The malignant transformation of oral lichen planus and oral lichenoid lesions: A systematic review

BackgroundDetermining the potential for malignant transformation of oral lichen planus (OLP) is complicated by difficulties in diagnosis, differentiation from oral lichenoid lesions (OLLs) and the phenomenon of premalignant lesions' exhibiting lichenoid characteristics. The authors of this systematic review evaluated evidence regarding malignant transformation of OLP and characterized transformation prevalence, clinical characteristics of OLP lesions developing into squamous cell carcinoma (SCC) and time to transformation.Types of Studies ReviewedThe authors searched PubMed, Embase and Thomson Reuters Web of Science in a systematic approach. They evaluated observational English-language studies involving human participants published in peer-reviewed journals. Inclusion required patients to have the diagnosis of OLP or OLL as confirmed with biopsy results on initial enrollment. They excluded all patients who had dysplasia on initial biopsy of OLP or OLL lesions.ResultsSixteen studies were eligible. Among 7,806 patients with OLP, 85 developed SCC. Among 125 patients with OLL, four developed SCC. The rate of transformation in individual studies ranged from 0 to 3.5 percent. The overall rate of transformation was 1.09 percent for OLP; in the solitary study in which investigators evaluated OLL, the rate of transformation was 3.2 percent. Patients' average age at onset of SCC was 60.8 years. The authors noted a slight predominance of female patients among those who experienced malignant transformation. The most common subsite of malignant transformation was the tongue. The average time from diagnosis of OLP or OLL to transformation was 51.4 months.Practical ImplicationsA small subset of patients with a diagnosis of OLP eventually developed SCC. The most common demographic characteristics of patients in this subset were similar to the most common demographic characteristics associated with OLP in general (that is, being female, being older and being affected in areas common to this condition). It is prudent for clinicians to pursue continued regular observation and follow-up in patients with these conditions, even in patients who do not fit a traditional high-risk category for oral SCC.     

Toll-like receptor 2 rs4696480 polymorphism and risk of oral cancer and oral potentially malignant disorder

ObjectivesThe aim of this study was to identify the possible association between TLR polymorphisms and an increased risk of developing head and neck cancer, including oral (OSCC) and laryngeal squamous cell carcinoma (LSCC), and oral potentially malignant disorders, such as oral lichenoid disease (OLD), including oral lichen planus (OLP) and oral lichenoid lesions (OLL).DesignThis case-control study included 40 OSCC, 35 LSCC, 175 OLD (129 OLP and 46 OLL) patients and 89 healthy controls, all of them from the Basque Country, Spain. Genetic polymorphisms in TLR1, TLR2, TLR4, TLR6, TLR9, and TLR10 were genotyped by TaqMan^® assays or pyrosequencing.ResultsThe chi-square analysis showed that the variant A of the SNP TLR2-rs4696480 polymorphism significantly increased the risk of OSCC (p = 0.03) and OLL (p = 0.02).ConclusionsThe TLR2-rs4696480 polymorphism may be relevant to OSCC and OLL susceptibility in this population encouraging further studies on the TLR2 pathway and its possible association with this group of oral potentially malignant disorders and oral cancer. This may also prove the use of TLR polymorphisms as risk markers for oral and laryngeal cancer.     

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.     

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.     

血管内皮生长因子在口腔扁平苔藓及鳞癌组织中的表达

目的探讨血管内皮生长因子在口腔扁平苔藓癌变及发病机制中的作用。方法采用免疫组化法,检测10例正常口腔黏膜、25例口腔扁平苔藓、11例口腔扁平苔藓伴不典型增生及14例口腔鳞癌,上皮组织中血管内皮生长因子的表达水平。结果血管内皮生长因子在24例口腔扁平苔藓标本中阳性表达2例,阴性表达22例,阳性表达率明显低于其它3组（P〈0.05）。扁平苔藓伴不典型增生及口腔鳞癌中血管内皮生长因子的阳性表达率均高于正常黏膜（P〈0.05）。结论血管内皮生长因子的表达异常可能在口腔扁平苔藓的发生发展及癌变的过程中起作用。     

High percentage of oral lichen planus and lichenoid lesion in oral squamous cell carcinomas

Objective: Oral lichen planus (OLP) and lichenoid lesions (OLL) are regarded as precursor lesions of oral squamous cell carcinoma (OSCC) with potential for malignant transformation. This potential is not clear due to difficulties in diagnosis of OLP and OLL. Our aim was therefore to evaluate previously identified OLP and OLL as precursor lesions in OSCC and to identify cancer related etiological factors such as smoking and alcohol consumption.

Material and methods: We retrospectively reviewed all cases (total 323, comprising 164 females and 159 males) with OSCC treated at the Department of Oral and Maxillofacial Diseases and Surgery, Helsinki University Hospital during 2015. Confirmed by histopathological biopsy, 58 (17.9%) had OLP and 13 had OLL (4.0%) as precursor lesion.

