the physician and pathologist, difficulties arise in distinguishing precancerous from cancerous lesions. MAGE-A antigens are tumor antigens that are found solely in malignant transformed cells. These antigens might be useful in distinguishing precancerous from cancerous lesions. The aim of this study was to verify this assumption by comparing MAGE-A expression in benign, precancerous, and cancerous lesions of the oral mucosa. Retrospectively, biopsies of different oral lesions were randomly selected. The lesions that were included are 64 benign oral lesions (25 traumatic lesions (oral ulcers), 13 dental follicles, and 26 epulis), 26 oral lichen planus, 123 epithelial precursor lesions (32 epithelial hyperplasia found in leukoplakias, 24 epithelial dysplasia found in leukoplakias, 26 erythroplasia with oral epithelial dysplasia, and 41 carcinomas in situ in erythroleukoplakias). The lesions were immunohistochemically stained with the poly-MAGE-A antibody 57B, and the results were compared. Biopsies of oral lichen planus, oral ulcers, dental follicles, epulis, and leukoplakia without dysplasia showed no positive staining for MAGE-A antigens. Leukoplakia with dysplasia, dysplasia, and carcinomata in situ displayed positive staining in 33%, 65%, and 56% of the cases, respectively. MAGE-A antigens were not detectable via immunohistochemistry in benign lesions of the oral mucosa. The staining rate of dysplastic precancerous lesions or malignant lesions ranged from 33% to 65%. The MAGE-A antigens might facilitate better differentiation between precancerous and cancerous lesions of the oral mucosa.     

Oral lichen planus and lichenoid reactions: etiopathogenesis, diagnosis, management and malignant transformation

Lichen planus, a chronic autoimmune, mucocutaneous disease affects the oral mucosa (oral lichen planus or OLP) besides the skin, genital mucosa, scalp and nails. An immune mediated pathogenesis is recognized in lichen planus although the exact etiology is unknown. The disease most commonly affects middle-aged females. Oral lichenoid reactions (OLR) which are considered variants of OLP, may be regarded as a disease by itself or as an exacerbation of an existing OLP, by the presence of medication (lichenoid drug reactions) or dental materials (contact hypersensitivity). OLP usually presents as white striations (Wickham's striae), white papules, white plaque, erythema, erosions or blisters. Diagnosis of OLP is established either by clinical examination only or by clinical examination with histopathologic confirmation. Direct immunofluorescence examination is only used as an adjunct to the above method of diagnosis and to rule out specific autoimmune diseases such as pemphigus and pemphigoid. Histopathologic features of OLP and OLR are similar with suggestions of certain discriminatory features by some authors. Topical corticosteroids are the treatment of choice for OLP although several other medications have been studied including retinoids, tacrolimus, cyclosporine and photodynamic therapy. Certain OLP undergo malignant transformation and the exact incidence and mechanisms are still controversial. In this paper, etiopathogenesis, diagnosis, management and malignant transformation of OLP and OLR have been reviewed.     

Amalgam-contact hypersensitivity lesions and oral lichen planus

OBJECTIVE: The purpose of this study was to investigate the relationship between amalgam restorations and oral lichen planus. STUDY DESIGN: Eighty-one patients with oral lichenoid lesions were characterized clinically and skin patch tested for amalgam or mercury hypersensitivity. Thirty-three of these patients had amalgam fillings in contact with oral lesions replaced and were followed to determine the outcome. RESULTS: Clinically, 2 patient groups were identified: (1) 30 patients with probable amalgam-contact hypersensitivity lesions (ACHLs) and (2) 51 patients with oral lichen planus (OLP) but no clear relationship with amalgam. Seventy percent of ACHL cases were patch test positive for amalgam or mercury compared with only 3.9% of OLP cases (P < .0001). Amalgam replacement resulted in lesion improvement in 93% of ACHL cases. No such improvement was observed in the OLP cases treated (P < .001). CONCLUSION: OLP is a heterogeneous condition within which an ACHL subgroup can be identified. ACHLs, but not other OLP lesions, respond favorably to amalgam replacement. A strong clinical association between lesions and amalgam restorations plus a positive patch test result was a good predictor of lesion improvement on amalgam replacement.     

Evaluation of premalignant potential in oral lichen planus using interphase cytogenetics

This study attempted to evaluate whether oral lichen planus (OLP) has the potential to progress to oral squamous cell carcinoma (OSCC) by comparing the degree of genetic instability between clinically-curable OLP and lesions that progressed to OSCC. Fifteen cases of steroid-responsive OLP and two cases of lichenoid dysplasia (LD) that progressed to OSCC were used for this study. Chromosome in situ hybridization (CISH) was performed for chromosomes 9 and 17. The fraction of polysomic and monosomic cells for chromosome 9 increased in mucosal epithelium compared to those of lymphocytes in OLP. This difference was statistically significant (P=0.0017, 0.0054, respectively). Two LD patients showed 15.38% and 22.58% of PI for chromosome 9. In OSCC that developed from LD, the fraction of monosomic cells for chromosome 9 increased by more than 70%. We concluded that LD should be treated as a high-risk premalignant lesion and strongly suggest that the monosomy of chromosome 9 may have a critical role in progress to malignancy from LD.