Results: Patients with OLP were slightly older than those without it. OLP was more common in females than in males (p?p?=?.006) and cancer relapses less common (p?=?.005). Smoking was less frequent in patients with OLP and OLL (p?p?Conclusion: Our findings confirm the importance of active follow-up of all patients with OLP and OLL even in patients who do not fit a traditional high-risk category for OSCC.     

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。     

US8Xerostomia

The lichenoid reactions are one of the most prevalent pathological reaction patterns of the oral mucosa. Oral lichen planus (OLP), lichenoid contact reactions (LCR) and graft-versus-host disease belong to this group of lichenoid reactions. Apart from a common clinical appearance, these disorders cannot be discriminated from each other by the use of histopathological techniques. New knowledge about the etiology behind LCR and GvHD can also, to some extent, be extrapolated to the immune mechanisms, which participate in the pathogeneses of OLP. Besides a discussion on different etiological aspects of OLP, this presentation will focus on treatment strategies used to manage lichenoid reactions. During recent years a debate has been conducted on the malignant potential of lichenoid reactions.     

DJ-1和PTEN在口腔鳞癌及癌前病变中的检测及意义

目的检测口腔鳞癌及癌前病变中DJ-1和PTEN的表达并分析其临床意义。方法免疫组织化学方法检测46例口腔鳞癌,16例口腔扁平苔藓,19例白斑和10例正常口腔黏膜标本中DJ-1、PTEN两种蛋白的分布,分析各个指标和病理参数的关系。结果口腔鳞癌组织中DJ-1增高,阳性率为89%（41/46）,与正常口腔黏膜、口腔白斑和口腔扁平苔藓相比,差异有统计学意义（P=0.000）;PTEN在口腔鳞癌组织中降低,阳性率为57%（26/46）,与正常口腔黏膜、白斑和口腔扁平苔藓对比,差异有统计学意义（P=0.000）。经Spearman等级相关检验,DJ-1和PTEN之间的相关系数r为-0.67,P〈0.01,差异具有统计学意义,表明DJ-1和PTEN之间存在负相关。结论 DJ-1、PTEN在口腔鳞癌发生过程中均起着一定的作用;DJ-1可能通过负性调控PTEN而导致口腔肿瘤的发生。     

Progressive increase of human papillomavirus carriage rates in potentially malignant and malignant oral disorders with increasing malignant potential

Introduction:  We investigated the potential role of human papillomaviruses (HPVs) in potentially malignant oral disorders, oral leukoplakia (OL) and oral lichen planus (OLP), and in oral squamous cell cancer (OSCC) in an Eastern Hungarian population with a high incidence of OSCC.
Methods:  Excised tumor samples (65 OSCC patients) and exfoliated cells from potentially malignant lesions (from 44 and 119 patients with OL and OLP, respectively) as well as from healthy controls (72 individuals) were analysed. OLPs were classified based on clinical appearance, 61 patients had erosive–atrophic lesions (associated with higher malignancy risk, EA-OLP) and 58 had non-erosive non-atrophic lesions (with lower risk of becoming malignant, non-EA-OLP), respectively. Exfoliated cells collected from apparently healthy mucosa accompanied each lesion sample. HPV was detected by MY/GP polymerase chain reaction (PCR) and genotyped by restriction analysis of amplimers. Copy numbers in lesions were determined using real-time PCR. Prevalence rates, copy number distributions, and association with risk factors and diseases were analysed using chi-square test, t -test, and logistic regression, respectively.
Results:  We detected HPVs significantly more frequently in lesions than in controls ( P  ≤ 0.001 in all comparisons). HPV prevalence increased gradually with increasing severity of lesions (32.8, 40.9, and 47.7% in OLP, OL, and OSCC, respectively). Copy number distribution patterns roughly corresponded to prevalence rates, but OLP and OL were comparable. HPV prevalence differed significantly between EA-OLP and non-EA-OLP groups (42.6 vs. 22.4%); EA-OLP group showed a prevalence similar to that found in OL.
Conclusion:  HPVs may be involved in the development or progression of not only OSCC but also of potentially malignant oral lesions.     

Oral lichenoid dysplasia: a clinicopathologic analysis

Three women had a diagnosis of oral lichen planus (OLP), which was made on the basis of clinical and histologic features. All three had persistent burning pain associated with large mucosal lesions. Changes in the color (red, red and white, white), configuration, and severity of the lesions were unpredictable and did not correlate well with topical corticosteroid therapy. Only one patient used tobacco (cigarettes)--this patient had recurrent oral candidiasis and was receiving multiple medications. One of the two nonsmokers was a denture wearer with a single episode of candidiasis. After 63, 32, and 56 (mean 50) months, carcinoma developed in all three. In retrospect, the initial biopsy specimens of two patients exhibited lichenoid dysplasia, whereas that of the third showed only lichenoid mucositis. Although speckled erythroplakia was the earliest clinical sign of a classic, nonregressing premalignant lesion, it already signaled the presence of invasive carcinoma. Some early epithelial dysplasias appear to have a robust inflammatory/immunologic response to the antigenically (but as yet not histologically) altered dysplastic epithelium and a high probability of at least temporary resolution. Mucosal erythema of obscure origin displaying spontaneous, usually temporary, partial to complete regression may be common to both purely inflammatory conditions like lichen planus and early epithelial dysplasia. We contend that some, if not most, cases of apparent malignant transformation of OLP likely represent red and white lesions that were dysplastic from their inception but that mimic OLP both clinically and histologically.     

口腔苔藓样病变的研究进展

口腔苔藓样病变(OLL)是一种与口腔扁平苔藓(OLP)极其相似的疾病,近年来,随着人们物质生活和医疗保健水平的提高,越来越多的患者接受了义齿修复、器官移植、化学治疗等医疗服务,使得OLL的患病率日趋升高。本文将近年来有关OLL的最新研究进展作一综述,以期能帮助口腔医生更加全面深入地认识这类疾病。     

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 squamous cell carcinoma around dental implants.

It is well documented that oral squamous cell carcinoma (OSCC) is related to risk factors such as smoking and alcohol consumption as well as premalignant lesions and conditions such as leukoplakia, oral lichen planus (OLP), and previous malignancy of the upper respiratory system and gastrointestinal tract. Osseointegrated dental implants are rarely reported in association with OSCC. This article presents 2 cases of OSCC adjacent to dental implants in patients at risk for oral cancer--1 was a heavy smoker with OLP; the other had a history of previous oral and colon cancer. Six additional cases of malignancy adjacent to dental implants were retrieved from the literature; the majority of cases had at least 1 recognized risk factor for oral cancer. Although such cases are rarely reported, patients at risk for oral cancer, especially those with multiple existing risk factors, that present with failing dental implants should be thoroughly evaluated to rule out the presence of malignancy disguised as peri-implant disease.     

口腔黏膜癌前病变和口腔鳞状细胞癌中Stat3的表达及意义

目的研究口腔黏膜癌前病变和口腔鳞状细胞癌(OSCC)中细胞信号传导和转录激活因子(Stat3)的表达及意义。方法采用免疫组化方法分别检测9例正常口腔黏膜,口腔扁平苔藓(OLP)和白斑(OLK)共8例,OLP、OLK伴异常增生22例,OSCC19例中Stat3的表达。结果Stat3阳性表达分布于细胞质和细胞核内。正常口腔黏膜、单纯增生、异常增生和OSCC中Stat3阳性表达率分别为11.11%(1/9)、12.50%(1/8)、59.09%(13/22)和84.21%(16/19)。OSCC与正常口腔黏膜、单纯增生、异常增生相比,差异有显著性(P<0.05);异常增生与正常口腔黏膜、单纯增生相比,差异有显著性(P<0.05);而单纯增生和正常口腔黏膜相比差异无显著性(P>0.05)。结论Stat3与口腔黏膜癌变的发生发展有着密切关系,对Stat3表达的研究将有助于口腔黏膜癌前病变癌变的检测和OSCC的早期诊断。     

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.     

iNOS在口腔扁平苔藓癌变过程中的表达研究

目的 :研究诱导型一氧化氮合酶 (iNOS)在口腔扁平苔藓、口腔鳞状细胞癌发展过程中的表达水平及其作用。方法 :以正常口腔黏膜作对照 ,采用免疫组化SP法检测 2 5例口腔扁平苔藓和 10例口腔鳞状细胞癌组织中的iNOS表达。结果 :正常口腔黏膜iNOS阴性表达 ;扁平苔藓组和鳞癌组iNOS表达较正常黏膜组均非常显著增加 (P <0 .0 1) ;扁平苔藓组与鳞癌组之间以及扁平苔藓组内部按上皮异常增生程度分组之间iNOS的表达均无显著差异 (P >0 .0 5 )。结论 :iNOS在口腔扁平苔藓伴上皮异常增生和鳞癌中高表达 ,在口腔鳞癌的发生发展中起着重要的作用。     

Thermal sensation and pain in oral lichen planus and lichenoid reaction

BACKGROUND: Our previous findings in oral lichen planus (OLP) and lichenoid reactions (LR) raised the question whether the histopathological changes observed in sensory and autonomic innervation produce oral sensory disorders. METHODS: Spontaneous pain was assessed using the Visual Analogue Scale (VAS). Thermal pain thresholds were measured with a contact thermostimulator and mechanical pain thresholds with an electronic algometer. RESULTS: Patients with OLP reported a higher intensity of spontaneous pain than LR patients (P = 0.001). Even erosive LRs were relatively painless. No thermal or mechanical hyperalgesia was detected in oral lesions. Highest separate cold pain threshold was measured in lesions affected by intense Candida growth. CONCLUSION: Together with previous histological findings, the present data suggest that increased somatic innervation and sympathetic denervation do not promote clinical pain sensitivity or hyperalgesia in oral mucosa and that these sensory functions are not affected by OLP and LR. Candida growth may function as secondary irritant modulating the pain responses.